The triad of vascular impairment, muscle atrophy, and cognitive decline represents critical age-related conditions that significantly impact health. Vascular impairment disrupts blood flow, precipitating muscle mass reduction seen in sarcopenia and the decline of neuronal functions characteristic of neurodegeneration. Our limited understanding of the intricate relationships within this triad hinders accurate diagnosis and effective treatment strategies. This review ana-lyzes the interrelated mechanisms that contribute to these conditions, with a specific focus on ox-idative stress, chronic inflammation, and impaired nutrient delivery. The aim is to understand the common pathways involved and to suggest comprehensive therapeutic approaches. Vascular dysfunctions hinder the circulation of blood and the transportation of nutrients, resulting in sar-copenia characterized by muscle atrophy and weakness. Vascular dysfunction and sarcopenia have a negative impact on physical function and quality of life. Neurodegenerative diseases exhibit comparable pathophysiological mechanisms that affect cognitive and motor functions. Preventive and therapeutic approaches encompass lifestyle adjustments, addressing oxidative stress, in-flammation, and integrated therapies that focus on improving vascular and muscular well-being. Better understanding of these links can refine therapeutic strategies and yield better patient out-comes. This study emphasizes the complex interplay between vascular dysfunction, muscle de-generation, and cognitive decline, highlighting the necessity for multidisciplinary treatment ap-proaches. Advances in this domain promise improved diagnostic accuracy, more effective thera-peutic options, and enhanced preventive measures, all contributing to a higher quality of life for the elderly population.

This study aimed to identify whether gyrate atrophy of the choroid and retina (GACR) heterozygous individuals have possible clinical manifestations and to explore the potential pathogenic mechanism. In this retrospective study, we surveyed a two-generation pedigree of an individual diagnosed with GACR. Two family members underwent ophthalmological, hematologic, and genetic tests. An arginine-restricted diet with vitamin B6 supplementation was implemented; clinical assessments were repeated every 3 months during follow-up. Relative OAT mRNA expression was determined using real-time quantitative polymerase chain reaction. The 19-year-old compound heterozygous daughter (OAT: c.1186C>T; c.748C>T), had bilateral high myopia, posterior staphyloma, chorioretinal atrophy, macular abnormalities, and elevated hematologic ornithine. The 54-year-old heterozygous mother (OAT: c.1186C>T), presented with bilateral severe myopia, asymmetric posterior staphyloma, retina and choroidal capillary layer atrophy, retinal pigment epithelium abnormalities, and mildly elevated hematologic ornithine. Compared to normal individuals, the daughter and mother had 29% and 46% relative OAT mRNA expression, respectively (P<0.001). We believe that this is the first report of a carrier of one OAT variant allele with mild phenotypes, suggesting that family members should be aware of the possible involvement of autosomal recessive conditions. Additional data suggests nonsense mediated decay-initiated mRNA degradation may cause GACR.

Can the type of implant rehabilitation influence peri-implant bone loss in case of full-arch mandibular prosthesis? The purpose of the study was to assess, by orthopantomograms (OPG), bone loss around implants in different types of implant-supported prosthetic rehabilitations and evaluate potential risk factors associated with the number and location of implants that may have an association with bone defect. A radiographic study was conducted on 22317 OPGs in the time range from 2010 to 2024. All OPGs with implant-supported prosthetic mandibular rehabilitations were included in the study. A total of 155 OPGs were evaluated, with peri-implant bone loss identified in 64 (41.3%). Distal implants (furthest from the center) across various positioning patterns were most susceptible to bone loss, with positions 3.6 and 4.6 demonstrating the most frequent occurrences (25 and 26 cases, respectively). χ² test revealed significant associations between both implant positioning pattern (p < 0.001) and number of implants (p < 0.001) with peri-implant bone loss. Also by updating the sample of OPGs, increased susceptibility to bone resorption was found for implants placed distal to the mental foramen compared to mesial ones in full-arch implant-supported fixed prostheses. Prospective clinical studies will then be useful to investigate this finding further.

Mandible is a bony structure of neuroectodermal origin with unique characteristics that support dentition and jaw movements. In the present study we investigated the effects of gestational exposure to a mixture of endocrine disrupting chemicals (EDCs) on mandibular growth in mice. The mixture under study (Mixture N1) has been associated with neurodevelopmental effects in both a human cohort and animal studies. Pregnant mice were exposed throughout gestation to 0.5x (times of pregnant women exposure levels), 10x, 100x and 500x of Mixture N1, or the vehicle, and the mandibles of the male offspring were studied in adulthood. Micro-CT analysis showed non-monotonic effects of Mixture N1 in the distances between specific mandibular landmarks and in the crown width of M1 molar, as well as changes in the mandibular bone characteristics. The alveolar bone volume was reduced, and the trabecular separation was increased in the 500X exposed mice. Bone volume in the condyle head was increased in all treated groups. The Alcian blue stained area of pre-hypertrophic chondrocytes in condyle’s head was increased in 0.5x, 10x and 100x groups, while the Safranin-O-stained area of mature hypertrophic chondrocytes was respectively reduced. This is the first indication that prenatal exposure to an epidemiologically defined EDC mixture, associated with neurodevelopmental impacts, can also affect mandibular growth in mammals.

Background:Caregiving for individuals with neurological disease involves providing physical, emotional, and social support, which can be a challenging and stressful experience. This study aims to compare the caregivers' burden, including the impact on mental and physical health, social support, and quality of life, in different neurodegenerative disorders. Methods:Fifty-five primary caregivers (F=41;mean age=53.07±12.29) of patients with Parkinson's Disease (PD=26), Multiple System Atrophy (MSA=16), and Amyotrophic Lateral Sclerosis (ALS=13), took part in the study. Standardized screening scales for the quality of life (EQ-5D/EQ-VAS and PQoL), levels of the caregiving burden (CBI and FSQ), and the assessment of the anxiety-depressive axis (HADS) were administered. Results: The mean CBI score was higher for caregivers of MSA patients (28.81±21.90) and ALS (25.15±16.23) than for caregivers of PD patients (16.08±10.34; p=0.036). Critical burden (cut-off>36) was present in the caregivers of MSA (31.3%), ALS (23.1%), and PD (19.2%) patients. Caregivers of patients with ALS had a worse perception of quality of life (EQ-5D total score) than caregivers of patients with MSA and PD (p

Ameloblastoma is an aggressive slow growing benign epithelial odontogenic tumor usually associated with an unerupted third molar. In this report, we present the case of a 71-year-old male with a large swelling on the left mandibular region causing a remarkable facial asymmetry. After clinical, radiological, and histopathological examinations the diagnosis of conventional ameloblastoma was made. To avoid probable recurrence our treatment choice was a segmental mandibular resection with the placement of a reconstructive titanium plate to maintain the space for subsequent bone graft.

Fatigue and dyspnea are the most commonly presented long-term complaints in individuals previously infected with SARS-CoV-2. The purpose of the study was to comprehensively evaluate diaphragm muscle function in COVID-19 survivors, as well as investigate whether potential diaphragm dysfunction will contribute to physical functioning impairment. 46 patients qualified to pulmonary rehabilitation were examined. Diaphragm muscle function parameters were evaluated using ultrasonography, while severity of dyspnea, aerobic capacity and amount of energy used by the body during physical activity were assessed by 6-minute walk test, mMRC scale and Metabolic Equivalent Task (MET), respectively. We identified 69.5% patients with diaphragm atrophy and 6.5% with diaphragm paralysis. Percentage of atrophy was not related to age, gender, BMI index, oxygen therapy use during COVID-19 infection course and severity of disease. Patients with presence of cough, fever and without loss of smell during COVID-19 course had a significantly greater values of diaphragm inspiratory thickness, while patients with cough and no smell disorders had a significantly lower percentage of diaphragm atrophy. Diaphragm functional parameters were strongly associated with selected variables of person's exercise tolerance, such as distance in 6-minute walk test, saturation level, fatigue and exertion in Borg scale. In conclusion, diaphragm muscle dysfunction is a serious long-term post-COVID aftermath and can be viewed as a major contributing factor of prolonged functional impairments.

Objective. The present study examined the potential use of computed tomography panoramic mandibular indices on cone beam CT (CBCT) for the assessment of bone density in postmenopausal women with low bone mass. Study design. We enrolled 104 postmenopausal women who performed dual energy X-ray absorptiometry (DXA) using a DXA scanner and mental foramen region CBCT using NewTom VGi EVO Cone Beam 3D system. We assessed the relationship between DXA parameters: lumbar, femoral neck and total hip T score, bone mineral density (BMD), and lumbar trabecular bone score (TBS) and the panoramic mandibular indices: computed tomography mandibular index superior (CTI(S)), computed tomography mandibular index inferior (CTI(I)) and computed tomography mental index (CTMI). Results. We found important correlations between the CTI(I), CTI(S) and CTMI and bone mass, quantitative evaluated as BMD and T-score and also quality using TBS score. Conclusion. CBCT measured indices CTI(S), CTI(I), CTMI are useful in assessing patients with low bone mass.

Background and Objectives: Age-related macular degeneration (AMD) is one of the major causes of central vision loss in the older age group and its dry form accounts for the majority of cases. Although several causes and mechanisms for the development and progression of AMD have previously been identified, the pathogenesis of this complex disease is still not entirely understood. As the inflammation and involvement of the immune system are strongly suggested to have a central role to promote the degenerative process and to stimulate the onset of complications, we aimed to analyze the prevalence of serum anti-retinal (ARA) and anti-endothelial cell antibodies (AECA) in patients with dry AMD and to determine their relationship with the clinical features of the disease, notably area of geographic atrophy (GA). Materials and Methods: We enrolled 41 patients with dry AMD and 50 sex- and age-matched healthy controls without AMD. The presence of ARA was determined by indirect immunofluorescence using monkey retina as an antigen substrate, while the presence of AECA was determined using cultivated human umbilical vein endothelial cells and primate skeletal muscle. Results: ARA were detected 36 (87.8%) AMD patients (titers range from 1:20 to 1:320) and in 16 (39.0%) (titers range from 1:10 to 1:40) of controls (p=0.0000). Twenty of the 41 patients (48.8%) were positive for AECA, while in a control group AECA were present only in 5 sera (10.0%). The titers of AECA in AMD patients ranged from 1:100 to 1:1000 and in the control group the AECA titers were 1:100 (p=0.0001). There were no significant correlations between the presence of AECA and disease activity. Conclusions: This study provides evidence for the possible involvement of an autoimmune process against retina and retinal vessel antigens in the pathogenesis of geographic atrophy associated with dry AMD.

Mandibular advancement devices (MAD) are an effective alternative treatment to CPAP. However, different maneuvers have been performed during the performance of drug sleep-induced endoscopy (DISE) to mimic the effect of MAD. Using the Selector Avance Mandibular (SAM) device, we aimed to identify MAD candidates during DISE using a titratable, reproducible, and measurable maneuver. This DISE-SAM protocol may help to find the relationship between the severity of the respiratory disorder and the degree of response, and to determine the advancement required to improve the collapsibility of the upper airway. Explorations were performed in 161 patients (132 males; 29 females) with a mean age of 46.81 (SD = 11.42) years, a BMI of 27.90 (SD = 4.19) kg/m2 and a mean AHI of 26.51 (SD = 21.23). Results showed no relationship between severity and MAD recommendation. Also, there was a weak positive relationship between the advancement required to obtain a response and the disease severity. Using the DISE-SAM protocol, the response and the range of mandibular protrusion were assessed, avoiding the inter-examiner bias of the jaw thrust maneuver. We suggest prescribing MAD as a single, alternative, or multiple treatment approaches following the SAM recommendations in a personalized design.

Objective: Interstitial fibrosis / tubular atrophy (IFTA) is a common, irreversible, and progressive form of chronic kidney allograft injury, and it is considered a critical predictor of kidney allograft outcomes. The extent of IFTA is estimated through a graft biopsy, while a non-invasive test is lacking. The aim of this study was to evaluate the feasibility and accuracy of an MRI radiomic-based machine learning (ML) algorithm in estimating the degree of IFTA in a cohort of transplanted patients. Approach: Patients who underwent MRI and renal biopsy within a 6-month interval from 1/1/2012 to 1/3/2021 were included. Stable MRI sequences were selected, and renal parenchyma, renal cortex and medulla were segmented. After image filtering and pre-processing, we computed radiomic features which were subsequently selected through a LASSO algorithm for their highest correlation with the outcome and lowest intercorrelation. Selected features and relevant patients’ clinical data were used to produce ML-algorithms using 70% of the study cases for feature selection, model training and validation with a 10-fold cross-validation, and 30% for model testing. Performances were evaluated using AUC with 95% confidence interval. Main results: 70 coupled tests (63 patients, 35.4% females, mean age 52.2 years) have been included and subdivided into a wider cohort of 50 for training and a smaller cohort of 20 for testing. For IFTA ≥ 25%, AUCs in test cohort were 0.60, 0.59, and 0.54 for radiomic features only, clinical variables only, and combined radiomic-clinical model, respectively. For IFTA ≥ 50%, AUCs in training cohort were 0.89, 0.84, 0.96, and in test cohort were 0.82, 0.83, and 0.86, for radiomic features only, clinical variables only, and combined radiomic-clinical model, respectively. Significance: An ML-based MRI radiomic algorithm showed promising discrimination capacity for IFTA>50%, especially when combined with clinical variables. These results need to be confirmed in larger cohorts.

MRI shows in-vivo the three archetypal patterns of CNS volume loss underlying progressive ataxias, namely spinal atrophy (SA), cortical cerebellar atrophy (CCA) and olivopontocerebellar atrophy (OPCA). The MRI-based CNS atrophy pattern was reviewed in 128 progressive ataxias. A CNS atrophy pattern was identified in 91 conditions: SA in Freidreich’s ataxia, CCA in 5 acquired and 72 (24 dominant, 47 recessive,1 X-linked) inherited ataxias, OPCA in Multi-System Atrophy and 12 (9 dominant, 2 recessive,1 X-linked) inherited ataxias. The MRI-based CNS atrophy pattern may be useful for genetic assessment, identification of shared cellular targets, and repurposing therapies or enlargement of drugs indications in progressive ataxias.

