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Intraocular or orbital foreign bodies when small or due to trivial trauma often go unnoticed or missed during examination especially a wooden foreign body. They can present as non-healing wounds and discharging fistulas with signs of chronic inflammation, cellulitis, foreign body granuloma or ocular complications such as corneal scars, traumatic cataract, hyphema, glaucoma, retinal tear and detachment. This case report highlights the importance of detailed history taking and proper diagnosis which plays an important role in the management of such cases.

Wire electrical discharge machining (WEDM) is an unconventional machining process that is being extensively used in the aerospace,medical devices, die, tooling, and automotive industries for machining high-hardness materials with conductivity. In the present work, WEDM of aluminium 6082 alloys was carried out since it influences diversified applications in manufacturing industries. The WEDM process includes an extensive number of variables that influence its execution. However, based on the literature survey, three process parameters such as pulse-on time (PTON), pulse-off time (PTOFF), and wire feed (WF) were taken into consideration. The factorial design was used for the selection of parameter levels and arrived at the 27 trails for the machining. The output responses of the WEDM, namely, surface roughness (SR), kerf width (KF), and metal removal rate (MRR) were measured, and its parameter optimization was also carried out to minimize the significant effect on productivity and the quality of components. The measured output response was compared with the predicted response surface methodology (RSM) results; it was found that the SR and KF values decreased with the increase of PTON. The MRR was increased with the increase of PTON.

Heart failure represents a major cause of morbidity and mortality worldwide. Single-cell transcriptomics have revolutionized our understanding of cell composition and associated gene expression. Through integrated analysis of single-cell and single-nucleus RNA-sequencing data generated from 27 healthy donors and 18 individuals with dilated cardiomyopathy, here we define the cell composition of the healthy and failing human heart. We identify cell-specific transcriptional signatures associated with age and heart failure and reveal the emergence of disease-associated cell states. Notably, cardiomyocytes converge toward common disease-associated cell states, whereas fibroblasts and myeloid cells undergo dramatic diversification. Endothelial cells and pericytes display global transcriptional shifts without changes in cell complexity. Collectively, our findings provide a comprehensive analysis of the cellular and transcriptomic landscape of human heart failure, identify cell type-specific transcriptional programs and disease-associated cell states and establish a valuable resource for the investigation of human heart failure.

Senescent cells contribute to pathology and dysfunction in animal models(1). Their sparse distribution and heterogenous phenotype have presented challenges for detecting them in human tissues. We developed a senescence eigengene approach to identify these rare cells within large, diverse populations of postmortem human brain cells. Eigengenes are useful when no single gene reliably captures a phenotype, like senescence; they also help to reduce noise, which is important in large transcriptomic datasets where subtle signals from low-expressing genes can be lost. Each of our eigengenes detected ~2% senescent cells from a population of ~140,000 single nuclei derived from 76 postmortem human brains with various levels of Alzheimer’s disease (AD) pathology. More than 97% of the senescent cells were excitatory neurons and overlapped with tau-containing neurofibrillary tangles (NFTs). Cyclin dependent kinase inhibitor 2D (CDKN2D/p19) was predicted as the most significant contributor to the primary senescence eigengene. RNAscope and immunofluorescence confirmed its elevated expression in AD brain tissue whereby p19-expressing neurons had 1.8-fold larger nuclei and significantly more cells with lipofuscin than p19-negative neurons. These hallmark senescence phenotypes were further elevated in the presence of NFTs. Collectively, CDKN2D/p19-expressing neurons with NFTs represent a unique cellular population in human AD with a senescence phenotype. The eigengenes developed may be useful in future senescence profiling studies as they accurately identified senescent cells in snRNASeq datasets and predicted biomarkers for histological investigation.

Rufomycin and ilamycin are synonymous for the same class of cyclopeptides, currently encompassing 33 structurally characterized isolates and 9 semisynthetic derivatives. Elucidation of new structures prioritized the consolidation of the names and established the structures of four diastereoisomeric rufomycins with a 2-piperidinone, named rufomycins 4–7, including full (1)H/(13)C NMR assignments. The characteristic HSQC cross-peak for the CH-5, the hemiaminal carbon in amino acid #5, allows assignment of the stereocenters C-4 and C-5 within this ring. Semisynthetic derivatives (rufomycinSS 1, 2, and 3) were prepared from a rufomycins 4 and 6 mixture to validate the structural assignments. Based on the X-ray crystal structures of rufomycins 2 and 4, considering the NMR differences of rufomycins 7 vs 4–6 compared to rufomycinSS 1 vs 2 and 3, and taking into account that two major conformers, A and B, occur in both rufomycinSS 2 and 3, structural modeling was pursued. Collectively, this paper discusses the NMR spectroscopic differences of the stereoisomers and their possible 3D conformers and correlates these with the anti-Mycobacterium tuberculosis activity. In addition, a look at the history prioritizes names and numbering schemes for this group of antibiotics and leads to consolidated nomenclature for all currently known members, natural and semisynthetic derivatives, and serves to accommodate future discoveries.

