Validation of no-biopsy pathway for the diagnosis of celiac disease in Asian adults: a multicenter retrospective study.

BACKGROUND AND AIM: While European Society of Pediatric Gastroenterology Hepatology and Nutrition advocates a no-biopsy pathway for the diagnosis of celiac disease (CeD) in children if IgA anti-tissue transglutaminase antibody (anti-tTG ab) titer is ≥10-fold upper limit of normal (ULN) and have a positive IgA anti-endomysial antibody (EMA); the data for anti-tTG Ab titer-based diagnosis of CeD in adults is still emerging. We planned to validate if IgA anti-tTG Ab titer ≥10-fold predicts villous abnormalities of modified Marsh grade ≥2 in Asian adult patients with CeD. METHODS: We recruited 937 adult patients with positive anti-tTG Ab from two databases, including AIIMS Celiac Clinic and Indian National Biorepository. The diagnosis of definite CeD was made on the basis of a positive anti-tTG Ab and the presence of villous abnormalities of modified Marsh grade ≥2. RESULTS: Of 937 adult patients with positive anti-tTG Ab, 889 (91.2%) showed villous abnormalities of modified Marsh grade ≥2. Only 47.6% of 889 adults with CeD had anti- tTG Ab titers of ≥10-fold. The positive predictive value (PPV) and specificity of anti tTG Ab titer ≥10-fold for predicting modified Marsh grade ≥2 were 99.8% and 98%, respectively. At anti-tTG Ab titer ≥11-fold, specificity and PPV were 100% for predicting villous abnormalities of modified Marsh grade ≥2. CONCLUSIONS: Approximately 50% of adults with CeD may benefit from the no biopsy pathway, reducing the health burden and risks of gastroscopy/anesthesia.

Impact of delay in the diagnosis on the severity of celiac disease.

BACKGROUND AND AIM: Celiac disease (CeD) has now become a global disease with a worldwide prevalence of 0.67%. Despite being a common disease, CeD is often not diagnosed and there is a significant delay in its diagnosis. We reviewed the impact of the delay in the diagnosis on the severity of manifestations of CeD. METHODS: We reviewed clinical records of 726 consecutive patients with CeD from the Celiac Clinic database and the National Celiac Disease Consortium database. We extracted specific data including the demographics, symptoms at presentation, time of onset of symptoms, time to diagnosis from the onset of the symptoms, and relevant clinical data including fold-rise in anti-tissue transglutaminase antibody (IgA anti-tTG Ab) and severity of villous and crypt abnormalities as assessed using modified Marsh classification. RESULTS: The median duration between the onset of symptoms and the diagnosis of CeD was 27 months (interquartile range 12-60 months). A longer delay in the diagnosis of CeD from the onset of symptoms was associated with lower height for age, lower hemoglobin, higher fold rise in IgA Anti tTG titers, and higher severity of villous and crypt abnormalities. About 18% of patients presented with predominantly non-gastrointestinal complaints and had a longer delay in the diagnosis of CeD. CONCLUSIONS: There is a significant delay in the diagnosis of CeD since the onset of its symptoms. The severity of celiac disease increases with increasing delay in its diagnosis. There is a need to keep a low threshold for the diagnosis of CeD in appropriate clinical settings.

A Case of Cobra Bite in a Term Pregnant Woman: The Obstetric and Wound Management Challenges.

Snake envenomation is a rare incident during pregnancy and potentially challenging to manage. Snakebites in pregnancy may lead to several complications such as teratogenicity, miscarriage, antepartum hemorrhage, and even intrauterine fetal death. Here, we report a case of a pregnant woman who presented to our emergency department with signs of systemic envenomation following an Indian cobra bite on her foot, highlighting the key obstetric and wound management challenges. She complained of severe pain at the site of the bite and progressive swelling, abdominal pain, and multiple episodes of vomiting, which started 45 min after the bite. She received 10 vials of polyvalent antivenom from a primary hospital and was then referred to our center. The patient underwent emergency cesarean section and later fasciotomy with free-flap reconstruction at the bitten site due to local tissue necrosis. The case was successfully managed by a multidisciplinary team consisting of an emergency physician, obstetrician, and plastic surgeon, saving 2 lives and the limb of the patient.

