Unusual photodynamic characteristics of the light-oxygen-voltage domain of phototropin linked to terrestrial adaptation of Klebsormidium nitens.

Phototropin (Phot), a blue light-sensing LOV domain protein, mediates blue light responses and is evolutionarily conserved across the green lineage. Klebsormidium nitens, a green terrestrial alga, presents a valuable opportunity to study adaptive responses from aquatic to land habitat transitions. We determined the crystal structure of Klebsormidium nitens Phot LOV1 domain (KnLOV1) in the dark and engineered different mutations (R60K, Q122N, and D33N) to modulate the lifetime of the photorecovery cycle. We observed unusual, slow recovery kinetics in the wild-type KnLOV1 domain (τ = 41 ± 3 min) compared to different mutants (R60K: τ = 2.0 ± 0.1 min, Q122N: τ = 1.7 ± 0.1 min, D33N: τ = 9.6 ± 0.1 min). Crystal structures of wild-type KnLOV1 and mutants revealed subtle but critical changes near the protein chromophore that is responsible for modulating protein dark recovery time. Our findings shed light on the unique structural and biochemical characteristics of the newly studied KnLOV1 and its evolutionary importance for phototropin-mediated physiology.

Adjunctive Approach to Therapeutic Laser and Exercise Therapies in Alleviating Pain and Disability in Patients with Low Back Pain: A Systematic Review.

Low back pain (LBP), a globally prevalent musculoskeletal condition, affects mobility, mental well-being, and overall quality of life. It is generally caused by disc degeneration, muscular strain, ligamentous sprain, or a disease located at the lumbar spine. Owing to this disability, the social and occupational interactions of an individual might get affected. Modern medicine frequently combines exercise therapy with light amplification by stimulated emission of radiation (LASER) therapy, especially high intensity LASER therapy (HILT) or low level LASER therapy (LLLT), to increase the efficacy of the treatment modalities for LBP. This review aimed to determine the effect of the combined approach of LASER and exercise therapies in managing pain and reducing disability in patients with LBP. PubMed, Google Scholar, Cochrane Library, MEDLINE, and PEDro were searched for full-text research articles published from 2000 to 2023. Overall, 3,913 records were screened from these databases and six high methodological quality studies (PEDro ≥ 5) were included in this review after eligibility assessment. Review manager 5.4.1 was utilized to evaluate the overall quality of the review articles. In conclusion, HILT and LLLT serve as effective adjuncts to exercise therapy in treating LBP, contributing to pain reduction and disability alleviation.

Dynamic and prognostic proteomic associations with FEV1 decline in chronic obstructive pulmonary disease.

Rationale: Identification and validation of circulating biomarkers for lung function decline in COPD remains an unmet need. Objective: Identify prognostic and dynamic plasma protein biomarkers of COPD progression. Methods: We measured plasma proteins using SomaScan from two COPD-enriched cohorts, the Subpopulations and Intermediate Outcomes Measures in COPD Study (SPIROMICS) and Genetic Epidemiology of COPD (COPDGene), and one population-based cohort, Multi-Ethnic Study of Atherosclerosis (MESA) Lung. Using SPIROMICS as a discovery cohort, linear mixed models identified baseline proteins that predicted future change in FEV1 (prognostic model) and proteins whose expression changed with change in lung function (dynamic model). Findings were replicated in COPDGene and MESA-Lung. Using the COPD-enriched cohorts, Gene Set Enrichment Analysis (GSEA) identified proteins shared between COPDGene and SPIROMICS. Metascape identified significant associated pathways. Measurements and Main Results: The prognostic model found 7 significant proteins in common (p < 0.05) among all 3 cohorts. After applying false discovery rate (adjusted p < 0.2), leptin remained significant in all three cohorts and growth hormone receptor remained significant in the two COPD cohorts. Elevated baseline levels of leptin and growth hormone receptor were associated with slower rate of decline in FEV1. Twelve proteins were nominally but not FDR significant in the dynamic model and all were distinct from the prognostic model. Metascape identified several immune related pathways unique to prognostic and dynamic proteins. Conclusion: We identified leptin as the most reproducible COPD progression biomarker. The difference between prognostic and dynamic proteins suggests disease activity signatures may be different from prognosis signatures.

