Mechanical resilience of the sessile tunicate Botryllus schlosseri.

We demonstrate that the sessile tunicate Botryllus schlosseri is remarkably resilient to applied loads by attaching the animals to an extensile substrate subjected to quasistatic equiradial loads. Animals can withstand radial extension of the substrate to strain values as high as 20% before they spontaneously detach. In the small to moderate strain regime, we found no relationship between the dynamic size of the external vascular bed and the magnitude of applied stretch, despite known force sensitivities of the vascular tissue at the cellular level. We attribute this resilience to the presence and mechanical properties of the tunic, the cellulose-enriched gel-like substance that encases the animal bodies and surrounding vasculature.

Effect of sunflower seed oil emollient therapy on newborn infant survival in Uttar Pradesh, India: A community-based, cluster randomized, open-label controlled trial.

BACKGROUND: Hospitalized preterm infants with compromised skin barrier function treated topically with sunflower seed oil (SSO) have shown reductions in sepsis and neonatal mortality rate (NMR). Mustard oil and products commonly used in high-mortality settings may possibly harm skin barrier integrity and enhance risk of infection and mortality in newborn infants. We hypothesized that SSO therapy may reduce NMR in such settings. METHODS AND FINDINGS: This was a population-based, cluster randomized, controlled trial in 276 clusters in rural Uttar Pradesh, India. All newborn infants identified through population-based surveillance in the study clusters within 7 days of delivery were enrolled from November 2014 to October 2016. Exclusive, 3 times daily, gentle applications of 10 ml of SSO to newborn infants by families throughout the neonatal period were recommended in intervention clusters (n = 138 clusters); infants in comparison clusters (n = 138 clusters) received usual care, such as massage practice typically with mustard oil. Primary analysis was by intention-to-treat with NMR and post-24-hour NMR as the primary outcomes. Secondary analysis included per-protocol analysis and subgroup analyses for NMR. Regression analysis was adjusted for caste, first-visit weight, delivery attendant, gravidity, maternal age, maternal education, sex of the infant, and multiple births. We enrolled 13,478 (52.2% male, mean weight: 2,575.0 grams ± standard deviation [SD] 521.0) and 13,109 (52.0% male, mean weight: 2,607.0 grams ± SD 509.0) newborn infants in the intervention and comparison clusters, respectively. We found no overall difference in NMR in the intervention versus the comparison clusters [adjusted odds ratio (aOR) 0.96, 95% confidence interval (CI) 0.84 to 1.11, p = 0.61]. Acceptance of SSO in the intervention arm was high at 89.3%, but adherence to exclusive applications of SSO was 30.4%. Per-protocol analysis showed a significant 58% (95% CI 42% to 69%, p < 0.01) reduction in mortality among infants in the intervention group who were treated exclusively with SSO as intended versus infants in the comparison group who received exclusive applications of mustard oil. A significant 52% (95% CI 12% to 74%, p = 0.02) reduction in NMR was observed in the subgroup of infants weighing ≤1,500 g (n = 589); there were no statistically significant differences in other prespecified subgroup comparisons by low birth weight (LBW), birthplace, and wealth. No severe adverse events (SAEs) were attributable to the intervention. The study was limited by inability to mask allocation to study workers or participants and by measurement of emollient use based on caregiver responses and not actual observation. CONCLUSIONS: In this trial, we observed that promotion of SSO therapy universally for all newborn infants was not effective in reducing NMR. However, this result may not necessarily establish equivalence between SSO and mustard oil massage in light of our secondary findings. Mortality reduction in the subgroup of infants ≤1,500 g was consistent with previous hospital-based efficacy studies, potentially extending the applicability of emollient therapy in very low-birth-weight (VLBW) infants along the facility-community continuum. Further research is recommended to develop and evaluate therapeutic regimens and continuum of care delivery strategies for emollient therapy for newborn infants at highest risk of compromised skin barrier function. TRIAL REGISTRATION: ISRCTN Registry ISRCTN38965585 and Clinical Trials Registry-India (CTRI/2014/12/005282) with WHO UTN # U1111-1158-4665.