Epicatechin has been described as a polyphenol compound that promotes skeletal muscle restructuring, by expressing muscle regulation factors, activation of satellite cells and modulation of the main pathways associated with catabolism. However, the literature shows contrasting results of therapeutic effects and treatment protocols. Thus, the aim of this systematic review was to analyze the current literature addressing the molecular mechanism and clinical protocol of epicatechin on skeletal muscular atrophy in humans and animals. A search was conducted in PubMed/MEDLINE, Embase, Web of Science, and Cochrane Library databases. The qualitative analysis showed a prevalence of the inhibitory action of epicatechin in myostatin expression and atrogenes FOXO, MAFbx and MuRF1. Epicatechin showed positive effects on increased follistatin and on the activation of the myogenic regulatory factors (Myf5, MyoD and myogenin). In addition, the studies evidenced the impact of epicatechin on the mitochondrias' biosynthesis in muscle fibers, activation of the signaling pathway of AKT/mTOR protein synthesis, and improvement of skeletal musculature performance, particularly when associated with physical training. Epicatechin showed promising clinical applicability through beneficial results under conditions that negatively affect the skeletal musculature. However, there is no protocol standardization allowing to draw more specific conclusions on its therapeutic use.

Background/Objectives: The primary life-threatening complication in Spinal-bulbar muscular atrophy (SBMA) is ventilatory failure, which results from the weakening of the bulbar and respiratory muscles. However, systematic studies assessing respiratory function over the long-term have not been performed. The present study analyzes the longitudinal patterns of respiratory function tests over a follow-up of 11 years, aiming to identify any potential, sustained decline during this time. Furthermore, we explored possible correlations between respiratory function tests and clinical and biochemical serum indices. Methods: We collected data from 9 genetically confirmed SBMA patients and conducted spirometric measurements twice a year for eleven years. The spirometric data included maximum inspiratory pressure (MIP), maximum expiratory pressure (MEP), and forced vital capacity (FVC)]. Additionally, we measured serum biochemical indices and SBMA functional rating scale (SBMAFRS) for clinical analysis. Results: All three respiratory function tests showed a descending trend. A major decrease was observed for MEP (52%) and MIP (42%), while this was minor for FVC (25%). SBMAFRS score correlated with the three pulmonary function tests. MIP and MEP correlated with creatine phosphokinase and creatinine levels, and FVC correlated with serum level of transaminases. Conclusions: This longitudinal study shows a progressive decline of spirometric data throughout life in patients with SBMA. Spirometric measures relative to maximal strength of the respiratory muscles (MIP and MEP) may have a better predictive value for pulmonary and muscular decline than FVC.

A progressive and chronic neurological condition called MSA (Multiple System Atrophy) is characterized clinically by varying degrees of dysautonomia, cerebellar ataxia, and parkinsonism. The concept of mitochondrial dysregulation in MSA is one perspective in handling this neurodegenerative disease. Damage to functional mitochondria is driven by the presence of ɑ-Synuclein-induced mitochondrial localization. The goal of MSA treatment up until now has been to reduce symptoms. One of the innovations in the treatment of MSA could be the novel idea based on mitochondrial reprogramming pathways. Mitochondrial reprogramming can be done in various ways in which the use of hydrogen, magnesium and low-dose hydrogen peroxide.

Chikungunya (CHIKV) and Mayaro (MAYV) viruses are arthritogenic alphaviruses that promote an incapacitating and long-lasting inflammatory muscle-articular disease. Despite studies pointing out the importance of skeletal muscle (SkM) in viral pathogenesis, the long-term consequences on its physiology after acute injury and the mechanism of persistence of symptoms are still poorly understood. Combining molecular, morphological, Nuclear Magnetic Resonance Imaging, and histological analysis, we conduct a temporal investigation of CHIKV and MAYV replication in a wild-type mice model, focusing on the impact on SkM composition, structure, and repair in the acute and late phases of infection. We found that viral replication and induced-inflammation promote fast loss of muscle mass and reduction of fibers cross sectional area, by inducing muscle-specific E3 ubiquitin ligases MuRF1 and Atrogin expression, that trigger protein breakdown, resulting in acute SkM fibers atrophy. After temporal reduction of inflammation and clearance of infectious viral particles, SkM atrophy persists until the late phase of infection. The genomic CHIKV and MAYV RNAs were still detected in SkM at the late phase, along with increased levels of chemokines and anti-inflammatory cytokines expression. In agreement with the involvement of inflammatory mediators on induced atrophy, neutralization of TNF and the reduction of oxidative stress using monomethyl fumarate, an agonist of Nrf2, decreases atrogens expression and atrophic fibers, while increasing weight gain in treated mice. Taken together, these data indicate that arthritogenic alphavirus infection could chronically impact body SkM composition and also harm repair machinery, contributing to a better understanding of mechanisms of arthritogenic alphaviruses pathogenesis and with description of potentially new targets of therapeutic intervention.

Mandibular third molar is the most frequently impacted tooth. Mandibular third molar impaction bears consequences on the adjacent mandibular second molar (MSM) like bone loss. It can be identified initially using orthopantomography (OPG). The objective is to compare the changes in the bone level distal to MSM between patients with extracted and non-extracted impacted man-dibular third molars (IMTM) using OPG. In this retrospective case-control study, 160 archived (OPGs) of 80 patients visiting the Dental Hospital of the University of Barcelona (HOUB) were randomly selected. The participants were stratified into two groups. The study group involved measuring the bone level distal to the mandibular second molar before and after the extraction of the IMTM. The control group, on the other hand, had bone levels measured twice within 3–6-month period without the extraction of the IMTM. The mean ages of patients in study and control groups were 35.5 ± 15.45 and 33 ± 16.49, respectively. Study group demonstrated signifi-cant (p < 0.05) bone gain after extraction, whereas control group demonstrated significant bone loss (p < 0.0001) after follow-up. Bone improvements were observed distal to the mandibular second molar after the extraction of the IMTM compared to those in control group.

Keywords: spinal muscular atrophy (SMA); survival of motor neuron 1 (SMN1); SMN2; SMN protein; antisense oligonucleotide (ASO); nusinersen; gene therapy; onasemnogene; risdiplam; small molecule, combination therapy

Background: Selection and application of suture materials, has gained more importance especially with the increasing number of patients seeking oral surgeries. Since lying in a bacterial-filled environment, sutures make the tissue prone to infection. Suture material plays an important role in the reduction of the risk of infection. This study aimed to assess the success rate of an antibacterial suture named Vicryl Plus in preventing bacterial growth in the surgical site of the mandibular third molar. Methods: 27 patients were included in this double-blinded randomized clinical trial study. Surgical Extraction of the mandibular wisdom tooth was done and the incision was managed by randomly using Vicryl Plus and Vicryl sutures. After 7 days, sutures were removed and assessed microbiologically. Predominant species of Streptococcus mutans and Lactobacillus were assessed as well as the total number of colonies on each suture. Results: There was a significant difference between two suture materials in colony number-length ratio of lactobacillus (p-value= 0.031) and total bacterial colonies (p-value=0.016); but not for S. mutans species (p-value=0.201). Conclusion: Antibacterial Vicryl suture can be a useful tool for the reduction in the rate of surgical site infection in high-risk cases and situations.

Loss of muscle mass and strength are progressing with aging. Exercise is a beneficial method to prevent physical disfunction and habitual exercise improve the muscle quality. Therefore, we evaluated the effects of a long-term habitual exercise on the senescence-accelerated mice prone8 (SAMP8). 27wk SAMP8 were used in this study. Mice were classified into 28 (28w) and 44 weeks old. The 44-week group was divided into the sedentary group (44w) and a group exercising for 16 weeks (44w+Ex). The 44w+Ex performed habitual exercise from 28 to 44 weeks. Additionally, grip strength tests were performed with mice aged 28 and 44 weeks. Mice were dissected and collected muscle samples and measured muscle weight at 44w. Gastrocnemius was decreased in 44w but were unchanged in 44w+Ex. Grip strength in 44w was lower trend, but there was no change in 44w+Ex. The phosphorylation levels of Akt and p70S6K as a protein synthesis marker were decreased in 44w. Cytochrome c oxidase subunit IV(COXIV) mRNA and protein levels decreased in 44w. These results suggested that long-term habitual exercise attenuated muscle mass and strength decline through improving muscle protein synthesis and mitochondrial function. In conclusion, long-term habitual exercise attenuated muscle mass and strength decline.

The aim of this article was to evaluate properties of new polymer material, based on PEEK, for FPDs in patients with parafunctions. Methods: Prospective clinical study involved patients with diagnosed signs and symptoms of parafunctions, restored with 100 units, PEEK based FPDs, veneered with composite material. During one year observation period the following parameters were evaluated: color changes, periodontal indices, treatment success using FDI criteria, occlusal parameters, patient-reported outcome measures (OHIP-49) and occurrence of complications. Results: Spectrophotometry revealed that 63% of bridges experienced changes for L*, a*, b* color parameters, but it was not clinically significant for patients. Periodontal indices (PI, GI, BOP) revealed statistically significant higher values around restorations. According to FDI criteria, therapy was considered successful and 86.7% of FPDs were acceptable. Computerized occlusal analysis demonstrated no significant difference in the number of occlusal contacts and the intensity of relative forces between restoration and control side. Results of OHIP-49 questionnaire showed improved patient’s quality of life. Complications appeared in a limited number of cases. Conclusion: PEEK based FPDs could be indicated for successful prosthodontic rehabilitation in patients with parafunctional activities, but further material improvements and long-term clinical trials should be conducted to analyze performance of this material in challenging cases, for patients with CMD and in implant therapy.

The maintenance of skeletal muscle mass plays a fundamental role in health and issues associated with quality of life. Mechanical signals are one of the most potent regulators of muscle mass, with a decrease in mechanical loading leading to a decrease in muscle mass. This concept has been supported by a plethora of of human- and animal-based studies during the last 100 years and has resulted in the commonly used term of “disuse atrophy”. These same studies have also provided a great deal of insight into the structural adaptations that mediate disuse-induced atrophy. For instance, disuse results in radial atrophy of fascicles, and this is driven, at least in part, by radial atrophy of the muscle fibers. However, the ultrastructural adaptations that mediate these changes remain far from defined. Indeed, even the most basic questions, such as whether the radial atrophy of muscle fibers is driven by the radial atrophy of myofibrils and/or myofibril hypoplasia, have yet to be answered. In this review, we thoroughly summarize what is known about the macroscopic, microscopic, and ultrastructural adaptations that mediated disuse-induced atrophy and highlight some of the major gaps in knowledge that need to be filled.

Doxorubicin (Dox) is a commonly used chemotherapeutic that can adversely affect skeletal muscle, including causing muscle atrophy. Dox is known to induce an event known as mitochondrial permeability transition (MPT) in cardiac muscle and this plays an important role in Dox-mediated cardiac toxicity. Further to this, recent evidence identifies MPT as a mechanism of atrophy in skeletal muscle, suggesting that MPT may underlie some of the Dox-related toxicity in skeletal muscle. To test this hypothesis, we used cultured human primary myotubes, C2C12 myotubes, and single adult mouse flexor digitorum brevis (FDB) muscle fibers in experiments involving Dox treatment with or without inhibitors of MPT. Dox treatment of myotubes caused myonuclear translocation of the mitochondrial protein apoptosis inducing factor (AIF) and increased mitochondrial reactive oxygen species (mROS), consistent with the known consequences of MPT. Furthermore, Dox caused atrophy in C2C12 myotubes grown on patterned plates, human primary myotubes, and single muscle fibers from adult mice. Notably, Dox-induced atrophy could be prevented by a wide variety of agents that inhibit MPT, as well as by inhibiting mROS or Caspase 3. In conclusion, our results indicate that MPT plays an important role in driving Dox-mediated skeletal muscle atrophy.

Glucocorticoids promote muscle atrophy by inducing a class of proteins called atrogenes, resulting in reductions in muscle size and strength. In this work, we evaluated whether a mouse model with pre-existing diet-induced obesity had altered glucocorticoid responsiveness. We observed that all animals treated with the synthetic glucocorticoid dexamethasone had reduced strength, but that obesity exacerbated this effect. These changes were concordant with more pronounced reductions in muscle size, particularly in Type II muscle fibers, and potentiated induction of atrogene expression in the obese mice relative to lean mice. Furthermore, we show that the reductions in lean mass do not fully account for the dexamethasone-induced insulin resistance observed in these mice. Together these data suggest that obesity potentiates glucocorticoid-induced muscle atrophy.

The aim of this study was to create a novel machine learning (ML) algorithm for predicting the post-pubertal mandibular length and Y-axis in females. Cephalometric data from 176 females with Angle Class I occlusion were used to train and test 7 ML algorithms. For all ML methods tested, the mean absolute errors (MAEs) for the 2-year prediction ranged from 2.78-5.40 mm and 0.88-1.48 degrees, respectively. For the 4-year prediction, MAEs of mandibular length and Y-axis ranged from 3.21-4.00 mm and 1.19-5.12 degrees, respectively. The most predictive factors for post-pubertal mandibular length were mandibular length at previous timepoints, age, sagittal positions of the maxillary and mandibular skeletal bases, mandibular plane angle, and anterior and posterior face heights. The most predictive factors for post-pubertal Y-axis were Y-axis at previous timepoints, mandibular plane angle, and sagittal positions of the maxillary and mandibular skeletal bases. ML methods were identified as capable of predicting mandibular length within 3 mm, and Y-axis within 1 degree. Compared to each other, all of the ML algorithms were similarly accurate, with the exception of MLP regressor.

In our country, the aging society is rapidly progressing, with an increase in patients with chronic kidney disease (CKD) and those undergoing dialysis, coupled with the aging of the population. As a result, the number of individuals with cognitive impairment (CI) is rising, and addressing this issue has become an urgent problem. One characteristic of dementia in CKD patients is the high frequency of vascular dementia, making the prevention through the management of classical risk factors such as hypertension, diabetes mellitus, dyslipidemia, smoking, etc., associated with atherosclerosis and arteriosclerosis. Other effective measures, including the use of renin-angiotensin system inhibitors, addressing anemia, exercise therapy, and lifestyle improvements, have been reported. Incidence and progression of CI may also be influenced by the type of dialysis or kidney replacement therapy, with reports suggesting that long-duration dialysis, low-temperature hemodialysis, peritoneal dialysis, and kidney transplantation (KTx) can have a possible preferable effect on preserving cognitive function.

