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Background: The coronavirus pandemic which had its origin in the Wuhan China has been spreading across the globe with far reaching complications and a variable clinical course. A variation of the laboratory parameters during the disease course remains a constant parameter to monitor the disease course and progression. Since the laboratory parameters are standardized globally, these may also act as uniform guidelines for the patients monitoring and treatment. Aims and Objectives: The aim of the study was to serial charting of the laboratory parameters in the recovered and expired patients of COVID-19 and to determine an associated prognostic significance. Materials and Methods: A retrospective observational study from the laboratory and medical records was conducted on the patients admitted from March 17, 2020, to May 31, 2020, at the tertiary care center dedicated to the treatment of RT-PCR confirmed COVID-19 positive patients. Results: The group of parameters showing a poor prognosis include a rising WBC count, high neutrophilic percentage, low lymphocyte percentage ( 15, low lymphocyte monocyte ratio < 3, rising blood urea nitrogen, serum creatinine levels, and serum electrolyte levels. The liver function tests variation reflecting a poor metabolic activity of the liver, namely, a low serum albumin and albumin globulin ratio, rising SGOT levels, and total bilirubin levels. A highly significant variation in the acute phase reactants showing an exponential rise such as the serum lactate dehydrogenase levels, serum ferritin, fibrinogen, C-reactive protein, and IL 6 levels an increased level of D Dimer (>3) and a prolongation of the APTT. Conclusion: The variation of the laboratory parameters acts as a fair marker for the disease progression. Since the disease shows a variable progression with a sudden worsening of the clinical symptoms, a comprehensive monitoring of the laboratory parameters serves to diagnose and treat the disease progression.

Aims: To find the knowledge and attitude among physiotherapy interns towards physiotherapy and total knee replacement in case of osteoarthritis of knee. Material and Methods : A cross-sectional observational study was carried out using a structured questionnaire. The structured questionnaire was designed to assess the knowledge and attitude among physiotherapy interns towards physiotherapy and total knee replacement in case of osteoarthritis of knee across the colleges in Gujarat. The data was analyzed by using the Statistical Package for Social Sciences (SPSS) statistical software, version 16. Results: Total 250 Interns students were participated in the study. Majority of Physiotherapy students believed 75-100% successful in improving functional mobility. Physiotherapy is effective in mild and moderate stage of osteoarthritis knee. Physiotherapy was considered as an alternative to total knee replacement by 85% of Interns, and they think that it can delay or avoid total knee replacement in patient with minimal symptoms, and if patient with minimal symptoms are advised for total knee replacement then they take an effort as to discuss with the orthopedic surgeons to take physiotherapy as first treatment option. Conclusion: Interns knowledge and attitude on Physiotherapy for osteoarthritis knee concludes that physiotherapy is effective in mild to moderate stage of osteoarthritis knee for improving functional mobility .Their opinion for advising criteria of total knee replacement to the individual having NPRS 8-10, Flexion range of motion restriction of 45-90 degrees, Extension range of motion restriction 0-45 degrees, Fixed flexion deformity, Medial Instability and ADL’s affection i.e. Getting out from chair, sit to stand, crossed leg sitting, squatting etc. Keywords : Osteoarthritis of knee, total knee replacement, Interns physiotherapy students. Physiotherapy.

DNA supercoiling has emerged as a major contributor to gene regulation in bacteria. The impact of DNA supercoiling on transcription dynamics in eukaryotes is less clear. Here, using single-molecule dual-color RNA imaging in budding yeast, we show that transcriptional bursting of the divergent and tandem GAL genes is coupled. Upon topoisomerase degradation, supercoils that buildup from transcription inhibit subsequent transcription at neighboring genes, thereby reducing their simultaneous bursting. GAL gene transcription is inhibited more by negative than by positive supercoiling accumulation. Unlike bacteria, wildtype yeast has sufficient topoisomerase levels to minimize inhibition from supercoils at adjacent genes. Overall, we discover fundamental differences in supercoiling-mediated gene regulation between bacteria and yeast and show that rapid supercoiling release in eukaryotes ensures proper gene expression of neighboring genes.One sentence summaryTranscription causes twisting of the DNA double helix, which can inhibit transcription of adjacent genes.