PIK3CA mutant tumors depend on oxoglutarate dehydrogenase.

Oncogenic PIK3CA mutations are found in a significant fraction of human cancers, but therapeutic inhibition of PI3K has only shown limited success in clinical trials. To understand how mutant PIK3CA contributes to cancer cell proliferation, we used genome scale loss-of-function screening in a large number of genomically annotated cancer cell lines. As expected, we found that PIK3CA mutant cancer cells require PIK3CA but also require the expression of the TCA cycle enzyme 2-oxoglutarate dehydrogenase (OGDH). To understand the relationship between oncogenic PIK3CA and OGDH function, we interrogated metabolic requirements and found an increased reliance on glucose metabolism to sustain PIK3CA mutant cell proliferation. Functional metabolic studies revealed that OGDH suppression increased levels of the metabolite 2-oxoglutarate (2OG). We found that this increase in 2OG levels, either by OGDH suppression or exogenous 2OG treatment, resulted in aspartate depletion that was specifically manifested as auxotrophy within PIK3CA mutant cells. Reduced levels of aspartate deregulated the malate-aspartate shuttle, which is important for cytoplasmic NAD+ regeneration that sustains rapid glucose breakdown through glycolysis. Consequently, because PIK3CA mutant cells exhibit a profound reliance on glucose metabolism, malate-aspartate shuttle deregulation leads to a specific proliferative block due to the inability to maintain NAD+/NADH homeostasis. Together these observations define a precise metabolic vulnerability imposed by a recurrently mutated oncogene.

A genetic mosaic mouse model illuminates the pre-malignant progression of basal-like breast cancer.

Basal-like breast cancer is an aggressive breast cancer subtype, often characterized by a deficiency in BRCA1 function and concomitant loss of p53 . While conventional mouse models enable the investigation of its malignant stages, one that reveals its initiation and pre-malignant progression is lacking. Here, we leveraged a mouse genetic system known as M osaic A nalysis with D ouble M arkers (MADM) to generate rare GFP-labeled Brca1 , p53 -deficient cells alongside RFP+ wildtype sibling cells in the mammary gland. The mosaicism resembles the sporadic initiation of human cancer and enables spatially resolved analysis of mutant cells in comparison to paired wildtype sibling cells. Mammary tumors arising in the model show transcriptomic and genomic characteristics similar to human basal-like breast cancer. Analysis of GFP+ mutant cells at interval time points before malignancy revealed a stepwise progression of lesions from focal expansion to hyper-alveolarization and then to micro-invasion. These stereotyped morphologies indicate the pre-malignant stage irrespective of the time point at which it is observed. Paired analysis of GFP-RFP siblings during focal expansion suggested that hyper-alveolarized structures originate from ductal rather than alveolar cells, despite their morphological similarities to alveoli. Evidence for luminal-to-basal transition at the pre-malignant stages was restricted to cells that had escaped hyper-alveoli and progressed to micro-invasive lesions. Our MADM-based mouse model presents a useful tool for studying the pre-malignancy of basal-like breast cancer. Summary statement: A mouse model recapitulates the process of human basal-like breast tumorigenesis initiated from sporadic Brca1, p53 -deficient cells, empowering spatially-resolved analysis of mutant cells during pre-malignant progression.

A genetic mosaic mouse model illuminates the pre-malignant progression of basal-like breast cancer.