Background - Mandibular flexion (MF) is a complex biomechanical phenomenon, which involves a deformation of the mandible, due mainly to the contraction of the masticatory muscles, and can have numerous clinical effects. The main aim of the current systematic review is to highlight the different factors that can increase MF, to help clinicians, identify patients to whom they should pay more attention. As a secondary outcome, we wanted to analyze the preventive measures and suitable techniques to be adopted to minimize the negative effects of this phenomenon on oral fixed rehabilitations. Methods - The review, which was carried out in accordance with the “Preferred Reporting Items for Systematic reviews and Meta-Analyses” (PRISMA) flowchart, was recorded in the “International Prospective Register of Systematic Reviews” (PROSPERO). As research questions, “Patient/Population, Intervention, Comparison and Outcomes” (PICO) questions were employed. Using the ROBINS-I technique, the risk of bias in non-randomized clinical studies was evaluated. Results - The initial electronic search identified over 1300 potential articles, of which 54 studies were included in this systematic review. Information regarding the relationship between MF and individual factors, mandibular movements, impression-taking and fixed rehabilitations were obtained. Conclusions – The studies included in this systematic review showed that MF is greater during protrusive movements, in the posterior areas of the lower jaw, and in patients with brachial facial type, greater jaw length, small gonial angle and less density, length and bone surface of the symphysis. The biomechanical effects of mandibular flexion on fixed restorations are debated. Prospective clinical and radiological observational studies should be conducted to evaluate the potential short-, medium- and long-term consequences of MF.

The goal was to create a novel machine learning (ML) model which can predict the magnitude and direction of pubertal mandibular growth in males with Class II malocclusion. Lateral cephalometric radiographs of 123 males at three time points (T1: 12, T2: 14, T3: 16 years old) were collected from an online database of longitudinal growth studies. Each radiograph was traced, and 7 different ML models were trained using 38 data points obtained from 92 subjects. 31 subjects were used as a test group, to predict post-pubertal mandibular length and Y-axis using input data from T1 and T2 combined (2-year prediction), and T1 alone (4-year prediction). Mean absolute errors (MAEs) were used to evaluate the accuracy of each model. For all ML methods tested using the 2-year prediction, the MAEs for post-pubertal mandibular length ranged from 2.11-6.07mm and 0.85-2.74° for the Y-axis. For all ML methods tested with 4-year prediction, the MAEs for post-pubertal mandibular length ranged from 2.32-5.28 mm and 1.25-1.72° for the Y-axis. Besides its initial length, the most predictive factors for mandibular length were found to be chronological age, upper and lower face heights, upper and lower incisor positions and inclinations. For the Y-axis, the most predictive factors were found to be Y-axis at earlier time points, SN-MP, SN-Pog, SNB and SNA. Whilst the potential of ML techniques to accurately forecast future mandibular growth in Class II cases is promising, a requirement for more substantial sample sizes exists to further enhance the precision of these predictions.

: In this study we evaluated, if single nucleotide polymorphisms (SNPs) in the genes encoding PTH, VDR, CYP24A1 and CYP27B1 are associated with Mandibular Retrognathism (MR). Samples from biologically-unrelated patients receiving orthodontic treatment were included in this study. Pre-orthodontic lateral cephalograms were used to determine the phenotype. Patients having a retrognathic mandible (SNB<78º) were selected as cases and those with an orthognathic mandible (SNB=78º–82º) were selected as controls. Genomic DNA was used for genotyping analysis of SNPs in PTH (rs694, rs6256 and rs307247), VDR (rs7975232), CYP24A1 (rs464653) and CYP27B1 (rs927650). Chi-squared or Fisher’s tests were used to compare genotype and allele distribution among groups. Haplotype analysis was performed for the SNPs in PTH. The established alpha was p<0.05. Multifactor dimensionality reduction (MDR) was used to identify SNP-SNP interactions. A total of 48 MR and 43 controls were included. In the genotype and allele distribution analysis, the SNPs rs694, rs307247 and rs464653 in were associated with MR (p<0.05). MDR analyses predicted the best interaction model for MR was rs694-rs927650, followed by rs307247-rs464653-rs927650. Some haplotypes in the PTH gene presented statistical significance. Our results suggest that SNPs in PTH, VDR, CYP24A1 and CYP27B1 genes are associated with the presence of mandibular retrognathism.

IgA nephropathy (IgAN) is one of the most common forms of glomerular disease. It is diagnosed by the dominant or co-dominant IgA deposition in the mesangial region by histopathological examination of kidney biopsy. Kidney biopsy has its own complication and not performed frequently. microRNA (miRNA) is a small RNA, which plays an important role at the post transcriptional level by downregulating mRNAs. We have tried to establish a miRNA based biomarker for IgAN. We quantified miR-148b and let-7b from plasma in IgAN patients and healthy controls. Logistic regression models and receiver operating curve analysis used to analyze the miRNAs quantity and Oxford MEST-C scoring parameters (M- Mesangial hypercellularity, E- Endocapillary hypercellularity, S- Segmental glomerulosclerosis, T- Tubular atrophy/Interstitial fibrosis, C- Crescents). miR-148b and let-7b levels in IgAN were found to be higher by 2.9 and 5.48 times than the healthy controls, respectively. let-7b was positively correlated with complement C3 levels. Similarly, miR-148b was positively correlated with estimated glomerular filtration rate (eGFR) and negatively correlated with S, T, and blood pressure (BP). The sensitivity, specificity, and area under the curve (AUC) of receiver operating characteristic (ROC) for miR-148b against T were 0.87, 0.77, and 0.85, respectively. The threshold value of miR-148b concentration was found to be 8479 to differentiate the severe condition of IgAN. Furthermore, the decrease in miR-148b concentration at a threshold point indicated the progression of the severity of the IgAN. It can also be used to predict the IgAN at an earlier stage.

The facultative loss of muscle mass and function during aging (sarcopenia) poses a serious threat to our independence and health. Much of what we know about sarcopenia derive from studies on small rodents which serve as models for the human condition. Here we used outbred male rats to study the natural history of sarcopenia with the aim to compare behavioral motor deficits with degree of muscle wasting and to find processes underlying the preclinical phase of sarcopenia. Selected metrics were validated in female rats. We used the soleus muscle because of its long duty cycles in everyday life and significance for postural control. The results show that gait and coordination remain intact through middle age (12-18 months; 40%-60% of median lifespan) when muscle mass relative to body weight is largely maintained. The muscle, however, show multiple signs of remodeling with a shift in myofiber-type composition towards type I, increased number of hybrid fibers and fibers expressing embryonic myosin. In parallel with the shift in fiber type prevalence, fiber type clustering increased. The latter combined with a transcriptional upregulation of nicotinic acetylcholine receptor subunit  (CHRN ), NCAM and Myogenin (MYOG) suggests a remodeling driven by myofiber denervation. Additional stigmata were increased number of central nuclei, transcriptional upregulation of Smad3, FBXO32, and MuRF1mRNAs; unaltered density of satellite cells (SC) and Catenin mRNA. In early (25-month-old) and advanced (30-month-old) aging, gait and coordination deteriorate as loss of muscle mass progresses. In late middle age and early aging because of a type II atrophy (>50%), followed by type I atrophy (>50%). Number of myofiber did not correlate with this process. At advance age, the atrophy is accompanied by a decrease in SC and Catenin mRNA while several transcripts upregulated earlier-on were downregulated. In contrast, glial-derived nerve growth factor (GDNF) mRNA abundance peaked at endpoint. We conclude that sarcopenia in the rat as in humans, has a long preclinical phase where the muscle undergoes extensive remodeling to preserve muscle mass and function. The data supports the notion that myofiber denervation is the instigating mechanism, initially affecting large type II motor units (MUs) and at more advanced stage also the smaller type I MUs.

Objective: Regeneration of bone defects remains a challenge for maxillofacial and reparative surgeons. The purpose of this histological study was to assess the osteogenic potential of octacalcium phosphate (OCP) and bone matrix gelatin (BMG) alone and in combination in artificially created mandibular bone defects in rats. The quality of the newly formed bone was also evaluated. Methods: Thirty-six male Sprague Dawley rats (6-8 weeks old with 120-150 g weight) were randomly divided into four groups. Defects (3 mm in diameter and 2 mm in depth) were created in the mandible of rats and filled with 6 mg of OCP, BMG or a combination of both (1/4 ratio), respectively. Defects were left unfilled in the control group. To assess osteoinduction and bone regeneration and determine the quality of the newly formed bone, tissue specimens were harvested at seven, 14, and 21 days post-implantation. The specimens were processed, stained with hematoxylin and eosin (H&E) and histologically analyzed under light microscopy. Results: In the experimental groups, new bone formation was initiated at the margins of defects from seventh day after implantation. At the end of the study period, the amount of the newly formed bone increased and the bone was relatively mature. Osteoinduction and new bone formation were greater in OCP/BMG group. In the control group, slight amount of new bone had been formed at the defect margins (next to host bone) on day 21. Conclusion: Combination of OCP/BMG may serve as an optimal biomaterial for treatment of mandibular bone defects.

Spinal muscular atrophy is a neuromuscular genetic condition associated with progressive muscle weakness and atrophy. Nusinersen is an antisense oligonucleotide therapy approved for the treatment of 5q spinal muscular atrophy in pediatric and adult patients. The objective of this clinical case series is to describe the efficacy and safety of nusinersen in treating spinal muscular atrophy in 20 pediatric and 18 adult patients across six treatment centers in Kuwait. Functional motor assessments (Children’s Hospital of Philadelphia Infant Test of Neuromuscular Disorders, Hammersmith Functional Motor Scale Expanded, and Revised Upper Limb Module) were used to assess changes in motor function following nusinersen treatment. Safety assessment involved clinical monitoring of adverse events. The results demonstrate clinically meaningful or considerable improvement in motor performance for nearly all patients, lasting over 4 years in some cases. 70% of patients in the pediatric cohort and 72% of patients in the adult cohort achieved clinically meaningful improvement in motor function following nusinersen treatment. Additionally, nusinersen was well-tolerated in both cohorts. These findings add to the growing body of evidence relating to the clinical efficacy and safety of nusinersen.

: Medial temporal lobe atrophy (MTA) remains an important imaging biomarker in brain magnetic resonance imaging (MRI) for diagnosing and evaluating Alzheimer's disease (AD). We compared the detection performance for determining significant MTA and the correlation with Scheltens' scale between two automatic volumetry software, NeuroQuant® and Aqua®, in non-AD and AD groups. Overall, 127 (non-AD, 54; AD, 73) individuals who underwent three-dimensional T1-weighted volumetric MRI in our hospital between January and August 2011 were enrolled and retrospectively analyzed using NeuroQuant® and Aqua®. The accuracy, sensitivity, and specificity for detecting significant MTA and the correlation for Scheltens' scale with the mean hippocampal volume of each software were evaluated. The study sample’s mean age was 78 (range, 59–97) years. Regarding accuracy and specificity, Aqua® was non-inferior to NeuroQuant®. Aqua® had significantly higher overall specificity than NeuroQuant® for detecting significant MTA. Additionally, the calculated mean hippocampal volume of Aqua® was more correlated with Scheltens' scale (Kendall's τ, - 0.48) than that of NeuroQuant® (Kendall's τ, - 0.20). The accuracy and specificity of Aqua® in detecting MTA are not inferior to those of NeuroQuant®. Additionally, Aqua® has a stronger correlation of mean hippocampal volume with Scheltens' scale than NeuroQuant®.

Skeletal muscle atrophy is one of the major side effects of high dose or sustained usage of glucocorticoids. Pyroptosis is a novel form of pro-inflammatory programmed cell death that may contribute to skeletal muscle injury. Trimetazidine, a well-known anti-anginal agent, can also improve skeletal muscle performance both in human and mice. We here showed that dexamethasone induced atrophy, evidenced by the increase of muscle atrophy F-box (Atrogin-1) and muscle ring finger 1 (MuRF1) expression , and the decrease of myotube diameter in C2C12 myotubes. Dexamethasone also induced pyroptosis, indicated by upregulated pyroptosis-related protein NLRP3, Caspase-1 and GSDMD. Knockdown of NLRP3 or GSDMD attenuated dexamethasone-induced myotube pyroptosis and atrophy. Trimetazidine administration ameliorated dexamethasone-induced muscle atrophy both in vivo and in vitro. Moreover, trimetazidine improved exercise tolerance, as evidenced by increased running distance and running time, as well as increased skeletal muscle mass in dexamethasone-treated mice. Mechanically, trimetazidine could reverse dexamethasone-induced activation of pyroptosis both in C2C12 myotubes and in mice. Taken together, our present study demonstrated that NLRP3/GSDMD pathway-mediated pyroptosis was involved in dexamethasone-induced skeletal muscle atrophy. Trimetazidine could partially alleviate dexamethasone-induced skeletal muscle atrophy, and increase the diameter of C2C12 myotubes via inhibiting pyroptosis. Thus, trimetazidine might be a potential therapeutic compound for the prevention of muscle atrophy in glucocorticoid-treated patients.

The management of patients with spinal muscular atrophy type 1 (SMA1) is constantly evolving. In just a few decades the medical approach has switched from an exclusively palliative therapy to a targeted therapy, transforming the natural history of the disease, improving survival time and quality of life, and creating new challenges and goals. Many nutritional problems, gastrointesti-nal disorders and metabolic and endocrine alterations are commonly identified in patients af-fected by SMA1 during childhood and adolescence. For this reason, a proper pediatric multidis-ciplinary approach is then required in the clinical care of these patients, with a specific focus on the prevention of most common complications. The purpose of this narrative review is to provide the clinician with a practical and usable tool about SMA1 patients care, through a comprehensive insight into the nutritional, gastroenterological, metabolic and endocrine management of SMA1. Considering the possible horizons opened thanks to new therapeutic frontiers, a nutritional and endo-metabolic surveillance is a crucial element to be considered for a proper clinical care of these patients.

Aim: the main aim of this study is to compare the onset of effectiveness of mental nerve block with lingual infiltration and inferior alveolar nerve block on patients visiting dental hospital for extraction of mandibular anterior teeth. Materials and methods: The study was set in a clinical setting. This was a randomized controlled double-blind cross study, where 25 subjects received two treatments at an interval of at least 1 week in a within a dental hospital.Inferior alveolar nerve block and lingual nerve block injection is given with 2mL lignocaine 2% with 1:2,00,000 epinephrine was administered for the right side. Mental nerve block along with lingual infiltration of the corresponding tooth was given with 2mL lignocaine 2% with 1:2,00,000 epinephrine was administered on the left side.Visual analogue scale (VAS) was used in this study, which consists of a scale with range of 0-10 pain severity on which 0 indicated absence of pain and 10 the worst pain possible. The patients were asked to give scores corresponding to his/her pain, after IANB, mental nerve block and lingual infiltration and these scores were recorde.Results: From the results we can see that patients gave scores between 3-4, stating that they had moderate pain during extraction after administration of IANB (54%) (graph 2) and VAS scores of 0-1 were given by patients, which is suggestive of no pain during extraction after administration of Mental nerve block and lingual nerve infiltration (62%)Conclusion: Within the limits of the study we can conclude that mental nerve block along with lingual infiltration is an effective way to completely and quickly anaesthetise the central incisor to the 1st premolar region.