Classification of idiopathic recurrent spontaneous miscarriage using FTIR and Raman spectroscopic fusion technology.

Recurrent spontaneous miscarriage refers to the repeated loss of two or more clinically detected pregnancies occurring within 24 weeks of gestation. No identifiable cause has been identified for nearly 50% of these cases. This group is referred to as idiopathic recurrent spontaneous miscarriage (IRSM) or miscarriage of unknown origin. Due to lack of robust scientific evidence, guidelines on the diagnosis and management of IRSM are not well defined and often contradictory. This motivates us to explore the vibrational fingerprints of endometrial tissue in these women. Endometrial tissues were collected from women undergoing IRSM (n = 20) and controls (n = 20) corresponding to the window of implantation. Attenuated total reflectance-Fourier transform infrared (ATR-FTIR) spectra were obtained within the range of 400-4000 cm-1 using Agilent Cary 630 FTIR spectrometer. Raman spectra were also generated within the spectral window of 400-4000 cm-1 using Thermo Fisher Scientific, DXR Raman spectrophotometer. Based on the limited molecular information provided by a single spectroscopic tool, fusion strategy combining Raman and ATR-FTIR spectroscopic data of IRSM is proposed. The significant features were extracted applying principal component analysis (PCA) and wavelet threshold denoising (WTD) and fused spectral data used as input into support vector machine (SVM), adaptive boosting (AdaBoost) and decision tree (DT) models. Altered molecular vibrations associated with proteins, glutamate, and lipid metabolism were observed in IRSM using Raman spectroscopy. FTIR analysis indicated changes in the molecular vibrations of lipids and proteins, collagen dysregulation and impaired glucose metabolism. Combination of both spectroscopic data using mid-level fusion (MLF: 92% using AdaBoost and DT models) and high-level fusion (HLF: 92% using SVM models) methods showed improved IRSM classification accuracy as compared to individual spectral models. Our results indicate that spectral fusion technology hold promise in enhancing diagnostic accuracy of IRSM in clinical settings. Validation of these findings in a larger patient population is underway.

Dual Use of Cannabis with Tobacco Is Associated with Increased Sugary Food and Drink Intake in Young People.

Rates of cannabis initiation among teenagers and young adults are increasing. Further, the use of various forms of cannabis (smoked or vaped) with nicotine (dual use) is increasingly common among young people. The health effects of dual use are lesser known, particularly in the context of high-potency cannabis products and across different routes of administration, which is ominous in terms of predicting future health outcomes. There is a long history of cannabis use being associated with decreased activity and increased snacking, both of which could portend an increased risk of metabolic and cardiovascular disease, particularly when these habits begin during formative years. However, modern forms of cannabis may not have these same effects. Here, we assess whether cannabis use alone and dual use of cannabis with nicotine impact dietary and exercise habits in young people. An anonymous, social media-based survey was designed based on the UC San Diego Inhalant Questionnaire and published diet and exercise questionnaires. A total of 457 surveys were completed. Young sole cannabis users represented 29% of responders, 16% were dual users of cannabis and nicotine, and 55% were non-users of either drug. Although the sole use of cannabis was not associated with dietary or activity differences relative to non-users, dual users of cannabis and nicotine reported higher consumption of unhealthy sugars. This novel finding of dual use being associated with increased sugar intake in young people raises concerns for an increased risk of metabolic syndrome and cardiovascular disease in this population.

Multi-omic signatures of sarcoidosis and progression in bronchoalveolar lavage cells.