Favipiravir is an established antiviral that is currently being assessed as an investigational drug for the treatment of COVID-19. Favipiravir is strikingly similar to two molecules that the World Health Organization (WHO) lists as essential medicines, which also consist of a six-membered aromatic N-heterocycle bearing a carboxamide function: the anti-tuberculosis agent, pyrazinamide, and nicotinamide, also known as vitamin B3 . We demonstrate the utility of 1 H nuclear magnetic resonance (NMR) profiling, an emerging pharmacopoeial tool, for the highly specific identification, selective differentiation of congeners, and subsequent detection of drug falsification or adulteration of these medicines. The straightforward comparison of basic 1-D 1 H NMR spectra, obtained with benchtop or advanced NMR instruments alike, offers a rapid identity assay and works independently of physical reference materials. This approach accelerates and advances pharmaceutical quality control measures under situations of increased drug demand and altered economy, such as during a pandemic.

Background: Diabetic retinopathy is a major microvascular complication of diabetes mellitus causing blindness in patients with diabetes mellitus. Lack of knowledge about diabetic retinopathy and its complications is the major cause for increasing blindness in India. The aim of the study is to evaluate the knowledge about diabetic retinopathy and its influence on attitude and practice in diabetic retinopathy among patients coming to a tertiary care centre in karnataka. Materials and Methods: Patients coming to tertiary care centre were interviewed by a single interviewer with questionnaire consisting of knowledge, attitude and practice questions prepared in English and responses noted and analysed. A pilot study was conducted in sample population before starting the study. Results: Out of 300 patients, 173 were males (57.7%) and 127 were females (42.3%). The minimum age of males and females was 31 and 32 years respectively. Among 300 diabetic patients, 163 patients (54.3%) had no knowledge about diabetic retinopathy compared to 137 patients(45.7%) who had knowledge about diabetic retinopathy which is statistically significant with p value (68.6%) compared to females (31.4%) which is statistically significant with p value of educational status and socioeconomic status increased, there was statistically significant increase in knowledge. Patients with longer duration of diabetes had good knowledge which is statistically significant. Patients with more knowledge and longer duration of diabetes were found to follow a good practice in diabetic retinopathy which is statistically significant with a p value of less than 0.05. Conclusion: Lack of knowledge about complications and screening methods is the cause for worsening the attitude and practice in diabetic retinopathy. Patient education at primary health care and community level can provide patients with positive attitude towards treatment and follow good practice patterns to prevent blindness due to diabetic retinopat

Following activation, macrophages undergo extensive metabolic rewiring1,2. Production of itaconate through the inducible enzyme IRG1 is a key hallmark of this process3. Itaconate inhibits succinate dehydrogenase4,5, has electrophilic properties6 and is associated with a change in cytokine production4. Here, we compare the metabolic, electrophilic and immunologic profiles of macrophages treated with unmodified itaconate and a panel of commonly used itaconate derivatives to examine its role. Using wild-type and Irg1-/- macrophages, we show that neither dimethyl itaconate, 4-octyl itaconate nor 4-monoethyl itaconate are converted to intracellular itaconate, while exogenous itaconic acid readily enters macrophages. We find that only dimethyl itaconate and 4-octyl itaconate induce a strong electrophilic stress response, in contrast to itaconate and 4-monoethyl itaconate. This correlates with their immunosuppressive phenotype: dimethyl itaconate and 4-octyl itaconate inhibited IκBζ and pro-interleukin (IL)-1β induction, as well as IL-6, IL-10 and interferon-β secretion, in an NRF2-independent manner. In contrast, itaconate treatment suppressed IL-1β secretion but not pro-IL-1β levels and, surprisingly, strongly enhanced lipopolysaccharide-induced interferon-β secretion. Consistently, Irg1-/- macrophages produced lower levels of interferon and reduced transcriptional activation of this pathway. Our work establishes itaconate as an immunoregulatory, rather than strictly immunosuppressive, metabolite and highlights the importance of using unmodified itaconate in future studies.

Pulmonary CTA is a commonly performed study and the radiologist's role is not limited to simply producing a report. The process from identifying the appropriate patients who will benefit from the study to improving performance in the radiology department requires the radiologist's involvement, expertise, and leadership. The focus of this narrative review is to highlight the different steps and the ways to improve the quality in the assessment of thromboembolic disease where the radiologists can have an impact. This article provides an update on the commonly used and more recently published clinical decision tools, specific parameter adjustments of pulmonary CTA for more challenging patients and potential improvement for the radiology department.

