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The IL-6–gp130–STAT3 signaling axis is a major regulator of inflammation. Activating mutations in the gene encoding gp130 and germline gain-of-function mutations in STAT3 (STAT3GOF) are associated with multi-organ autoimmunity, severe morbidity, and adverse prognosis. To dissect crucial cellular subsets and disease biology involved in activated gp130 signaling, the gp130-JAK-STAT3 axis was constitutively activated using a transgene, L-gp130, specifically targeted to T cells. Activating gp130 signaling in T cells in vivo resulted in fatal, early onset, multi-organ autoimmunity in mice that resembled human STAT3GOF disease. Female mice had more rapid disease progression than male mice. On a cellular level, gp130 signaling induced the activation and effector cell differentiation of T cells, promoted the expansion of T helper type 17 (TH17) cells, and impaired the activity of regulatory T cells. Transcriptomic profiling of CD4+ and CD8+ T cells from these mice revealed commonly dysregulated genes and a gene signature that, when applied to human transcriptomic data, improved the segregation of patients with transcriptionally diverse STAT3GOF mutations from healthy controls. The findings demonstrate that increased gp130-STAT3 signaling leads to TH17-driven autoimmunity that phenotypically resembles human STAT3GOF disease. Editor's summary: Gain-of-function mutations in the transcription activator STAT3 cause an autoimmune disease called STAT3GOF syndrome. A challenging feature of this syndrome is the phenotypic heterogeneity of the individual STAT3 mutations. By manipulating an upstream activator instead of STAT3 itself, Baumgartner et al. developed a mouse model that recapitulated more aspects of the disease. Mice with constitutive activation of the cytokine receptor subunit gp130 in T cells developed fatal, multi-organ inflammation with changes in T cell profiles and gene expression that were similar to those in patients with STAT3GOF autoimmunity, suggesting that this model may be useful for investigating the disease and exploring therapeutic options. —Leslie K. Ferrarelli [ABSTRACT FROM AUTHOR]

Background: Asymmetry of abdominal muscles is a potential cause for lowback pain. Most studies assume the rotational strength towards non dominant side to be more but no studies have been conducted to objectively measure the asymmetry. In subjects with spinal deformity like scoliosis which has a rotational component to it, it can be presumed that there could be asymmetry between the oblique force couplehowever this study aims to find out whether this asymmetry exists in normal healthy individuals. By using manual muscle testing for assess- ing oblique muscle strength only gross asymmetry can be detected. Therefore there is a need for more objective measure to detect subtle discrepancies within strength of both sides. Objective: The objective of this study is to measure the strength of external and internal oblique on both side using handheld dynamometer and to compare the strength on both sides. Methodology:30 healthy young individuals in the age group of 18-30 years were selected to participate in the study. All subjects were right hand dominant.External oblique and internal oblique muscle strength was mea- sured in KGs using a Jamartypeofhydraulichandhelddynamometer. Results: There was a significant difference between the strength of external obliques on right and left side with strength on right side being more whereas there was no significant difference between strength of internal oblique between right and left side. [ABSTRACT FROM AUTHOR]

Spent coffee grounds (SCG) valorisation can produce high-value products to supply cosmetics, petroleum and pharmaceutical industries among others. An overview of the various products achievable from spent coffee grounds valorisation are established, while the effect of temperature, reaction time and solid-to-liquid loading ratio on the yield of caffeine extracted from SCG was investigated. The best extraction solvent between (i) dichloromethane, (ii) 1-ethyl-3-methylimidazolium chloride (IL) and (iii) water was established. Characterisation of SCG using Technical Association of the Pulp and Paper (TAPPI) methods was carried out. Variations of parameters were established using the Box-Behnken design of experiment (DOE) which varied the investigated parameters; (i) temperature (88 - 120 °C), (ii) reaction time (15 - 35 min) and (iii) solid-to-liquid loading ratio (5 g SCG per 10 -25 mL). The conventional extraction method used dichloromethane as the extraction solvent, whereas the green method used the ionic liquid and water in a Parr pressure reactor. High performance liquid chromatography (HPLC) quantified the yield of extracted caffeine. Recrystallised caffeine is analysed using scanning electron microscopy (SEM), transition electron microscopy (TEM) and energy dispersive spectroscopy (EDS) for its structural properties, crystalline structure and physical analysis, while differential scanning calorimetry (DSC) established the purity of extracted caffeine achieved from each extraction solvent. The expected yield of caffeine is between 4.67 and 8.0 mg/g SCG. According to this experimental methodology, at 120 °C, 25 min reaction time and 25 mL solvent volume the extraction yield ranged from 2.83 to 3.67 mg/g SCG. [ABSTRACT FROM AUTHOR]