BACKGROUND: Sarcoidosis is a heterogeneous granulomatous disease with no accurate biomarkers of disease progression. Therefore, we profiled and integrated the DNA methylome, mRNAs, and microRNAs to identify molecular changes associated with sarcoidosis and disease progression that might illuminate underlying mechanisms of disease and potential biomarkers. METHODS: Bronchoalveolar lavage cells from 64 sarcoidosis subjects and 16 healthy controls were used. DNA methylation was profiled on Illumina HumanMethylationEPIC arrays, mRNA by RNA-sequencing, and miRNAs by small RNA-sequencing. Linear models were fit to test for effect of sarcoidosis diagnosis and progression phenotype, adjusting for age, sex, smoking, and principal components of the data. We built a supervised multi-omics model using a subset of features from each dataset. RESULTS: We identified 1,459 CpGs, 64 mRNAs, and five miRNAs associated with sarcoidosis versus controls and four mRNAs associated with disease progression. Our integrated model emphasized the prominence of the PI3K/AKT1 pathway, which is important in T cell and mTOR function. Novel immune related genes and miRNAs including LYST, RGS14, SLFN12L, and hsa-miR-199b-5p, distinguished sarcoidosis from controls. Our integrated model also demonstrated differential expression/methylation of IL20RB, ABCC11, SFSWAP, AGBL4, miR-146a-3p, and miR-378b between non-progressive and progressive sarcoidosis. CONCLUSIONS: Leveraging the DNA methylome, transcriptome, and miRNA-sequencing in sarcoidosis BAL cells, we detected widespread molecular changes associated with disease, many which are involved in immune response. These molecules may serve as diagnostic/prognostic biomarkers and/or drug targets, although future testing is required for confirmation.

Incidence of and risk factors for small vulnerable newborns in north India: a secondary analysis of a prospective pregnancy cohort.

BACKGROUND: Globally, recent estimates have shown there have been 3·6 million stillbirths and neonatal deaths in 2022, with nearly 60% occurring in low-income and middle-income countries. The Small Vulnerable Newborn Consortium has proposed a framework combining preterm birth (<37 weeks of gestation), small for gestational age (SGA) by INTERGROWTH-21st standard, and low birthweight (<2500 g) under the category small vulnerable newborns (SVN). Reliable data on SVN from sub-Saharan Africa, central Asia, and south Asia are sparse. We aimed to estimate the incidence of SVN and its types, and quantify risk factors, both overall and trimester-specific, from a pregnancy cohort in north India. METHODS: In the GARBH-Ini (Interdisciplinary Group for Advanced Research on Birth Outcomes-DBT India Initiative) pregnancy cohort, 8000 participants were enrolled with less than 20 weeks' gestation between May 11, 2015, and Aug 8, 2020, at a secondary-care hospital in north India. The cohort was followed up across the antenatal period for a detailed study on preterm birth. We conducted a secondary analysis of cohort data for the outcome of SVN, classified into its types: preterm-SGA, preterm-nonSGA, and term-SGA. We estimated the relative risk and population attributable fraction of candidate risk factors for SVN (modified Poisson regression) and its types (multinomial regression). FINDINGS: 7183 (89·9%) of 7990 participants completed the study. Among 6206 newborns included for analysis, the incidence of SVN was 48·4% (35·1% term-SGA newborns [n=2179], 9·7% preterm-nonSGA newborns [n=605], and 3·6% preterm-SGA newborns [n=222]). Compared with term-nonSGA newborns, proportions of stillbirths and neonatal deaths within 72 h of birth among SVN were three times and 2·5 times higher, respectively. Preterm-SGA newborns had the highest incidence of stillbirth (15 [6·8%] of 222) and neonatal deaths (six [4·2%] of 142). Low body-mass index (BMI <18·5 kg/m2) of participants at the start of pregnancy was associated with higher risk for preterm-SGA (adjusted relative risk [RR] 1·61 [95% CI 1·17-2·22]), preterm-nonSGA (1·35 [1·09-1·68]), and term-SGA (1·44 [1·27- 1·64]), with population attributable fraction ranging from 8·7% to 13·8%. Pre-eclampsia (adjusted RR 1·48 [95% CI 1·30-1·71]), short cervical length (1·15 [1·04-1·26]), and bacterial vaginosis (1·13 [0·88-1·45]) were other important antenatal risk factors. INTERPRETATION: In a comprehensive analysis of SVN and its types from north India, we identified risk factors to guide prioritisation of interventions. Complemented with risk-stratification tools, this focused approach will enhance antenatal care, and accelerate achievement of Sustainable Development Goals-namely, to end preventable deaths of newborns and children younger than 5 years by 2030 (target 3·2). FUNDING: Department of Biotechnology, Government of India and Grand Challenges India-Biotechnology Industry Research Assistance Council, Government of India. TRANSLATION: For the Hindi translation of the abstract see Supplementary Materials section.

ZnCl2-catalysed transfer hydrogenation of carbonyls and chemoselective reduction of the CC bond in α,ß-unsaturated ketones.