Background: Congenital dyserythropoietic anemias (CDAs) are a very rare and heterogeneous group of disorders characterized by ineffective erythropoiesis. CDA II is caused by mutations in the SEC23B gene. The most common mutation reported in India is c.1385A>G, p.Y462C. There is no simple and cost-effective confirmatory diagnostic test available for CDA, and therefore, many patients remain undiagnosed. High-resolution melting (HRM) analysis is a polymerase chain reaction (PCR) based technique applied to identify genetic differences and scan nucleic acid sequences. HRM can be used to rapidly screen the common mutation causing CDA II in the Indian population. Objective: To study the use of High-Resolution Melting Curve Analysis to detect common mutation causing CDA II in the Indian population.Method:10 Indian families havingSEC23B (Y462C) mutation causing CDA II are considered for this study. HRM was used to check the presence of Y462C mutation. To verify the reliability of the HRM analysis, we compared results with the results of Sanger sequencing. This helped us to confirm the diagnosis.Results: We have described clinical, hematological, and genetic data of ten patients suffering from CDAII. According to HRM and Sanger sequencing, a homozygous SEC23B (Y462C) mutation was present in all patients, whereas a heterozygous Y462C mutation was present in their parents. Conclusion: Our data showed that High-Resolution Melting (HRM) analysis could be used to rapidly screen common SEC23B mutations that cause CDA II in the Indian population.HRM technique leads to an accurate diagnosis of CDA II patients and does not need further diagnostic workup.

The ICH guidelines recommend reporting thresholds for regular impurities in drug substances at the level of 0.05% or 0.03% (w/w) depending on the maximum daily intake. Therefore, any instrumental method of analysis applicable to the impurity analysis should be able to detect and quantify the analytes at those levels. This investigation was designed to verify the suitability of (1)H NMR spectroscopy for the detection of impurities, as a first step in the process before attempting quantification. In order to minimize demand on equipment, this study employed a 400 MHz instrument for structural confirmation and signal assignments of choline (1) and O-(2-hydroxyethyl)choline (2), a known impurity. The limit of detection (LOD) of 2 in 10 mg of 1 was established as 0.01% on a 400 MHz instrument and 2% on a 60 MHz (benchtop) NMR spectrometer, respectively. Thus, impurities for which quantification is required are readily detected at 400 MHz or above. These results are in contrast to the widespread belief that (1)H NMR sensitivity is insufficient for pharmaceutical impurity analysis. Further, our experiments revealed that as low as. The choice of solvent was recognized as a critical parameter for (1)H NMR LOD analysis. Furthermore, publicly available NMR raw data (HMDB) proved to be valuable for unveiling the otherwise cryptic information hidden in complex signal patterns via (1)H NMR iterative Full Spin Analysis. Finally, the study uncovered the less noticed, yet characteristic, (14)N-(1)H coupling in the -N(+)(CH(3))(3) groups, adding further strong arguments for the Raw NMR Data Initiative. Collectively, the data prove that the analytical capabilities of high-field NMR easily fulfill the ICH requirements for detection of impurity analysis. This study explores the potential of (1)H NMR spectroscopy to detect an impurity in the presence of an actual substance of interest which makes it a step closer to achieving regulatory standards.

Gliomas are classified by combining histopathologic and molecular features, including isocitrate dehydrogenase (IDH) status. Although IDH-wild-type diffuse astrocytic glioma (DAG) shows a more aggressive phenotype than IDH-mutant type, lack of knowledge regarding relevant molecular drivers for this type of tumor has hindered the development of therapeutic agents. Here, we examined human IDH-wild-type DAGs and a glioma mouse model with a mosaic analysis with double markers (MADM) system, which concurrently lacks p53 and NF1 and spontaneously develops tumors highly comparable with human IDH-wild-type DAG without characteristic molecular features of glioblastoma (DAG-nonMF). During tumor formation, enhancer of zeste homolog (EZH2) and the other polycomb repressive complex 2 (PRC2) components were upregulated even at an early stage of tumorigenesis, together with an increased number of genes with H3K27me3 or H3K27me3 and H3K4me3 bivalent modifications. Among the epigenetically dysregulated genes, frizzled-8 (Fzd8), which is known to be a cancer- and stem cell reprogramming–related gene, was gradually silenced during tumorigenesis. Genetic and pharmacologic inhibition of EZH2 in MADM mice showed reactivation of aberrant H3K27me3 target genes, including Fzd8, together with significant reduction of tumor size. Our study clarifies a pathogenic molecular pathway of IDH-wild-type DAG-nonMF that depends on EZH2 activity and provides a strong rationale for targeting EZH2 as a promising therapeutic approach for this type of glioma. Significance: EZH2 is involved in the generation of IDH-wild-type diffuse astrocytic gliomas and is a potential therapeutic target for this type of glioma.

Thiocolchicoside is a natural product analogue often used for its spasmolytic action. To know more about its stability under various stress conditions, the drug was stirred in acid, base and peroxide solutions. In acid hydrolysis, two products were obtained and in both, the glucose got cleaved. In one of them the acetyl group also got cleaved. A set of two diastereomers were formed during the peroxide mediated hydrolysis. The base mediated hydrolysis resulted in formation of three novel degradants. They have six membered rings in their structures instead of a seven membered cycloheptatrienone. Structures of known and novel degradation products have been elucidated by extensive analysis of HRMS, 1D and 2D NMR spectroscopic techniques.