OBJECTIVES: Our objective was to elicit the perspectives of survivors of child trafficking on addressing trafficking in the pediatric emergency department (ED) and, secondarily, to provide a survivor-derived framework to help pediatric emergency medicine (PEM) providers discuss trafficking with their patients. METHODS: We conducted in-depth, semistructured interviews with young adults who experienced trafficking as children and/or as adolescents. In the interviews, we employed a novel video-elicitation method designed by the research team to elicit detailed participant feedback and recommendations on the pediatric ED through an interactive, immersive discussion with the interviewer. A grounded theory approach was employed. RESULTS: Seventeen interviews were conducted revealing the following themes, which we present in an integrated framework for PEM providers: (1) fear is a significant barrier; (2) participants do want PEM providers to ask about trafficking, and it is not harmful to do so; (3) PEM providers should address fear through emphasizing confidentiality and privacy and encouraging agency; (4) PEM providers should approach the patient in a direct, sensitive, and nonjudgmental manner; and (5) changes to the ED environment may facilitate the conversation. Suggested wordings and tips from survivors were compiled. CONCLUSIONS: Trafficking survivors feel that the pediatric ED can be a place where they can be asked about trafficking, and that when done in private, it is not harmful or retraumatizing. Fear is a major barrier to disclosure in the pediatric ED setting, and PEM providers can mitigate this by emphasizing privacy and confidentiality and increasing agency by providing choices. PEM providers should be direct, sensitive, and nonjudgmental in their approach to discussing trafficking.

Mutations in TUBB4A result in a spectrum of leukodystrophy including Hypomyelination with Atrophy of Basal Ganglia and Cerebellum (H-ABC), a rare hypomyelinating leukodystrophy, often associated with a recurring variant p.Asp249Asn (D249N). We have developed a novel knock-in mouse model harboring heterozygous (Tubb4aD249N/+) and the homozygous (Tubb4aD249N/D249N) mutation that recapitulate the progressive motor dysfunction with tremor, dystonia and ataxia seen in H-ABC. Tubb4aD249N/D249N mice have myelination deficits along with dramatic decrease in mature oligodendrocytes and their progenitor cells. Additionally, a significant loss occurs in the cerebellar granular neurons and striatal neurons in Tubb4aD249N/D249N mice. In vitro studies show decreased survival and dysfunction in microtubule dynamics in neurons from Tubb4aD249N/D249N mice. Thus Tubb4aD249N/D249N mice demonstrate the complex cellular physiology of H-ABC, likely due to independent effects on oligodendrocytes, striatal neurons, and cerebellar granule cells in the context of altered microtubule dynamics, with profound neurodevelopmental deficits., eLife digest Inside human and other animal cells, filaments known as microtubules help support the shape of the cell and move proteins to where they need to be. Defects in microtubules may lead to disease. For example, genetic mutations affecting a microtubule component called TUBB4A cause a rare brain disease in humans known as H-ABC. Individuals with H-ABC display many symptoms including abnormal walking, speech defects, impaired swallowing, and several cognitive defects. Abnormalities in several areas of the brain, including the cerebellum and striatum contribute to these defects. . In these structures, the neurons that carry messages around the brain and their supporting cells, known as oligodendrocytes, die, which causes these parts of the brain to gradually waste away. At this time, there are no therapies available to treat H-ABC. Furthermore, research into the disease has been hampered by the lack of a suitable “model” in mice or other laboratory animals. To address this issue, Sase, Almad et al. generated mice carrying a mutation in a gene which codes for the mouse equivalent of the human protein TUBB4A. Experiments showed that the mutant mice had similar physical symptoms to humans with H-ABC, including an abnormal walking gait, poor coordination and involuntary movements such as twitching and reduced reflexes. H-ABC mice had smaller cerebellums than normal mice, which was consistent with the wasting away of the cerebellum observed in individuals with H-ABC. The mice also lost neurons in the striatum and cerebellum, and oligodendrocytes in the brain and spinal cord. Furthermore, the mutant TUBB4A protein affected the behavior and formation of microtubules in H-ABC mice. The findings of Sase, Almad et al. provide the first mouse model that shares many features of H-ABC disease in humans. This model provides a useful tool to study the disease and develop potential new therapies.