This manuscript describes chemoselective reduction of CC in α,ß-unsaturated ketones and the transfer hydrogenation of aldehydes and ketones catalysed by ZnCl2-phosphinamino-triazolyl-pyridine (0.5 mol%) using KOH/iPrOH as a H2 source. A detailed mechanistic study using DFT calculations (B3LYP-D3/def2-TZVP) revealed the key role of metal-ligand cooperation (MLC) in the catalytic reaction demonstrating the non-innocent behaviour of the phosphine ligand.

The interplay of covalency, cooperativity, and coupling strength in governing C-H bond activation in Ni2E2 (E = O, S, Se, Te) complexes.

Dinickel dichalcogenide complexes hold vital multifaceted significance across catalysis, electron transfer, magnetism, materials science, and energy conversion. Understanding their structure, bonding, and reactivity is crucial for all aforementioned applications. These complexes are classified as dichalcogenide, subchalcogenide, or chalcogenide based on metal oxidation and coordinated chalcogen, and due to the associated complex electronic structure, ambiguity often lingers about their classification. In this work, using DFT, CASSCF/NEVPT2, and DLPNO-CCSD(T) methods, we have studied in detail [(NiL)2(E2)] (L = 1,4,7,10-tetramethyl-1,4,7,10-tetraazacyclododecane; E = O, S, Se and Te) complexes and explored their reactivity towards C-H bond activation for the first time. Through a comprehensive analysis of the structure, bonding, and reactivity of a series of [(NiL)2(E2)] complexes with E = O, S, Se, and Te, our computational findings suggest that {Ni2O2} and {Ni2S2} are best categorised as dichalcogenide-type complexes. In contrast, {Ni2Se2} and {Ni2Te2} display tendencies consistent with the subchalcogenide classification, and this aligns with the earlier structural correlation proposed (Berry and co-workers, J. Am. Chem. Soc. 2015, 137, 4993) reports on the importance of the E-E bond strength. Our study suggests the reactivity order of {Ni2O2} > {Ni2S2} > {Ni2Se2} > {Ni2Te2} for C-H bond activation, and the origin of the difference in reactivity was attributed to the difference in the Ni-E bond covalency, and electronic cooperativity between two Ni centres that switch among the classification during the reaction. Further non-adiabatic analysis at the C-H bond activation step demonstrates a decrease in coupling strength as we progress down the group, indicating a correlation with metal-ligand covalency. Notably, the reactivity trend is found to be correlated to the strength of the antiferromagnetic exchange coupling constant J via developing a magneto-structural-barrier map - offering a hitherto unknown route to fine-tune the reactivity of this important class of compound.

Adherence to antihypertensive medication and its associated factors among patients with hypertension attending a tertiary hospital in Kathmandu, Nepal.

Hypertension is a major risk factor for cardiovascular disease, which is the leading cause of premature mortality and morbidity globally. Despite the evidences of the availability of effective treatment for hypertension, its management remains suboptimal. Medication adherence is the most crucial factor for blood pressure control. It is important to identify the factors associated with adherence to antihypertensive treatment for better management. Hence, this study assessed the level of antihypertensive medication adherence and its associated factors among patients with hypertension visiting a tertiary-level hospital in Kathmandu, Nepal. An analytical cross-sectional study was carried out among 308 diagnosed patients with hypertension who were prescribed antihypertensive medication. The Morisky Medication Adherence Scale (MMAS-8) was used to assess medication adherence. Data was collected through face-to-face interviews and analysed using SPSS v26. A bivariate and multivariate logistic regression model was used to assess the factors associated with low medication adherence. More than half (61%) of the study participants had moderate to high levels of medication adherence. Upon bivariate analysis, there was a significant association between presence of side effects, blood pressure status, forgetfulness, high cost, fear of taking medicine lifelong and irregular follow-up with a low level of adherence. Upon multivariate the logistic regression analysis, forgetfulness [Adjusted Odd's Ratio (AOR) 22.5, 95% Confidence Interval(CI) 10.56-47.86], high cost (AOR 3.8, 95%CI 1.25-11.60) and fear of taking medicines lifelong (AOR 6.04, 95%CI 2.96-12.33) were found to be associated factors of low level of adherence. There is an urgency to develop evidence-based strategies to improve the level of adherence to antihypertensive medications among patients with hypertension. Strategies like reminder messaging, setting alarms, expanding the scope of national health insurance and proper counselling to reduce fear could help to improve medication adherence. Hence, the feasibility and effectiveness of such intervention should be explored in future studies.