The magnetised 51 kton Iron Calorimeter (ICAL) detector proposed to be built at INO is designed with a focus on detecting 1-20 GeV muons. The magnetic field will enable the measurement of the momentum of the $\mu^-$ and $\mu^+$ generated from the charge current interactions of $\nu_\mu$ and $\bar\nu_\mu$ separately within iron in the detector, thus permitting the determination of the neutrino mass ordering/hierarchy, among other important goals of ICAL. Hence it is important to determine the magnetic field as accurately as possible. The mini-ICAL detector is an 85-ton prototype of ICAL, which is operational at Madurai in South India. We describe here the first measurement of the magnetic field in mini-ICAL using Hall sensor PCBs. A set-up developed to calibrate the Hall probe sensors using an electromagnet. The readout system has been designed using an Arduino Nano board for selection of channels of Hall probes mounted on the PCB and to convert the analog voltage to a digital output. The magnetic field has been measured in the small gaps (provided for the purpose) between iron plates in the top layer of mini-ICAL as well as in the air just outside the detector. A precision of better than 3% was obtained, with a sensitivity down to about 0.03 kGauss when measuring the small fringe fields outside the detector., Comment: 13 pages, 17 figures, latex

Heart failure represents a major cause of morbidity and mortality worldwide. Single cell transcriptomics have revolutionized our understanding of cell composition and associated gene expression across human tissues. Through integrated analysis of single cell and single nucleus RNA sequencing data generated from 45 individuals, we define the cell composition of the healthy and failing human heart. We identify cell specific transcriptional signatures of heart failure and reveal the emergence of disease associated cell states. Intriguingly, cardiomyocytes converge towards a common disease associated cell state, while fibroblasts and myeloid cells undergo dramatic diversification. Endothelial cells and pericytes display global transcriptional shifts without changes in cell complexity. Collectively, our findings provide a comprehensive analysis of the cellular and transcriptomic landscape of human heart failure, identify cell type specific transcriptional programs and states associated with disease, and establish a valuable resource for the investigation of human heart failure.

APOE is the strongest genetic risk factor for late-onset Alzheimer’s disease. ApoE exacerbates tau-associated neurodegeneration by driving microglial activation. However, how apoE regulates microglial activation and whether targeting apoE is therapeutically beneficial in tauopathy is unclear. Here we show that overexpressing an apoE metabolic receptor LDLR (low-density lipoprotein receptor) in P301S tauopathy mice markedly reduces brain apoE, and ameliorates tau pathology and neurodegeneration. LDLR overexpression (OX) in microglia cell-autonomously downregulates microglial Apoe expression, and is associated with suppressed microglial activation as in apoE-deficient microglia. Both apoE-deficiency and LDLR-OX strongly drive microglial immunometabolism towards enhanced catabolism over anabolism, whereas LDLR-overexpressing microglia also uniquely upregulate specific ion channels and neurotransmitter receptors upon activation. ApoE-deficient and LDLR-overexpressing mice harbor enlarged pools of oligodendrocyte progenitor cells (OPCs), and show greater preservation of myelin integrity under neurodegenerative conditions. They also show less reactive astrocyte activation in the setting of tauopathy.

Favipiravir is an established antiviral that is currently being assessed as an investigational drug for the treatment of COVID-19. Favipiravir is strikingly similar to two molecules that the World Health Organization (WHO) lists as essential medicines, which also consist of a six-membered aromatic N-heterocycle bearing a carboxamide function: the anti-tuberculosis agent, pyrazinamide, and nicotinamide, also known as vitamin B

Hexokinase (EC 2.7.1.1, Adenosine Tri Phosphate (ATP): D-hexose-6-phosphotransferase) is a crucial regulatory enzyme of the glycolytic pathway (Embden-Meyerhof pathway). Hexokinase deficiency is associated with chronic non-spherocytic haemolytic anaemia (HA) with some exceptional cases showing psychomotor/mental retardation and fetus death. The proband is a four-and-half-year-old female child born of a four-degree consanguineous marriage hailing from South India with autosomal recessive congenital HA associated with developmental delay. She was well till 3 months of her age post an episode of diarrhoea when she was noted to be severely anaemic and requiring regular transfusions. The common causes of HA, haemoglobinopathies, red cell membranopathies and common red cell enzymopathies (G6PD, GPI, PK and P5N) were ruled out. Targeted analysis of whole exome sequencing (WES) using an insilico gene panel for hereditary anaemia was performed to identify pathogenic variants in the patient. Next-generation sequencing revealed a novel homozygous variant in hexokinase gene c.2714CA (p. Thr905Lys) in exon-18. The pathogenic nature of the variant p. Thr905Lys in the

The aim of this study is to determine the effect of Pranayama in controlling symptoms and improvement in pulmonary function in adolescent asthmatic children who were not on long-term inhalational anti-asthmatics. Sixty children in the age group of 10-15 years who were mild to moderate asthmatics according to GINA (Global Initiative for Asthma 2018) guidelines, and not on any long term medications. Thirty were assigned randomly to the study group and was advised to do pranayama routinely for 30 minutes daily. Out of the 30 children in study group 24 children showed significant improvement compared to 2 in the control group during nine month follow-up period. Out of 30 patients in the study group on follow up 24 children significantly improved on Pulmonary Function Tests. 5 had poor pulmonary function test with episodic respiratory symptoms and 1 had severe attack. Out of 30 patients in the control group on follow up 28 had poor pulmonary function test and only 2 significantly improved. A statistically significant higher FEV1 values were observed in the study group compared to the control group in the end of the study period with p. Breathing exercise which is a cost effective method can improve the quality of life. As a complementary therapy Pranayama can be advised in mild to moderate asthmatic.