Basal-like breast cancer (BLBC) is highly aggressive, and often characterized by BRCA1 and p53 deficiency. Although conventional mouse models enabled the investigation of BLBC at malignant stages, its initiation and pre-malignant progression remain understudied. Here, we leveraged a mouse genetic system known as mosaic analysis with double markers (MADM) to study BLBC initiation by generating rare GFP+Brca1, p53-deficient mammary cells alongside RFP+ wild-type sibling cells. After confirming the close resemblance of mammary tumors arising in this model to human BLBC at both transcriptomic and genomic levels, we focused our studies on the pre-malignant progression of BLBC. Initiated GFP+ mutant cells showed a stepwise pre-malignant progression trajectory from focal expansion to hyper-alveolarization and then to micro-invasion. Furthermore, despite morphological similarities to alveoli, hyper-alveolarized structures actually originate from ductal cells based on twin-spot analysis of GFP-RFP sibling cells. Finally, luminal-to-basal transition occurred exclusively in cells that have progressed to micro-invasive lesions. Our MADM model provides excellent spatiotemporal resolution to illuminate the pre-malignant progression of BLBC, and should enable future studies on early detection and prevention for this cancer.

Synthesis of tetracyclic indoles via intramolecular α-arylation of ketones.

An intramolecular palladium(0)-mediated α-arylation of ketones applied to the synthesis of various substituted tetracyclic indoles is reported. Most significantly, the efficiency of the transformation was enhanced by the use of monoligated Pd(0) complexes. This methodology was extended to double α-arylation of ketones using one-pot reactions with either simultaneous addition or sequential addition of two aryl halides for producing aryl substituted tetracyclic indoles.

Etiology and Antimicrobial Resistance Profile of Superficial Pyogenic Infections from a Tertiary Care Hospital, Western Rajasthan, India.

BACKGROUND: Superficial Pyogenic Infection (SPI) is the type of a pyogenic infection, which involves the infections of the skin, subcutaneous tissue, and soft tissue. These infections can cause significant morbidity. Antimicrobial Resistance (AMR) has emerged due to the rampant use of broadspectrum agents in superficial pyogenic infections. OBJECTIVE: The aim of the study was to identify the microbial profile of superficial pyogenic infections and study their antimicrobial resistance. METHODS: A cross-sectional observational study was carried out at the Department of Microbiology of a tertiary care hospital in the western region of Rajasthan. Samples included pus, aspirate from the abscess, necrotic tissue, and post-surgical drainage from infected skin at different sites of the patients attending OPD or admitted in IPD and ICU of the hospital. Identification of isolates was carried out by standard bacteriological techniques. The Antibiotic Susceptibility Testing (AST) of bacterial isolates was done by Kirby Bauer disk diffusion method on Mueller Hinton agar (HiMedia, India), and in a few cases, by automated Microscan system as recommended by the Clinical and Laboratory Standards Institute (CLSI), Wayne, USA. RESULTS: A total of 2283 various specimens were obtained from different areas of healthcare facilities. Pathogenic bacterial isolates were recovered from 303 specimens. Staphylococcus aureus and Escherichia coli were found to be the main offenders. The effective antibiotics for gram-positive isolates were clindamycin, cotrimoxazole, linezolid, tetracycline, and vancomycin, and for gram-negative bacteria, meropenem, imipenem and amikacin were seen to be effective. CONCLUSION: This study can help formulate a local antibiotic policy which will restrict the unsupervised antibiotic use and strengthen antibiotic stewardship practices in the hospitals.

Evaluation of different pre-treatment behaviour modification techniques in 4-7-year olds: A randomised controlled trial.

