Rhizopus homothallicus, an emerging pathogen causing cavitary lung lesions.

Introduction: Rhizopus homothallicus is an emerging pathogen that causes pulmonary mucormycosis. Case Presentation: We report a case of pneumonia caused by R. homothallicus in a 54-year-old type 2 diabetic patient. The organism was isolated from bronchoalveolar lavage fluid and preliminarily identified by fungal morphology and finally by sequencing of the internal transcribed spacer region. Conclusion: Mucormycosis may be associated with cavitary lung lesions against a backdrop of poorly controlled diabetes or other immunosuppressed states. Pulmonary mucormycosis may have variable clinical and radiological presentations. Therefore, strong clinical suspicion and prompt management can address the high fatality associated with the disease.

Aquaporins Display a Diversity in their Substrates.

Aquaporins constitute a family of transmembrane proteins that function to transport water and other small solutes across the cell membrane. Aquaporins family members are found in diverse life forms. Aquaporins share the common structural fold consisting of six transmembrane alpha helices with a central water-transporting channel. Four such monomers assemble together to form tetramers as their biological unit. Initially, aquaporins were discovered as water-transporting channels, but several studies supported their involvement in mediating the facilitated diffusion of different solutes. The so-called water channel is able to transport a variety of substrates ranging from a neutral molecule to a charged molecule or a small molecule to a bulky molecule or even a gas molecule. This article gives an overview of a diverse range of substrates conducted by aquaporin family members. Prime focus is on human aquaporins where aquaporins show a wide tissue distribution and substrate specificity leading to various physiological functions. This review also highlights the structural mechanisms leading to the transport of water and glycerol. More research is needed to understand how one common fold enables the aquaporins to transport an array of solutes.

A pregnancy hormone-cell death link promotes enhanced lupus-specific immunological effects.

Women of reproductive age demonstrate an increased incidence of systemic lupus erythematosus, and reproductive hormones have been implicated in disease progression. Additionally, pregnancy can be associated with disease "flares", the reasons for which remain obscure. While apoptotic bodies are believed to provide an autoantigenic trigger in lupus, whether autoantigenic constituents vary with varying cellular insults, and whether such variations can be immunologically consequential in the context of pregnancy, remains unknown. As assessed by antigenicity and mass spectrometry, apoptotic bodies elicited by different drugs demonstrated the differential presence of lupus-associated autoantigens, and varied in the ability to elicit lupus-associated cytokines from lupus splenocytes and alter the phenotype of lupus B cells. Immunization of tamoxifen-induced apoptotic bodies in lupus-prone mice generated higher humoral autoreactive responses than did immunization with cisplatin-induced apoptotic bodies, and both apoptotic bodies were poorly immunogenic in healthy mice. Incubation of lupus splenocytes (but not healthy splenocytes) with the pregnancy hormone human chorionic gonadotropin (hCG) along with tamoxifen-induced apoptotic bodies (but not cisplatin-induced apoptotic bodies) induced increases in the secretion of lupus-associated cytokines and in the up-modulation of B cell phenotypic markers. In addition, levels of secreted autoantibodies (including of specificities linked to lupus pathogenesis) were enhanced. These events were associated with the heightened phosphorylation of several signaling intermediates. Observations suggest that hCG is a potential disease-promoting co-stimulant in a lupus-milieu; when combined with specific apoptotic bodies, it enhances the intensity of multiple lupus-associated events. These findings deepen mechanistic insight into the hormone's links with autoreactive responses in lupus-prone mice and humans.

Computational analysis of protein-protein interaction network of differentially expressed genes in benign prostatic hyperplasia.