Congenital malformations of the female genital tract result from embryological maldevelopment of Mullerian or paramesonephric ducts. Mullerian duct anomalies (MDAs) are due to agenesis, defective fusion or resorption during embryological development. Unicornuate uterus results due to defective lateral fusion of Mullerian duct. This report discussed a case of pregnancy in rudimentary horn of unicornuate uterus which resulted in rupture of the horn. A patient 35 year old G2A1 with spontaneous conception with 4 months pregnancy came to emergency room with complaints of pain in abdomen and giddiness. On examination her general condition was moderate with pulse rate of 128 bpm, blood pressure of 90/60 mmHg, pallor was present. On per abdomen examination guarding, rigidity and diffuse tenderness was present. On per vaginum examination, uterus size could not be appreciated. Her haemoglobin level was 6 gm%. Ultrasonography of abdomen showed presence of unicornuate uterus with ruptured right horn with fetus in the abdominal cavity and presence of hemoperitoneum. Immediate resuscitative measures were performed, blood transfusion was started and simultaneously patient was shifted to operation theatre for exploratory laparotomy. Intraoperatively hemoperitoneum with unicornuate uterus with non communicating ruptured accessory horn on right side was present and foetus in peritoneal cavity was seen. Ruptured horn was excised and uterus was repaired. The accessory horn and foetus were sent for histopathology examination which was suggestive of placenta increta with gestational hypertrophy and hyperplasia of myometrium with normal tube and ovary. Patient tolerated the procedure well.

The goal of operative treatment of shaft of humerus fractures is to reestablish length, alignment, and rotation with stable fixation that allows early motion and ideally early weight bearing on the fractured extremity. Various methods of treating middle and distal humeral shaft fractures have continued to evolve from closed methods, external fixation, antegrade and retrograde intramedullary nailing, and conventional plating to minimally invasive osteosynthesis. Plate osteosynthesis remains the gold standard of fixation for humeral shaft fractures. biological plate osteosynthesis is important to preserve bone vascularity, also to improve consolidation, to reduce the infection rate, to avoid bone grafting. MIPO techniques avoid direct exposure of the fracture site and transform the implants in an internal extramedullary splint. More flexible fixation should encourage the formation of callus while less precise indirect reduction will reduce operative trauma. This study determines the safety of MIPPO technique and also to evaluate the clinical, radiological, and functional outcomes in the treatment of humeral shaft fractures (middle & distal one third).

INTRODUCTION: Intraarticular fractures of the tibial plateau and periarticular fractures of the proximal tibia, caused by high energy trauma pose a therapeutic dilemma. We present the use of hybrid external fixation system which includes Ilizarov ring fixator and AO rod external fixator connected with indigenously manufactured connecting clamps and short shafts augmented with or without minimal internal fixation1. AIM OF THE STUDY: 1. To assess the performance of the Hybrid External Fixator in the treatment of different types of proximal tibial fractures. 2. To evaluate the functional outcome, soft tissue healing and fracture union and radiological outcome. 3. To evaluate the biomechanical and biological advantage of hybrid external fixator. BIOMECHANICS : The mechanical characteristics of hybrid external fixation system can be called as SOLID ELASTIC. It gives solid enough for stabilization and providing micromotion which enhances good callus formation. MATERIALS: From August 2010 to November 2011, 21 caes of periarticular fractures of the proximal tibia were treated by use of 5/8 th Ilizarov ring, AO tubular external fixator and with indigenously manufactured connecting clamps & short shaft in a hybrid mode. All cases were prospectively followed up and studied. Almost all the cases (99%) had sustained Road traffic Accidents (high velocity injuries) except one case which had sustained injury by fall of cement wall over her leg. Minimum follow up – 1.5 months , maximum follow up – 12 months, mean follow up – 6.42 months .All the patients were in the age group of 26 to 65 years, mean age is 43.09. METHOD: SELECTION OF CASES: Inclusion Criteria: 1. Tibial plateau fractures according to Schatzkar classificafion Type 4, Type 5 and Type 6. 2. Proximal 1/4 extra articular tibial fractures (severely comminuted) 3. Open Proxial tibial fractures according to Gustillo Anderson Classification Gr 2, Gr 3A, 3B, 3C 4. Proximal tibial fracture with compartment syndrome after Fasciotomy. 5. High velocity proximal tibial fracture in impending compartment syndrome. Exclusion Criteria : 1. Schatzkar type 1 , type 2 and type 3. 2. More than 2 weeks old fractures. 3. Proximal tibial fractures with neurological disorder. 4. Proximal tibial fractures with paralytic disorder. SURGICAL TECHNIQUE: Reduce the articular surface initially. Determine the wire position. Minimum of 2 0r 3 wires are needed. Position the wires in the safe zone. Wire should be inserted 14 mm distal to the tibial plateau so that the capsule will not be pierced by wires.Each wire should be placed 30 – 50 degrees wide apart as possible. Olive wires are used to reduce and compress the fragments.place the shanz screws and assemble the frame. RESULTS: After analyzing the above characters we have obtained. Excellent results in 7 patients ( 33. 3% ), Good in 9 (42.35% ), Fair in 4 (19.04% ), Failure in 1(4.76% ) patient. CONCLUSION : The hybrid external fixator method we have applied is safe as regards of soft tissue healing and the limited number of complications associated directly to this method of application. We recommend a mini open reduction with percutaneous cannulated cancellous screw (one or two for securing interfragmentary compression) or olive wires with hybrid external fixator. This is the best method for closed (Schatzkar type 4, 5, 6) as well as open proximal tibial fractures.

