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Background: The women who have been pregnant more than four times are fewer than 18or over 35-years-old, or have at least one medical issue before or during pregnancy, the pregnancy is considered high-risk. Increased maternal and foetal mortality and morbidity are linked to these risk factors. MTP in itself is a blind and risky procedure and performing it in High Risk Pregnancy (HRP) is a challenge for obstetrics and gynecology personnel. When performed with all pre, intra and post-op precautions, results are good and patient-friendly. Aims and Objectives: Aims of the study were to calculate the number, high-risk factors, method used, and its outcome of MTP in HRP. Materials and Methods: The present study was a retrospective observational study done at QMH, KGMU, Lucknow performed on subjects admitted for MTP from January 2018 to December 2018. Total admitted patients seeking MTP were 450 out of which 93 belonged to High-Risk Group who underwent surgical and medical abortion accordingly. All precautions and norms defined by Govt. of India were taken care of. Cases were evaluated on the basis of high-risk factors- Age, parity, obstetrical and medical illnesses, and interval since last delivery. Results: Out of 93 high-risk cases, 88 cases were of 1st trimester and 5 were of 2nd trimester abortion. Six cases required suction evacuation while seven cases were managed medically using medical abortion kit. Contraception was given to all subjects according to their needs. Seventy-one women were of more than 35 yrs, while two were teenagers. 21 women were grand multipara. Women of obstetrical risk were 17 while the rest were having medical illnesses. Conclusion: This study concludes that there are a large number of high-risk groups for MTP again showing unmet need and lack of specialized counseling of HR patients according to their mental and physical condition. Early recognition of pregnancy and timely intervention can be lifesaving in these women and proper contraceptive counseling is required to prevent future pregnancies.

A 56-year-old woman with mixed connective tissue disease, who was on maintenance immunosuppression, developed asymptomatic left ventricular…, A 56-year-old woman with mixed connective tissue disease, who was on maintenance immunosuppression, developed asymptomatic left ventricular dysfunction, ventricular arrhythmia, and high troponin I. Heart catheterization showed normal coronaries and biopsy-proven, virus-negative lymphocytic myocarditis. A biopsy-guided immunosuppression upgrade effectively treated autoimmune myocarditis, which resulted in ventricular function recovery, resolution of arrhythmia, and of troponin release. (Level of Difficulty: Advanced.), Graphical abstract

Fatty liver is closely associated with elevated concentrations of nonesterified fatty acids (NEFA) and a low level of very low-density lipoproteins (VLDL) in blood of dairy cows. High NEFA inhibit the VLDL synthesis and assembly, and cause hepatic triacylglycerol (TAG) deposition. Sirtuin 3 (SIRT3), a mitochondrial deacetylase, antagonizes NEFA-induced TAG accumulation through modulating expressions of fatty acid synthesis and oxidation genes in cow hepatocytes. However, the role of SIRT3 in the VLDL synthesis and assembly was largely unknown. Here we aimed to test whether SIRT3 would recover the synthesis and assembly of VLDL in cow hepatocytes induced by high NEFA. Primary cow hepatocytes were isolated from 3 Holstein cows. Hepatocytes were infected with SIRT3 overexpression adenovirus (Ad-SIRT3), SIRT3-short interfering (si) RNA, or first infected with Ad-SIRT3 and then incubated with 1.0 mM NEFA (Ad-SIRT3 + NEFA). Expressions of key genes in VLDL synthesis and the VLDL contents in cell culture supernatants were measured. SIRT3 overexpression significantly increased the mRNA abundance of microsomal triglyceride transfer protein (MTP), apolipoprotein B100 (ApoB100) and ApoE (p < 0.01), and raised VLDL contents in the supernatants (p < 0.01). However, SIRT3 silencing displayed a reverse effect in comparison to SIRT3 overexpression. Compared with NEFA treatment alone, the Ad-SIRT3 + NEFA significantly upregulated the mRNA abundance of MTP, ApoB100 and ApoE (p < 0.01), and increased VLDL contents in the supernatants (p < 0.01). Our data demonstrated that SIRT3 restored the synthesis and assembly of VLDL in cow hepatocytes challenged with NEFA, providing an in vitro basis for further investigations testing its feasibility against hepatic TAG accumulation in dairy cows during the perinatal period.