Purpose: The aim of this study is to evaluate and compare the effectiveness of five pre-treatment behaviour modification techniques in 4-7-year olds in reducing dental anxiety by evaluating pulse rate, partial pressure of oxygen, systolic blood pressure, diastolic blood pressure, salivary flow rate, salivary pH, and through modified facial anxiety scale. Material and Methods: Using simple random sampling technique (drawing of lots), 125 children were equally distributed into 5 groups of 25 each: Group 1: tell-show-do (control); Group 2: tell-show-play-doh; Group 3: Playmobil Dentist; Group 4: mobile dentist games; Group 5: role play as dentist. Samples in each group were treated in a single appointment after using the behaviour modification techniques. Class I or Class II cavities were prepared on carious primary molar and restored using glass ionomer cement. Patient's anxiety level was assessed by recording blood pressure, pulse rate, oxygen saturation, salivary pH, salivary flow rate, and facial anxiety scale at different time intervals, that is before the treatment, during the treatment, and after the treatment. Results: All the intervention Groups (Groups 2-5) showed reduced anxiety scores in both physiological and facial anxiety compared to the control group, that is tell, show do. The modified distraction techniques aid in better modification. Conclusion: Tell-show-play-doh, Playmobil dentist games, mobile dentist games and role play as dentist are effective distraction techniques as compared to conventional tell-show-do techniques which can be incorporated in day-to-day clinical practice to reduce dental anxiety in paediatric patients.

Effects of emollient therapy with sunflower seed oil on neonatal growth and morbidity in Uttar Pradesh, India: a cluster-randomized, open-label, controlled trial.

BACKGROUND: Newborn oil massage is a widespread practice. Vigorous massage with potentially harmful products and forced removal of vernix may disrupt skin barrier integrity. Hospitalized, very-preterm infants treated with sunflower seed oil (SSO) have demonstrated improved growth but community-based data on growth and health outcomes are lacking. OBJECTIVES: We aimed to test whether SSO therapy enhances neonatal growth and reduces morbidity at the population level. METHODS: We conducted an open-label, controlled trial in rural Uttar Pradesh, India, randomly allocating 276 village clusters equally to comparison (usual care) and intervention comprised of promotion of improved massage practices exclusively with SSO, using intention-to-treat and per-protocol mixed-effects regression analysis. RESULTS: We enrolled 13,478 and 13,109 newborn infants in demographically similar intervention and comparison arms, respectively. Adherence to exclusive SSO increased from 22.6% of intervention infants enrolled in the first study quartile to 37.2% in the last quartile. Intervention infants gained significantly more weight, by 0.94 g · kg-1 · d-1 (95% CI: 0.07, 1.82 g · kg-1 · d-1, P = 0.03), than comparison infants by intention-to-treat analysis. Restricted cubic spline regression revealed the largest benefits in weight gain (2-4 g · kg-1 · d-1) occurred in infants weighing <2000 g at birth. Weight gain in intervention infants was higher by 1.31 g · kg-1 · d-1 (95% CI: 0.17, 2.46 g · kg-1 · d-1; P = 0.02) by per-protocol analysis. Morbidities were similar by intention-to-treat analysis but in per-protocol analysis rates of hospitalization and of any illness were reduced by 36% (OR: 0.64; 95% CI: 0.44, 0.94; P = 0.02) and 44% (OR: 0.56; 95% CI: 0.40, 0.77; P < 0.001), respectively, in treated infants. CONCLUSIONS: SSO therapy improved neonatal growth, and reduced morbidities when applied exclusively, across the facility-community continuum of care at the population level. Further research is needed to improve demand for recommended therapy inside hospital as well as in community settings, and to confirm these results in other settings.This trial was registered at www.isrctn.com as ISRCTN38965585 and http://ctri.nic.in as CTRI/2014/12/005282.

Pan-Cancer Drivers Are Recurrent Transcriptional Regulatory Heterogeneities in Early-Stage Luminal Breast Cancer.