With the change of technology, many organizations have started using human resource information systems (HRIS). HRIS is featured to contribute to various activities (human resources management) in an organization. In this research paper, we have studied the role, functions, objectives, benefits of HRIS in business organisations. This paper is based on the information collected by various sources i.e. Published literature books, reference books, Research papers, published in conference proceedings, research papers published in peer reviewed research journals, Government and industry resolutions journals, periodicals.

APOE is the strongest genetic risk factor for late-onset Alzheimer’s disease. ApoE exacerbates tau-associated neurodegeneration by driving microglial activation. However, how apoE regulates microglial activation and whether targeting apoE is therapeutically beneficial in tauopathy is unclear. Here we show that overexpressing a low-density lipoprotein receptor (LDLR) transgene in P301S tau transgenic mice markedly reduces brain apoE and ameliorates tau pathology and neurodegeneration. ApoE specifically interacts with a high-molecular-weight tau species, and highly correlates with phospho-tau and insoluble tau levels. Microglial expression of the LDLR transgene reduces intracellular apoE and is associated with less microglial activation. snRNA-seq analysis of apoE-deficient or LDLR-overexpressing brains reveals that apoE deficiency drives microglial catabolism and increases the oligodendrocyte progenitor cell population. LDLR overexpression shares overlapping mechanisms, but uniquely upregulates microglial expression of specific ion channels and neurotransmitter receptors in tauopathy. A subset of disease-associated astrocytes with both neuroprotective and neurotoxic gene signatures is also identified.

Innate lymphoid cells (ILCs) were originally classified based on their cytokine profiles, placing natural killer (NK) cells and ILC1s together, but recent studies support their separation into different lineages at steady-state. However, tumors may induce NK cell conversion into ILC1-like cells that are limited to the tumor microenvironment and whether this conversion occurs beyond this environment remains unknown. Here, we describe Toxoplasma gondii infection converts NK cells into ILC1-like cells that are distinct from both steady-state NK cells and ILC1s in uninfected mice. These cells were Eomes-dependent, indicating that NK cells can give rise to Eomes– Tbet-dependent ILC1-like cells that circulate widely and persist independent of ongoing infection. Moreover, these changes appear permanent, as supported by epigenetic analyses. Thus, these studies markedly expand current concepts of NK cells, ILCs, and their potential conversion.

Seven piperic acid amides along with their lower homologs (12) were synthesized using HATU-DIPEA coupling reagent. All the synthesized derivatives were evaluated for their antibacterial activities against Staphylococcus aureus, Pseudomonas aeruginosa, and vancomycin-resistant P. aeruginosa. They were found to be more active on P. aeruginosa than on S. aureus. However, they did not exhibit potent activity on Vancomycin resistant P. aeruginosa. Among the tested compounds, methylenedioxycinnamic acid amide of anthranilic acid (MDCA-AA, 2a) was found to be most active against S. aureus with MIC of 3.125 μg/ml. The PAS and INH amides of piperic acid were screened against Mycobacterium tuberculosis H37Ra strain. They were found to be most active among all the tested compounds but were found to be less active than the standard drug, isoniazid.

Innate lymphoid cells (ILCs) were originally classified based on their cytokine profiles, placing natural killer (NK) cells and ILC1s together, but recent studies support their separation into different lineages at steady-state. However, tumors may induce NK cell conversion into ILC1-like cells that are limited to the tumor microenvironment and whether this conversion occurs beyond this environment remains unknown. Here we describeToxoplasma gondiiinfection converts NK cells into cells resembling steady-state ILC1s that are heterogeneous and distinct from both steady-state NK cells and ILC1s in uninfected mice. Most toxoplasma-induced ILC1s were Eomes-dependent, indicating that NK cells can give rise to Eomes−Tbet-dependent ILC1-like cells that circulate widely and persist independent of ongoing infection. Moreover, these changes appear permanent, as supported by epigenetic analyses. Thus, these studies markedly expand current concepts of NK cells, ILCs, and their potential conversion.