Spinal muscular atrophy 5q (SMA) is the most common neuromuscular inherited disease in neonates which is associated with homozygous deletion of exon 7 in the SMN1 gene. Recently established drugs can improve the motor functions of SMA infants when treated in the pre-symptomatic stage. With aim of providing an early diagnosis, newborn screening (NBS) for SMA using real-time PCR assay with dried blood spots (DBS) was performed in Saint-Petersburg from January 2022 through November 2022. Here, 36,140 newborns were screened by GenomeX real-time PCR-based screening test, and three genotypes were determined. Homozygous deletion carriers (4 newborns), heterozygous carriers (772 newborns) and wild-type individuals (35,364 newborns) were identified. All four newborns screened positive for homozygous SMN1 deletion were confirmed by alternate methods. Two of the newborns had two copies of SMN2, and two of the newborns had three copies. We determined Saint-Petersburg spinal muscular atrophy incidence of 1 in 9,035 and SMA carrier frequency of 1 in 47. In conclusion, it can be summarized that providing both timely SMN1 information and confirmation along with SMN2 copy number as part of SMA newborn screening algorithm can significantly improve clinical follow-up, family members testing, and SMA patients' treatment.

A three-arm, randomized, placebo controlled clinical study has been performed to evaluate the effects of a lyophilized pineapple extract titrated in bromelain (Brome-Inf®), and purified bro-melain on pain, swelling, trismus and quality of life (QoL) after the surgical removal of the lower third molars. Moreover, the need for non-steroidal anti-inflammatory drugs (NSAIDs) has also been evaluated and compared with a placebo group. The study included 42 people that required the extraction of a single mandibular third molar under local anesthesia. The patients were ran-domized and distributed to receive Brome-Inf®, purified bromelain or placebo and started the treatment the day of surgery and continued it for the next 7 days. The primary outcome was the requirement of NSAIDs in the three groups. The outcome variables were pain, swelling and trismus, which were measured postoperatively at 1, 3, and 7 days. The differences in the efficacy of the freeze-dried pineapple extract and single-component bromelain were also evaluated. At the end of the study, the assumption of ibuprofen (from days 1-7) was statistically higher in the placebo group (p

To demonstrate if botulinum toxin type A (BoNT-A) improves mandibular range of motion and muscle sensibility to palpation in refractory myofascial pain (MFP) patients. METHODS: Eighty consecutive female subjects with refractory MFP, were randomly divided into four equal groups (n=20): BoNT-A low (BoNTA-L/10 U in each temporalis and 30 U in each masseter), BoNT-A medium (BoNTA-M/20 U in each temporalis and 50 U in each masseter), BoNT-A high (BoNTA-H/25 U in each temporalis and 75 U in each masseter) and saline solution 0.9% (SS, placebo control group/0.4 mL in each temporalis and 0.6 mL in each masseter). Clinical measurements of the mandibular movements included: pain-free opening, maximum unassisted and assisted opening, and right and left lateral movements. Palpation tests were performed bilaterally in masseter and temporalis muscle. Results were expressed as median, minimum, maximum, and means ± standard deviation (SD). Chi-Square Test was used to compare differences among groups. A 5% probability level was considered significant in all tests RESULTS: Regardless of dose, all parameters of mandibular range of motion significantly improve after 180 days in BoNT- A groups, when compared to the control group. Pain to palpation on muscles, significantly reduced in all BoNT- A groups regardless of dose, when compared to the control group, after 28 and 180 days of treatment. CONCLUSIONS: Independent of doses, BoNT-A improved mandibular range of motion and muscle sensibility to palpation in refractory MFP patients when compared to SS injections.

Spinal muscular atrophy is a neuromuscular disorder caused by mutationsin both copies of the survival motor neuron gene 1 (SMN1) which lead to reduction in the production of the SMN protein. Currently, there are several therapies that have been approved for SMA, with much more undergoing active research. While various biomarkers have been proposed for assessing the effectiveness of SMA treatment, a universally accepted one still hasnot been identified. This study aimed to investigate whether the number of gems in cell nuclei could serve as a potential biomarker for SMA. To gain insight into whether the number of gems in cell nuclei varies based on their SMN genotype and whether the increase in gems number is associated with therapeutic response, we utilized fibroblast cell cultures obtained from a patient with SMA type II and from healthy individual. We have discovered a remarkable difference in the number of gems found in the nuclei of these cells, specifically when counting gems per 100 nuclei. Then the SMA fibroblasts were treated with antisense oligonucleotides the beneficial effects in correcting the abnormal splicing of SMN2 exon 7 have been demonstrated. It was observed that there was a significant increase in the number of gems in the treated cells compared to the intact SMA cells. The results obtained significantly correlate with an increase of full-length SMN transcripts share. Based on our findings, it is evident that the quantity of gems can be regarded as a reliable biomarker for SMA drugs development.

Previous studies have found that individuals with limited motor capabilities due to acquired neurological injury (e.g., spinal cord injury and stroke) can make accurate action possibility judgements for neurologically healthy individuals. Previous studies have shown that people with limited motor capabilities may rely on previous motor experience (i.e., pre-injury) when making action possibility judgments for others. In the present study, we examined whether having severely limited previous motor experience from birth, as a consequence of spinal muscle atrophy (SMA), alters the action possibility judgments made for neurologically healthy individuals. Participants with SMA and Neurologically Healthy (NH) sex- and age-matched controls performed a perceptual-motor judgment task using the Fitts’s law paradigm (see Fitts, 1954). Participants observed apparent motion videos of reciprocal aiming movements with varying indices of difficulty (ID, see: Manson et al., 2014). For each movement, participants predicted the shortest movement time (MT) at which a neurologically healthy young adult could perform the task while maintaining accuracy. Between-group comparisons revealed that participants with SMA predicted significantly longer MTs compared to controls. Regression analyses revealed that predicted MTs of both NH and SMA participants exhibited a Fitts’s law relationship (i.e., the predicted MTs significantly increased as movement difficulty increased). A supplementary analysis on the SMA group revealed no differences in predicted MTs between the participants with some and no motor function as assessed by the SMA health index. Overall, these results provide evidence that participants with SMA who have limited or no motor experience may make more conservative action possibility judgments for others. Critically, our finding that the pattern of action possibility judgements (e.g., the slopes of the regression lines) were not different between SMA and NH groups provides evidence that limited previous motor experience may not completely impair action possibility judgements.

Background: Multiple system atrophy (MSA) is a rapidly progressive neurodegenerative disorder that has no curative treatment. Diagnosis is based on a set of criteria established by Gilman (1998 and 2008) and recently updated by Wenning (2022). We aim to determine the effectiveness of [123I]Ioflupane SPECT in MSA, especially at the initial clinical suspicion. Methods: Cross-sectional study of patients at initial clinical suspicion of MSA, referred for [123I]Ioflupane SPECT. Results: 139 patients (68 men, 71 women) were included, 104 being MSA-probable and 35 MSA-possible. MRI was normal in 89.2% while SPECT was positive in 78.45%. SPECT showed high sensitivity (82.46%) and positive predictive value (86.24), reaching maximum sensitivity in MSA-P (97.26%). Significant differences were found when relating both SPECT assessments in the healthy-sick and inconclusive-sick groups. We also found an association when relating SPECT to the subtype (MSA-C or MSA-P), as well as to the presence of parkinsonian symptoms. Lateralization of striatal involvement was detected (left side). Conclusions: [123I]Ioflupane SPECT is a useful and reliable tool for diagnosing MSA, with good effectiveness and accuracy. Qualitative assessment shows a clear superiority when distinguishing between the healthy-sick categories, as well as between the parkinsonian (MSA-P) and cerebellar (MSA-C) subtypes at initial clinical suspicion.

Aggregated alpha-synuclein (-synuclein) is the main component of Lewy bodies (LBs), Lewy neurites (LNs), and glial cytoplasmic inclusions (GCIs), which are pathological hallmarks of idiopathic Parkinson’s disease (IPD) and multiple system atrophy (MSA), respectively. Initiating factors that culminate in forming LBs/LNs/GCIs remain elusive. Several species of -synuclein exist, including phosphorylated and nitrated forms. It is unclear which -synuclein post-translational modifications (PTMs) appear within aggregates throughout disease pathology. Herein we aimed to establish the predominant synuclein PTMs in post-mortem IPD and MSA pathology using immunohistochemistry. We examined the patterns of three -synuclein PTMs (pS87, pS129, nY39) simultaneously in pathology-affected regions of 15 PD, 5 MSA, 6 neurologically normal controls. All antibodies recognized LBs, LNs, and GCIs, albeit to a variable extent. pS129 -synuclein antibody was particularly immunopositive for LNs and synaptic dot-like structures followed by nY39 -synuclein antibody. GCIs, neuronal inclusions, and small threads were positive for nY39 -synuclein in MSA. Quantification of the LB scores revealed that pS129 -synuclein was the dominant and earliest -synuclein PTM followed by nY39 -synuclein, while lower amounts of pSer87 -synuclein appeared later in disease progression in PD. These results may have implications for novel biomarker and therapeutic developments.

The present review focuses on recent clinical trials that analyze the efficacy of intravitreal therapeutic agents for the treatment of dry age-related macular degeneration (AMD), such as neuroprotective drugs, and complement inhibitors, also called immunomodulatory or anti-inflammatory. A systematic literature search was performed to identify randomized controlled trials published prior to January 2019. Patients affected by dry AMD treated with intravitreal therapeutic agents were included. The changes in the correct visual acuity and the reduction in geographic atrophy progression were evaluated. Several new drugs have shown some promising results, including those targeting the complement cascade and agents called neuroprotective. The action potential of the two groups of drugs is to block the complement cascade model for immunomodulating agents, and prevent the degeneration and apoptosis of ganglion cells for the neuroprotectors, respectively. To the best of knowledge, and after extensive studies on the matter, there are still many investigations to be carried out on dry AMD in collaboration between researchers. They will have to identify truly effective molecules, understand the practical potential of pluripotent stem cells, and refine gene therapies. Only in-depth clinical trials will be able to allow the most appropriate and personalized treatments for each dry AMD patient.

Background/Objectives: This study aims to investigate the influence of root canal morphology and various treatment variables on the outcomes of root canal treatments (RCT) in mandibular second molars, assessed through cone-beam computed tomography (CBCT) imaging. Methods: A total of 150 CBCT images were examined, comprising 100 cases of persistent endodontic infections and 50 from previously treated root canals with normal apices in mandibular second molars. CBCT was utilized to evaluate root canal configuration, the radiographic quality of coronal restorations and treated canal systems, and the presence of periapical lesions. Statistical analyses were performed to explore correlations between these factors. Results: The presence of a C-shaped root canal configuration did not demonstrate a significant correlation with periapical lesions (p=0.05). Factors influencing endodontic treatment outcomes included the presence of missing canals (p=0.018), underfilling or overfilling (p=0.045), and inadequate coronal restoration (p=0.006). The presence of a missing canal was identified as the variable most significantly associated with periapical lesions (OR=3.103). Leaky canals were more commonly observed in C-shaped root canals (p&lt;0.001). Conclusions: Regardless of the root canal morphology of mandibular second molars, successful RCT depends on thorough disinfection to eliminate any untreated canals, precise three-dimensional filling of the canals at the correct working length, and a securely sealed coronal restoration to prevent leakage.

Background and Objectives: The prevalence of osteoporosis is high, reportedly affecting 200 million people worldwide. A major problem associated with osteoporosis is that femoral fractures cause a decline in general function and loss of independence, greatly reducing patients’ quality of life. Notably, osteoporosis is an asymptomatic chronic metabolic disease, and its detection is thus often delayed. Interestingly, mandibular cortical index (MCI) classification using dental panoramic radiography is reportedly useful for early detection of osteoporosis. However, this visual classification method can lead to differences in diagnosis among surgeons. Therefore, this preliminary study was performed to analyze cone-beam computed tomography (CBCT) data and examine an objective MCI classification using the findings obtained. Materials and Methods: MCI classification (classified as C1, C2, or C3) was performed by three examiners on 70 women (91 sites) aged ≥20 years. The mandibular cortical width of all sites was measured using CBCT images. Results: The results showed that the mandibular cortical width was not particularly correlated with age or number of present teeth, and no significant quantitative differences were found between C1 and C2. However, coronal CBCT images of C2 revealed multiple characteristic bone trabecular structures. Conclusions: These structures may be an important finding affecting the classification of two-dimensional dental panoramic radiography images.

The deficiency of Survival Motor Neuron (SMN) protein causes Spinal Muscular Atrophy (SMA), a rare neuromuscular disease that affects different organs. SMN is a key player in RNA metabolism regulation. An intriguing aspect of SMN function is its relationship with plasma membrane-associated proteins. Here, we provide a first demonstration that SMN affects the ATP-binding cassette transporter A1, (ABCA1), a membrane protein critically involved in cholesterol homeostasis. In human fibroblasts, we showed that SMN associates to ABCA1 mRNA, and impacts its subcellular distribution. Consistent with the central role of ABCA1 in the efflux of free cholesterol from cells, we observed a cholesterol accumulation in SMN-depleted human fibroblasts. These results were also confirmed in a SMA type I patient-derived fibroblasts. These findings not only validate the intimate connection between SMN and plasma mem-brane-associated proteins, but also highlight a contribution of dysregulated cholesterol efflux in SMA pathophysiology.

(1) Background/Objectives: Accurate determination of chronological age is crucial in legal dental identification. This study aimed to compare the effectiveness of different formulas in estimating the age of a Brazilian subpopulation by analyzing the pulp/tooth ratio of the maxillary canine and mandibular second premolar in panoramic and periapical radiographs. (2) Methods: The sample consisted of panoramic and periapical radiographs of 247 individuals. The file of each radiograph was opened in the Adobe Photoshop CS4® program to outline and obtain values in pixels for calculating the pulp/tooth ratio. Statistical analysis was conducted using the SPSS program, with a significance level set at 5%. (3) Results: The interclass correlation coefficient demonstrated excellent intra-observer agreement (0.990 – 0.999). The determination coefficients (R2) suggested that only 30-35% of the actual age results could be explained by the pulp/tooth ratio. Smallest differences were observed with Cameriere's formula for the mandibular second premolar on panoramic radiographs (+4.1 years). The greatest differences were found with the formulas for the mandibular second premolar in panoramic radiographs of the Korean (+12.5 years) and Portuguese (-12.1 years) populations. (4) Conclusions: The equations employed allowed for estimating the age of a Brazilian subpopulation and showed little agreement between the actual age and the estimated age.