PI3K/AKT signaling alters glucose metabolism in uterine microenvironment of women with idiopathic recurrent spontaneous miscarriage.

BACKGROUND: This study aims to identify metabolomic signatures in uterine fluid of women with idiopathic recurrent spontaneous miscarriage (IRSM) during window of implantation (WOI). Also, glucose transporters GLUT3 and GLUT4 and proteins of PI3K-Akt signaling pathway in endometrial tissue are assessed. METHODS: Paired uterine fluid and endometrial biopsies were collected during WOI from women with IRSM (n = 24) and healthy women with azoospermic male partners as controls (n = 15). NMR metabolomics was used to identify the dysregulated metabolites in uterine fluid of IRSM women. Additionally, proteins and glucose transporters were investigated in the endometrial tissue using immunohistochemistry (IHC) and western blotting. RESULTS: Uterine fluid metabolomics indicated eleven metabolites to be significantly downregulated in IRSM. While expression levels of PI3K (p85), PI3K (p110), p-Akt (Thr308), p-Akt (Ser473), GLUT3 and GLUT4 were significantly downregulated in endometrial tissue of these women, p-IKK α/ß (Ser176/180) and p-NFkBp65 (Ser536) were significantly increased. CONCLUSION: Our findings suggest that dysregulation of PI3K/Akt pathway in the uterine microenvironment could be a likely cause of endometrial dysfunction, thereby affecting implantation. Further studies on the downstream effects of the Akt signaling pathway in-vitro for improved understanding of the Akt-mediated cellular responses in IRSM is, therefore, warranted.

Patients taking benralizumab, dupilumab, or mepolizumab have lower postvaccination SARS-CoV-2 immunity.

BACKGROUND: Biologic therapies inhibiting the IL-4 or IL-5 pathways are very effective in the treatment of asthma and other related conditions. However, the cytokines IL-4 and IL-5 also play a role in the generation of adaptive immune responses. Although these biologics do not cause overt immunosuppression, their effect in primary severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) immunization has not been studied completely. OBJECTIVE: Our aim was to evaluate the antibody and cellular immunity after SARS-CoV-2 mRNA vaccination in patients on biologics (PoBs). METHODS: Patients with severe asthma or atopic dermatitis who were taking benralizumab, dupilumab, or mepolizumab and had received the initial dose of the 2-dose adult SARS-CoV-2 mRNA vaccine were enrolled in a prospective, observational study. As our control group, we used a cohort of immunologically healthy subjects (with no significant immunosuppression) who were not taking biologics (NBs). We used a multiplexed immunoassay to measure antibody levels, neutralization assays to assess antibody function, and flow cytometry to quantitate Spike-specific lymphocytes. RESULTS: We analyzed blood from 57 patients in the PoB group and 46 control subjects from the NB group. The patients in the PoB group had lower levels of SARS-CoV-2 antibodies, pseudovirus neutralization, live virus neutralization, and frequencies of Spike-specific B and CD8 T cells at 6 months after vaccination. In subgroup analyses, patients with asthma who were taking biologics had significantly lower pseudovirus neutralization than did subjects with asthma who were not taking biologics. CONCLUSION: The patients in the PoB group had reduced SARS-CoV-2-specific antibody titers, neutralizing activity, and virus-specific B- and CD8 T-cell counts. These results have implications when considering development of a more individualized immunization strategy in patients who receive biologic medications blocking IL-4 or IL-5 pathways.

Activin A: a marker of mineral bone disorder in children with chronic kidney disease?