The heterogeneous composition of solid tumors is known to impact disease progression and response to therapy. Malignant cells coexist in different regulatory states that can be accessed transcriptomically by single-cell RNA sequencing, but these methods have many caveats related to sensitivity, noise, and sample handling. We revised a statistical fluctuation analysis called stochastic profiling to combine with 10-cell RNA sequencing, which was designed for laser-capture microdissection (LCM) and extended here for immuno-LCM. When applied to a cohort of late-onset, early-stage luminal breast cancers, the integrated approach identified thousands of candidate regulatory heterogeneities. Intersecting the candidates from different tumors yielded a relatively stable set of 710 recurrent heterogeneously expressed genes (RHEG), which were significantly variable in >50% of patients. RHEGs were not strongly confounded by dissociation artifacts, cell-cycle oscillations, or driving mutations for breast cancer. Rather, RHEGs were enriched for epithelial-to-mesenchymal transition genes and, unexpectedly, the latest pan-cancer assembly of driver genes across cancer types other than breast. These findings indicate that heterogeneous transcriptional regulation conceivably provides a faster, reversible mechanism for malignant cells to evaluate the effects of potential oncogenes or tumor suppressors on cancer hallmarks. SIGNIFICANCE: Profiling intratumor heterogeneity of luminal breast carcinoma cells identifies a recurrent set of genes, suggesting sporadic activation of pathways known to drive other types of cancer.See related articles by Schaff and colleagues, p. 1853 and Sutcliffe and colleagues, p. 1868.

Premalignant Oligodendrocyte Precursor Cells Stall in a Heterogeneous State of Replication Stress Prior to Gliomagenesis.

Cancer evolves from premalignant clones that adopt unusual cell states to achieve transformation. We previously pinpointed the oligodendrocyte precursor cell (OPC) as a cell of origin for glioma, but the early changes of mutant OPCs during premalignancy remained unknown. Using mice engineered for inducible Nf1-Trp53 loss in OPCs, we acutely isolated labeled mutant OPCs by laser-capture microdissection, determined global gene-expression changes by bulk RNA sequencing, and compared with cell-state fluctuations at the single-cell level by stochastic profiling, which uses RNA-sequencing measurements from random pools of 10 mutant cells. At 12 days after Nf1-Trp53 deletion, bulk differences were mostly limited to mitotic hallmarks and genes for ribosome biosynthesis, and stochastic profiling revealed a spectrum of stem-progenitor (Axl, Aldh1a1), proneural, and mesenchymal states as potential starting points for gliomagenesis. At 90 days, bulk sequencing detected few differentially expressed transcripts, whereas stochastic profiling revealed cell states for neurons and mural cells that do not give rise to glial tumors, suggesting cellular dead-ends for gliomagenesis. Importantly, mutant OPCs that strongly expressed key effectors of nonsense-mediated decay (Upf3b) and homology-dependent DNA repair (Rad51c, Slx1b, Ercc4) were identified along with DNA-damage markers, suggesting transcription-associated replication stress. Analysis of 10-cell transcriptomes at 90 days identified a locus of elevated gene expression containing an additional repair endonuclease (Mus81) and Rin1, a Ras-Raf antagonist and possible counterbalance to Nf1 loss, which was microdeleted or downregulated in gliomas at 150 days. These hidden cell-state variations uncover replication stress as a potential bottleneck that must be resolved for glioma initiation. SIGNIFICANCE: Profiling premalignant cell states in a mouse model of glioma uncovers regulatory heterogeneity in glioma cells-of-origin and defines a state of replication stress that precedes tumor initiation.See related articles by Singh and colleagues, p. 1840 and Schaff and colleagues, p. 1853.

Fragmentation of Small-Cell Lung Cancer Regulatory States in Heterotypic Microenvironments.