This study evaluated changes over time in skeletal muscle atrophy, expressions of skeletal muscle anabolic and catabolic genes, and mitochondrial activity by skeletal muscle type in an adenine-induced chronic kidney disease (CKD) model. A CKD model was successfully established by feeding male Wistar rats a 0.75% adenine diet for 4 weeks starting at 8 weeks of age. Control and CKD groups were sacrificed at 12 and 20 weeks of age. Back muscles were analyzed histologically, and succinate dehydrogenase (SDH) staining was performed to evaluate mitochondrial activity. Gene expressions of myogenic determination gene number 1 and myogenin as indicators of muscle anabolism, atrogin-1 and muscle RING-finger protein-1 (MuRF1) as indicators of muscle catabolism, and peroxisome proliferator-activated receptor-γ coactivator-1-α as a marker of mitochondrial biogenesis were assessed. Type I and type II muscle cross-sectional areas (CSAs) were decreased at 12 weeks, but type I muscle CSA recovered at 20 weeks. SDH staining was lower in CKD than control rats at 12 weeks, but no significant difference was observed at 20 weeks. Increased expressions of myogenin, atrogin-1, and MuRF-1 were observed only at 12 weeks, but no differences were observed at 20 weeks. The adenine-induced CKD rat model appears to show changes in muscle atrophy over time.

Atrophy quantification is fundamental for understanding brain development and diagnosing and monitoring brain diseases. FSL-SIENA is a well-known fully-automated method that has been widely used in brain magnetic resonance imaging studies. However, intensity variations arising during image acquisition that may compromise evaluation, analysis and even diagnosis. In this work, we study whether intensity standardisation can improve longitudinal atrophy quantification. We considered seven methods comprising z-score, fuzzy c-means, Gaussian mixture model, kernel density, histogram matching, white stripe, and removal of artificial voxel effects by linear regression (RAVEL). We used a total of 330 scans from two publicly-available datasets, ADNI and OASIS. In scan-rescan assessments, that measures robustness to subtle imaging variations, intensity standardisation did not compromise the robustness of FSL-SIENA significantly (p>0.1). In power analysis assessments, that measures the ability to discern between two groups of subjects, three methods led to consistent improvements in both datasets with respect to the original: fuzzy c-means, Gaussian mixture model, and kernel density estimation. Reduction in sample size using these three methods ranged from 17% to 95%. The performance of the other four methods was affected by spatial normalisation, skull stripping errors, presence of periventricular white matter hyperintensities, or tissue proportion variations over time. Our work evinces the relevance of appropriate intensity standardisation in longitudinal cerebral atrophy assessments using FSL-SIENA.

The effect of prostaglandin E1 (PGE1) encapsulated in nanoparticles (Nano PGE1) on motor dysfunction and muscle atrophy induced by sciatic nerve injury (SNI) was investigated in rats, and was compared with PGE1 encapsulated in lipid microspheres (Lipo PGE1) or PGE1 clathrated in cyclodextrin (PGE1-CD). The hind limb muscle weight ratio decreased until 2 weeks after SNI. All 3 PGE1 formulations significantly improved SNI-induced motor dysfunction. Nano PGE1 significantly promoted recovery from muscle atrophy at 2 and 3 weeks after SNI. Lipo PGE1 was also effective, but multiple doses were required. Compared with the SNI control group, the Nano PGE1 group showed upregulation of vascular endothelial growth factor (VEGF) and agrin expression in the injured sciatic nerve and atrophic muscles. Nano PGE1 accumulated prominently at the site of nerve injury and persisted for longer than Lipo PGE1 or PGE1-CD. Expression of all EP receptors was detected in the normal sciatic nerve, and EP2 expression increased after SNI. Finally, Nano PGE1 promoted ERK1/2 and Akt phosphorylation. These findings suggest that PGE1 released from nanoparticles accumulates at sites of nerve injury and increases VEGF production by augmenting ERK1/2 phosphorylation via EP receptor signaling, thus promoting tissue repair and regeneration.

Spinal muscular atrophy (SMA) is an orphan disease characterized by progressive degeneration of spinal alpha motor neurons. In recent years, nusinersen and several other drugs have been approved for the treatment of this disease. Transcutaneous spinal cord stimulation (tSCS) modulates spinal neuronal networks, resulting in changes in locomotion and posture in patients with severe spinal cord injury and stroke. We hypothesize that tSCS can activate motor neurons that are intact and restored by medication, slow the decline in motor activity, and contribute to the development of motor skills in SMA patients. Thirty-seven children and adults with SMA types 2 and 3 participated in the study. The median duration of drug treatment was over 20 months. Application of tSCS was performed during physical therapy for 20-40 minutes per day for ~12 days. Outcome measures were specific SMA motor scales, goniometry of contractured joints, forced vital capacity. Significant increases in motor function, improved respiratory function, and decreased contracture were observed in both types 2 and 3 SMA participants. The magnitude of functional changes was not associated with participants age. Further studies are needed to elucidate the reasons for the beneficial effects of spinal cord electrical stimulation in SMA.

Astaxanthin (AX) is a carotenoid that exerts potent antioxidant activity and acts in the lipid bilayer. This study aimed to investigate the effects of AX on muscle atrophy-mediated disturbance of mitochondria that have a lipid bilayer. Tail suspension was used to establish muscle- atrophied mouse models. AX diet fed to tail-suspension mice prevented loss of muscle weight and decreased myofiber size in the soleus muscle. Additionally, AX improved down-regulation of mitochondrial respiratory chain complexes II and III in the soleus muscle after tail suspension. To confirm the AX phenotype in the soleus muscle, we examined its effects on mitochondria using Sol8 myotubes derived from the soleus muscle. We found that AX was preferentially detected in the mitochondrial fraction; it significantly suppressed mitochondrial complex III-driven production of reactive oxygen species in Sol8 myotubes. Moreover, AX inhibited the activation of caspase 3 via inhibiting the release of cytochrome c into the cytosol in antimycin A-treated Sol8 myotubes. These results suggested that AX inhibited mitochondrial oxidative stress through a mitochondria-mediated apoptosis pathway and thus prevented muscle atrophy.

Titin is a giant protein that functions as a molecular spring in sarcomeres. Titin interplays the contraction of actin-containing thin filaments and myosin-containing thick filaments. The breakdown product of titin has been measurable in urine as urinary titin N-fragments. Urinary titin N-fragment was originally reported to be a useful biomarker in the diagnosis of muscle dystrophy. Recently, the urinary titin N-fragment has been increasingly gaining attention as a novel biomarker of muscle atrophy and intensive care unit-acquired weakness in critically ill patients, in whom titin loss is a possible pathophysiology. Furthermore, several studies reported that the urinary titin N-fragment also reflected muscle atrophy and weakness in patients with chronic illnesses. It may be used to predict the risk of post-intensive care syndrome or to monitor patients’ condition after hospital discharge for better nutritional and rehabilitation management. We provide several tips on the use of this promising biomarker in post-intensive care syndrome.

Spinal and bulbar muscular atrophy (SBMA), also known as Kennedy’s disease, is a debilitating neuromuscular disease characterized by progressive muscular weakness and neuronal degeneration, affecting 1-2 individuals per 100,000 globally. While SBMA is relatively rare, recent studies have shown a significantly higher prevalence of the disease within the indigenous population of Western Canada compared to the general population. The disease is caused by a pathogenic expansion of polyglutamine residues in the androgen receptor protein, which acts as a key transcriptional regulator for numerous genes. SBMA has no cure, and current treatments are primarily supportive and focused on symptom management. Recently, a form of precision medicine known as antisense therapy has gained traction as a promising therapeutic option for numerous neuromuscular diseases. Antisense therapy uses small synthetic oligonucleotides to confer therapeutic benefit by acting on pathogenic mRNA molecules, serving to either degrade pathogenic mRNA transcripts or helping to modulate splicing. Recent studies have explored the suitability of antisense therapy for the treatment of SBMA, primarily focused on antisense-mediated mRNA knockdown approaches. Advancements in understanding the pathogenesis of SBMA and the development of targeted therapies offer hope for improved quality of life for individuals affected by this debilitating condition. Continued research is essential to optimize these genetic approaches, ensuring their safety and efficacy.

Recent studies have been able to detect α-synuclein (αSyn) seeding in formaldehyde-fixed paraffin-embedded (FFPE) tissues from patients with synucleinopathies using seed amplification assays (SAAs), but with relatively low sensitivity due to limited protein extraction efficiency. With the aim of introducing an alternative option to frozen tissues, we developed a streamlined protein extraction protocol for evaluating disease-specific seeding in FFPE human brain. We evaluated the protein extraction efficiency of different tissue preparations, deparaffinizations, and protein extraction buffers using formaldehyde-fixed and FFPE tissue of a single Lewy body disease (LBD) subject. Alternatively, we incorporated heat-induced antigen-retrieval and dissociation using a commercially available kit. Our novel protein extraction protocol has been optimized to work with 10 sections of 4.5-µm-thickness or 2-mm-diameter micro-punch of FFPE tissue that can be used to seed SAAs. We demonstrated that extracted proteins from FFPE still preserve seeding potential and further show disease-specific seeding in LBD and multiple system atrophy. To the best of our knowledge, our study is the first to recapitulate disease-specific αSyn seeding behavior in FFPE human brain, with structural validation. Our findings open new perspectives in re-evaluating archived human brain tissue, extending the disease-specific seeding assays to larger cohorts to facilitate molecular subtyping of synucleinopathies.

Extreme atrophy of the maxilla poses still challenging for the clinicians. Some of the techniques used could be complex, risky, expensive, time consuming and should be performed, preferably, only by skilled surgeons. Most the commonly used techniques have been reported to have very high success percentages; however, sometimes complications may occur. In this regard, Premaxillary Device (PD) is a technique that has been devised to render more simple the reconstruction of extremely atrophic maxilla, trying to avoid more complicated and risky surgical procedures. Finite Element Analysis (FEA) allows evaluation of several differen aspects of dental implant biomechanics. Our results showed that the use of PD allows an optimal distribution of the stresses on the basal bone, avoiding tension peaks that could determine bone resorption or, even, implant failure. ANSYS has been used to perform this type of localized finite element analysis; with this type of analysis, it was possible to analyze the peri-crestal area of the plant more precisely and the PD through a more accurate reconstruction of the mesh element, which allowed us to mathematically solve the FEA solution. A most favorable biomechanical behavior has been found for the materials such as titanium alloys and reduce stress levels for bone, implants, screws, and abutments. Moreover, the stress values did not exceed bone strength limits for basal bone and titanium alloy. In conclusion, from a biomechanical point of view, PD could be considered a viable alternative for rehabilitation of severe atrophic maxilla.

The autosomal recessive disorder Ataxia-Telangiectasia is caused by dysfunction of the stress response protein ATM. In the nucleus of proliferating cells, ATM senses DNA double-strand breaks and coordinates their repair. This role explains T-cell dysfunction and tumor risk. However, it remains unclear whether this function is relevant for postmitotic neurons and underlies the cerebellar atrophy, since ATM is cytoplasmic in postmitotic neurons. Here, we used ATM-null mice that survived early immune deficits by bone-marrow transplantation, and reached initial neurodegeneration stages at 12 months of age. Global cerebellar transcriptomics demonstrated ATM depletion to trigger upregulations in most neurotransmission and neuropeptide systems. Downregulated transcripts were found for the ATM interactome component Usp2, many non-coding RNAs, ataxia genes Itpr1, Grid2, immediate early genes and immunity factors. Allelic splice changes affected prominently neuropeptide machinery, e.g. Oprm1. Validation experiments with stressors were performed in human neuroblastoma cells, where ATM localized only to cytoplasm, similar to brain. Effect confirmation in SH-SY5Y cells occurred after ATM depletion and osmotic stress better than nutrient / oxidative stress, not after ATM kinase inhibition or DNA stressor bleomycin. Overall, we provide pioneer observations from a faithful A-T mouse model, which suggest general changes in synaptic and dense-core vesicle stress adaptation.

This study employed e-Vol DX cone beam computed tomography (CBCT) software to assess dentin remnants in the furcation area of mesial canals in mandibular molars during root canal retreatment (RCR). Four groups (Reciproc®, ProTaper Next®, Race Evo®, Protaper Gold®) were subjected to RCR, and CBCT images were captured before (T1) and after (T2) treatment. Measurements of remaining dentin thickness at 1 mm and 3 mm below the furcation were scrutinized. Results revealed no significant differences in mean thicknesses of mesiobuccal (MB) and mesiolingual (ML) canals at 1 mm and 3 mm from the furcation pre-treatment (T1). Post-treatment (T2) showed analogous findings, with no significant differences in mean thicknesses. However, disparities surfaced between MB and ML canals at both distances, both before and after retreatment. In essence, the evaluated instruments exhibited safety in RCR, implying their appropriateness for use in critical areas of mandibular molars without inducing excessive wear. This study underscores the instruments' reliability in navigating danger zones during RCR, contributing valuable insights for dental practitioners handling complex root canal scenarios in mandibular molars.

Abstract: Radiation-induced skin injury can be a serious cutaneous damage and have specific characteristics. Asymptomatic periods are classified as the latent stage. The skin barrier plays a critical role in the modulation of skin permeability and hydration and protects the body against a harsh external environment. However, an analysis on the skin barrier dysfunction against radiation exposure in the latent stage has not been conducted. Thus, we investigated whether skin barrier is impaired by irradiation in the latent stage and aimed to identify the molecules involved in skin barrier dysfunction. We analyzed skin barrier function and its components in SKH-1 mice that received 20 and 40 Gy local irradiation. Increased transepidermal water loss and skin pH were observed in the latent stage of the irradiated skin. Skin barrier components, such as structural proteins and lipid synthesis enzymes in keratinocyte, increased in the irradiated group. Interestingly, we noted sebaceous gland atrophy and increased serine protease and inflammatory cytokines in the irradiated skin during the latent period. This finding indicates that the main factor of skin barrier dysfunction in the latent stage of radiation-induced skin injury is sebaceous gland deficiency, which could be an intervention target for skin barrier impairment.