Benign prostatic hyperplasia (BPH) is a commonly occurring disease in aging men. It involves cellular proliferation of stromal and glandular tissues leading to prostate enlargement. Current drug therapies show several adverse effects such as sexual dysfunctions and cardiovascular side effects. Therefore, there is a need to develop more effective medical treatment for BPH. In this regard, we aimed to identify genes which play a critical role in BPH. We have obtained the dataset of differentially expressed genes (DEGs) of BPH from NCBI GEO. DEGs were investigated in the context of their protein-protein interactions (PPI). Hub genes i.e. genes associated with BPH were scrutinized based on the topological parameters of the PPI network. These were analyzed for functional annotations, pathway enrichment analysis and transcriptional regulation. In total, 38 hub genes were identified. Hub genes such as transcription factor activator protein-1 and adiponectin were found to play key roles in cellular proliferation and inflammation. Another gene peroxisome proliferator activated receptor gamma was suggested to cause obesity, a common comorbidity of BPH. Moreover, our results indicated an important role of transforming growth factor-beta (TGF-ß) signaling and smooth muscle cell proliferation which may be responsible for prostate overgrowth and associated lower urinary tract symptoms frequently encountered in BPH patients. Zinc finger protein Snai1 was the most prominent transcription factor regulating the expression of hub genes that participate in TGF-ß signaling. Overall, our study has revealed significant hub genes that can be employed as drug targets to develop potential therapeutic interventions to treat BPH.

Unilateral hyper-translucent lung: a rare case report of bronchial atresia.

A young female patient with chronic left side chest pain warranted a work-up. Chest X-ray suggested left hyper-translucency. High resolution computed tomography scan revealed left atretic apicoposterior segmental bronchus with an area of hyper-translucency suggestive of bronchial atresia. Fiberoptic bronchoscopy findings were normal. Spirometry showed moderate restriction with mild obstruction. It is a rare developmental anomaly characterised by interruption of normal bronchial continuity. Most commonly, it involves the apicoposterior segmental bronchus of left upper lobe as seen in our case. Since it is a benign condition, surgical treatment or any aggressive method of treatment is not required. However, intervention may be required in case of life threatening complications.

Haemoglobin drives inflammation and initiates antigen spread and nephritis in lupus.

Haemoglobin (Hb) has well-documented inflammatory effects and is normally efficiently scavenged; clearance mechanisms can be overwhelmed during erythrocyte lysis. Whether Hb is preferentially inflammatory in lupus and triggers broad anti-self responses was assessed. Peripheral blood mononuclear cells (PBMCs) derived from SLE patients secreted higher levels of lupus-associated inflammatory cytokines when incubated with human Hb than did PBMCs derived from healthy donors, an effect negated by haptoglobin. Ferric murine Hb triggered the preferential release of lupus-associated cytokines from splenocytes, B cells, CD4 T cells, CD8 T cells and plasmacytoid dendritic cells isolated from ageing, lupus-prone NZM2410 mice, and also had mitogenic effects on B cells. Pull-downs, followed by mass spectrometry, revealed interactions of Hb with several lupus-associated autoantigens; co-incubation of ferric Hb with apoptotic blebs (structures that contain packaged autoantigens) revealed synergies-in terms of cytokine release and autoantibody production in vitro-that were also restricted to the lupus genotype. Murine ferric Hb activated multiple signalling pathways and, in combination with apoptotic blebs, preferentially triggered MAP kinase signalling specifically in splenocytes isolated from lupus-prone mice. Infusion of murine ferric Hb into lupus-prone mice led to enhanced release of lupus-associated cytokines, the generation of a spectrum of autoantibodies and enhanced-onset glomerulosclerosis. Given that the biased recognition of ferric Hb in a lupus milieu, possibly in concert with lupus-associated autoantigens, triggers inflammatory responses and the generation of lupus-associated cytokines, and also stimulates the generation of potentially pathogenic lupus-associated autoantibodies, neutralization of Hb could have beneficial effects.

Mortality analysis of COVID-19 cases during the second wave and its comparison with the first wave: A hospital-based study.