The effect of ellagic acid (EA), a naturally occurring polyphenolic compound, on the secretion of apolipoproteins from human hepatocytes, HepG2, was investigated. The levels of apoB and apoA-1 secreted in the cell culture medium were determined by sandwich ELISA. EA did not affect cell viability at the tested concentrations (up to 50 µM). EA suppressed the secretion of apoB and enhanced that of apoA-1 from HepG2 cells. However, cellular apoB levels were increased, suggesting that EA inhibited the trafficking of apoB during the process of secretion. In contrast, the increase in the cellular levels of apoA-1 was consistent with its secreted levels. These results indicate that EA inhibits the secretion of apoB from hepatocytes and increases the secretion of apoA-1. Both of these effects are beneficial for lipoprotein metabolism in the prevention of lifestyle-related diseases. The detailed mechanism underlying these effects of EA on lipoprotein metabolism should be elucidated in the future, but this naturally occurring polyphenolic compound might be antihyperlipidemic. Based on these results, EA is suggested as a candidate food-derived compound for the prevention of hyperlipidemia.

Massive transfusion protocols (MTPs) facilitate the organized delivery of blood components for traumatically injured patients. MTPs vary across institutions, and ratios of blood components can change during clinical management. As a result, significant amounts of components can be wasted. We completed a review of all MTP activations from 2015 to 2018, providing an in-depth analysis of waste in our single Level 1 trauma center. An interdepartmental group analyzed patterns of blood component wastage to guide three quality improvement initiatives. Specifically, we (1) completed a digital timeline for each MTP activation and termination, (2) improved communications between departments, and (3) provided yearly training for all personnel about MTP deployment. The analysis identified an association between delayed MTP deactivations and waste (RR = 1.48, CI 1.19&ndash, 1.85, p = 0.0005). An overall improvement in waste was seen over the years, but this could not be attributed to increased closed-loop communication as determined by the proportion of non-stop activations (F(124,3) = 0.98, not significant). Delayed MTP deactivations are the primary determinant of blood component waste. Our proactive intervention on communications between groups was not sufficient in reducing the number of delayed deactivations. However, implementing a digital timeline and regular repetitive training yielded a significant reduction in wasted blood components.

BACKGROUND Unsafe abortions are a major cause of maternal morbidity and mortality. Medical abortion, which is preferred over surgical abortion by most women may provide excellent alternative to unsafe abortion and their attendant risks. The primary aim of this research is to compare the efficacy and acceptability of two regimens with different time interval between mifepristone and misoprostol for first trimester MTP. MATERIALS AND METHODS The study was carried out in 150 pregnant women opting for MTP during first trimester by medical method. Pelvic ultrasound was done before giving drugs to assess the correct gestational age, intrauterine location of pregnancy and to exclude any obvious pelvic pathology. Women enrolled in the study were randomized to one of the two groups which differ in the time of administration of misoprostol. All 150 women were given Mifepristone 200mg on Day 1. However, 75 women in the study group were given misoprostol 600mcg on Day 2 and remaining 75 women in the control group were given misoprostol 600mcg on Day 3. The effects regarding efficacy, induction abortion interval, side effects and acceptability of two regimens were noted. RESULTS 1) 98.66% cases in study group and 94.66% in control group had successful abortions (p value>0.05) 2) 94% of cases preferred 24 hours study protocol rather than established protocol of 48 hours for any future MTP (p value < 0.02). CONCLUSION The research work helps to derive a conclusion that medical abortion using misoprostol administration 24 hours after mifepristone appears to be equally efficacious and more acceptable than that of the established protocol of 48 hours.