This paper presents the design and construction of a small-scale low-speed open circuit wind tunnel suitable for experimental testing and analysis of aerodynamic phenomena. The wind tunnel is specifically designed for low-speed applications, focusing on flows within velocities of 35 meters per second with turbulence conditions below 10 percent. The design process of a wind tunnel involves considerations such as dimensions, design parameters, and instrumentation to ensure accurate flow measurements, with key components including a settling chamber, contraction section, test section, diffuser, and drive system working together to remove disturbances, create uniform flow, minimize blockage effects, and generate required airflow for accurate aerodynamic testing. This paper highlights the design considerations, key components, construction techniques, and the significance of the wind tunnel for aerodynamic testing, validation of simulations, and education. The designed wind tunnel is capable of producing controlled and repeatable low-speed flow conditions, making it suitable for a wide range of applications, including aerodynamic testing of scaled-down models, validation of Computational Fluid Dynamics (CFD) simulations, and educational purposes. The small-scale design allows for cost-effective construction and operation while maintaining reliable results. [ABSTRACT FROM AUTHOR]

This meta-analysis aims to inform clinical practice of treatment strategies for adolescents with major depressive disorder (MDD). The efficacy of three empirically validated treatments was compared to determine the most effective treatment. These were: cognitive-behavioural therapy (CBT), selective serotonin reuptake inhibitor (SSRI) pharmacotherapy, and combination CBT and SSRI therapy. Inclusion criteria required studies to report a reliable and valid pre- and post-treatment measure and adequate data for Hedge's "g" effect size to be calculated. Forty-nine studies meeting the above inclusion criteria were found and included in the analysis. Although all three treatment strategies were found to be effective, analysis revealed no significant difference in treatment outcome among CBT, SSRI, and combination therapy. An investigation of moderator variables revealed months to follow-up to significantly influence the relationship between treatment type and treatment outcome. Given that CBT has no side effects, is more cost effective, and is equally as effective as SSRI therapy and combination therapy, the current study makes a strong case for CBT as a first-line treatment strategy for adolescents with MDD.

Background: Lungs are the major organ involved in infectious and occupational diseases almost secondarily involved in all forms of terminal diseases. Autopsy plays an important role in identifying and understanding the pathology of various respiratory diseases and lung lesions to find out the parenchymal pathology. Aims and Objectives: This study aims to study the histopathological spectrum of non-neoplastic lung lesions in medicolegal autopsy and to assess the frequency of spectrum of lung lesions. Materials and Methods: The present retrospective study was carried out in the Department of Pathology, Shyam Shah Medical College, Rewa, M.P., for a period of 18 months from July 2020 to January 2022. All 98 consecutive specimens of medicolegal autopsy were included with age from newborn to 70 years irrespective of gender and cause of death. The results were analyzed based on gross and microscopic findings. Results: Among the 98 cases studied, 82 cases (84%) were of diseased and 16 cases (16%) were of non-diseased lung. The most common age group affected was 30-39 years with 30% of affected cases followed by 20-29 years with 21% of affected cases. Among 82 cases, the most common pulmonary lesion was pneumonia in 46% (45/98) of the total cases followed by congestion and edema seen in 22% (21/98) of the cases. Conclusion: Histopathological study of lung autopsy helps in providing information for clinical diagnosis of non-neoplastic lung lesions that act as a tool for better clinical assessment and help to establish a correct prophylactic measure. The histopathological examination (HPE) helps in establishing the final cause of death. The HPE helps in establishing the final cause of death. Therefore, autopsy study is very helpful in refining the vision and diagnostic setup for better evaluation. [ABSTRACT FROM AUTHOR]