Background: Early diagnosis of postoperative complications is an urgent task, allowing timely prescribing of appropriate therapy and reducing the cost of patient treatment. Prognostic models based on various data could help in the early diagnosis of postoperative complications after cardiac surgery. Objectives: The purpose of the study was to determine whether an integrated approach based on clinical data along with metabolites and biomarkers had greater predictive value than the models built on less data. Methods: The study included patients (n=62) admitted for planned cardiac surgery (coronary artery bypass grafting with cardiopulmonary bypass), who were retrospectively divided into two groups depending on the presence (n=26) or absence (n=36) of postoperative complications of all types. Clinical and laboratory data on the first day after surgery were analyzed. Additionally, patients' blood samples were collected before and on the first day after surgery to determine biomarkers (interleukin-6, procalcitonin, NT-proBNP, high-sensitivity troponin T) and metabolites (8 aromatic and 2 dicarboxylic acids were detected using gas chromatography-mass spectrometry). Results: Patients before surgery, compared with healthy donors, differed in the concentration of metabolites (p &lt; 0.05), and had concentrations of a number of biomarkers exceeding the corresponding reference values. Multivariate PLS-DA models, predicting the presence or absence of postoperative complications, were built using clinical data (ROC-AUC=0.71), concentrations of metabolites and biomarkers (ROC-AUC=0.60), and the entire data set (ROC-AUC=0.75). For comparison we built univariate models using the EuroScore2 (ROC-AUC=0.59) and SOFA (ROC-AUC=0.76) scales; concentrations of lactate (ROC-AUC=0.71), the dynamic changes of 4-hydroxyphenyllactic acid (ROC-AUC=0.69), and the sum of three sepsis-associated metabolites (ROC-AUC=0.70). The proposed complex model using entire data set was comparable to the SOFA scale, which confirms the expediency of searching for new predictive models based on a variety of factors.

Milk serves as a crucial source of natural bioactive compounds essential for human nutrition and health. The gastrointestinal digestion of milk proteins releases various biologically active peptides that positively impact human health and enhance physiological performance. With the growing production of cheese, Greek yogurt, and other dairy products, the volume of unutilized acid whey is significantly increasing. Acid whey, containing almost all whey proteins and approximately one-quarter of casein, presents a valuable raw material for generating peptides with potential health benefits. These peptides exhibit properties such as antioxidant, antimicrobial, anti-inflammatory, anticarcinogenic, antihypertensive, antithrombotic, opioid, mineral-binding, and growth-stimulating activities, contributing to improved human immunity and the treatment of chronic diseases. Enzymatic hydrolysis of milk proteins has been developed as a method to produce these peptides, facilitating their use in food fortification. To incorporate whey into functional beverages, it undergoes fermentation by lactic acid bacteria with proteolytic activity. To specifically enrich these beverages with peptides exhibiting targeted bioactivities, it is essential to select lactic acid bacteria strains possessing the requisite protease profiles. Additionally, the sensory properties of the final product can be enhanced using starter cultures with diverse metabolic capabilities, even in the absence of added flavoring agents. Given the imperative to develop waste-free technologies and enhance the profitability of the dairy industry, there is a growing need to efficiently utilize and transform acid whey into a broad spectrum of valuable products and food additives. This approach is justified not only by the nutritional benefits of the bioactive components in whey but also by the commercial potential of safe and health-enhancing products.

The paper focuses on the application of a multilevel, integrative and territorial approach to the protection of cultural heritage through planning instruments in Serbia. It points out the problems of the sectoral approach and discusses international recommendations that can be integrated into the planning methodology. The case study is the area of Djerdap National Park, which has an already established international and national importance. The research suggests that the cultural heritage in the area, with the exception of the Roman limes, is still recognized at the level of individual localities. The study emphasizes the importance of aligning all levels of governance to safeguard the whole spatial entity rather than focusing solely on its particular areas. The interna-tional and national importance of the planning area contributes to the strengthening of awareness of heritage and its institutional protection. However, the vitality of the area, which is key to its sustainable development, comes from the local level. Planning documents contribute to the inte-gration of local values and local communities into development programs and projects.

The impact of interaction SS with MJO on rainfall along Java Island to East Nusa Tenggara has been studied using daily rainfall observation data from 2140 weather observation stations, which are also equipped with GSMaP, OLR, and ERA5 data. There were 61 SS events found, 17 during active MJO and 44 in inactive MJO. Rainfall increases more in the western study area when the active MJO and more in the eastern study area when the inactive MJO is due to SS. SS reduces rainfall in the Jakarta region, regardless of the activity or inactivity of the MJO. SS causes extreme rainfall to only occur in a small part of certain areas, so it tends to significantly reduce the possibility of extreme rainfall. In the southern part of the IMC, SS predominates over MJO in supporting increased water vapor transport. Large-scale synoptic circulations like the monsoon, SS, and MJO can interact with local land-sea wind circulation to produce spatiotemporal variability in rainfall on Java Island. Rainfall mostly increases in the afternoon and decreases in the morning when SS occurs, whether there is MJO or not. Convective instability analysis indicates that SS increases precipitation, most likely by lowering CIN and raising VIMFC.

In order to shorten the detection time and improve the average precision on embedded devices, A lightweight and high accuracy model is proposed for passion fruit in complex environments (backlight, occlusion, overlap, sunny, cloudy, rainy). Firstly, replacing the backbone network of YOLOv5 with a lightweight GhostNet model reduces the number of parameters and computation while improving detection speed. Secondly, a new feature branch is added to the GhostNet network, and the feature fusion layer in the neck network is reconstructed to effectively combine the lower-level and higher-level features, which not only improves the accuracy of the model but also maintains its lightweight. Finally, the knowledge distillation methods are used to transfer the knowledge from the more capable teacher model to the less capable student model, which significantly improving the detection accuracy. The improved model is denoted as G-YOLO-NK. The average accuracy of the G-YOLO-NK network is 96.00%, which is 1.00% higher than the original YOLOv5s model. Furthermore, the improved model size is 7.14MB, reduced to half of the original model, and the real-time detection frame rate is 11.25 FPS on the Jetson Nano. Compared to the state-of-the-art model, the proposed model outperforms them in terms of average precision and detection performance. The present work provides an effective model for real-time detection of passion fruits in complex orchard scenes, which can provide valuable technical support for the development of orchard picking robots and greatly improve the intelligence level of orchards.

The Simultaneous Localization And Mapping (SLAM) scanner is an easy and portable Light Detection And Ranging (LiDAR) data acquisition device. Its main output is a 3D point cloud covering the scanned scene. Regarding the importance of accuracy in the survey domain, this paper aims to assess the accuracy of two SLAM scanners: the NavVis VLX and the BLK2GO Scanner. This assessment is conducted for both outdoor and indoor environments. In this context, two types of reference data are used: the Total Station (TS) and the static scanner Z+F Imager 5016. To carry out the assessment, four comparisons are tested: cloud to cloud, cloud to mesh, mesh to mesh, and edge detection board assessment. However, the results of the assessments confirm that the accuracy of indoor SLAM scanner measurements (5 mm) is greater than that of outdoor ones (between 10 mm and 60 mm). Moreover, the comparison of cloud to cloud provides the best accuracy regarding direct accuracy measurement without manipulations. Finally, based on the high accuracy, scanning speed, flexibility, and the accuracy differences between tested cases, it is confirmed that SLAM scanners are effective tools for data acquisition.

In recent years, electroencephalogram (EEG) emotion recognition has emerged as a research hotspot in the field of artificial intelligence (AI). Despite advancements in EEG-based emotion recognition, room for enhancing performance persists due to EEG signal redundancy and limitations in feature extraction, leading to inefficient models and emotional information loss. To fully utilize EEG's emotional information and improve recognition accuracy while reducing computational costs, this paper proposes a Convolutional-Recurrent Hybrid Network with a dual-stream adaptive approach and an attention mechanism (CSA-SA-CRTNN). Firstly, the model utilizes a CSAM module to assign corresponding weights to EEG channels. Then, an adaptive dual-stream convolutional-recurrent network (SA-CRNN and MHSA-CRNN) is applied to extract local spatial-temporal features. After that, the extracted local features are concatenated and fed into a temporal convolutional network with a multi-head self-attention mechanism (MHSA-TCN) to capture global information. Finally, the extracted EEG information is used for emotion classification. We conducted binary and ternary classification experiments on the DEAP dataset, achieving 99.26% and 99.15% accuracy for arousal and valence in binary classification, and 97.69% and 98.05% in ternary classification, surpassing relevant algorithms. Additionally, the model's efficiency is significantly higher than other models, achieving better accuracy with lower resource consumption.

Glycosidic linkage analysis was conducted on the unfractionated polysaccharides in the alcohol-insoluble residues (AIRs) prepared from six red seaweeds (Gracilariopsis sp., Prionitis sp., Mastocarpus papillatus, Callophyllis sp., Mazzaella splendens, and Palmaria palmata) using GC-MS/FID analysis of partially methylated alditol acetates (PMAAs). The cell walls of P. palmata primarily contained mixed-linkage xylans and small amounts of sulfated galactans and cellulose. In contrast, the unfractionated polysaccharides of the other five species were rich in galactans displaying diverse 3,6-anhydro-galactose and galactose linkages with varied sulfation patterns. Different levels of cellulose were also observed. This glycosidic linkage method offers advantages for cellulose analysis over traditional monosaccharide analysis that is known for underrepresenting glucose in crystalline cellulose. Relative linkage compositions calculated from GC-MS and GC-FID measurements showed that anhydro sugar linkages generated more response in the latter detection method. This improved linkage workflow presents a useful tool for studying polysaccharide structural variations across red seaweed species. Furthermore, for the first time, relative linkage compositions from GC-MS and GC-FID measurements, along with normalized FID and total ion current (TIC) chromatograms without peak assignments, were analyzed using principal component analysis (PCA) as a proof-of-concept demonstration of the technique's potential to differentiate various red seaweed species.

Background: Educating college students about the importance of good sleep habits could lead to the adoption of healthier sleep routines, including sufficient sleep duration and sleep quality. The current pre-post study examines the impact of completing a sleep education program called “Sleep 101” on (1) sleep hygiene practices, (2) sleep quality, and (3) weekday and weekend sleep behaviors among college students. “Sleep 101” is an interactive online course developed to educate college students about the importance of sleep by addressing basic sleep physiology, the impact of sleep on mood, academic and physical performance, the interactions between sleep and various substances, and common sleep disorders. Methods: 338 college students were recruited from a midsized public university in the US and invited to participate in “Sleep 101”, of which 25 participants completed the baseline and post-intervention questionnaire. The Sleep Hygiene Index (SHI) was utilized to evaluate sleep hygiene practices, while standard questions were employed to assess weekday and weekend sleep behaviors and overall sleep quality. Results: Those who completed the study demonstrated a significant increase in weekday sleep duration and were less likely to engage in negative prior bedtime activities. In addition, 40% of those who completed baseline and post-intervention assessments noticed improvements in their sleep quality. Conclusion: These findings suggest that a brief online program is beneficial in improving sleep behaviors among college and could be a scalable approach to addressing current sleep issues and preventing future sleep problems in college students.

The profile of secondary metabolites occurring in apple cuticular layer is not only characteristic for particular apple cultivar, but also dynamically reflects various external factors in growing environment. In this study, the possibility to authenticate apple samples based on analysis of their cuticular layer extracts was investigated. Ultra-high-performance liquid chromatography coupled to high resolution tandem mass spectrometry (UHPLC-HRMS/MS) was employed for obtaining metabolomic fingerprints. In total, 274 authentic apple samples, four cultivars harvested within the seasons 2020 to 2022 in the Czech Republic and Poland were analysed. The generated complex data processed by univariate and multivariate statistical methods enabled to build classification models for discrimination of apple cultivars as well as their geographical origin. The models showed very good performance in differentiation of Czech and Polish samples for three of four cultivars: ‘Gala’, ‘Golden Delicious’ and ‘Idared’, moreover, the validity of the models was verified over harvest seasons. The diagnostic markers, besides metabolites of triterpene biosynthetic pathway, mainly represented wax esters. ‘Jonagold’, which is known to be susceptible to mutations, was the only cultivar for which the unambiguous classification of geographical origin was not possible.

Superior fiber quality is one of the most important objectives in cotton breeding. To detect the genetic basis underlying fiber quality, an F2 population containing 413 plants was constructed by crossing Jifeng 914 and Jifeng 173, both of which have superior fiber quality, with Jifeng 173 being better. Five fiber quality traits were investigated in the F2, F2:3, F2:4, and F2:5 populations. Quantitative trait loci (QTL) mapping was conducted based on a high-density genetic map containing 11,488 single nucleotide polymorphisms (SNPs) and spanning 4,202.12 cM in length. Transgressive segregation patterns and complex correlations in the five tested traits were observed. A total of 108 QTLs were found, including 27 for fiber length (FL), 16 for fiber strength (FS), 24 for micronaire (MC), 17 for fiber uniformity (FU), and 24 for fiber elongation rate (FE). Chromosome A7 contained 12 QTL, ranking the first. No QTL was found on chromosome D1 and D11. Each QTL contributed 1.98%–21.45% to the phenotypic variation (PV), including 13 major effect QTLs that contributed more than 10% toward PV. Two QTLs could be repeatedly detected in three populations, including qFL-D3-2 in F2, F2:4, and F2:5 with 9.18%–21.45% of PV, qFS-A11-1 in F2:3, F2:4 and F2:5 with 6.05%–10.41% of PV. Another seven stable QTLs could be detected in two populations, including four major effect QTLs: qFL-A12-3, qFS-D10-2, qMC-D6-2, and qMC-D8-1. Fourteen QTL-overlapping regions were found, which might explain the complex correlations among the five phenotypic traits. Four regions on chromosome A11, D3, D6, and D10 covered by both stable and major effect QTLs are promising for further fine mapping. The genomic regions of the two QTLs detected in three populations and the four major effect QTLs contain 810 genes. Gene functional analysis revealed that the annotated genes are mainly involved in protein binding and metabolic pathways. Fifteen candidate genes in the qFL-D3-2 region are highly expressed in fiber or ovules during fiber initiation, elongation, secondary cell wall thickening, or maturation stages. qRT-PCR revealed that Ghir_D03G005440.1 and Ghir_D03G011310.1 may play a role in promoting fiber initiation, Ghir_D03G006470.1 may be beneficial for promoting fiber elongation. This study provides more information for revealing the molecular genetic basis underlying cotton fiber quality.

Currently there are fewer depth models applied to pepper picking detection, while the existing generalized neural networks have problems such as large model parameters, long training time, and low model accuracy.In order to solve the above problems, this paper proposes a Yolo-chili target detection algorithm for chili pepper detection. First, the classical target detection algorithm yolov5 is used as a benchmark model, and an adaptive spatial feature pyramid structure combining the attention mechanism and the idea of multi-scale prediction is introduced to improve the model's detection effect on occluded peppers and small target peppers. Secondly, a three-channel attention mechanism module is introduced to improve the algorithm's long-distance recognition ability and reduce the interference of redundant testers. Finally, the quantized pruning method is used to reduce the model parameters and realize the lightweight processing of the model. Applying the method to the homemade chili pepper dataset, the AP value of chili pepper reaches 93.11%; the accuracy rate is 93.51% and the recall rate is 92.55%.The experimental results show that yolo-chili is able to achieve accurate and real-time pepper detection under complex orchards.

