Mammary gland involution is the most dramatic example of physiological cell death. It occurs through an initial phase of lysosomal-mediated cell death (LCD) followed by mitochondrial-mediated apoptosis. Zinc (Zn) activates both LCD and apoptosis in vitro. The Zn transporter ZnT2 imports Zn into vesicles and mitochondria and ZnT2-overexpression activates cell death in mammary epithelial cells (MECs). We tested the hypothesis that ZnT2-mediated Zn transport is critical for mammary gland involution in mice. Following weaning, ZnT2 abundance increased in lysosomes and mitochondria, which paralleled Zn accumulation in each of these organelles. Adenoviral expression of ZnT2 in lactating mouse mammary glands in vivo increased Zn in lysosomes and mitochondria and activated LCD and apoptosis, promoting a profound reduction in MECs and alveoli. Injection of TNFα, a potent activator of early involution, into the mammary gland fat pads of lactating mice increased ZnT2 and Zn in lysosomes and activated premature involution. Exposure of cultured MECs to TNFα redistributed ZnT2 to lysosomes and increased lysosomal Zn, which activated lysosomal swelling, cathepsin B release, and LCD. Our data implicate ZnT2 as a critical mediator of cell death during involution and importantly, that as an initial involution signal, TNFα redistributes ZnT2 to lysosomes to activate LCD.

The pandemic of Serious Acute Respiratory Syndrome Corona Virus-2 (SARS-CoV-2) that produces corona virus disease (COVID-19) has challenged the entire mankind by rapidly spreading globally in 210 countries affecting over 25 million people and about 1 million deaths worldwide. It continues to spread, afflicting the health system globally. So far there is no remedy for the ailment and the available antiviral regimens have been unsatisfactory for the clinical outcomes and the mode of treatment has been mainly supportive for the prevention of COVID-19-induced morbidity and mortality. From the time immortal the traditional plant-based ethno-medicines have provided the leads for the treatment of infectious diseases. Phytopharmaceuticals have provided potential and less toxic antiviral drugs as compared to conventional modern therapeutics which are associated with severe toxicities. The ethnopharmacological knowledge about plants has provided food supplements and nutraceuticals as a promise for prevention and treatment of the current pandemic. In this review article, we have attempted to comprehend the information about the edible medicinal plant materials with potential antiviral activity specifically against RNA virus which additionally possess property to improve immunity along with external and internal respiration and exhibit anti-inflammatory properties for the prevention and treatment of the disease. This will open an arena for the development of novel nutraceutical herbal formulations as an alternative therapy that can be used for the prevention and treatment of COVID-19.

Purpose We evaluated T helper lymphocyte profile, including novel Th17 subsets Th17.1 (secrete IFN-γ, associate with corticosteroid resistance) and PD1+Th17 (secrete TGF-β1, implicated in fibrosis), and related cytokines in peripheral blood of Takayasu arteritis (TAK). Materials and Methods We evaluated circulating Th1, Th2, Th17, Th17.1, PD1+CD4+ T lymphocytes, PD1+Th17, and Treg lymphocytes, inflammatory (IFN-γ, IL-4, IL-6, IL-17A, IL-23, IL-1β, TNF-α) and regulatory (IL-10, TGF-β1) cytokines in peripheral blood of TAK (n = 57; median age 35 (interquartile range 26–45) years; 40 females) in a cross-sectional design. We studied inflammatory and regulatory cytokines in culture supernatant of peripheral blood mononuclear cells (PBMCs) from TAK following stimulation with anti-CD3/anti-CD28 and their modulation by tacrolimus (immunosuppressive) with/without tadalafil (anti-fibrotic). Furthermore, we followed up immunosuppressive-naïve active TAK (n = 16) and compared T helper lymphocyte populations and cytokines before and after immunosuppressive therapy. Healthy controls (HC, n = 21) and sarcoidosis (disease control, n = 11) were compared against TAK. Results TAK had higher Th17, Th17.1 and PD1+Th17 lymphocytes than HC (p < 0.001), and higher PD1+CD4+ T lymphocytes than sarcoidosis (p < 0.001). Th17 lymphocytes associated with active TAK after multivariable-adjusted logistic regression (p = 0.008). TAK had greater cytokine secretion from PBMCs (IFN-γ, IL-17A, IL-10 versus HC; IL-6, TNF-α, IL-1β versus HC or sarcoidosis) (p < 0.05). In-vitro, PBMCs from TAK showed reduced secretion of all inflammatory cytokines with tacrolimus, with synergistic reduction in IL-17A, IL-6, IL-1β and IL-10 following addition of tadalafil to tacrolimus. Serial follow-up of immunosuppressive-naïve TAK (n = 16) showed reduction in serum IL-6 and TGF-β1 (p < 0.05) and IL-6 in culture supernatant (p < 0.05) following immunosuppressive therapy. Conclusion Novel Th17 sub-populations (Th17.1 and PD1+Th17) are elevated in TAK. Th17 lymphocytes associate with active TAK. In-vitro experiments on cultured PBMCs suggest promise for further evaluation of a combination of immunosuppressive tacrolimus with anti-fibrotic tadalafil (or other anti-fibrotic therapies) in clinical trials of TAK.

