Medical Research Archives

Introduction Individuals with Gastroesophageal Reflux Disease (GERD) often experience airway inflammation and bronchoconstriction as a result of reflux aspiration and/or vagally mediated reflexes. The Impulse Oscillometry System (IOS) is a sensitive, non-invasive tool that can detect subtle changes in airway resistance. While there are few studies exploring airway resistance in GERD globally, no studies have been conducted in Sri Lanka. Therefore, we aim to compare the airway resistance using IOS in medical undergraduates with and without symptomatic GERD. Methods A cross-sectional study was conducted among 811 medical undergraduates (31.1% male; mean age 22.9 years) at the Faculty of Medicine, Rajarata University of Sri Lanka. Symptomatic GERD was screened using the validated GerdQ, and a cutoff of[≥]8 was used to diagnose those with GERD symptoms. Of the 242 (29.8%) with GERD symptoms, 188 with chronic respiratory diseases or recent respiratory symptoms were excluded, and 50 with GERD symptoms and 50 healthy, age- and sex-matched controls were recruited. Lung function was assessed using IOS and spirometry, according to American Thoracic Society (ATS) and European Respiratory Society (ERS) guidelines. Results Prevalence of symptomatic GERD among medical undergraduates was 29.8% (242/811). The common symptoms among GERD were heartburn (89.6%, 217/242) and regurgitation (85.5%, 207/242). Oscillometry parameters including, R5-R20 Hz (15.29% vs 9.69%, p=0.002), Fres (14.95 1/s vs 13.37 1/s, p = 0.04), and AX (0.66 vs 0.48, p = 0.02) were significantly higher in students with symptomatic GERD (mean = 15.29%) than in healthy controls (mean = 9.69%; p = 0.002). However, spirometry parameters including FEV1, FVC, and PERF did not differ between the GERD-positive and control groups. Conclusion Individuals with symptomatic GERD demonstrated a higher peripheral airway resistance compared to controls, whereas no significant difference was observed in upper airway resistance. This could be due to the gastric acid stimulation of vagal nerve terminations in the lower part of the esophageal wall, leading to increased resistance in the peripheral airways through vagally mediated bronchoconstriction.

Previously, we have demonstrated that certain ferric salts common in Archean waters, such as iron trichloride and ferric ammonium citrate, can protect liposomes from destruction by short-wavelength UVC light. In this study, we investigate the propagation of 254 nm UV radiation through aqueous FeCl3 solutions and its interactions with liposomes. We then consider these findings in the context of early Earth UV environment, discuss their implications for our hypothesis of the Darwinian evolution of liposomes, and integrate them with our previous experimental results.

Purpose: Impaired balance and fall risk in individuals with respiratory conditions highlight the importance of respiratory-postural integration during upright activity. However, breathing and postural control are often studied separately, limiting understanding of their interaction. Singing imposes concurrent ventilatory and trunk control demands, yet respiratory-postural responses during standing singing remain unclear. We examined the effects of vocalisation and tempo on respiratory-postural responses during standing, and whether age and singing experience moderated these responses. Methods: Eighty healthy younger (18-35yr; n=35) and older ([&ge;]60yr; n= 45) adults completed rhythmically paced speaking and singing tasks at slow, normal, and fast tempos while standing on a force platform. Respiratory rate (RR), mediolateral and anteroposterior sway, peripheral oxygen saturation, and perceived breathlessness were measured. Generalised estimating equations assessed vocalisation, tempo, and their interaction, with moderation by age and singing experience. Results: RR showed a vocalisation x tempo interaction (p<.001), with higher RR during slow speaking and greatest increases during fast singing. Singing increased postural sway relative to speaking, particularly mediolaterally (p<.001), with tempo-related increases in anteroposterior sway (p<.001). Older adults exhibited greater postural sway overall (p values[&le;].040) but similar task-dependent modulation to younger adults. Singing experience attenuated RR increases during fast singing (p=.033) and was associated with greater mediolateral sway (p=.004). Perceived breathlessness increased with tempo but was not associated with vocalisation; SpO2 was unchanged. Conclusions: Standing singing was associated with tempo-dependent respiratory and postural responses. Age and singing experience showed distinct associations with these responses. Task-dependent respiratory-postural coordination appeared preserved among participants.