Small-cell lung cancers derive from pulmonary neuroendocrine cells, which have stem-like properties to reprogram into other cell types upon lung injury. It is difficult to uncouple transcriptional plasticity of these transformed cells from genetic changes that evolve in primary tumors or secondary metastases. Profiling of single cells is also problematic if the required sample dissociation activates injury-like signaling and reprogramming. Here we defined cell-state heterogeneities in situ through laser capture microdissection-based 10-cell transcriptomics coupled with stochastic-profiling fluctuation analysis. In labeled cells from a small-cell lung cancer mouse model initiated by neuroendocrine deletion of Rb1-Trp53, variations in transcript abundance revealed cell-to-cell differences in regulatory state in vitro and in vivo. Fluctuating transcripts in spheroid culture were partly shared among Rb1-Trp53-null models, and heterogeneities increased considerably when cells were delivered intravenously to colonize the liver. Colonization of immunocompromised animals drove a fractional appearance of alveolar type II-like markers and poised cells for paracrine stimulation from immune cells and hepatocytes. Immunocompetency further exaggerated the fragmentation of tumor states in the liver, yielding mixed stromal signatures evident in bulk sequencing from autochthonous tumors and metastases. Dozens of transcript heterogeneities recurred irrespective of biological context; their mapped orthologs brought together observations of murine and human small-cell lung cancer. Candidate heterogeneities recurrent in the liver also stratified primary human tumors into discrete groups not readily explained by molecular subtype but with prognostic relevance. These data suggest that heterotypic interactions in the liver and lung are an accelerant for intratumor heterogeneity in small-cell lung cancer. SIGNIFICANCE: These findings demonstrate that the single-cell regulatory heterogeneity of small-cell lung cancer becomes increasingly elaborate in the liver, a common metastatic site for the disease.See related articles by Singh and colleagues, p. 1840 and Sutcliffe and colleagues, p. 1868.

Pedicled Flap vs. Free Flap Reconstruction in Head and Neck Cancers: Clinical Outcome Analysis from a Single Surgical Team.

Head and neck cancers are one of the leading causes of morbidity and mortality in Indian population. Reconstruction and restoration of function are also of paramount importance in these patients. The aim of this study was to report outcomes for free flaps and pedicle flaps in patients with oral cavity cancers. A retrospective analysis of 628 patients with oral cavity cancers who underwent reconstruction with either free flaps or pedicle flaps during 2014-2020 was done. The median age of the cohort was 49 years. The free flap reconstruction was performed in 481 (76%) and pedicle flap in 147 (24%) patients. Among free and pedicle flaps, 27 (5.6%) and 3 (2.1%) respectively had major flap complications and 25 (5.1%) and 14 (9.9%) respectively had minor complications. CCI score > 4 was associated with higher events (p = 0.02) in free flap group. The outcomes of free flaps are similar in comparison to pedicle flaps in patients with oral cavity cancers. The higher CCI score is significantly associated with increased flap-related complications for the free flap group.

Bacterial pathogens from lower respiratory tract infections: A study from Western Rajasthan.

Respiratory tract infections are the most common diseases that are associated with social burden for the patient. Western Rajasthan has cases of Cystic fibrosis due to migrant population. The dry and dusty environment has led to prevalence of silicosis and COPD. As per IDSA (2018) guidelines, patients attending Out-Patient Department do not need microbiological investigations for lower respiratory tract infections (LRTI) except for influenza and tuberculosis. AIMS: This study was conducted to identify the bacterial aetiology of LRTI among patients who attended AIIMS, Jodhpur, and to ascertain the current scenario of bacterial susceptibility in respiratory tract infections in order to optimize empiric therapy in Hospitals ad community. METHODS AND MATERIAL: In total, 1,775 lower respiratory tract samples were received in Bacteriology Section of Microbiology Department (January 2017 to December 2018). Bartlett's criteria were stringently used to assess quality of specimen. Semiquantitative cultures were done for tracheal aspirate and bronchoalveolar lavage samples. Following culture, the isolated organisms were identified and antimicrobial sensitivity was performed according to CLSI. RESULTS: Total 769 bacterial pathogens were isolated from 1,775 samples collected from cases of VAP, HAP, CAP, COPD, and cystic fibrosis. Pseudomonas species was the commonest isolate (31%), followed by Klebsiella pneumonia (21.3%), Acinetobacter species (17.5%), Escherichia coli (15.4%), and Staphylococcus aureus (5%). Others include Group A ß-hemolytic Streptococcus, Burkholderia cepacia complex, Stenotrophomonas maltophilia, and Nocardia. Gram-negative organisms showed increased resistance to routinely used antibiotics. Gram-positive organisms showed 100% susceptibility to vancomycin, linezolid, and clindamycin. CONCLUSIONS: Cotrimoxazole, ßL-ßLIs, aminoglycosides, and all second-line antibiotics tested were effective for treatment of RTIs.