A case report of pseudoaneurysm of coronary artery within a month of percutaneous coronary intervention.

Background: Coronary artery pseudoaneurysms (PSAs) are uncommon and have poorly understood natural history. Unlike true aneurysms, PSAs do not have all the three layers of the vessel in the aneurysmal wall. The PSAs are most commonly seen after an overzealous percutaneous coronary intervention (PCI) which causes damage to the vessel wall. They usually develop slowly after PCI and PSAs within a month of a PCI are not so common. The PSA may be asymptomatic or present with recurrent angina. Case summary: Here, we report a case of symptomatic PSA to right coronary artery (RCA). The patient had a myocardial infarction for which a PCI was performed to deploy a drug-eluting stent (DES) in the RCA. The patient had in-stent restenosis (ISR) within a week of PCI for which plain old balloon angioplasty (POBA) was performed. The patient continued to have unstable angina and within a month of POBA was diagnosed as a case of PSA by intravascular ultrasound. A covered stent was deployed which effectively sealed off the PSA and resumed normal blood flow to distal vessel. Patient has been doing well on medication [aspirin 75 mg once daily, atorvastatin 80 mg once daily, and P2Y12 platelet inhibitor (Ticagrelor) 90 mg twice daily]. Discussion: The PSAs usually take 6-9 months to develop. However, PSAs have been reported within 1-2 months of PCI. This case also shows that PSAs can occur within a month of PCI. It is possible that over-aggressive and/or high-pressure dilatation and/or deep engagement during POBA performed to open up the ISR could have damaged the struts of the DES and compressed it against the vascular wall. The resultant vascular wall injury could have been the cause of early PSA formation in this case. Hence, cardiologists should be vigilant enough to suspect PSA, especially in a patient presenting with angina. The case also shows that covered stents are a viable option to treat early presentations of PSA.

Case series of coronary artery aneurysms after Everolimus eluting stent implantation and comparison with Sirolimus eluting stents.

BACKGROUND: Coronary artery aneurysms after drug eluting stents are rare. We present a case series of type II coronary aneurysms after implantation of Everolimus eluting stents including patients developing giant aneurysms with a toxic course. CASE PRESENTATION: Over a span of 3.5 years at our center 2572 patients were implanted Everolimus eluting stents out of which 4 patients developed coronary type II aneurysms an incidence of 0.00156 whereas 5838 patients were implanted Sirolimus eluting 2nd generation stents out of which 2 patients developed similar aneurysms with an incidence of 0.00034. The slight increase in incidence in Everolimus stents does not reach statistical significance (p = 0.054) and is limited by single centre non randomized study. We also propose a hypothesis that the slight increase in the incidence maybe due to allergy to Methacrylate present in Everolimus eluting Xience stent's primer which is absent in other Sirolimus eluting stents used at our center but that needs to be further investigated. We also found some patients who developed giant aneurysms including Left main aneurysms. In our series operative repair of these patients had better outcomes than covered stent deployment but larger trials maybe needed to confirm the same. CONCLUSIONS: Coronary artery aneurysms after stent implantation are rare but occasionally giant aneurysms are formed with a toxic course. The incidence and morphology of aneurysms after Everolimus and Sirolimus eluting stent deployment do not differ much.

Scale of the issue: Mapping the impact of the COVID-19 lockdown on pangolin trade across India.

Recent studies have linked COVID-19 induced restrictions to an increase in wildlife crime, with severe yet unknown implications for severely threatened taxa like pangolins. We analyze publicly available online seizure reports involving pangolins across India before (2018-2019) and during the pandemic (March-August 2020), using a longitudinal study design to estimate how lockdowns have impacted pangolin trade. Our analysis indicates a significant increase in seizures reported during the lockdown months of March to August 2020, in comparison to the same period in 2018 and 2019. We discuss the drivers behind this spike in pangolin trade and offer potential conservation measures.

Global COVID-19 lockdown highlights humans as both threats and custodians of the environment.