Purpose: Stimulability testing involves the evaluation of multiple aspects of a patient's behavior, but the results are most frequently consolidated into a single domain (i.e., "stimulable"). The current study performs preliminary content, construct, concurrent, and predictive validation for the Multidimensional Stimulability Profile for Voice (MSP-V), a rating scale designed to measure multiple domains during stimulability testing (Degree of Change, Rapidity of Change, Generalization, Patient-rated Voice Quality, Patient-rated Voice Feel, and an overall rating of Stimulability Level). Methods: 78 patients with voice disorders (24 functional, 15 structural, 39 neurological) were administered the MSP-V by five speech-language pathologists (SLPs). Content validity was evaluated via the Content Validity Index (CVI) completed by nine voice-specialized SLPs. Construct validity was evaluated via exploratory factor analysis. Concurrent validity was assessed by determining whether MSP-V domains scaled in the expected direction compared to categorical stimulability ratings (e.g., "Highly stimulable" vs. "Stimulable"). Predictive validity was assessed by examining the relationship between MSP-V domains and voice disorder diagnosis, return to voice therapy, and patient-reported practice outside of therapy. Results: The CVI reached the critical value for clinician-rated and patient-rated domains. Two distinct factors were identified during EFA, one consisting of clinician-rated domains and the other of patient-rated domains. All MSP-V domains showed the expected directional relationships as categorical stimulability ratings. No domains differed significantly between disorder etiologies. The Rapidity of Change and Stimulability Level domains both significantly predicted return for voice therapy, where participants who rated lower on each domain were more likely to return to for voice therapy. No domains were predictive of patient-reported practice. Conclusions: The MSP-V is a clinically feasible tool with emerging content, construct, concurrent, and predictive validity that could be used to provide increased clarity and precision in stimulability testing documentation for research and practice.

The Spike protein (S-protein) of the Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV2) exhibits important and negative effects on human cells. Accordingly, the adverse effects of COVID-19 mRNA vaccines could be due to the presence of circulating spike and need to be mitigated. One of the biological activities of the Spike protein (and, indirectly, of the Spike-producing vaccines) is the high induction of apoptosis and pro-inflammatory gene expression in different cellular systems. We have recently demonstrated that Aged Garlic Extract (AGE) and its components S-allyl-Cysteine (SAC) and S1-propenyl-I-Cysteine (S1PC) are potent inhibitors of the expression of pro-inflammatory genes induced by treatment of the bronchial epithelial IB3-1 cells with the Spike RNA-based BNT162b2 vaccine. The main purpose of the present study was to determine (a) whether treatment of the IB3-1 bronchial epithelia cells with the BNT162b2 vaccine is associated with activation of the apoptotic pathway and (b) whether AGE, SAC and S1PC have any effect of therapeutic relevance on this experimental model system. We have exposed IB3-1 cells to increasing amounts of the BNT162b2 vaccine and, after 3 days of culture, apoptosis was assessed using the Annex V and the Caspase 3/7 apoptosis assays. The results obtained demonstrated highly significant increase of the percentage of apoptotic cells after treatment of IB3-1 cells with the BNT162b2 vaccine. The percentage of apoptotic cells was found to be significantly reduced in cell populations treated with the BNT162b2 vaccine in the presence of AGE, SAC and S1PC. The main conclusion of the results of our study is that Aged Garlic Extracts, and its components S-allyl-Cysteine and S1-propenyl-l-Cysteine are able to mitigate the pro-apoptotic effects of the Spike-producing BNT162b2 vaccine using the bronchial epithelial IB3-1 cell line as experimental model system. The efficacy of the reversion of BNT162b2 induced apoptosis suggests that AGE, SAC and S1PC should be considered for the development of protocols aimed at counteracting apoptosis induced by the Spike mRNA-based COVID-19 vaccines. This might be of potential clinical relevance, since one of the biological adverse effects of Spike protein (and, indirectly, of the Spike-producing vaccines) is the high induction of apoptosis in different cellular systems.