Objectives: This study was undertaken to determine the characteristics of COVID-19 deaths during the second wave and to compare these characteristics with the mortality during the first wave in a dedicated COVID hospital (DCH). Study Design: It was a hospital record-based descriptive study. Methodology: The study was conducted in a tertiary care COVID hospital, using a standard death audit proforma. The data were analyzed to know various demographic characteristics and factors related to mortality during the second wave from March to June 2021. The findings were compared with the mortality data during the first wave from April to July 2020 at the same hospital. Results: A total of 264 deaths occurred at the center during the study period with a mortality rate of 22.8%. Male cases were more in number, the age group was 21-70 years, the highest number of mortality was seen in the mid of the study period, duration of stay was five days on average and common causes of death were pneumonia alone or with acute respiratory distress syndrome with sepsis. In comparison to the first wave, the mortality rate was four times higher, the age group was younger and opportunistic infections viz. mucormycosis and aspergillosis were present during the second wave. Conclusion: The mortality rate was significantly higher and the younger age groups were involved during the second wave, with opportunistic fungal infections due to the use of immunomodulators.

Are numbers deceptive? Is death auditing a solution for death analysis, among the COVID-19 deceased?: A study from a dedicated COVID-19 hospital in Faridabad, Haryana.

BACKGROUND: COVID-19 pandemic has havocked the entire world and India has not been spared. The focus is not only on the containment but on the reduction in mortality also. The objective of the study was to know the trend of COVID-19 deaths in a 510-bedded dedicated COVID-19 hospital and to determine the cause of death and various factors associated with these deaths. METHOD: A descriptive study was conducted in a COVID-dedicated hospital setting to analyze deaths occurring during April--July, 2020 using a standard death audit proforma. RESULTS: A total number of 95 COVID-19 patients died in ICU. The mortality rate among ICU patients varied from 24.6% to 52.9%. Most of the cases were referred from other hospitals. About 64% of the deceased was admitted in severe condition and 34% of cases were referred on ventilator support. The week-wise trend revealed a positive association between the number of deaths and the number of referred cases as well as the number of patients received on ventilator support and in severe condition. About one-third of cases were late in seeking treatment at health centers with the same weekly trend. Being unaware of the condition (1%) and the stigma associated with the disease (32%) were the reasons behind it. Common direct causes of death were pneumonia (73%), pneumonia complicated with sepsis (16%), and acute respiratory disease syndrome (ARDS) (7%). CONCLUSION: High case fatality rate in the ICU of a referral COVID-dedicated hospital is mainly because of the admission of patients in severe conditions.

Human Chorionic Gonadotropin Influences Systemic Autoimmune Responses.

Immunopathological outcomes in Systemic Lupus Erythematosus (SLE; or lupus) are believed to be autoantibody-mediated. Conditions which promote a Th2 skew (such as pregnancy) should encourage antibody production, worsening antibody-mediated diseases while ameliorating Th1/Th17-mediated diseases. Although an increased propensity toward autoreactivity can be observed in pregnant lupus patients and in pregnant lupus-prone mice, whether a unique human pregnancy-specific factor can contribute to such effects is unknown. This study assessed whether human chorionic gonadotropin (hCG, a pregnancy-specific hormone of diverse function) at physiological concentrations could mediate stimulatory influences on immune parameters in non-pregnant, lupus-prone mice, in light of the hormone's ameliorating effects on Th1-mediated autoimmunity in murine models. Results demonstrate that administration of hCG heightened global autoreactivity in such mice; antibodies to dsDNA, RNP68, Protein S, Protein C, ß2-glycoprotein 1, and several phospholipids were enhanced, and hormone administration had adverse effects on animal survival. Specifically in splenic cell cultures containing cells derived from lupus-prone mice, hCG demonstrated synergistic effects with TLR ligands (up-modulation of costimulatory markers on B cells) as well as with TCR stimuli (enhanced proliferative responses, enhanced levels of cytokines, and the phosphorylation of p38). In both instances, enhanced synthesis of lupus-associated cytokines was observed, in addition to the heightened generation of autoantibodies reactive toward apoptotic blebs. These results suggest that selective transducive, proliferative, and differentiative effects of hCG on adaptive immune cells may drive autoreactive responses in a lupus environment, and may also potentially provide insights into the association between the presence of higher hCG levels (or the administration of hCG) with the presence (or appearance) of humoral autoimmunity.