BACKGROUND To increase the incidence of safe and legalised abortions, it is important to know the clients. This study is a 6 years research of the records of MTP performed at the public hospital attached to a medical college, to know the trend, socio-demographic and obstetric status of the women undergoing MTP. The objectives of the study were to find trend, sociodemographic factors, obstetric status and complications of MTPs. MATERIALS AND METHODS A study of the records of all the MTP operations performed at the gynaecology department of the hospital from 2010 to 2016. Data analysis was done on MS excel. RESULTS Most women who underwent MTP were young, sexually active women and had completed 2 child family. Along with MTP, younger women preferred IUCD and elder women preferred Tubal Ligation as contraception. There is an overall gradual increase in the incidence of MTPs conducted which could be attributed to increase in population of the city and nearby areas. CONCLUSION In this study, most of the women preferred MTP after 2nd Pregnancy and at the age of 21-35 years. Most women accepted permanent method of sterilization after MTP shows that women had completed family by the age of 30 years and had no access to effective contraceptive services. MTPs thus seems to be used as an emergency treatment for failed contraception. This trend should be discouraged but at the same time safe abortion should be legalised to safeguard the health of the women.

B cells (BC) play a critical role in systemic lupus erythematosus (SLE). BC depletion therapy still remains an attractive option, despite the disappointing results of randomized controlled trials (RTCs).Twelve patients with SLE [3 males, mean age 43.8 yrs (25-55)] with severe multiorgan involvement all including kidney (3 patients with Class IV, 4 with Class III/V and 5 with Class V, according to the International Society of Nephrology/Renal Pathology Society glomerulonephritis classification), skin lesions [10], severe polyarthralgias with arthritis [10], polyserositis [2], and lymphadenopathy [5] have been prospectively treated with an intensified B cell depletion therapy (IBCDT) protocol due to their resistance or intolerance to previous therapy (six cases) or as a front line immunosuppressive treatment in 6 women with unsatisfactory therapeutic compliance or as a specific request of a short-time immunosuppression for gestational perspectives.Rituximab (RTX) 375 mg/sm on days 1, 8, 15, 22, and 2 more doses after 1 and 2 months, associated with 2 IV administrations of 10mg/kg of cyclophosphamide and 3 methylprednisolone pulses (15mg/kg) followed by oral prednisone (0.8 mg/kg/day, rapidly tapered to 5mg/day by the end of the 3rd month after RTX). No further immunosuppressive maintenance therapy has been given.Patients had been followed-up for a mean of 44.5 (24-93)months. Significant decreases (p0.05) were found in the levels of ESR (baseline mean value: 55.0mm; 3 months: 36; end of follow-up: 13), anti-dsDNA antibodies (baseline: 185 U; 3 months: 107; end of follow-up: 15), and proteinuria (baseline: 4.9 g/24h; 3 months: 0.97; end of follow-up: 0.22). C4 values (baseline 11 mg/dl) significantly increased (p0.05) after 3 months (22 mg/dl) and at the end of the follow-up (20mg/dl). Of the 12 patients, 9 (75%) have remained well after one cycle of IBCDT, with no flare (mean 51.6 months [25-93]). Three patients relapsed after 36, 41, and 72 months, respectively. Following re-treatment, they again showed complete remission over 18-48 months of observation.A promising role of RTX in an intensified protocol of induction therapy can be envisaged in patients for whom avoiding immunosuppressive maintenance therapy and sparing steroids are particularly appealing. Moreover, our data confirm in one of the longest follow-up available, the opportunity to reconsider the regimens of BL depletion in the treatment of the most severe or refractory forms of SLE despite the disappointing results of RCTs.