[Purpose] By pairing repeated peripheral muscle fatigue induction with a functional and ADL-based assessment, this study tests whether hand muscle fatigue alone is sufficient to im pair fine motor performance in healthy adults performing ADL-inspired tasks. [Participants and Methods] Thirty healthy male and female university students performed 11 tasks twice, once in the pre-fatigue condition and once in the post-fatigue condition. The performance of each task was graded on a 0-4 scale. The score and the time to finish the task (TTFT) were recorded twice, for both the pre- and post-fatigue phases. Maximum force gen eration (MFG) of each participant's grip was recorded prior to the tasks in the pre-fatigue phase and again in the fatigue condition after performing the fatigue protocol. [Results] Muscle fatigue did not have a significant effect on the fine motor performance of the thirty participants, neither (TTFT) nor the scores of each task (p > 0.05) (r=0.08). In contrast, hand muscle fatigue led to a significant decrease in the mean (MFG) for both males and females (p<0.01). [Conclusion] Hand muscle fatigue led to a significant decrease in the mean grip MFG for both sexes. However, this reduction did not translate into impaired fine motor performance during ADL-like tasks. Consequently, under muscle fatigue, hand grip changes during fine tasks tested are rare and have minor to no impact on hand performance. This study suggests that acute peripheral muscle fatigue can coexist with preserved fine motor performance in healthy populations.

Background and Objectives: Area-based hypoxic burden, termed as hypoxic dip area (HDA) has been studied as a novel obstructive sleep apnea (OSA) metric that may better characterize intermittent hypoxemia in OSA and thereby better predict outcomes. However, to be of use in routine clinical care, a physiological normative value is necessary. Here we attempt to use several large cohorts to establish a percentile-based threshold that can classify individuals with normal vs. abnormal physiological profiles. Methods: Data from 10 cohorts (EPISONO, FINS, Dayfun, MrOS, MESA, SHHS, APPLES, WSC, CFS, and AIRS [Mount Sinai Clinical Cohort]; n=14,031 subjects) were included. HDA was defined as the area bounded by SpO2 nadirs ([&ge;]2% desaturation) flanking left/right peaks. The 97.5th percentile of HDA among asymptomatic subjects (n=136) from EPISONO, FINS, and DAYFUN (aged 20-52 years; 46 [33.8%] male) was used to define normal and elevated HDA levels. Physiological features, clinical comorbidities, and incident cardiovascular disease (CVD) events and mortality were compared between normal/elevated HDA groups. Sensitivity analyses were conducted using age-, sex-, and BMI-adjusted threshold derived from multivariable regression model. Results: The 97.5% percentile cutoff of HDA was 8.6%min/h, classifying 4,500 individuals as normal HDA and 9,531 as elevated HDA. Individuals with elevated HDA ([&ge;]8.6%min/h) demonstrated greater nocturnal hypoxemia (lower baseline SpO2, higher T90, T85, T80 and oxygen desaturation index), higher AHI (apnea-hypopnea index) and arousal index, and greater daytime sleepiness as well as a higher prevalence of lifetime CVD and hypertension across cohorts. Elevated HDA was related with a higher prevalence of incident CVD events and mortality in unadjusted analyses, although these associations were attenuated after adjustment for confounding factors. Results were similar using alternative thresholds derived from multivariable regression analyses. Conclusions: A physiologically derived cutoff of 8.6% min/h for HDA effectively distinguishes physiological profiles across respiratory, arousal, and oxygenation domains and generalizes across multiple cohorts. Those with elevated HDA had a higher prevalence of incident CVD outcomes, although observed relationships were attenuated after further adjustment. Our findings provide a physiologically interpretable threshold for HDA that can be readily used in clinical use.

Background: Pulmonary arterial hypertension (PAH) is a serious disease with poor prognosis, especially in infants or preterm babies and there is still no optimal treatment for this disease. Noradrenalin (NE) is a vasoactive mediator which is released by sympathetic ganglion. According to previous studies, NE/1-adrenoreceptors is not only in regulating normal physiologic responses, but also in the pathogenesis of PAH. However, the mechanisms of NE in PAH are not fully understood. Methods: Human PASMC (PASMC) was used in this study. Cell viability assay and Wound healing assay were used to evaluate the proliferation and migration of PASMC. Immunoprecipitation and western blots analysis were used to investigate the mechanisms which involved in NE-induced PASMC proliferation. Results: We investigated that NE could induce human PASMC proliferation and migration. Furthermore, we first find that endothelin 1 (ET-1) signaling pathway plays an important role in NE-induced PASMC proliferation. ET1 is a critical molecular which is known for regulating cell growth and migration. We investigated that NE could increase NE-1 secretion, further enhancing ET-1 bind to its receptors. For further clarifying the downstream signals in NE/ET-1 induced PASMC proliferation, we detected the phosphorylation and expression levels of ERK and JNK. Conclusions: By combining the results from ours and previous studies, we believed that JNK/c-jun pathway may play an important role in NE-induced PASMC proliferation. Key Words: Noradrenaline; Pulmonary Arterial Hypertension; Pulmonary Artery Smooth Muscle Cells; Endothelin-1; JNK/c-Jun Signaling.