Oxidized Hemoglobin Is Antigenic and Immunogenic in Lupus.

Hemolysis-associated anemia is characteristic of diseases such as atherosclerosis, lupus, malaria, and leishmaniasis; the toxic effects of free hemoglobin (Hb) have been extensively described. This study was based on the premise that release of this sequestered, inflammatory molecule can result in deleterious immunological consequences, particularly in the context of pre-existing lupus. IgG anti-Hb responses were detected in the sera of lupus patients. Lupus-prone mice exhibited heightened plasma Hb levels, and ferric (Fe3+) Hb triggered preferential release of lupus-associated cytokines from splenocytes derived from aging lupus-prone mice. Anti-Hb B cell precursor frequencies were heightened in such mice, which also expressed increased titers of anti-Hb antibodies in serum and in kidney eluates. Fe3+ Hb preferentially increased the functional maturation of bone marrow-derived dendritic cells (BMDCs) from lupus-prone mice, effects abrogated upon the inhibition of Stat3. Hb interacted with lupus-associated autoantigens extruded during apoptosis and coincubation of Hb and apoptotic blebs had additional maturation-inducing effects on lupus BMDCs. Immunization with Hb in lupus-prone mice induced antigen spreading to lupus-associated moieties; Hb-interacting autoantigens were preferentially targeted and increased complement deposition and glomerulosclerosis were observed. Hb therefore demonstrates both antigenicity and immunogenicity and triggers specific immuno-pathological effects in a lupus milieu.

Hemorrhagic pleural effusion due to pseudo-pancreatic cyst.

Hemorrhagic pleural effusion is a common clinical entity still diagnosis is often missed. An unusual and often over-looked cause of pleural effusion is an intra-abdominal process including complication arising due to pancreatitis. We report a rare case of massive left sided hemorrhagic pleural effusion in a patient due to pancreatic pathology.

Gross congenital malformation at birth in a government hospital.

A hospital-based cross-sectional study was undertaken to determine proportion of gross congenital malformation (GCMF) occurring at intramural births. Rate of GCMF was found to be 16.4/1000 consecutive singleton births (>28 weeks) with three leading malformation as anencephaly (44.68%), talipes equinovarus (17.02%) and meningomyelocele (10.63%). Higher risk of malformed births were noticed amongst un-booked (2.07%) in-comparison to booked (1.01%) mothers; women with low level of education (up to 8 years [2.14%] vs. at least 9 years of schooling [0.82%]); gravida status of at least 3 (2.69%) followed by 1 (1.43%) and 2 (1.0%) respectively; pre-term (5.13%) vs. term (0.66%); cesarean section (4.36%) versus vaginal delivery (0.62%). Mortality was significantly higher among congenitally malformed (17.35%) than normal (0.34%) newborns. With-in study limitation, emergence of neural tube defect as the single largest category of congenital malformation indicates maternal malnutrition (especially folic acid) that needs appropriate attention and management.

Insights into structural mechanisms of gating induced regulation of aquaporins.

Aquaporin family comprises of transmembrane channels that are specialized in conducting water and certain small, uncharged molecules across cell membranes. Essential roles of aquaporins in various physiological and pathophysiological conditions have attracted great scientific interest. Pioneering structural studies on aquaporins have almost solved the basic question of mechanism of selective water transport through these channels. Another important structural aspect of aquaporins which seeks attention is that how the flow of water through the channel is regulated by the mechanism of gating. Aquaporins are also regulated at the protein level, i.e. by trafficking which includes changes in their expression levels in the membrane. Availability of high resolution structures along with numerous molecular dynamics simulation studies have helped to gain an understanding of the structural mechanisms by which water flux through aquaporins is controlled. This review will summarize the highlights regarding structural features of aquaporins, mechanisms governing water permeation, proton exclusion and substrate specificity, and describe the structural insights into the mechanisms of aquaporin gating whereby water conduction is regulated by post translational modifications, such as phosphorylation.