Renal failure in obstetrics is rare but important complication, associated with significant mortality and long term morbidity.1,2 It includes acute renal failure due to obstetrical complications or due to deterioration of existing renal disease. AIMS AND OBJECTIVES: To evaluate the etiology and outcome of renal failure in obstetric patients. METHODS: We prospectively analyzed 30 pregnant and puerperal women with acute renal failure or pre-existing renal disease developing renal failure during pregnancy between November 2007 to sep-2009. Patients who presented/developed ARF during the hospital stay were included in this study. RESULTS: Among 30 patients, mean age was 23 years and 33 years age group. 12 cases (40%) patients were primigravidae and 9(30%) patients were multigravidae and 9 cases (30%) presented in post-partum period. Eighteen cases (60%) with ARF were seen in third trimester, followed by in postpartum period 9 cases (30%). Most common contributing factors to ARF were Pre-eclampsia, eclampsia and HELLP syndrome 60%, sepsis 56.6%, post abortal ARF 10%. DIC 40%. Haemorrhage as the aetiology for ARF was present 46%, APH in 20% and PPH in 26.6%. The type of ARF was renal in (63%) and prerenal (36%); Oliguric seen in 10 patients (33%) and high mortality (30%). Among the 20 pregnant patients with ARF, The average period of gestation was 33±2 weeks (30 -36 weeks), 5 cases (25%) presented with intrauterine fetal demise and 18 cases (66%) had preterm vaginal delivery and 2 cases (10%) had induced abortion. And the average birth weight was 2±0.5 kg (1.5 kg). Eight cases (26%) required dialysis. 80% of patients recovered completely of renal functions. 63% patients recovered without renal replacement therapy whereas 17% required dialysis. the maternal mortality was 20%, the main reason for mortality was septic shock and multi organ dysfunction (66%). CONCLUSION: ARF related pregnancy was seen commonly in the primigravidae and in the third trimester, the most common reasons were pregnancy induced hypertension, HELLP syndrome and obstetric haemorrhage and resulted in high risk condition for fetal and maternal mortality. The most effective measures still remain the careful prevention and the aggressive management of the obstetric complications. Ideal care for women with acute renal failure in pregnancy or post-partum requires a multidisciplinary approach that includes maternal-fetal medicine, critical care medicine, nephrology and neonatology specialties.

Among all the metabolites present in the plasma, lipids, mainly triacylglycerol and diacylglycerol, show extensive circadian rhythms. These lipids are transported in the plasma as part of lipoproteins. Lipoproteins are synthesized primarily in the liver and intestine and their production exhibits circadian rhythmicity. Studies have shown that various proteins involved in lipid absorption and lipoprotein biosynthesis show circadian expression. Further, intestinal epithelial cells express circadian clock genes and these genes might control circadian expression of different proteins involved in intestinal lipid absorption. Intestinal circadian clock genes are synchronized by signals emanating from the suprachiasmatic nuclei that constitute a master clock and from signals coming from other environmental factors, such as food availability. Disruptions in central clock, as happens due to disruptions in the sleep/wake cycle, affect intestinal function. Similarly, irregularities in temporal food intake affect intestinal function. These changes predispose individuals to various metabolic disorders, such as metabolic syndrome, obesity, diabetes, and atherosclerosis. Here, we summarize how circadian rhythms regulate microsomal triglyceride transfer protein, apoAIV, and nocturnin to affect diurnal regulation of lipid absorption.

The plasma level of apolipoprotein B (apoB) is among the strongest risk factors for coronary artery disease. Microsomal triglyceride transfer protein (MTP) plays a key role in the lipidation of nascent apoB and the secretion of apoB-containing lipoproteins enriched with triglycerides and is thus a promising target for the treatment of hyperlipidemia. Yet, the development of MTP inhibitors to lower plasma lipid concentrations has been hindered by adverse effects on hepatic steatosis. A study recently published in Nature Medicine identifies microRNA-30c (miR-30c) as a potent repressor of MTP that controls plasma apoB-containing lipoprotein levels, in addition to decreasing hepatic lipid synthesis through direct targeting of lysophosphatidylglycerol acyltransferase 1 (LPGAT1). These findings identify miR-30c as a novel therapeutic target that coordinately reduces lipid biosynthesis and lipoprotein secretion to suppress circulating apoB lipoproteins, while sparing the liver from steatosis.

Metatarsophalangeal (MTP) joint osteoarthritis (OA), also known as hallux rigidus (HR), is the most common degenerative arthropathy of the foot and is often the result of trauma. There are multiple methods of addressing the patient’s pain and limited function. Arthrodesis is the gold standard to manage severe MTP arthritis with a highly significant union rate. With various techniques of arthrodesis available, ranging from cannulated screw fixation, Kirschner wires, as well as plate and screw fixation, the orthopedic surgeon has multiple modalities to address this ailment; however, when these fail due to infection, the armament is limited. Through the idea of articulating antibiotic spacers in other regions of the body such as the knee and hip, we present a novel technique to the creation of an antibiotic spacer in the setting of a failed infected MTP arthrodesis.

"The sharp rise in obesity and metabolic diseases such as insulin resistance and diabetes are thought to contribute to [male as well as female fertility problems]..."