Background: Low vision is a significant cause of visual morbidity in India, yet information on the demographic profile, disease patterns, and assistive technology (AT) utilisation among individuals seeking rehabilitation services remains limited. This study assessed the socio-demographic characteristics, morbidity profile, prior healthcare pathways, and awareness and use of AT among individuals attending a vision rehabilitation clinic. Methods: A cross-sectional analysis was conducted among 1,067 patients attending a tertiary care vision rehabilitation centre. Data were collected on demographics, socioeconomic status, visual acuity, morbidity patterns, prior health system contact, and awareness, usage, and unmet need for assistive products (APs). Results: Males comprised 68.7% of participants, with most (45.1%) aged 18 to 29 years. A majority were unemployed (88.6%), from joint families (75.3%), and economically weaker (95% earning <3 lakh/year). Optic atrophy (13.2%), retinitis pigmentosa (20.8%), rod-cone dystrophy (9.9%), and Stargardts disease (9.8%) were among the leading causes of visual impairment. Most participants had severe visual loss, with 94.8% having <1/60 vision. Only 20.4% possessed a disability card (UDID) despite being eligible. Nearly all patients (99%) had visited multiple health centres before reaching rehabilitation. Conclusion: The study highlights a predominantly young, unemployed population with hereditary ocular diseases and profound visual loss. Awareness and utilisation of assistive technologies remain critically low, underscoring the need for early referral pathways, improved AT training, financial support, and UDID uptake to enhance functional rehabilitation.

Cardiac tissue is primarily made up of cardiomyocytes, which are regulated by the autonomic nervous system. We have used and developed approaches such as patch clamping and electrical stimulation-combined calcium imaging, computer modeling, optogenetics and chemogenetics combining with video-based Short-Time Fourier transformation (STFT) method to study the physiological activities of cardiomyocytes. The action potential of cardiomyocytes was found to be synchronized with calcium signals, which can be grouped into two categories by STFT. A mathematical model was developed to simulate the changes in electrical activities within cardiomyocytes caused by energy depletion, especially for 2-deoxy-D-glucose (2DG) treatment. Optogenetic and chemogenetics tools, such as ChR2(H134R), OptoXR-{beta}2AR and hM3Dq accelerated beating, while GR, ACR1 and hM4Di inhibited cardiomyocytes beating. A video-based STFT method was developed to visualize the beating frequency during these manipulations. An in vitro co-culture method was developed to study the relationship between sympathetic neuronal firing and calcium dynamics in cardiomyocytes. In vivo, electrocardiograph (ECG) measurements showed that Clozapine N-oxide (CNO) caused heart rates increasement in cTnT-hM3Dq virus injected mouse. However, it had no impact on cTnT-hM4Di virus injected mouse. This study provides comprehensive methodologies for studying cardiomyocyte physiology and manipulating heart rates in vitro and in vivo.

Valproic acid/sodium valproate (VPA) is a widely prescribed anticonvulsant and has also been used against certain tumor cells. It is a potent modulator of gene expression. Its ability to induce apoptosis has been well documented in HeLa cells. However, another form of cell death - mitotic catastrophe - has not yet been explored in VPA-treated HeLa cells. Here, we investigated the effects of VPA treatment on mitotic catastrophe characteristics, including morphological features and their frequencies, fluorescence intensity signals of caspase-2 and p53, and the expression and abundance of DNMT1 and DNMT3B. An increased frequency of mitotic catastrophe was observed not only morphologically, but also through enhanced induction of caspase-2, involvement of p53, at least under more drastic VPA treatment, but without a decrease in DNMT1 or DNMT3B levels. Additionally, enhancement of mitotic catastrophe coincided with a reduction in mitotic chromosome abnormalities. Increased DNMT3B expression following VPA action, may be favored by previously reported chromatin decondensation induced by this drug. Enhanced CpG methylation of specific DNA sites could thus be promoted. In conclusion, VPA was shown to trigger metabolic pathways linked to different forms of cell death in HeLa cells, supporting its oncosuppressive potential.