Qualitative research sample size determination has always been a contentious and confusing issue. Studies are often vague when explaining the processes and justifications that have been used to determine sample size and strategy. Some provide no mention of sampling at all, whilst others rely too heavily on the concept of saturation for determining an eventual sample size in qualitative studies. In consideration of the many real-world factors that often influence qualitative studies, this article contributes a strategic and holistic approach to a priori and ongoing mapping of sample size determination in qualitative research via an analytical tool termed DEJA. Utilising a four-step approach, DEJA guides users to articulate and understand the various considerations that influence sampling based on the unique characteristics of their study and research approach. Thus, DEJA begins to move beyond saturation alone by articulating the multiplicity of considerations in qualitative research sample size determination. [ABSTRACT FROM AUTHOR]

Coronavirus disease-19 (COVID-19) caused by SARS-CoV-2 is a novel viral infectious disease, which broke out in the end of winter season 2019 in China and soon became a pandemic. Characteristically there was severe local and systemic immune-inflammatory response to the virus, damaging the respiratory system and other organ systems. The morbidity and mortality caused by the disease are producing tremendous impact on health. The understanding about pathogenesis and manifestations of the disease was obscure. To date, no classic treatment or preventive measure was available for COVID-19 other than symptomatic and supportive care or few drugs under trial. A possibility exists that maintaining vitamin A adequate levels can protect the affected respiratory mucosa, increase antimicrobial activity, produce better antibody response, and have antiinflammatory effects, thereby promoting repair and healing as well. It has been discussed in the review that by various mechanisms, immune regulation through vitamin A supplementation is beneficial to boost immunity in the current outbreak situation when the population is susceptible to the disease. There is a high possibility that vitamin A supplementation to cases as well as population at risk of COVID-19 has a key role in prevention and control. Hence, it is believed that along with other therapeutic and preventive measures, maintaining vitamin A sufficiency during and prior to the development of active disease may act as an adjuvant in population at risk and cases to prevent and control COVID-19. [ABSTRACT FROM AUTHOR]

Background: Meningitis is a severe infection affecting the central nervous system requiring early management to prevent debilitating consequences and death. Detection of meningitis can be done by the analysis of cerebrospinal fluid cellularity and biochemistry (glucose and protein concentration). Urine reagent strips can be used to assess these variables and reach to the diagnosis of meningitis early, thereby, reducing the delay in the initiation of its treatment. Aims and Objectives: The current study aimed to determine the efficacy of urine reagent strips for the analysis of CSF. Materials and Methods: The current prospective study was done in a tertiary care center in Rewa, M.P., on 100 cerebral spinal fluid (CSF) samples obtained from the children suspected of meningitis, which were, then, analyzed by both the conventional methods of CSF analysis (including routine biochemical and microscopic analysis) the index test, utilizing the Combur-10 urine reagent strips for the estimation of CSF cell, protein, and glucose. These results were, then, correlated to calculate the diagnostic utility of urine reagent strips for the rapid diagnosis of meningitis. Results: The sensitivity, specificity, and diagnostic accuracy of urine reagent strips for the detection of cell count >10/cumm were 81.81%, 98.21%, and 91%, respectively, and 78.57%, 81.25%, and 79% for detection of protein >30 mg/dL. Reagent strips showed a sensitivity and specificity of 96.85% and 79.41% for the detection of glucose levels <50 mg/dL. The two methods showed an almost perfect degree of agreement for the detection of leucocytes with Cohen's kappa value of 0.86. Conclusion: Reagent strips can be a helpful bedside screening test for the detection of meningitis and also in resource-limited settings. [ABSTRACT FROM AUTHOR]