BACKGROUND: Activin A has been shown to enhance osteoclast activity and its inhibition results in bone growth. The potential role of activin A as a marker of chronic kidney disease-mineral bone disease (CKD-MBD) and its relationship with other markers has not been studied in children with CKD. METHODS: A cross sectional study was conducted among 40 children aged 2 to 18 years with CKD (Stage 2 to 5; 10 in each stage) and 40 matched controls. Activin A, cathepsin K, FGF-23, PTH, serum calcium, phosphorous and alkaline phosphatase in both groups were measured and compared. The correlation of activin A and markers of CKD-MBD was studied. A p value of < 0.05 was considered significant. RESULTS: The mean age of children with CKD was 9.30 ± 3.64 years. Mean levels of activin A in cases were 485.55 pg/ml compared to 76.19 pg/ml in controls (p < 0.001). FGF-23 levels in cases were 133.18 pg/ml while in controls it was 6.93 pg/ml (p < 0.001). Mean levels of cathepsin K were also significantly higher in cases as compared to controls. There was a progressive increase in activin A and cathepsin K levels with increasing stage of CKD. Activin A had a significant positive correlation with serum creatinine (r = 0.51; p < 0.001). CONCLUSIONS: Activin A levels progressively rise with advancing CKD stage. These findings suggest that activin A can be a potential early marker of CKD-MBD in children.

Effect of myofascial release and muscle energy technique on patients with chronic neck pain: a scoping review.

PURPOSE: To identify the effects of muscle energy techniques and myofascial release in patients with chronic neck pain. METHODS: To conduct a literature search and identification; PRISMA-ScR guidelines were followed. Relevant articles were searched for from the following medical and health sciences electronic databases: PubMed, EBSCOhost, CENTRAL of the Cochrane Library, and the Physiotherapy Evidence-Based Database (PEDro). Patients with chronic neck pain were eligible for the scoping review. RESULTS: Seven articles were included in this review. This scoping review found that there is heterogeneity in the prescription of MFR and MET and a greater tendency to check three major physical dimensions (pain, range of motion, and disability). Various studies have opted for distinct intervention regimens, resulting in disparities in the frequency of weekly interventions, which can range from biweekly to five times a week. These inconsistencies may lead to perplexity among practitioners, as each intervention modality demonstrates favorable outcomes for individuals with persistent cervical discomfort. Moreover, a significant proportion of research projects have employed the numeric pain rating scale (NPRS) and visual analog scale (VAS) for data quantification. CONCLUSION: According to results, majority of the studies were focused on pain and missing components of range of motion and quality of life. Work-related factors can act as risk factors for chronic neck pain. Future investigations should adopt a comprehensive methodology and incorporate QoL assessments of quality of life.

Asthma Pathogenesis: Phenotypes, Therapies, and Gaps: Summary of the Aspen Lung Conference 2023.

Although substantial progress has been made in our understanding of asthma pathogenesis and phenotypes over the nearly 60-year history of the Aspen Lung Conferences on asthma, many ongoing challenges exist in our understanding of the clinical and molecular heterogeneity of the disease and an individual patient's response to therapy. This report summarizes the proceedings of the 2023 Aspen Lung Conference, which was organized to review the clinical and molecular heterogeneity of asthma and to better understand the impact of genetic, environmental, cellular, and molecular influences on disease susceptibility, heterogeneity, and severity. The goals of the conference were to review new information about asthma phenotypes, cellular processes, and cellular signatures underlying disease heterogeneity and treatment response. The report concludes with ongoing gaps in our understanding of asthma pathobiology and provides some recommendations for future research to better understand the clinical and basic mechanisms underlying disease heterogeneity in asthma and to advance the development of new treatments for this growing public health problem.

Biochemical and immunomodulatory insights of extracellular matrix from decellularized human whole cervix: recellularization andin vivoECM remodeling interplay.

Extracellular matrix (ECM) rich whole organ bio-scaffolds, preserving structural integrity and essential growth factors, has potential towards regeneration and reconstruction. Women with cervical anomalies or trauma can benefit from clinical cervicovaginal repair using constructs rich in site specific ECM. In this study, complete human cervix decellularization was achieved using a modified perfusion-based stir bench top decellularization method. This was followed by physico-chemical processes including perfusion of ionic agents, enzymatic treatment and washing using detergent solutions for a duration of 10-12 d. Histopathological analysis, as well as DNA quantification confirmed the efficacy of the decellularization process. Tissue ultrastructure integrity was preserved and the same was validated via scanning electron microscopy and transmission electron microscopy studies. Biochemical analysis and structural characterizations like Fourier transform infrared, Raman spectroscopy of decellularized tissues demonstrated preservation of important proteins, crucial growth factors, collagen, and glycosaminoglycans.In vitrostudies, using THP-1 and human umbilical vein endothelial cell (HUVEC) cells, demonstrated macrophage polarization from M1 to M2 and vascular functional genes enhancement, respectively, when treated with decellularized human cervical matrix (DHCp). Crosslinked DHC scaffolds were recellularized with site specific human cervical epithelial cells and HUVEC, showing non-cytotoxic cell viability and enhanced proliferation. Furthermore, DHC scaffolds showed immunomodulatory effectsin vivoon small rodent model via upregulation of M2 macrophage genes as compared to decellularized rat cervix matrix scaffolds (DRC). DHC scaffolds underwent neo-vascularization followed by ECM remodeling with enhanced tissue integration.