Objectives: To investigate whether the PneumoRator wearable sensor could accurately assess Respiratory Rate (RR) and signs of air hunger (SAH) compared with clinician-observed assessment in adults with and without breathing pattern disorder (BrPD). Design: A pilot cross-sectional observational study. Setting: A research laboratory on a university campus. Participants: Healthy adults aged 18-40, who were not pregnant, no smokers or history of cardiovascular, respiratory or neurological illness. Thirty consented to the study, Twenty-nine had full data for analysis. Interventions: Participants wore the PneumoRator chest-worn sensor continuously for 10 minutes while seated at rest. Main outcome measures: Respiratory Rate was compared between PneumoRator-derived measurements and randomised 1-minute observer manual counts. Clinician-observed SAH and BrPD were assessed using the Breathing Pattern Assessment Tool (BPAT). Participants also completed the Nijmegen Questionnaire. PneumoRator signals were analysed to identify large-volume breaths as potential SAH events. Results: Thirty participants were recruited. Twelve participants met BPAT criteria for BrPD and four met Nijmegen Questionnaire criteria. There was no significant difference between manual and PneumoRator RR measurements (p=0.89). No significant difference was observed between methods for SAH detection (p=0.17). Participants with clinician-observed SAH demonstrated significantly higher PneumoRator signal amplitudes than those without SAH (p=0.035). Conclusion: The PneumoRator produced RR measurements comparable to clinician assessment and demonstrated potential for identifying signs of air hunger. Findings from this pilot study indicate that the PneumoRator device shows promise as a tool for continuous RR monitoring and as an adjunct to BrPD assessment. Larger clinical validation studies are now warranted.

Semi-occluded vocal tract (SOVT) exercises are widely used in voice training and therapy, but their immediate electroglottographic (EGG) effects remain incompletely characterized. In this pilot methodological study, six female community singers completed a no-straw baseline recording and then 1-min straw-phonation exercises with four straws (Household metal, Metal VoiceStraw, plastic, and paper), each followed by a no-straw EGG recording. Thirty 1s recordings were analyzed with a standardized pipeline including contact quotient (CQ), waveform skewness, contact-phase rise/fall timing, temporal skewness (s_t), a normalized derivative asymmetry index (NDAI), average-cycle morphology, and EGG spectral descriptors. Relative to baseline, group-mean CQ was higher after all four straws (by 0.027-0.058), waveform skewness and NDAI were lower, and the EGG spectral centroid was lower (by 9.6-15.3%). Contact-phase timing asymmetry did not change consistently: s_t exceeded baseline after three straws and fell below it after one, and the rise/fall ratio decreased in three to five of six participants depending on the straw. Four participants ranked the Metal VoiceStraw first and two ranked paper first. Because every straw condition followed the baseline, warm-up and order effects cannot be separated from straw effects. These hypothesis-generating results identify CQ, waveform skewness, and EGG spectral centroid as candidate endpoints for a larger controlled study

Background: Temporomandibular disorders (TMDs) are common conditions in the general population. Several therapeutic approaches are available, but there is no consensus on the most effective, particularly in physiotherapy. Objectives: To assess the efficacy of manual therapy (MT) and therapeutic exercise (TE) in reducing pain in patients with TMDs. Methods: Four databases (MEDLINE, PEDro, EMBASE, CINAHL) were searched up to March 2025. We included randomized controlled trials (RCTs) evaluating the effects of MT and/or TE in individuals with TMDs, compared to any other rehabilitation treatment, with pain intensity as the primary outcome. The methodological quality was assessed using the PEDro scale. A network meta-analysis was performed to compare the effectiveness of different rehabilitative approaches. Results: 25 RCTs for a total of 1,540 people were included. The main comparisons were: MT and/or TE vs no treatment or placebo, occlusal splint, and instrumental physiotherapy. In most studies, MT and TE were more effective than controls in reducing pain. However, the network meta-analysis indicated that multimodal treatments were the most effective. The methodological quality of the included studies ranged from 3 to 9 points. Conclusion: MT and TE are effective strategies for reducing pain in subjects with TMDs and should be used as first-line interventions before more invasive treatments; the combination of dry needling and manual therapy appears to be the most effective approach. Nonetheless, the variability in study quality suggests that further high-quality research is needed to confirm these findings.