The temporary immersion system bioreactor named GreenTray®[2], [3]presents advantages over the existing ones. Firstly, there is no need to use forceps to move the shoots or plantlets in or out of the recipient, neither the use of scalpel to divide them. Secondly, the basis of the shoot can remain in the GreenTray® and can sprout again in several cycles of growth. These two characteristics reduce the costs in the process of micropropagation. Besides, shoots or plantlets development is enhanced by the aeration of the recipient, thus enriching with CO2 the recipient atmosphere. The chapter describes and provides images and values of interest in (1) the micropropagation process of some commercial Prunus or Pyrus rootstocks; (2) the plantlet growth under autotrophic conditions; and (2) the inoculation of plants with pathogens that reproduce in vitro the symptoms observed in vivo, using the GreenTray® bioreactor.

The aim of this retrospective study was to compare the clinical outcomes of treating isolated surgical neck fractures of the humerus using either the intramedullary nail or the MIROS (Minimally Invasive Reduction and Osteosynthesis System®) system. The study included 42 patients who underwent surgical treatment at the Polyclinic from January 2014 to June 2020. The results indicated that both treatments were effective; however, the MIROS system exhibited a higher complication rate. Intramedullary nailing was more reliable, thus recommended as the primary treatment method. This study underscores the importance of selecting the appropriate fixation technique to minimize complications and enhance patient outcomes.

Aiming at the problems of inaccurate segmentation of long object and information loss of small object in real-time semantic segmentation algorithm, this paper proposes a lightweight multi-branch real-time semantic segmentation network based on BiseNetV2. The new auxiliary branch makes full use of spatial details and context information to cover the long object in the field of view. Meanwhile, in order to ensure the inference speed of the model, the asymmetric convolution is used in each stage of the auxiliary branch to design a structure with low computational complexity. In the multi-branch fusion stage, the alignment and fusion module is designed to provide guidance information for deep and shallow feature mapping, so as to make up for the problem of feature misalignment in the fusion of information at different scales, and thus reduce the loss of small target information. In order to further improve the model’s awareness of key information, a global context module is designed to capture the most important features in the input data. The proposed network uses NVIDIA GeForce RTX 3080 Laptop GPU experiment, on the road street view data set Cityscapes and CamVid average occurring simultaneously ratio reached 77.1% and 78.4% respectively, with running speed of 127 frames/s respectively and 112 frames/s. The experimental results show that the proposed algorithm can achieve real-time segmentation and improve the accuracy significantly, showing good semantic segmentation performance

Excess nitrogen in agricultural drainage poses a serious threat to the water quality safety of the Yellow River basin. Utilizing aquatic plants to modify the rhizosphere microbial community structure and facilitate nitrogen transformation is a crucial strategy for mitigating regional water eutrophication. Our results revealed that the denitrification rate (DR), dissimilatory nitrate reduction to ammonium rate (DNRAR) and nitrogen fixation rate (NFR) of rhizosphere sediments exhibited a significant increase in artificially cultivated ditch. Compared with those in natural ditches, the richness of the bacterial community and the relative abundances of Bacteroidota, Verrucomicrobiota, Firmicutes, Anaeromyxobacter and Geobacter, which are involved mainly in the nitrogen cycle, in the rhizosphere sediments of artificially cultivated ditch were significantly greater due to improvements in environmental conditions. In artificially cultivated ditch, the dominant functional genes affecting DRNARs in the rhizosphere sediments of P. australis were nrfC and nrfA, while DRs were driven mainly by norB and napA, which were influenced by the nitrogen and carbon levels; and the dominant functional genes affecting NFRs in the rhizosphere sediments of T. orientalis were nifD, nifK and nifH. Our results provide a scientific basis for the use of aquatic plants for mitigating excess nitrogen levels in agricultural drainage.

Strawberry root rot caused by Neopestalotiopsis clavispora is one of the main diseases of strawberry and significantly impacts the yield and quality of strawberry fruit. There are now no effective control techniques available except for fungicide sprays, which may directly impact consumers. Biological control is becoming an alternative method for the control of plant diseases to replace or decrease the application of traditional synthetic chemical fungicides. Trichoderma is widely used as a biological agent for controlling strawberry root rot. In order to provide resources for screening the highly effective biocontrol fungus for controlling strawberry root rot caused by Neopestalotiopsis clavispora, the biocontrol mechanism,the control effects of Trichoderma asperellum CMT10 against strawberry root rot and growth-promoting effects on strawberry seedlings were investigated by plate culture, microscopy observation and root drenching methods.The results showed that CMT10 had obvious competitive, antibiotic and hyperparasitism effects on Neopestalotiopsis clavispora CMGF3. The CMT10 could quickly occupy nutritional space, and the inhibition rates of CMT10 against CMGF3 in confrontation culture on 7 d was 65.49%. The inhibition rates of volatile metabolite and fermentation metabolite produced by CMT10 against CMGF3 were 79.67% and 69.84%, respectively. The mycelium of strain CMT10 can act as hyperparasites by making contacting, winding and penetrating hyphae of CMGF3. Pot experiment showed that the biocontrol efficacy of CMT10 on strawberry root rot caused by Neopestalotiopsis clavispora was 63.00%. CMT10 had obvious promotion effect on strawberry growth, the plant height, root length, total fresh weight, root fresh weight, stem fresh weight and root dry weight, with the promotion rates were 20.09%, 22.39%, 87.11%, 101.58%, 79.82% and 72.33%, respectively. Overall, this study showed the ability of Trichoderma asperellum CMT10 to control strawberry root rot and their potential to develop as novel biocontrol agents to replace chemical fungicides for eco-friendly, sustainable agriculture.

In this paper we study a class of impulsive delayed neural networks with parameter uncertainties and reaction-diffusion terms. Using the properties of M-matrices and some inequality techniques, some sufficient conditions are derived to guarantee the global exponential stability of the given system. The results obtained are presented by simple algebraic inequalities, which are certainly more concise than previous methods. Finally, the validity and usefulness of our results are illustrated by arithmetic examples.

Pyrops candelaria is one of the common pests of fruit trees, but the research on the pathogenic microorganisms it may carry is very limited. Therefore, it is essential to reveal the pathogenic microbes it carries and their potential hazards. This study found a new virus from the transcriptome of P. candelaria, which was first reported in P. candelaria and named as PyCaV (Pyrops candelaria associated virus). RACE and bioinformatics assay revealed that the full-length of PyCaV is 10855 bp with the polyA tail, containing a single open reading frame (ORF) encoding a polyprotein consisting of 3171 amino acid (aa). The virus has a typical Iflavirus structure, including two rhv domains, a RNA helicase domain (HEL), a 3C cysteine protease domain (Pro), and a RNA-dependent RNA polymerase domain (RdRp). Further phylogenetic analysis revealed that this virus belongs to family Iflaviridae and sequence alignements analysis suggedted PyCaV is new member in unassigned genus of family Iflaviridae. Further in-depth analysis of virus-infection-part showed that PyCaV is distributing in the whole longan lanternfly, including its head, chest, and abdomen, but more PyCaV was identified in the chest. The distribution of PyCaV in different parts of P. candelaria was further explored, which showed that more PyCaV were detected in its piercing-sucking mouthparts and chest viscera. Statistical analysis showed that the PyCaV infection was affected by time and locations.

Apis mellifera, especially weak ones, are highly vulnerable to Carpoglyphus lactis mites, which can rapidly infest and consume stored pollen, leading to weakened colonies and potentially colony collapse. This study aimed to ascertain and investigate the prevalence of this mite in honeybee colonies across 9 provinces in the Republic of Korea (ROK). A total of 615 honeybee colonies were collected, from 66 apiaries during the spring and 58 apiaries during the summer of 2023. A 1,242 bp segment of the the Cytochrome c oxidase subunit 1 (COI) gene was amplified using the polymerase chain reaction method. The detection levels of C. lactis in the honeybees were compared between winter and summer. Based on the COI sequence analysis, the nucleotide sequence similarity of C. lactis mites isolated in the ROK with those from China (NC048990.1) was found to be 99.5%, and with those from the United Kingdom (KY922482.1) was 99.3%. This study is the first report of C. lactis in Korean apiaries. The findings in this study demonstrate a significantly higher detection rate in winter, which is 4.1 times greater than that in summer (p &lt; 0.001). Furthermore, the results underscore the usefulness of molecular diagnostic techniques for detecting C. lactis mites.

Our previous studies demonstrated a tight connection between simvastatin (SIM) inhibition of B16.F10 murine melanoma cell proliferation in vivo and in vitro and strong suppression of the subunit α of hypoxia inducible factor 1 (HIF-1) (HIF-1 α) production in these cancer cells. Since the translation of HIF-1α is modulated by signaling pathways coordinated by Akt, SIM effects on the link between these two regulatory factors and cancer cell metabolism under normoxia was investigated, which to our knowledge have never been described before. To achieve the proposed aim, SIM effects on cell metabolism were analysed at mRNA (via RNA-seq and RT-qPCR) as well as protein level (via western blot and catalytic activity of the key enzymes) Our data suggested that SIM might orientate glucose transport and metabolism to ensure replenishment of tricarboxylic acid (TCA) cycle activity. Moreover, it seems that SIM enhanced biosynthetic role of TCA over its energy role to further support synthesis of lipid-derived signaling molecules. Thus, under normoxia SIM treatment orientated lipid metabolism to stimulate isoprenoid and prostaglandin synthesis which might favor melanoma cell survival and aggressiveness.

COX II containing a dual core CuA active site is one of the three core subunits of mitochondrial Cco, which plays a significant role in the physiological process. In this report, the full-length cDNA of COXⅡ gene was cloned from Sitophilus zeamais, which had an ORF of 684 bp encoding 227 amino acids residues. The predicted COXⅡ protein had a molecular mass of 26.2 kDa with pI value of 6.37, and multiple sequence alignment and phylogenetic analysis indicated that Sitophilus zeamais COXⅡ had high sequence identity 78.51% with the COXⅡ of other insect species, especially similarity to sitophilus oryzae. This gene was subcloned into the prokaryotic expression vector pET-32a, and induced by IPTG in E.coli Transetta (DE3) expression system. Finally the COXⅡ with 6-His tag was purified using affinity chromatography with Ni²⁺-NTA agarose. WB showed the recombinant COXⅡ was about 44 kD, and the concentration of fusion protein was 50μg/mL. UV-spectrophotometer and infrared spectrometer analysis showed that recombinant COXⅡ could catalyze the oxidation of substrate Cytc, and influenced by AITC. It was found that AITC could form a hydrophobic region with COXⅡ protein via molecular docking, besides, a sulfur atom of AITC structure could form a length of 2.9 Å hydrogen bond with Leu-31. These results will provide valuable information for elucidating the role of COXⅡ in Sitophilus zeamais responses to AITC, meanwhile, it will helpful to carry out a point mutation in AITC binding sites for the future research.

In this paper, we extend the KdVSKR equations in (1+1)-dimension and (2+1)-dimension to fractional KdVSKR equations with modified Riemann-Liouville derivative. The (2+1)-dimensional KdVSKR equation, which is a recent extension of (1+1)-dimensional KdVSKR equation, can model the resonances of solitons in shallow water. By means of the Hirota bilinear method, finite symmetry group method and consistent Riccati expansion method, many new interaction solutions have been derived. Soliton-cnoidal interaction solution of the (1+1)-dimensional fractional KdVSKR equation has been derived for the first time. For the (2+1)-dimensional frac-tional KdVSKR equation, two-wave interaction solutions and three-wave interaction solutions, including dark-soliton-sine interaction solution, bright-soliton-elliptic interaction solution, and lump-hyperbolic-sine interaction solution, have been derived. Impact of the fractional order on the shapes of these solutions has been illustrated by figures. Three-wave interaction solutions of fractional systems have not been reported in the existing references. The research idea in this paper can be applied to other fractional differential equations.

With the burgeoning growth of online retail, the issue of counterfeit products has become a significant threat to both consumer trust and brand integrity, posing challenges to sustainable market practices. Online retail platforms are promoted to redesign their channel structures and enhance brand traceability to tackle counterfeits using blockchain technology. To investigate the interactions between blockchain technology and the channel structures of online retail platforms, we design a game theory model incorporating a manufacturer with(out) blockchain participation selling products via an online retail platform that operates an agency channel and/or a reselling channel. We show that the critical trade-off of blockchain participation comprises the brand assurance effect of the blockchain, the channel competition intensification effect, and the blockchain adoption cost. The platform is capable of strategically designing the channel structure to encourage (while discouraging) blockchain participation by the manufacturer. Our analysis highlights the complementarity between blockchain participation and the channel structure. Furthermore, the effect of the consumer’s belief in the reselling channel, the commission fee in the agency channel, and the substitutability between channels are investigated in depth. The research provides valuable insights for online retail platforms and policymakers seeking to foster a sustainable and trustworthy e-commerce ecosystem.

Antimicrobial peptides represent a promising alternative to traditional drugs in relation to cost, toxicity and, primarily, the growing problem of drug resistance. Here we report on the activity against HSV-1 and HSV-2 of a previously described wide-spectrum synthetic decapeptide, Killer Peptide (KP). As determined by plaque reduction assays, treatment with KP at 100 μg/mL resulted in a reduction in the viral yield titer of 3.5 Logs for HSV-1 and 4.1 Logs for HSV-2. Further evaluation of KP antiviral activity focused on the early stages of virus replicative cycle, including the determination of the residual infectivity of viral suspensions treated with KP. A direct effect of the peptide on viral particles, impairing virus absorption and penetration, was shown. The toxicity profile proved to be extremely good with a selectivity index of 29.6 for HSV-1 and 156 for HSV-2. KP was also active against an acyclovir (ACV)-resistant HSV-1 strain, while HSV-1 subcultures in the presence of sub-inhibitory doses of KP did not lead to the emergence of resistant strains. Finally, the antiviral action of KP proved to be synergistic with that of ACV. Overall, these results demonstrate that KP could represent an interesting addition/alternative to acyclovir for antiviral treatment.