The complex signaling dynamics of transcription factors can encode both qualitative and quantitative information about the extracellular environment, which increases the information transfer capacity and potentially supports accurate cellular decision-making. An important question is how these signaling dynamics patterns are translated into functionally appropriate gene regulation programs. To address this question for transcription factors of the nuclear factor κB (NF-κB) family, we profiled the single-cell dynamics of two major NF-κB subunits, RelA and c-Rel, induced by a panel of pathogen-derived stimuli in immune and nonimmune cellular contexts. Diverse NF-κB-activating ligands produced different patterns of RelA and c-Rel signaling dynamic features, such as variations in duration or time-integrated activity. Analysis of nascent transcripts delineated putative direct targets of NF-κB as compared to genes controlled by other transcriptional and posttranscriptional mechanisms and showed that the transcription of more than half of the induced genes was tightly linked to specific dynamic features of NF-κB signaling. Fibroblast and macrophage cell lines shared a cluster of such "NF-κB dynamics-decoding" genes, as well as cell type-specific decoding genes. Dissecting the subunit specificity of dynamics-decoding genes suggested that target genes were most often linked to both RelA and c-Rel or to RelA alone. Thus, our analysis reveals the cell type-specific interpretation of pathogenic information through the signaling dynamics of NF-κB.

In this manuscript, we have reported first time the densities, ρ, speeds of sound, u, and refractive indices n D for pure 1-alkyl-3-methylimidazolium bromide [Cnmim][Br] (n = 4, 6 and 8), poly ethylene glycol 400 and their binary mixtures at 0.1 MPa, covering entire range of compositions and temperature ranges from 293.15 K to 323.15 K. The measured properties have been used to derive excess molar volumes, V m E , excess molar isentropic compressibilities, K s , m E , and refractive indices deviation, Δ ∅ n D . The values of V m E , K s , m E and Δ ∅ n D have been fitted to Redlich–Kister polynomial equation for evaluation of binary coefficients. The variation in excess properties have been discussed in terms of hydrogen bonding and ion-dipole interaction. The V m E and K s , m E were largely negative and decrease with increasing temperature and size of alkyl chain of ionic liquid. The Δ ∅ n D is small negative. The experimental n D of the binary mixtures were predicted by several mixing rules. The experimental V m E were reviewed by Prigogine–Flory–Patterson (PFP) theory and Extended real association model (ERAS).

Summary The directed migration of cells sculpts the embryo, contributes to homeostasis in the adult, and, when dysregulated, underlies many diseases [ 1 , 2 ]. During these processes, cells move singly or as a collective. In both cases, they follow guidance cues, which direct them to their destination [ 3 , 4 , 5 , 6 ]. In contrast to single cells, collectively migrating cells need to coordinate with their neighbors to move together in the same direction. Recent studies suggest that leader cells in the front sense the guidance cue, relay the directional information to the follower cells in the back, and can pull the follower cells along [ 7 , 8 , 9 , 10 , 11 , 12 , 13 , 14 , 15 , 16 , 17 , 18 , 19 ]. In this manner, leader cells steer the collective and set the collective’s overall speed. However, whether follower cells also participate in steering and speed setting of the collective is largely unclear. Using chimeras, we analyzed the role of leader and follower cells in the collectively migrating zebrafish posterior lateral line primordium. This tissue expresses the chemokine receptor Cxcr4 and is guided by the chemokine Cxcl12a [ 20 , 21 , 22 , 23 ]. We find that leader and follower cells need to sense the attractant Cxcl12a for efficient migration, are coupled to each other through cadherins, and require coupling to pull Cxcl12a-insensitive cells along. Analysis of cell dynamics in chimeric and protein-depleted primordia shows that Cxcl12a-sensing and cadherin-mediated adhesion contribute jointly to direct migration at both single-cell and tissue levels. These results suggest that all cells in the primordium need to sense the attractant and adhere to each other to coordinate their movements and migrate with robust directionality.