INTRODUCTION: Sleep disturbance is a under-recognized problem among patients with chronic obstructive pulmonary disease and may affect health-related quality of life. Data regarding sleep quality and daytime sleepiness remain limited. This study aimed to determine prevalence of poor sleep quality and daytime sleepiness among patients with chronic obstructive pulmonary disease. METHODS: This cross-sectional study was conducted in patients with chronic obstructive pulmonary disease from March to June 2025. 398 patients were enrolled. Sleep quality and daytime sleepiness were assessed using standardized questionnaires. Data were entered into Microsoft Excel 2016 and analyzed using Statistical Package for the Social Sciences version 20.0. Point estimates at 95% confidence interval were calculated along with frequency and percentage for binary data and mean and standard deviation for continuous data. RESULTS: Among 398 COPD patients, 210 (52.78%; 95% CI, 47.86% to 57.62%) had poor sleep quality (PSQI>5) and 184 (46.23%; 95% CI, 41.39% to 51.14%) had excessive daytime sleepiness (ESS>10). Most participants had moderate-to-very severe COPD (77.89%; 95% CI, 73.56% to 81.69%), with a mean CAT score of 24.36(+/-8.16). Frequent exacerbations occurred in 63.07% (95% CI, 58.22% to 67.66%) of patients. Sleep latency was prolonged, sleep duration was reduced (mean 5.55 +/- 0.80 hours), and daytime dysfunction was common. CONCLUSIONS: Poor sleep quality and excessive daytime sleepiness are highly prevalent among COPD patients and are significantly associated with disease severity and exacerbation frequency. These findings highlight the need for routine sleep screening in COPD care, alongside targeted interventions to improve sleep, symptom control, and quality of life.

The human bony labyrinth has attracted increasing interest because of its taxonomic, evolutionary, and functional significance. Although sexual dimorphism has been reported in several aspects of the temporal bone, the extent to which sex, age, size, and allometry contribute to labyrinth shape variation remains poorly understood. Here, we investigated patterns of sexual shape variation in the human bony labyrinth using three-dimensional geometric morphometrics in a sample of 98 archaeological individuals from South America with known genomic sex. Centroid size and allometric effects were assessed in a subset of 90 individuals with comparable metric scaling. In addition to analysing the complete labyrinth, the cochlea and semicircular canals were examined separately to evaluate region-specific patterns of sexual shape variation. Principal Component Analysis showed extensive overlap between females and males, and overall labyrinth shape did not differ significantly between sexes. Males exhibited significantly larger labyrinths than females, and centroid size explained a small but significant proportion of overall shape variation. Regional analyses showed no evidence of significant sexual shape differences in the cochlea or in any individual semicircular canal when analysed separately. In contrast, the combined semicircular canal system exhibited subtle but significant sexual shape variation independent of centroid size, whereas morphological disparity did not differ between sexes. The geometric comparison of the female and male consensus configurations further showed that sexual shape variation was regionally heterogeneous. Whereas the cochlea exhibited a pattern of localized changes with low directional coherence, the semicircular canals displayed more coordinated regional shape changes. The male consensus also exhibited slightly higher canal circularity across all three semicircular canals, particularly the posterior canal, while differences in canal-plane orientation remained minimal. These findings demonstrate that sexual shape variation in the human bony labyrinth is subtle and anatomically partitioned among its components. Although significant sex differences in centroid size were detected across most anatomical regions, overall labyrinth shape and cochlear morphology were primarily influenced by allometry, whereas significant sex-related shape differences were detected only when the semicircular canals were considered as an integrated anatomical system. These findings demonstrate that sexual dimorphism in the human bony labyrinth is subtle but regionally heterogeneous, with the cochlea and semicircular canals exhibiting distinct patterns of shape variation, suggesting that these structures are influenced by different developmental, functional, and evolutionary processes.