The properties of the annual, semiannual and triennial oscillations (AO, SAO and TO) in the middle atmosphere have been investigated using the TIMED/SABER temperature data. The Lomb-Scargle and wavelet spectra were used to determine the dominant oscillations in the background temperature field. The AO is prominent at the mid-latitudes. The AO amplitudes present an asymmetry between the two Hemispheres, being larger in the mesosphere than in the stratosphere. The SAO dominates the tropical regions, with three amplitude maxima at altitudes of 45, 75, and 85 km. The SAOs in the upper mesosphere (75 km) are out of phase with those in the mesopause (85 km) in the tropical regions, which can generate an enhancement of 11 K at each equinox, contributing to the lower mesospheric inversion layer. The TO is significant in the tropical region, with amplitude being maximum at 35, 45 and 85 km. Result shows that there may be potential interaction by the TO with SAO at 85km at the equator. The relation between ENSO and TO has also been discussed. The ENSO signal may modulate the amplitude of the TO, mainly in the lower stratosphere. The real origin of the TO may lie in the wave-mean-flow interaction.

As the world population grows, fulfilling the need for biomaterials in the healthcare system becomes increasingly important. Biomaterials, which include metals, polymers, ceramics, and composites, play an important role in the creation of medical devices that improve people's lives. The European Society for Biomaterials described biomaterials as non-biological materials used in medical devices to interact with biological systems. This definition has developed to encompass materials that treat, assess, or replace tissues or bodily functions. Biocompatibility, as defined by the FDA, is a key feature of biomaterials, as is the requirement to fulfil design requirements such as mechanical performance, geometry, and electrical control. Over the last decade, advances in regenerative medicine and tissue engineering have boosted biomaterials' usage in medical applications dramatically. Despite its promise, scientists, engineers, and physicians continue to face significant challenges due to the complexity of biomaterials. Biomaterials have various benefits, including biodegradability, non-toxicity, and biocompatibility, making them extremely useful for replacing, sustaining, or improving biological activities in damaged tissues. They are used in a wide range of applications, including tissue engineering implants, human tissue healing and regeneration, medication delivery systems, and biosensors. This study gives insights into the fundamental characteristics, case studies, and ethical issues associated with the usage and use of biomaterials, further examining their potential and significance in healthcare and medicine.

The paper describes the new method for image compression based on coordinated group signal transformation. The algorithm is a type of difference coding. Coordinated processing significantly simplifies the difference signal conversion scheme using a single group codec for all signals. The described method considers color channels as correlated signals of a multi-channel communication system. The specifics of the processed data required modification of the coordinated group processing algorithm. First, we changed how to calculate the difference signals to prevent data loss. Secondly, the group codec was supplemented with a neural network to improve the quality of reconstructed images. We considered the following types of neural networks: fully connected, recurrent, convolution, and convolution in the Fourier space. Based on the simulation results, it is best to use fully connected neural networks if the goal is to minimize processing delay time. These networks have a response time of 13 ms. On the other hand, if the priority is to improve quality in cases where delays are not critical, then convolution neural networks in the Fourier space should be used. These networks have a response time of 140 ms and are of significant interest.

In electromagnetic ultrasonic testing, it is difficult to recognize small-size bottom cracks by time of flight (ToF), and the lift-off fluctuation of the probe affects the accuracy and consistency of the inspection results. In order to overcome the difficulty, a novel EMAT (electromagnetic acoustic transducer)-PEC (pulse eddy current) composite sensor is designed. We use amplitude of bottom echo recorded by EMAT to identify the tiny bottom crack as well as the amplitude of PEC signals picked up by the integrated symmetric coils to measure the average lift-off of the probe in real time. Firstly, the effects of lift-off and bottom cracks on amplitude of bottom echo are distinguished combining the theoretical analysis and finite element method (FEM). And then an amplitude correction method based on the fusion of EMAT and PEC signals is proposed to reduce the impact of lift-off on the defect signal. The experimental results demonstrate that the designed composite sensor can effectively detect the bottom crack as small as 0.1mm* 0.3mm. The signal fusion method can accurately correct the amplitude of defect signal and the relative error is less than ±8%.

The studied solar pot is a recent invention, which gained a utility model protection in 2021 from the Hungarian Intellectual Property Office under patent number 5489. The device is made for environmentally friendly cooking or heating (by utilizing solar energy) of foods and liquids. Its structure is similar to a double pipe heat exchanger, it has an outer mantle and an inner cooking tank. The goals of the paper are proposing a new physically-based mathematical model describing the solar pot and carrying out computer experiments with it, assembling an experimental system of the pot connected with a solar collector and performing measurements on it. Based on the results, the solar pot can successfully be used for cooking or sterilizing foods or liquids during the studied time period, in Hungary.

The research reported on this paper was aimed at improving the overall efficiency of a PDO certified artisanal cheese production process. Being a PDO certified foodstuff by the EU, it is considered to have properties and qualities determined by the geographical environment in which is made, with its production taking place in a specific and determined geographical location, in this case the Serra da Estrela region. In that sense, the authors conducted a mapping according to a systemic perspective of the processes involved in the context of manufacturing and distribution of certified Serra da Estrela cheese. Numerous methods were used throughout the process, such as a systemic design analysis, and techniques derived from ethnographic methods, which led to the collection of data in the field and consequently provided the immersion of the researcher in genuine work situations. Critical points were identified and emphasized in the systemic map with the purpose of encouraging initiatives to address and overcome the gaps and inefficiencies detected. The systemic design analysis triggered the development of design work. Observations following an ethnographic approach identified ergonomic risks in cheese making during the process of cutting excess chips, fostering the emergence of musculoskeletal disorders at the wrist. A tool that fits best to the task at hand was developed. A prototype of the new tool enabled collecting feedback from use in the work context, in order to inform product development. The domains of agricultural production and microbiology, considering the specific microorganisms developed trough the ripening process of the cheese, turned out to be aspects of high importance for the issue under focus, contributing to a broader understanding of the ripening process and its risks, simultaneously improving the efficiency and success of cheese production. If it were not for the systemic analysis, which served as a link between the boundaries of distinct domains such as the risk of microorganism contamination, ergonomics, energy efficiency, legislation and regulation policies, transportation challenges and economic viability, approached throughout the research. Simultaneously creating bridges between them, the various problems might not have been detected in the first place, as they are usually addressed in specialized disciplines, predetermined by the restrictions of each specific area of knowledge. As a consequence of the development of this research, which was based on an analysis that sought to establish possible connections between various disciplines and tried to constantly maintain a holistic perspective, making new connections and observing the issues from a new angle, apart from the already established methodologies. All this allowed to lay out the seeds for the development of a plan to tackle the critical points identified by the systemic analysis reported in this paper.

Abstract: Transcription factors are crucial pre-transcriptional regulatory mechanisms that can modulate the expression of downstream genes by binding to their promoter regions. DOF (DNA binding with One Finger) proteins are a unique class of transcription factors with extensive roles in plant growth and development. Our previous research indicated a decrease in iron content in chlorotic bamboo leaves. However, to our knowledge, genes related to iron metabolism pathways in bamboo species have not yet been studied. Therefore, in the current study, we identified iron metabolism-related (IMR) genes in bamboo and determined the transcription factors that significantly influence them. Among these, DOFs were found to have widespread effects and potentially significant impacts on their expression. We identified specific DOF members in Dendrocalamus latiflorus with binding abilities through homology with Arabidopsis DOF proteins, and established connections between some of these members and IMR genes using RNA-seq data. Additionally, molecular docking confirmed the binding interactions between these DlDOFs and the DOF binding sites in the promoter regions of IMR genes. The co-expression relationship between the two gene sets was further validated using q-PCR experiments. This study paves the way for research into iron metabolism pathways in bamboo and lays the foundation for understanding the role of DOF transcription factors in D. latiflorus.

Tussilago farfara L. is a traditional medicinal plant valued for its potentially health-promoting metabolites. Its herbal raw material has been recognized and used since ancient times and continues to be widely used in traditional medicine. Introducing these plants to in vitro cultivation is a challenging task, but once the protocol is developed, such cultures can provide an abundant and inexhaustible source of plant material. In this study, we report the successful induction and growth of vigorous T. farfara L. callus in vitro. Callus induction was achieved on solid media in darkness, whereas it appeared inefficient under light conditions and in suspension culture. We present a detailed description of callus growth kinetics, morphological analysis, photosynthetic activity and biochemical parameters (including protein content and photosynthetic pigments) supported by histological studies. Furthermore, we observed potential for organogenesis and somatic embryogenesis. This method for in vitro propagation of T. farfara, along with callus culture maintenance, offers a wide range of applications in pharmacy and could benefit the environment by minimizing the depletion of natural populations of this species.

Surgical site infections (SSIs) are a major concern in public healthcare, leading to increased morbidity, pro-longed hospital stays length, and significant economic costs. Understanding the epidemiology and risk fac-tors of SSIs is crucial for developing effective prevention and management strategies. In the last century, CDC ‘s HICPAC improved a bundle for prevention of HAIs based on the use of aseptic procedures, disin-fection of the skin and correct use of antibiotics for SSIs. In our country, Gelli-Bianco law introduced the national health guidelines system that include the prophylaxis antibiotic therapy pre- and post-surgery. The aim of our study is to evaluate adherence and appropriateness of the use of antibiotic-preoperative prophylaxis in a province of southern Italy and to identify risk factors that may influence the development of an SSI. The study found many statistically significant associations among the factors examined, i.e. the timing of administration adherent to guidelines, with 47% of the analyzed files administering antibiotics within 60 min before the intervention and 62.7% using intravenous administration.

Severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) continues to be a global threat due to its ability to evolve and generate new subvariants, leading to new waves of infection. Additionally, other coronaviruses like Middle East respiratory syndrome coronavirus (MERS-CoV, formerly known as hCoV-EMC) which first emerged in 2012, persists and continues to present a threat of severe illness to humans. The continued identification of novel coronaviruses, coupled with the potential for genetic recombination between different strains, raises the possibility of new coronavirus clades of global concern emerging. As a result, there is a pressing need for pan-CoV therapeutic drugs and vaccines. After extensive optimization of an HCV protease inhibitor screening hit, a novel 3CLPro inhibitor (MK-7845) was discovered and subsequently profiled. MK-7845 exhibited nanomolar in vitro potency with broad spectrum activity against a panel of clinical SARS-CoV-2 subvariants and MERS-CoV. Furthermore, when administered orally, MK-7845 demonstrated a notable reduction of viral burdens by &gt;6 log orders in the lungs of transgenic mice infected with SARS-CoV-2 (K18-hACE2 mice) and MERS-CoV (K18-hDDP4 mice).

The wetlands in northeastern Bangladesh are home to some of the most prolific and valuable ecosystems on the planet, offering a wide range of benefits to both the local and wider communities. A limited number of research on this topic have been carried out in various wetlands in coastal hilsa, but none have been located in the northeastern region of Bangladesh. Thus, the goal of this study was to better understand the most commercially relevant species (anadromous hilsa) in northeastern Bangladesh as well as to assess the wetland ecosystem services more thoroughly with the contribution of their fish genetic resources. In addition to laboratory studies, fieldwork was done in the fishing settlements along the Surma River, Hakaluki Haor, and Tanguar Haor. The study classified 77 fish species into 21 subcategories of ecosystem services, of which 56% were not threatened, 17% were vulnerable, and 10% were highly endangered. The species Hilsa was found to be the most economically significant, accounting for 1% of the GDP overall. The study determined if the hilsa stock of the examined wetlands maintains a single or several subpopulations in comparison to other parts of the country when they migrate from saline water to northeastern Bangladesh (freshwater). But when compared to other groups, the FST score was between 0.000 to 0.017, indicating that the populations are identical and that there is genetic material sharing between them. Additionally, these statistics imply that the Sylhet haor and adjacent river systems contain a single stock of Hilsa fish. Nevertheless, a number of stresses and risks, including overexploitation, illicit and destructive fishing, siltation, and natural disasters like flash floods, have been linked to changes in the supply of hilsa and other ecosystem services. This study also emphasizes the necessity of policy attention and research to address the concerns.

This paper is focused on typical rural settlements in the Stara Planina Mountain area in Serbia. They are distinguished by their authenticity, identity and character, and they have still not been destroyed by inappropriate development as is the case in some other mountain areas in Serbia, where the effects of urbanization, globalization and homogenization are obvious. Consequently, there is a need to prevent these effects in mountain areas where there is a threat of disbalance between development and the inherited natural and cultural values. The paper starts from several important concepts that relate contemporary approaches to cultural heritage preservation, place morphology and planning future development. The concept definitions from recent documents from related fields are used. These concepts are then applied to the area of Stara Planina Mountain and its rural settlements. The necessity for an integrative approach to planning this area with significant natural and anthropogenic potential is pointed out, including its integration into international programs of sustainable development.

The main purpose of this study is the determination of the optimal data acquisition and processing parameters of electric and seismic tomographic techniques, for the investigation of complex geological environments. Two different study areas, in central-east Peloponnese and SW Attica were selected, where a detailed geological mapping and surface geophysical survey were carried out. The applied geophysical survey included the application of electrical resistivity tomography (ERT) and seismic refraction tomography (SRT). The geoelectrical measurements were acquired with different arrays and electrode configurations. Moreover, various types of seismic sources were used at seventeen shot locations along the seismic arrays. For the processing of geoelectrical data, clustered datasets were created increasing the depth of investigation and the discriminatory capability. The seismic data processing included: (a) creation of synthetic models and seismic records to determine the effectiveness and capabilities of the technique, (b) spectral analysis of the seismic records to determine the optimal seismic source type and (c) inversion of the field data to create representative subsurface velocity models. The results of the two techniques successfully delineated the complex subsurface structure that characterizes these two geological environments. The application of the ERT combined with the SRT, are the two dominant, high-resolution techniques for the elucidation of complex subsurface structures.

Cocoa (Theobroma Cacao, L.) represents an important market that gained relevance and became an esteemed commodity thanks to cocoa powder, chocolate, and other related products. This work has analyzed 59 cocoa powder samples from the European market. Three distinct subgroups were identified: organic or conventional, alkalized or not alkalized, and raw or roasted processing. The impact of the technological process was evaluated on the pH, color, and compositional traits, as content of biogenic amines and salsolinol. The phenolic fraction was also investigated trough both common and emerging methods. Results depict that the influence of the agronomical practices (organic/conventional) did not affect significatively (p&lt;0.05) the composition of cocoa powders; similarly, the roasting process was not discriminative for the compounds traced. On the other hand, the alkalinization process greatly impacted on color, and pH, no matter of cocoa provenience, obtention, or other processes, also resulting reducing the phenolic fraction of treated samples. Principal components analysis confirmed that the alkali process acts on pH, color, and phenolic composition, but not on other bioactives molecules (BAs and salsolinol). All samples resulted safe while alkalized powders have a great reduction in beneficial biocompounds. A novel strategy could be to emphasize non-alkalized powders in the label, to meet the demand for more beneficial products.