Transcriptional activation of eukaryotic genes is accompanied, in general, by a change in the sensitivity of promoter chromatin to endonucleases. The structural basis of this alteration has remained elusive for decades; but the change has been viewed as a transformation of one structure into another, from “closed” to “open” chromatin. In contradistinction to this static and deterministic view of the problem, a dynamical and probabilistic theory of promoter chromatin has emerged as its solution. This theory, which we review here, explains observed variation in promoter chromatin structure at the level of single gene molecules and provides a molecular basis for random bursting in transcription—the conjecture that promoters stochastically transition between transcriptionally conducive and inconducive states. The mechanism of transcriptional regulation may be understood only in probabilistic terms.

Aim the present study was to determine the prevalence of WMSDs in laboratory Personnel. Objective of the study was to evaluate the main health disorders (Neck Pain) of laboratory workers. Both male and female and laboratory personnel having worked experience of one or more than one year were included in the study. Laboratory personnel having any pathology related to neck and recent trauma or surgery to neck or shoulder were excluded from the study. Cross sectional descriptive study using a self-administered questionnaire was used. Laboratory personnel having work experience of one or more than one year were taken. An informed written consent was taken from the laboratory personnel who fulfilled the inclusion criteria. They were asked to fill a self-administered questionnaire which was then evaluated. The total number of participants was 120. The mean age was 28 years and the overall disability rate was 82.5%. The reasons for developing neck pain can be due to Cumulative trauma disorders (CTD) or repetitive strain injuries (RSI) or occupational overuse syndromes (OOS) of the musculoskeletal system or work related musculoskeletal disorders. These situations often lead to development of overuse syndromes, persistence of symptoms thus becoming recurrent and/or chronic. Thus, Neck pain is significantly prevalent in laboratory a personnel who is dependent on gender as well as BMI and not dependent on years of experience.

Despite the widespread use of glucocorticoids (GCs), their anti-inflammatory effects are not understood mechanistically. Numerous investigations have examined the effects of glucocorticoid receptor (GR) activation prior to inflammatory challenges. However, clinical situations are emulated by a GC intervention initiated in the midst of rampant inflammatory responses. To characterize the effects of a late GC treatment, we profiled macrophage transcriptional and chromatinscapes with Dexamethasone (Dex) treatment before or after stimulation by lipopolysaccharide (LPS). The late activation of GR had a similar gene-expression profile as from GR pre-activation, while ameliorating the disruption of metabolic genes. Chromatin occupancy of GR was not predictive of Dex-regulated gene expression, contradicting the "trans-repression by tethering" model. Rather, GR activation resulted in genome-wide blockade of NF-κB interaction with chromatin and directly induced inhibitors of NF-κB and AP-1. Our investigation using GC treatments with clinically relevant timing highlights mechanisms underlying GR actions for modulating the "inflamed epigenome."

Background: Through the years, breast cancer management evolved toward conservation surgery. It is obvious that the clinical management requires a multidisciplinary approach to restoration of activity if daily living and quality of life after modified radical mastectomy. Aims and Objectives: The objectives of the study were to measure pain after physiotherapy intervention, to measure chest expansion after physiotherapy intervention, and to measure and improve shoulder range of motion (ROM) after physiotherapy intervention. Materials and Methods: This was a cross-experimental study in which initial data were recorded from the medical records, and then, after assuming proper resting status of the patient, the patients were assessed first numeric pain rating scale (NRS) for pain, ROM of shoulder joint, and chest expansion before and after the physiotherapy treatment given till patient get discharged. Results: In the present study, a total of 7 participants were included who fulfilled inclusion criteria. All the participants underwent routine physiotherapy treatment started from the day 1 till discharged, and NRS for pain, ROM of shoulder joint, and chest expansion all parameters were statistically significant (P < 0.005). Conclusion: The present study concluded that physiotherapy is more effective in modified radical mastectomy.