Summary The apolipoprotein E (APOE) gene is the strongest genetic risk factor for Alzheimer’s disease and directly influences tauopathy and tau-mediated neurodegeneration. ApoE4 has strong deleterious effects on both parameters. In the brain, apoE is produced and secreted primarily by astrocytes and by activated microglia. The cell-specific role of each form of apoE in the setting of neurodegeneration has not been determined. We generated P301S Tau/Aldh1l1-CreERT2/apoE3flox/flox or Tau/Aldh1l1-CreERT2/apoE4flox/flox mice. At 5.5 months of age, after the onset of tau pathology, we administered tamoxifen or vehicle and compared mice at 9.5 months of age. Removing astrocytic APOE4 markedly reduced tau-mediated neurodegeneration and decreased phosphorylated tau (pTau) pathology. Single-nucleus RNA sequencing analysis revealed striking gene expression changes in all cell types, with astrocytic APOE4 removal decreasing disease-associated gene signatures in neurons, oligodendrocytes, astrocytes, and microglia. Removal of astrocytic APOE4 decreased tau-induced synaptic loss and microglial phagocytosis of synaptic elements, suggesting a key role for astrocytic apoE in synaptic degeneration.

Background: PPIUCDs are the only postpartum family planning method for couples requesting a highly effective and reversible, yet long acting, family planning method that can be initiated during the immediate postpartum in lactating women. The public health benefits from PPIUCDs stemmed from the women’s increased accessibility to PPIUCDs following facility births, as PPIUCDs could be offered at health facilities after childbirth. It is an attempt to reduce unmet family planning need. The specific aims of this study were to assess the acceptability, feasibility expulsion rate and complications of PPIUCD insertion among women delivering at term in our institute who were eligible and counselled for PPIUCD.Methods: Prospective study undertaken at Dr. Vaishampayan memorial government medical college, Solapur, Maharashtra conducted from September 2015 to August 2017. All women undergoing delivery at term in this institute and not having any contraindications for postpartum IUCD insertion were counseled for PPIUCD.Results: A total 3032 were eligible for PPIUCD insertion and were counseled for the same. 1.97% women accepted PPIUCD insertion while 98.03% of them declined insertion. 1124 underwent caesarean section while 1908 had vaginal delivery. Among vaginal delivery group rate of acceptance was 1.20% while that in caesarean section group was 3.29%.Conclusions: The present study concluded that overall acceptance of PPIUCD in our institute is 1.97 %. Considering fear of complications related to IUCD and partner refusal as major causes of refusal for PPIUCD in our study, emphasis on this aspect during counseling can improve acceptance.

Hospital acquired infections are infections that are neither present nor incubating when a patient enters hospital 1 . Despite progress in public health and hospital care, infections continue to develop in hospitalized patients, and may also affect hospital staff. 2 About nine per cent of inpatients have a hospital acquired infection at point of time. (3) Their effects vary from discomfort, functional disability and emotional stress to prolonged or permanent disability . Small proportion of patient deaths each year are primarily attributable to hospital acquired infections (2,3) . The economic costs are considerable. The increased length of stay for infected patients is the greatest contributor to cost. 2 The development of a surveillance process to monitor this rate is an essential first step to identify local problems and priorities, and evaluate the effectiveness of infection control activity. Surveillance, by itself, is an effective process to decrease the frequency of hospital-acquired infections. 2,5 This study was undertaken as a part of surveillance system for MICU to find out incidence of device associated infection rate, causative microorganisms and their antibiotic sensitivity pattern. In this study the attack rate of catheter associated Urinary Tract Infection was 52.63% and incidence of 83.33% per 1000 catheter days. Most common organisms isolated were Klebsiella (63.63%,) E-Coli (31.81% ) and Pseudomonas (4.54%). Eighty one percent of Klebsiella isolates, 76.47% of E. Coli isolates and 87.5% of Pseudomonas isolates were resistant for antibiotics tested. Out of total isolates tested, 58.82% were resistant to Gentamycin, 100% isolates were resistant to Ampicillin and Cefotaxim, 80% were resistant to Ciprofloxacin, 87.5% were resistant to Sulphamethaxazole and 42.10% were resistant to Furantoin. The proportion of days spent in the ICU in which the patient's treatment included invasive devices is increasing, in fact 25-50% of nosocomial infections are due to combined effect of the patient's own flora and invasive devices . Catheter-associated urinary tract infection (UTI), Central line-associated bloodstream infection (BSI), Ventilator-associated pneumonia (VAP) are among leading causes of mortality and morbidity among ICU patients.