Compartmental Clearance of Infratemporal Fossa for T4b Carcinoma of Buccal Mucosa/Alveolus: Clinical Outcomes.

T4 b carcinoma of oral cavity has poor outcomes. The aim for analysis is to evaluate the clinical outcomes with infratemporal fossa clearance for stage T4b carcinoma of oral cavity. Fifty four patients out of maintained data of 528 patients of oral cavity carcinoma were evaluated for current retrospective analysis. All had T4b disease on imaging and underwent bite composite resection with ITF clearance. The median age of the cohort was 52 years. At last follow-up, 28 patients were alive. Twenty two patients had loco-regional recurrence (ITF recurrence 7), and 16 patients had distant metastasis. At median follow-up of 29 months, 2-year loco-regional control, DFS and OS were 52%, 54% and 54%, respectively. Perineural invasion, pathological tumour stage, node positive and ITF tissue involvement were associated with poor oncological outcomes. ITF clearance is feasible in clinical practice and provides curative option for this group.

An injection abscess due to M. fortuitum: A rare case report.

An iatrogenic injection abscess is usually easy to treat if caused by aerobic bacteria but some rapidly growing mycobacteria (RGM), namely, Mycobacterium fortuitum, M. chelonae, and M. abscessus are associated with postinjection abscess and may cause delayed wound healing. RGM can cause mild localized cellulitis or abscess to osteomyelitis following penetration injuries or unsafe injection practices. A 7-year-old girl was presented to pediatric surgery OPD with abscess formation over the right buttock. Incision and drainage from abscess were performed in OPD and pus sample was sent for aerobic bacterial culture and sensitivity. On gram stain plenty of pus cells with no microorganism were seen and growth on blood agar after 48 h of aerobic incubation at 37°C showed small off-white pinpoint, smooth butyrous waxy colonies. Smear prepared from blood agar showed uniformly stained short, slender, faintly stained gram-positive bacilli, for which acid-fast staining (1% and 20% H2SO4) was performed that showed acid-fast bacilli. The isolate was further identified by the molecular method and was confirmed to be Mycobacterium fortuitum by genotype Mycobacterium CM VER 1.0 (HAIN LIFESCIENCE, BioMerieux India Pvt. Ltd.).

Characterizing the cellular architecture of dynamically remodeling vascular tissue using 3-D image analysis and virtual reconstruction.

Epithelial tubules form critical structures in lung, kidney, and vascular tissues. However, the processes that control their morphogenesis and physiological expansion and contraction are not well understood. Here we examine the dynamic remodeling of epithelial tubes in vivo using a novel model system: the extracorporeal vasculature of Botryllus schlosseri, in which the disruption of the basement membrane triggers rapid, massive vascular retraction without loss of barrier function. We developed and implemented 3-D image analysis and virtual reconstruction tools to characterize the cellular morphology of the vascular wall in unmanipulated vessels and during retraction. In both control and regressed conditions, cells within the vascular wall were planar polarized, with an integrin- and curvature-dependent axial elongation of cells and a robust circumferential alignment of actin bundles. Surprisingly, we found no measurable differences in morphology between normal and retracting vessels under extracellular matrix (ECM) disruption. However, inhibition of integrin signaling through focal adhesion kinase inhibition caused disruption of cellular actin organization. Our results demonstrate that epithelial tubes can maintain tissue organization even during extreme remodeling events, but that the robust response to mechanical signals-such as the response to loss of vascular tension after ECM disruption-requires functional force sensing machinery via integrin signaling.

Does adherence to evidence-based practices during childbirth prevent perinatal mortality? A post-hoc analysis of 3,274 births in Uttar Pradesh, India.