Comparison of the clinical effectiveness of Class IV Laser therapy and therapeutic ultrasound in patients with chronic neck pain: a randomized controlled trial / Comparação da eficácia clínica da terapia a laser Classe IV e do ultrassom terapêutico em pacientes com dor cervical crônica: um estudo controlado e randomizado

INTRODUCTION: Chronic neck pain (CNP) is a common musculoskeletal problem that affects a large proportion of the population and lasts longer than three months. It has a high cost in terms of life, disability, and healthcare. Several modalities have effectively provided immediate and long-term relief for CNP; however, the comparative clinical effectiveness of these modalities is limited. OBJECTIVES: The study aimed to determine the clinical effectiveness of Class IV Laser therapy and Therapeutic Ultrasound (TUS) in patients with CNP. METHODS AND MATERIALS: Forty-four patients with CNP of both genders were recruited from an age range of 20­45 years from the Department of Musculoskeletal Physiotherapy of Maharishi Markandeshwar Institute of Physiotherapy, MM(DU), Ambala, India. They were divided into two groups at random: the LASER group A (n = 22) and the TUS group B (n = 22). The intervention duration was 2 weeks with 6 treatment sessions. Pre- and post-treatment outcome measures were assessed with the Visual Analog Scale (VAS), Algometer, Goniometer, and Neck Disability Index (NDI) questionnaires at baseline and after 2 weeks of intervention. The LASER group received a target dose of 10 joules per cm2 at a power of 10 watts, with a continuous dosage frequency. The TUS group underwent a continuous mode ultrasound (3 MHz, 1 W/cm2) for 6 minutes. The Shapiro-Wilk test was used to assess the normality of the data. For parametric and non-parametric data analysis within the group, the paired t-test and Wilcoxon signed rank were used. The independente t-test and Mann-U Whitney test were used for the group comparison of parametric and non-parametric data, respectively. RESULTS: In both groups, there was a significant improvement in all the outcome measures (p<0.001). There was a statistically significant difference between the two interventions in VAS, Pain Pressure Threshold (PPT), and NDI (p<0.05). CONCLUSION: Class IV Laser therapy is clinically more effective than therapeutic ultrasound in treating patients with chronic neck pain.

INTRODUÇÃO: A dor cervical crônica (DCC) é um problema musculoesquelético comum que afeta uma grande proporção da população e dura mais de três meses. Ela tem um alto custo em termos de vida, incapacidade e assistência médica. Várias modalidades têm proporcionado alívio imediato e de longo prazo para a dor cervical crônica; entretanto, a eficácia clínica comparativa dessas modalidades é limitada. OBJETIVOS: O objetivo do estudo foi determinar a eficácia clínica da terapia a laser de classe IV e do ultrassom terapêutico (UST) em pacientes com DCC. MÉTODOS E MATERIAIS: Quarenta e quatro pacientes com DCC de ambos os sexos, em uma faixa etária de 20 a 45 anos, foram recrutados do Departamento de fisioterapia musculoesquelética do Instituto de Fisioterapia Maharishi Markandeshwar, MM (DU), Ambala, Índia. Eles foram divididos em dois grupos de forma aleatória: o grupo LASER A (n = 22) e o grupo UST B (n = 22). A duração da intervenção foi de 2 semanas com 6 sessões de tratamento. As medidas de resultado pré e pós-tratamento foram avaliadas com os questionários Escala Visual Analógica (EVA), Algometer, Goniometer e Índice de Incapacidade do Pescoço (IIP) na linha de base e após 2 semanas de intervenção. O grupo LASER recebeu dose alvo de 10 joules por cm2 na potência de 10 watts, com frequência de dosagem contínua. O grupo UST foi submetido a ultrassom em modo contínuo (3 MHz, 1 W/cm2) por 6 minutos. O teste de Shapiro-Wilk foi utilizado para avaliar a normalidade dos dados. Para análise dos dados paramétricos e não paramétricos dentro do grupo, foram utilizados o teste t pareado e o posto sinalizado de Wilcoxon. O teste t independente e o teste Mann-U Whitney foram utilizados para comparação de grupos para dados paramétricos e não paramétricos, respectivamente. RESULTADOS: Em ambos os grupos, houve uma melhora significativa em todas as medidas de resultado (p<0,001). Houve uma diferença estatisticamente significativa entre as duas intervenções na EVA, Limiar de pressão de dor (PPT) e IIP (p<0,05). CONCLUSÕES: A terapia a laser de classe IV é clinicamente mais eficaz do que o ultrassom terapêutico no tratamento de pacientes com dor cervical crônica.