Issues related to pharmaceutical quality are arising at an alarming rate. Pharmaceutical quality concerns both the Active Pharmaceutical Ingredients (APIs) and the Finished Drug Product/ Formulation. Recently, there has been a significant increase in the number of reports of harmful impurities in marketed drug formulations. Impurities range from solvents, reactants, adulterants, and catalysts to synthetic byproducts. Quality concerns in commercial preparations may also arise due to shelf life stability. Furthermore, a number of falsified and substandard drug cases have been reported. Most of the techniques which are currently in place can, at best, detect the impurities, but cannot identify them unless they are already known and can be compared to a standard. On the other hand, (1)H NMR spectroscopy detects all the hydrogen containing species, typically provides information to elucidate structures partially or even completely, and through its absolute quantitative capabilities even can detect the presence hydrogen-free species indirectly. The structural properties that produce (1)H NMR signals as characteristic representations of a given molecule are the chemical shifts (δ in ppm) and coupling constants (J in Hz). Along with the line widths (ω(1/2) in Hz), these parameters are bound to both the molecule and the NMR experimental conditions by the quantum mechanical (QM) principles. This means that the (1)H NMR spectra of APIs can be precisely calculated and compared to the experimental data. This review explains how (1)H NMR spectroscopy coupled with Full Spin Analysis can contribute towards the quality control of pharmaceuticals by improving structural dereplication and achieving simultaneous quantification of both APIs and their contaminants.

Summary Systematic understanding of immune aging on a whole-body scale is currently lacking. We characterized age-associated alterations in immune cells across multiple mouse organs using single-cell RNA and antigen receptor sequencing and flow cytometry-based validation. We defined organ-specific and common immune alterations and identified a subpopulation of age-associated granzyme K (GZMK)-expressing CD8+ T (Taa) cells that are distinct from T effector memory (Tem) cells. Taa cells were highly clonal, had specific epigenetic and transcriptional signatures, developed in response to an aged host environment, and expressed markers of exhaustion and tissue homing. Activated Taa cells were the primary source of GZMK, which enhanced inflammatory functions of non-immune cells. In humans, proportions of the circulating GZMK+CD8+ T cell population that shares transcriptional and epigenetic signatures with mouse Taa cells increased during healthy aging. These results identify GZMK+ Taa cells as a potential target to address age-associated dysfunctions of the immune system.

Chikungunya virus (CHIKV), an emerging alphavirus, has infected millions of people. However, the factors modulating disease outcome remain poorly understood. Here, we show in germ-free mice or in oral antibiotic-treated conventionally housed mice with depleted intestinal microbiomes that greater CHIKV infection and spread occurs within 1 day of virus inoculation. Alteration of the microbiome alters TLR7-MyD88 signaling in plasmacytoid dendritic cells (pDCs) and blunts systemic production of type I interferon (IFN). Consequently, circulating monocytes express fewer IFN-stimulated genes and become permissive for CHIKV infection. Reconstitution with a single bacterial species, Clostridium scindens, or its derived metabolite, the secondary bile acid deoxycholic acid, can restore pDC- and MyD88-dependent type I IFN responses to restrict systemic CHIKV infection and transmission back to vector mosquitoes. Thus, symbiotic intestinal bacteria modulate antiviral immunity and levels of circulating alphaviruses within hours of infection through a bile acid-pDC-IFN signaling axis, which affects viremia, dissemination, and potentially transmission.

Domperidone, a gastroprokinetic agent, is a common drug to treat emesis. It was subjected to acid, base-mediated hydrolysis, peroxide-mediated oxidation, photolysis and thermal degradation according to ICH guidelines to observe stability of the selected drug under the stress conditions. Although the drug is resistant to base hydrolysis, photolysis and thermal stressors, two degradants (DP-ISO1 and DP-ISO2) were formed in acid mediated hydrolysis. Oxidation with hydrogen peroxide also resulted in one product (DP-OX). All three degradants were isolated from the crude reaction mixture by preparative high-performance liquid chromatography and supercritical fluid chromatography. Structures of isolated compounds were unambiguously characterized as 5-chloro-1-(1-(3-(6-chloro-2-oxo-2,3-dihydro-1H-benzo[d]imidazol-1-yl)propyl)piperidin-4-yl)-1,3-dihydro-2H-benzo[d]imidazol-2-one (DP-ISO1), 5-chloro-1-(3-(4-(5-chloro-2-oxo-2,3-dihydro-1H-benzo[d]imidazol-1-yl)piperidin-1-yl)propyl)-1,3-dihydro-2H-benzo[d]imidazol-2-one (DP-ISO2), 4-(5-chloro-2-oxo-2,3-dihydro-1H-benzo[d]imidazol-1-yl)-1-(3-(2-oxo-2,3-dihydro-1H-benzo[d]imidazol-1-yl)propyl)piperidine 1-oxide (DP-OX) by analysis of mass spectrometry, 1D and 2D nuclear magnetic resonance spectra. To the best of our knowledge, DP-ISO1 and DP-ISO2 are new and DP-OX was previously reported as domperidone impurity.

Keywords: Stereochemistry; 2,2,5-trisubsituted tetrahydrofuran; Malabaricanes; Ocotillone type dammaranes; 1H NMR splitting