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Background The COVID19 pandemic is a disaster of unprecedented proportions with global repercussions. Psychological preparedness, the primed cognitive awareness and anticipation of dealing with emotional responses in an adverse situation, has assumed a compelling relevance during a health disaster of this magnitude. Methods An anonymized eSurvey was conducted in India to assess psychological preparedness towards the ongoing pandemic with a focus on knowledge, management of own and others’ emotional response and anticipatory coping mechanisms amongst the survey population. An adapted version of the qualitative Psychological Preparedness for Natural Disaster scale validated by the World Health Organization was widely circulated over the internet and various social media platforms for assessment. Results are expressed as median ± standard deviation). Descriptive stats were used and figures downloaded from surveymonkey.com. Results Of the 1120 respondents (M: F 1.7:1, age 35 years ±14.1) most expressed a high level of perceived knowledge and confidence of managing COVID-19, such as awareness of the symptoms of the illness (95.1%), actions needed (94.4%), hospital to report to (88.9%), and emergency contact number (89.1%). A majority monitored news bulletins and scientific journals regarding COVID-19 regularly (95%). However, nearly one-third (29.2%) could not assess their likelihood of developing COVID-19, and 17.5% were unaware of the difference between a mild and severe infection. Twenty- three per cent (23.3%) were unfamiliar with the materials needed in an acute illness situation. Conclusion Psychological disaster preparedness is reasonable, although lacking in specific domains. Timely but focused interventions can be a cost-efficient administrative exercise which federal agencies may prioritize working on.

Backgrounds/Aims: In the absence of national registry of laparoscopic cholecystectomy (LC) or its complications, it is impossible to determine incidence of bile duct injury (BDI) in India. We conducted an e-survey among practicing surgeons to determine prevalence and management patterns of BDI in India. Our hypothesis was that majority of surgeons would have experienced a BDI during LC despite large experience and that most surgeons who have a BDI tend to manage it themselves. Methods: An 18-question e-survey of practicing laparoscopic surgeons in India was done. Results: 278/727 (38%) surgeons responded. 240/278 (86%) respondents admitted to a BDI during LC and 179/230 (78%) affirmed to more than one BDI. A total of 728 BDIs were reported. 36/230 (15%) respondents experienced their first BDI even after ＞10 years of practice and 40% had their first BDI even after having performed ＞100 LCs. 161/201 (80%) of the respondents decided to manage the BDI themselves, including 56/99 (57%) non-biliary surgeons and 44/82 (54%) surgeons working in non-biliary center. 37/201 (18%) respondents admitted to having a mortality arising out of a BDI; the mortality rate of BDI was 37/728 (5%) in this survey. Only 13/201 (6%) respondents have experienced a medico-legal case related to a BDI during LC. Conclusions: Prevalence of BDI is high in India and occurs despite adequate experience and volume. Even inexperienced non-biliary surgeons working in non-biliary centers attempt to repair the BDI themselves. BDI is associated with significant mortality but litigation rates are fortunately low in India.

Background and Aim: Pancreaticoduodenal arcade aneurysms (PDAAs) are uncommon lesions associated with a significant risk of rupture and mortality. This study describes the etiology, clinical presentation, and endovascular management strategies of PDAAs across a spectrum of indications. Methods: The clinical records of patients with PDAAs referred for endovascular management from January 2018 till November 2019 were retrospectively reviewed. Data on presenting symptoms, associated etiologies, and outcomes after endovascular treatment were collected and studied. Results: We found 15 patients with false and 1 patient with true aneurysm of pancreatoduodenal arcade (PDA). The associated conditions were coeliac artery stenosis, severe necrotizing pancreatitis, and chronic pancreatitis or iatrogenic (postendoscopic papillotomy and percutaneous metallic biliary stenting). The main presenting feature was gastrointestinal bleed, while 2 patients had abdominal pain and 1 had gastric outlet obstruction. A multiphase computed tomography scan demonstrated the ruptured aneurysm in all patients. Site of origin of PDAA influenced the choice of transarterial endovascular strategy (coiling for aneurysms of main trunk of arteries and glue injection for those arising from small arterial branches). This was carried out in an emergency setting for 12 patients and as an elective procedure in 4 patients. Technical success was demonstrated in all patients and clinical success in 14. The two patients who had rebleed were salvaged by repeat endovascular procedure. Postembolization syndrome was seen in three patients. Conclusions: With advancing technology, endovascular strategies continue to evolve. Careful attention to ensure hemodynamic resuscitation and stability, correction of preexisting coagulopathy and attention to technique can lead to the possibility of endovascular approaches as a dependable option in the management of ruptured PDAAs.