Fat is delivered to tissues by apoB-containing lipoproteins synthesized in the liver and intestine with the help of an intracellular chaperone, microsomal triglyceride transfer protein (MTP). Leptin, a hormone secreted by adipose tissue, acts in the brain and on peripheral tissues to regulate fat storage and metabolism. Our aim was to identify the role of leptin signaling in MTP regulation and lipid absorption using several mouse models deficient in leptin receptor (LEPR) signaling and downstream effectors. Mice with spontaneous LEPR B mutations or targeted ablation of LEPR B in proopiomelanocortin (POMC) or agouti gene related peptide (AGRP) expressing cells had increased triglyceride in plasma, liver, and intestine. Furthermore, melanocortin 4 receptor (MC4R) knockout mice expressed a similar triglyceride phenotype, suggesting that leptin might regulate intestinal MTP expression through the melanocortin pathway. Mechanistic studies revealed that the accumulation of triglyceride in the intestine might be secondary to decreased expression of MTP and lipid absorption in these mice. Surgical and chemical blockade of vagal efferent outflow to the intestine in wild-type mice failed to alter the triglyceride phenotype, demonstrating that central neural control mechanisms were likely not involved in the observed regulation of intestinal MTP. Instead, we found that enterocytes express LEPR, POMC, AGRP, and MC4R. We propose that a peripheral, local gut signaling mechanism involving LEPR B and MC4R regulates intestinal MTP and controls intestinal lipid absorption.

Thus far, liver, intestine, heart, and placenta have been shown to secrete apolipoprotein (apo) B-containing lipoproteins. In the present study, we first investigated lipoproteins in human follicular fluid (FF), surrounding developing oocytes within the ovary, as well as in corresponding plasma samples (n = 12). HDL cholesterol within FF correlated well with plasma HDL cholesterol (r = 0.80, P

Contains fulltext : 59289teusink.pdf (Publisher’s version ) (Closed access) BACKGROUND/AIMS: Apolipoprotein E (apoE)-deficient mice develop hepatic steatosis and secrete reduced levels of VLDL-TG. METHODS AND RESULTS: We examined the effects of apoE-deficiency on intracellular lipid homeostasis and secretion of triglycerides (TG). We show that intracellular TG turnover and activities of diacylglycerol acyltransferase (DGAT) and microsomal triglyceride transfer protein (MTP) are similar in Apoe(-/-) and wild type mice. In addition, apoB synthesis was not decreased in Apoe(-/-) cells. Thus, the accumulation of lipid in these cells is not attributable to perturbed TG turnover, apoB synthesis, and the activities of DGAT and MTP. Inhibition of MTP had a more profound impact on the secretion of VLDL-TG from wild type hepatocytes than Apoe(-/-) hepatocytes, indicating that MTP was more limiting for the production of VLDL-TG from wild type cells. In marked contrast to the MTP-deficient model of fatty liver, electron microscopy of lipid-stained liver sections of Apoe(-/-) mice revealed an accumulation of lipid in numerous small, putative ER-derived vesicles and in the cytosol. No abnormalities were observed in the Golgi of Apoe(-/-) mice. CONCLUSIONS: These results suggest that the removal of lipids from the early or intermediary compartments of the secretory pathway of hepatocytes is impaired in Apoe(-/-) mice.

Patients suffering from familial hypercholesterolemia (FH) are characterized by increased plasma levels of low-density lipoprotein cholesterol (LDL-C) levels and are at increased risk for premature cardiovascular disease (CVD). Current guidelines emphasize the need to aggressively lower LDL-C in FH patients, and statins are the cornerstone in the current regimen. However, additional therapies are eagerly awaited, especially for those patients not tolerating statin therapy or not reaching the goals for therapy. Our understanding of LDL metabolism has improved over the last years and an increasing number of potential novel targets for therapy have been recently identified. Apart from novel targets, we have also been confronted with novel modalities of treatment, such as mRNA antisense therapy. Some of these emerging therapies have proven to be effective in lowering plasma LDL-C levels and are as such expected to have beneficial effects on CVD. Hopefully, they will enrich our armamentarium against the severe dyslipidemia observed in FH patients in the not too distant future.