Phosphorylation of Ser-180 of rat aquaporin-4 shows marginal affect on regulation of water permeability: molecular dynamics study.

Water permeation through rat aquaporin-4 (rAQP4), predominantly found in mammalian brain is regulated by phosphorylation of Ser-180. The present study has been carried out to understand the structural mechanism of regulation of water permeability across the channel. Molecular dynamics (MD) simulations have been carried out to investigate the structural changes caused due to phosphorylation of Ser-180 in the tetrameric assembly of rAQP4 along with predicted C-terminal region (255-323). The interactions involving opposite charges are observed between cytoplasmic loops and the C-terminal region during MD simulations. This results in movement of C-terminal region of rAQP4 towards the cytoplasmic mouth of water channel. Despite this movement, there was a gap between C-terminal region and cytoplasmic mouth of the channel through which water molecules were able to gain entry into the channel. The interactions between C-terminus and loop D of neighboring monomers in a tetrameric assembly appear to prevent the complete closure of cytoplasmic mouth of the water channel. Further, the rates of water permeation through phosphorylated and unphosphorylated rAQP4 have also been compared. The simulation studies showed a continuous movement of water in a single file across pore of unphosphorylated as well as phosphorylated rAQP4.

Birth audit.

OBJECTIVE: To describe profile of births occurring in teaching institution on selected parameters. MATERIALS AND METHODS: Considering feasibility, four months were systematically chosen for two-year time frame over a decade to gather selected information of consecutive singleton intramural births from log books of labor room on structured pro-forma. Data management was done using software package and analysis carried out by computing descriptive statistics (%) and Chi-square test. RESULTS: It was observed that there were a total of 2862 and 1527 singleton births (>28 weeks) recorded for the sampled time-frame of 2009 and 1999 respectively reflecting increased quantum of institutional deliveries over time-span. Out of 2862 births, monthly distribution was 21.8% (Jan), 20% (Apr), 37.2% (July) and 21.1% (Oct) with similar picture for 1999. The birth according to 8-hourly timeframe was computed to be 31.6% (12 am-8 am), 34.3% (8 am-4 pm) and 34.0% (4 pm to 12 am) for 2009 while it was 28.6%, 38.6% and 32.8% for 1999 (P < 0.05). Births took place through-out seven days of week; however, Sunday (12.0%) was the least popular day while Thursday (18.7%) recorded maximum proportion of births during 2009. Slightly higher proportion of pre-term births were recorded during 2009 (21.76%) in comparison to 1999 (18.53%). The caesarian section rose to 26.1% from 20.2% (P < 0.05) while M:F ratio at birth was 1.28 and 1.17 with similar proportion (92.3%; 93.0%) of newborns being discharged live during 2009 and 1999 respectively. CONCLUSION: It provides snapshots of birth occurring in a teaching hospital and within study constraints finding could be utilized for improving quality of care, health communication, better utilization of human resource and logistics.

Early birth registration at a center in rural India.

BACKGROUND: Registration of birth is mandatory in India however due to various issues compliance for timely birth registration has been poor. OBJECTIVE: The objective of this study was to determine time elapsed between birth and registration and describe the socio-demographic profile of registered births at a rural center. MATERIALS AND METHODS: A cross-sectional descriptive study was undertaken and all births registered at a primary health center of a block during the period 2010 and 2011 were retrieved and data collection carried using structured proforma based on birth formats under civil registration system (CRS). House to house visit was undertaken to identify births without registration. RESULTS: A total of 340 and 276 births were registered during 2010 and 2011 respectively. Time elapsed between birth and registration was computed to be lower, i.e., 9.38 days (±7.46) during 2011 in-comparison with 10.52 days (±8.73) in 2010. On a positive note, higher level of education and marriage of women beyond legal age of 18 years was noticed in 2011 in comparison with 2010. Overall, institutional birth stood at a very encouraging note (66.2%). All (100%) births during the study period were registered at this (rural) or higher center (urban) depending on the place of delivery. An omission/commission of birth format is highlighted that needs urgent attention of the authorities. DISCUSSION: Majority (>92%) of birth registration occurred with-in the stipulated period of 21 days as prescribed under CRS and our study indicates early birth registration in a rural area of Haryana, India.