The global lockdown to mitigate COVID-19 pandemic health risks has altered human interactions with nature. Here, we report immediate impacts of changes in human activities on wildlife and environmental threats during the early lockdown months of 2020, based on 877 qualitative reports and 332 quantitative assessments from 89 different studies. Hundreds of reports of unusual species observations from around the world suggest that animals quickly responded to the reductions in human presence. However, negative effects of lockdown on conservation also emerged, as confinement resulted in some park officials being unable to perform conservation, restoration and enforcement tasks, resulting in local increases in illegal activities such as hunting. Overall, there is a complex mixture of positive and negative effects of the pandemic lockdown on nature, all of which have the potential to lead to cascading responses which in turn impact wildlife and nature conservation. While the net effect of the lockdown will need to be assessed over years as data becomes available and persistent effects emerge, immediate responses were detected across the world. Thus, initial qualitative and quantitative data arising from this serendipitous global quasi-experimental perturbation highlights the dual role that humans play in threatening and protecting species and ecosystems. Pathways to favorably tilt this delicate balance include reducing impacts and increasing conservation effectiveness.

Engineering Escherichia coli for the utilization of ethylene glycol.

BACKGROUND: A considerable challenge in the development of bioprocesses for producing chemicals and fuels has been the high cost of feedstocks relative to oil prices, making it difficult for these processes to compete with their conventional petrochemical counterparts. Hence, in the absence of high oil prices in the near future, there has been a shift in the industry to produce higher value compounds such as fragrances for cosmetics. Yet, there is still a need to address climate change and develop biotechnological approaches for producing large market, lower value chemicals and fuels. RESULTS: In this work, we study ethylene glycol (EG), a novel feedstock that we believe has promise to address this challenge. We engineer Escherichia coli (E. coli) to consume EG and examine glycolate production as a case study for chemical production. Using a combination of modeling and experimental studies, we identify oxygen concentration as an important metabolic valve in the assimilation and use of EG as a substrate. Two oxygen-based strategies are thus developed and tested in fed-batch bioreactors. Ultimately, the best glycolate production strategy employed a target respiratory quotient leading to the highest observed fermentation performance. With this strategy, a glycolate titer of 10.4 g/L was reached after 112 h of production time in a fed-batch bioreactor. Correspondingly, a yield of 0.8 g/g from EG and productivity of 0.1 g/L h were measured during the production stage. Our modeling and experimental results clearly suggest that oxygen concentration is an important factor in the assimilation and use of EG as a substrate. Finally, our use of metabolic modeling also sheds light on the intracellular distribution through central metabolism, implicating flux to 2-phosphoglycerate as the primary route for EG assimilation. CONCLUSION: Overall, our work suggests that EG could provide a renewable starting material for commercial biosynthesis of fuels and chemicals that may achieve economic parity with petrochemical feedstocks while sequestering carbon dioxide.

AC Conductivity Measurements of Ultradilute Colloidal Suspensions in HEPES Buffer.

Impedance spectroscopy was used to probe the AC conductivity of extremely dilute colloidal suspensions (2.5 × 10-5 ≤ Φw/v ≤ 4.0 × 10-2) comprising of polystyrene microspheres (PS; κa ≫ 1 and ζ = -65 mV), gold nanoparticles (Au NPs; κa > 1 and ζ = -26 mV), and Au-coated PS metallodielectric particles (Au-PS) in HEPES buffer. When AC electric fields of strength 10 mV and 1 MHz were applied via 100 µm gap interdigitated microelectrodes across 10 µL samples, a highly resistive (θcapacitive < 1°) and nonmonotonic response was obtained with particle concentrations at steady state. While the suspensions were less resistive (than the buffer) below a critical concentration, they became more resistive above it. More interestingly, particle-particle interactions took place in suspensions with concentrations as low as 0.005% w/v. We believe this unique behavior is linked to the ion size asymmetry in the HEPES molecule that provides an ideal microenvironment for counterionic polarization around the particles. The exact mechanism of polarization in HEPES, however, still remains elusive as the current theoretical models for simple electrolytes fail to explain our data.

Deciphering forest change: Linking satellite-based forest cover change and community perceptions in a threatened landscape in India.