BACKGROUND: Evidence-based practices that reduce childbirth-related morbidity and mortality are core processes to quality of care. In the BetterBirth trial, a matched-pair, cluster-randomised controlled trial of a coaching-based implementation of the WHO Safe Childbirth Checklist (SCC) in Uttar Pradesh, India, we observed a significant increase in adherence to practices, but no reduction in perinatal mortality. METHODS: Within the BetterBirth trial, we observed birth attendants in a subset of study sites providing care to labouring women to assess the adherence to individual and groups of practices. We observed care from admission to the facility until 1 hour post partum. We followed observed women/newborns for 7-day perinatal health outcomes. Using this observational data, we conducted a post-hoc, exploratory analysis to understand the relationship of birth attendants' practice adherence to perinatal mortality. FINDINGS: Across 30 primary health facilities, we observed 3274 deliveries and obtained 7-day health outcomes. Adherence to individual practices, containing supply preparation and direct provider care, varied widely (0·51 to 99·78%). We recorded 166 perinatal deaths (50·71 per 1000 births), including 56 (17·1 per 1000) stillbirths. Each additional practice performed was significantly associated with reduced odds of perinatal (OR: 0·82, 95% CI: 0·72, 0·93) and early neonatal mortality (OR: 0·78, 95% CI: 0·71, 0·85). Each additional practice as part of direct provider care was associated strongly with reduced odds of perinatal (OR: 0·73, 95% CI: 0·62, 0·86) and early neonatal mortality (OR: 0·67, 95% CI: 0·56, 0·80). No individual practice or single supply preparation was associated with perinatal mortality. INTERPRETATION: Adherence to practices on the WHO SCC is associated with reduced mortality, indicating that adherence is a valid indicator of higher quality of care. However, the causal relationships between practices and outcomes are complex. FUNDING: Bill & Melinda Gates Foundation. TRIAL REGISTRATION DETAILS: ClinicalTrials.gov: NCT02148952; Universal Trial Number: U1111-1131-5647.

Disseminated Gastrointestinal Basidiobolomycosis (GIB) in an infant from Western India.

Basidiobolomycosis is an infection due to the fungus Basidiobolus ranarum, an environmental saprophyte found worldwide. We are reporting youngest case of Gastrointestinal Basidiobolomycosis (GIB) in a two month old boy from India. He presented with a mass in right iliac fossa with the signs of intestinal obstruction. Histopathology of the lesion showed broad aseptate hyphae. It disseminated to kidneys. Aspirate culture from nephrostomy yielded growth of B. ranarum. It is important to differentiate it from mucormycosis to institute right therapy. Culture remains the gold standard for its diagnosis.

Patient-experience during delivery in public health facilities in Uttar Pradesh, India.

In India, most women now delivery in hospitals or other facilities, however, maternal and neonatal mortality remains stubbornly high. Studies have shown that mistreatment causes delays in care-seeking, early discharge and poor adherence to post-delivery guidance. This study seeks to understand the variation of women's experiences in different levels of government facilities. This information can help to guide improvement planning. We surveyed 2018 women who gave birth in a representative set of 40 government facilities from across Uttar Pradesh (UP) state in northern India. Women were asked about their experiences of care, using an established scale for person-centred care. We asked questions specific to treatment and clinical care, including whether tests such as blood pressure, contraction timing, newborn heartbeat or vaginal exams were conducted, and whether medical assessments for mothers or newborns were done prior to discharge. Women delivering in hospitals reported less attentive care than women in lower-level facilities, and were less trusting of their providers. After controlling for a range of demographic attributes, we found that better access, higher clinical quality, and lower facility-level, were all significantly predictive of patient-centred care. In UP, lower-level facilities are more accessible, women have greater trust for the providers and women report being better treated than in hospitals. For the vast majority of women who will have a safe and uncomplicated delivery, our findings suggest that the best option would be to invest in improvements mid-level facilities, with access to effective and efficient emergency referral and transportation systems should they be needed.