Solitary fibrous tumour of lung.

Fibrous tumours arising entirely within the substance of the lung are rare. We report one such rare case in whom the diagnosis was established after surgical removal.

Transgenesis-mediated reproductive dysfunction and tumorigenesis: effects of immunological neutralization.

Human chorionic gonadotropin (hCG) was initially thought to be made only during pregnancy, but is now known to also be synthesized by a variety of cancers and is associated with poor patient prognosis. Transgenic expression of ßhCG in mice causes hyper-luteinized ovaries, a loss in estrous cyclicity and infertility, increased body weight, prolactinomas and mammary gland tumors. Strategies were devised to generate antibody responses against hCG to investigate whether reversal of the molecular processes driving tumorigenesis would follow. hCG-immunized transgenic mice did not exhibit increases in body weight or serum prolactin levels, and gross ovarian and pituitary morphology remained normal. While non-immunized transgenic animals demonstrated heightened levels of transcripts associated with pituitary tumorigenesis (HMG2A, E2F1, CCND1, PRL, GH, GAL, PTTG1, BMP4) and decreased levels of CDK inhibitors CDKN1B (p27), CDKN2A (p16) and CDKN2c (p18), immunization led to a reversal to levels found in non-transgenic animals. Serum derived from transgenic (but not non-transgenic) mice led to enhanced transcription as well as expression of VEGF, IL-8, KC (murine IL-8) and MMP-9 in tumor cells, effects not seen when sera derived from hCG-immunized transgenic mice was employed. As the definitive indication of the restoration of the reproductive axis, immunization led to the resumption of estrous cyclicity as well as fertility in transgenic mice. These results indicate that hCG may influence cancer pathogenesis and progression via several distinct mechanisms. Using a stringent in vivo system in which ßhCG acts both a "self" antigen and a tumor-promoting moiety (putatively akin to the situation in humans), the data builds a case for anti-gonadotropin vaccination strategies in the treatment of gonadotropin-dependent or secreting malignancies that frequently acquire resistance to conventional therapy.

Body image satisfaction among female college students.

OBJECTIVE: To determine body image satisfaction among newly entrant women students in a professional institution. MATERIALS AND METHODS: A cross-sectional study using body image satisfaction described in words was undertaken, which also explored relationship with body mass index (BMI) and other selected co-variables such as socio-demographic details, overall satisfaction in life, and particularly in academic/professional life, current health status using 5-item based Likert scale. Height, weight, hip and waist circumference measurement was carried out using standard protocol. Data collection was carried through personal interview using pre-designed, pre-tested semi-structured interview schedule by female investigators during August-September 2010 and analysis carried out by computing percentages and Chi-square test. RESULTS: Out of 96 study samples, 16.66%, 51.04%, and 32.29% girl students perceived their body image as fair, good and excellent, respectively while overall 13.54% were dissatisfied with their body image. The body image satisfaction had significant relationship with image perception (P<0.001), current general health status (P<0.001) and self weight assessment (P<0.001). Mother's education had a statistically significant (P=0.004) but negative relationship with outcome variable. Students with low weight (BMI <18.5 kg/m(2)) had a significantly higher (85.71%) prevalence of body image satisfaction while overweight students (BMI≤23 kg/m(2)) had a significantly higher (54.54%) prevalence of dissatisfaction (P<0.001). DISCUSSION: High body image satisfaction is reported in this study and was found to be significantly related to anthropometric measurements. On an encouraging note, this level needs to be preserved for overall mental and healthy development of students. Proactive preventive measures could be initiated on personality development, acceptance of self and individual differences while maintaining optimum weight and active life style.