Aims: Our primary aim was to determine the immediate effects of using a supported stepping device on the real-time locomotor behavior of pre-walking infants with Down syndrome (DS). Our secondary aim was to characterize the role of the caregiver in facilitating infant locomotor behavior by quantifying infant-initiated and caregiver-initiated walker movement, and to test whether walker movement encourages stepping behavior. Methods: Pre-walking infants with DS played with their caregiver in two conditions--with and without assistance from a wheeled suspension walker. To examine changes across development, we recorded infants across one to four sessions from 10 to 19 months of age. Results: Across developmental stages, we found that suspension walkers robustly increased infants' locomotor behavior: The walker increased upright time, percent time stepping, stepping rate, upright bout rate, percent time locomoting, and total bout rate. Most walker movement was initiated by caregivers, and infants stepped more while the walker was moving compared to stationary. Conclusions: Even without practice, pre-walking infants with DS were able to take advantage of the suspension walker to increase their locomotor behavior. Caregivers facilitated infants' activity by moving the walker. Future work will examine the potential of overground suspension walkers for home-based intervention.

Perceptual experiments show that listeners recognize female speakers with lower accuracy than male speakers. Automatic speaker recognition systems may also show performance bias against female speakers even when training data sets are gender balanced. The underlying reasons for this discrepancy are unclear. Here, we apply geometric morphometrics to quantify sex-related morphological vocal tract disparity -- the extent of shape variation -- across both resting and articulatory configurations. We find that male speakers exhibit greater disparity in both resting and articulatory configurations. This morphological idiosyncrasy may in turn generate more discriminable acoustic signatures and offer a biological explanation for higher recognition accuracies for male voices by humans and machines. Our results suggest that innate variation in vocal tract morphology may contribute to performance bias in voice technology and voice perception by human listeners.

Forms I&prime, I&Prime, and I RuBisCOs were recently identified in bacterial metagenome-assembled genomes (MAGs) and are significant for evolutionarily bridging form I, which is responsible for the major part of carbon fixation on Earth, and other forms. Pioneering studies focused mainly on the biochemical and structural characteristics of "form I-related" RuBisCOs and deduced the evolution of this protein family over phylogenetic relationships among form I and form I-related sequences. We here surveyed form I-related sequences in public databases and conducted phylogenetic analyses incorporating the updated diversity of form I-related RuBisCOs. This study yielded two major outcomes regarding RuBisCO evolution. First, the analyses presented here suggest uncertainties overlooked in the previously published studies. It appeared to be difficult to conclude (i) the phylogenetic relationship among forms I, I&prime, and I&Prime, (ii) the monophyly of form I&prime, or (iii) the monophyly of form I. Second, we identified a gene encoding form I RuBisCO in an archaeal MAG, and this protein is likely involved in the pentose bisphosphate pathway. The results presented here suggest that the evolutionary route leading to form I in RuBisCO evolution remains unsettled.

Nerve Growth Factor (NGF) supports neuronal survival, plasticity, and growth by binding to p75NTR and TrkA receptors. There is a strong link between NGF and the cholinergic hippocampus, and changes in NGF pathways are observed in Alzheimer's disease (AD). Research shows NGF's neuroprotective and regenerative effects on cholinergic neurons, with positive results in AD models and clinical studies. However, NGF therapy faces challenges: limited blood-brain barrier crossing and dose-dependent pain. To address pain, a mutated NGF called CHF6467 was developed. Thanks to the R100E mutation, it prevents binding to p75NTR while maintaining TrkA affinity, which helps reduce pain side effects. Understanding CHF6467's mechanism remains a challenge. In this context, untargeted metabolomics is effective for uncovering unforeseen responses, making it suitable for assessing CHF6467's overall effects. Building on our previous research and recognizing the importance of amyloid-{beta} peptide as a critical pathological marker of AD, we used NMR-metabolomics to study the effect of CHF6467 on SH-SY5Y cells. The study examined metabolomic profiles of cells treated with CHF6467, with and without A{beta}(1-42), using NMR. Results show CHF6467 influences the metabolic changes caused by A{beta}(1-42), inducing biochemical effects consistent with the promotion of phospholipid precursors, reduced glutamate excitotoxicity, and restored energy metabolism.