Global conservation efforts have traditionally focused on biodiversity hotspots and other priority landscapes. However, large areas outside priority sites have high conservation value and are referred to as neglected landscapes. The Eastern Ghats of India is an unexplored forest landscape of high conservation value with several endemic and threatened species reported, and is also home to many indigenous forest-dwelling communities. However, it remains a neglected area for conservation and only 3.53% of this landscape is protected. Here, we examine the effectiveness of protected areas in neglected landscapes in preventing forest degradation, and how community perceptions can be used to understand satellite-based landscape change analyses at village level. This study was conducted in Papikonda National park (PNP) and its unprotected buffers in India's Eastern Ghats. Forest degradation was higher in the buffer (32%) than inside PNP (12%) between 1991 and 2014. Communities attributed shifting cultivation, plantations and over-extraction of forest resources as being the major drivers of forest degradation. Community observations of change were not significantly correlated with spatial measures of change. Forest degradation was higher outside the PA at a landscape level and inside the PA at the village level, therefore the PA was effective in reducing degradation at the landscape level but not at the village level inside the PA. We further discuss the role of community observations in interpreting forest degradation in neglected forest landscapes.

Multiple Cerebral Venous Sinus Thrombosis as Fist Manifestation of Primary Anti-Phospholipid Antibody Syndrome.

Antiphospholipid antibody syndrome (APS) is an autoimmune disorder, mainly found in young females, presenting with vascular thrombosis and/or obstetric complications. Thrombosis at anatomically significant sites may lead to considerable morbidity and/or mortality. We here present a case of primary APS presenting with sudden onset bilateral multiple cerebral venous sinus thrombosis. The patient, a 17 year old female with no prior rheumatological history, presented with sudden onset bilateral painful blindness and massive proptosis. MRI venography was instrumental in diagnosis. She also had significant thrombocytopenia. Except for the visual dimness, the other symptoms responded to therapy. Such massive cerebral venous thrombosis is extremely rare in primary APS.

Virus-Induced Silencing of Key Genes Leads to Differential Impact on Withanolide Biosynthesis in the Medicinal Plant, Withania somnifera.

Withanolides are a collection of naturally occurring, pharmacologically active, secondary metabolites synthesized in the medicinally important plant, Withania somnifera. These bioactive molecules are C28-steroidal lactone triterpenoids and their synthesis is proposed to take place via the mevalonate (MVA) and 2-C-methyl-d-erythritol-4-phosphate (MEP) pathways through the sterol pathway using 24-methylene cholesterol as substrate flux. Although the phytochemical profiles as well as pharmaceutical activities of Withania extracts have been well studied, limited genomic information and difficult genetic transformation have been a major bottleneck towards understanding the participation of specific genes in withanolide biosynthesis. In this study, we used the Tobacco rattle virus (TRV)-mediated virus-induced gene silencing (VIGS) approach to study the participation of key genes from MVA, MEP and triterpenoid biosynthesis for their involvement in withanolide biosynthesis. TRV-infected W. somnifera plants displayed unique phenotypic characteristics and differential accumulation of total Chl as well as carotenoid content for each silenced gene suggesting a reduction in overall isoprenoid synthesis. Comprehensive expression analysis of putative genes of withanolide biosynthesis revealed transcriptional modulations conferring the presence of complex regulatory mechanisms leading to withanolide biosynthesis. In addition, silencing of genes exhibited modulated total and specific withanolide accumulation at different levels as compared with control plants. Comparative analysis also suggests a major role for the MVA pathway as compared with the MEP pathway in providing substrate flux for withanolide biosynthesis. These results demonstrate that transcriptional regulation of selected Withania genes of the triterpenoid biosynthetic pathway critically affects withanolide biosynthesis, providing new horizons to explore this process further, in planta.

Redesigning metabolism based on orthogonality principles.

Modifications made during metabolic engineering for overproduction of chemicals have network-wide effects on cellular function due to ubiquitous metabolic interactions. These interactions, that make metabolic network structures robust and optimized for cell growth, act to constrain the capability of the cell factory. To overcome these challenges, we explore the idea of an orthogonal network structure that is designed to operate with minimal interaction between chemical production pathways and the components of the network that produce biomass. We show that this orthogonal pathway design approach has significant advantages over contemporary growth-coupled approaches using a case study on succinate production. We find that natural pathways, fundamentally linked to biomass synthesis, are less orthogonal in comparison to synthetic pathways. We suggest that the use of such orthogonal pathways can be highly amenable for dynamic control of metabolism and have other implications for metabolic engineering.