Glucose-6-phosphate dehydrogenase deficiency with coinherited Gaucher disease: A rare association.

ABSTRACT: Anemia coexisting with Gaucher disease (GD) is often associated with non-hemolytic processes. Few cases of GD with autoimmune hemolytic anemia have been reported. However, literature on GD with concomitant nonimmune hemolytic anemia is scarce. A 1-year 6-month-old male child presented in 2018 with complaints of palpable mass in left upper abdomen, fever, cough, and vomiting. On examination, he had pallor, hepatosplenomegaly of 2 cm and 8 cm below costal margin, respectively. A clinical diagnosis of hemolytic anemia was suspected. Complete blood count revealed Hb---6.7 g/dL, TLC---8.9 × 10 3 /µL, platelet count---180 × 10 3 /µL. Peripheral smear showed predominantly microcytic hypochromic anemia with moderate degree of anisocytosis, many nucleated red blood cells, few schistocytes, polychromatophils and corrected reticulocyte count 7.89%. S. Bilirubin was 1.1 mg/dL. Hb high-performance liquid chromatography (HPLC) of the child and his parents was within normal limit. Hematological work up revealed negative results for direct Coombs' test, osmotic fragility test, and sickling test. Test for Glucose-6-phosphate dehydrogenase deficiency was positive (39 units/trillion RBC, normal 146--376). He was transfused intermittently and given steroids to manage his anemia. He was on regular follow up during which his blood counts revealed persistent anemia and thrombocytopenia. In view of this, bone marrow was performed to exclude myelofibrosis. Aspirate smears were cellular and showed normoblastic erythroid hyperplasia. Numerous large histiocytes with basophilic fibrillary cytoplasm exhibiting "crumpled tissue paper" appearance were seen. Similar findings were seen on bone marrow trephine biopsy. Genetic testing revealed pathogenic variations in the GBA gene. Beta glucosidase enzyme levels were low while chitotriosidase was raised (1109.19 nmol/hr/mL). A final diagnosis of G6PD with GD was made. The present study shows rare association of GD with Glucose-6-phosphate dehydrogenase deficiency.

Involving older people in the preparedness, response, and recovery phases in humanitarian emergencies: a theoretical framework on ageism, epistemic injustice, and participation.

Humanitarian emergencies disproportionally affect older people. Although defining an older person by an age range can help alert us to emerging or changing needs and potential vulnerabilities during humanitarian emergencies, ageing is not necessarily synonymous with increasing vulnerability, and individual variations exist due to the heterogeneity of older people. In general, reduced access to safety, health services, clean water, and appropriate food puts older people at increased risk of poor health outcomes during humanitarian emergencies, including disability, injury, malnutrition, and mental health issues. The theoretical framework presented in this Personal View explains how ageism, further compounded by intersecting oppression, leads to the exclusion of older people from the preparedness, response, and recovery phases of humanitarian emergencies. The exclusion of older people is discriminatory, violates core humanitarian and bioethical principles, and leads to an epistemic injustice. We suggest that humanitarian actors implement participatory approaches with older people in humanitarian contexts. Through these approaches, solutions will be identified by and together with older people, leading to community-driven and context-appropriate ways to include the needs and strengths of older people in the preparedness, response, and recovery phases of humanitarian emergencies.