Search

Background: Many couples do not have adequate documentation following fertility treatments., Aims: To conduct a survey to understand the information needs of assisted reproductive technology physicians when assessing the reasons affecting treatment outcomes after intrauterine insemination (IUI) and in vitro fertilisation (IVF)., Settings and Design: Online survey., Materials and Methods: Anonymous online survey of 14 parameters related to IUI treatment and 21 parameters related to IVF treatment, followed by recommendation of selected parameters for routine documentation., Statistical Analysis Used: Frequency distribution calculation of responses., Results: For IUI, total motile sperm count and post-wash sperm count and motility and for IVF, the quality and number of gametes, embryo number and morphology were the most important parameters., Conclusion: The study creates recommendations for the minimum information desirable in the fertility treatment documentation given to the couple undergoing treatment., Competing Interests: There are no conflicts of interest., (Copyright: © 2023 Journal of Human Reproductive Sciences.)

Background/aims: In patients undergoing endoscopic retrograde cholangiopancreatography (ERCP), calcineurin activates zymogen, which results in pancreatitis. In this study, we aimed to determine the efficacy of tacrolimus, a calcineurin inhibitor, in preventing post-ERCP pancreatitis (PEP)., Methods: This was a prospective pilot study in which patients who underwent ERCP received tacrolimus (4 mg in two divided doses); this was the Tac group. A contemporaneous cohort of patients was included as a control group. All patients were followed-up for PEP. PEP was characterized by worsening abdominal pain with an acute onset, elevated pancreatic enzymes, and a duration of hospital stay of more than 48 hours. Serum tacrolimus levels were measured immediately before the procedure in the Tac group., Results: There were no differences in the baseline characteristics between the Tac group (n=48) and the control group (n=51). Only four out of 48 patients (8.3%) had PEP in the Tac group compared to eight out of 51 patients (15.7%) who had PEP in the control group. The mean trough tacrolimus level in patients who developed PEP was significantly lower (p<0.05)., Conclusion: Oral tacrolimus at a cumulative dose of 4 mg safely prevents PEP. Further randomized controlled studies are warranted to establish the role of tacrolimus in this context.

Introduction: Systemic inflammation triggered by bacterial products like lipopolysaccharides (LPS) in the circulation is an important factor leading to decompensation in patients with chronic liver disease (CLD). High-density lipoprotein cholesterol (HDL-C) has a significant role in innate immune response to LPS in the circulation and could therefore increase the risk for decompensation in patients with CLD. In this study, we have explored the role of HDL-C as a prognostic marker for decompensation., Methods: This was a prospective, observational, cohort study where consecutive patients with CLD were included. Patients with cholestatic liver disease and hepatocellular carcinoma were excluded. Fasting lipids were measured in all patients at the time of recruitment. Each patient was carefully followed up for development of decompensation events such as new-onset/worsening ascites, hepatic encephalopathy, or variceal bleed during follow-up., Results: A total of 170 patients were included (mean age 60 ± 11.5 years, M : F = 6 : 1). At the end of follow-up, 97/170 patients (57%) had decompensation events. Mean HDL-C levels were significantly lower among patients with decompensation (27.5 ± 15 mg/dL vs. 43.5 ± 13.9 mg/dL; p value 0.004). Using ROC analysis, cut-off for HDL-C of 36.4 mg/dL was identified. On multivariate analysis, HDL-C (OR = 6.072; 95% CI 2.39-15.39) was found to have an independent association with risk of decompensation., Conclusions: HDL-C level (<36.4 mg/dL) is a reliable marker for risk of decompensation and can be a useful addition to existing prognostic scoring systems in CLD. It can be a valuable tool to streamline treatment protocols and prioritise liver transplantation., Competing Interests: There are no conflicts of interest to report., (Copyright © 2021 Harshavardhan Rao B et al.)

Background: Intra-abdominal lymphadenopathy due to tuberculosis (TB) poses a diagnostic challenge due to difficulty in tissue acquisition. Although endoscopic ultrasound guided fine needle aspiration/biopsy (EUS-FNA/B) has shown promise in the evaluation of mediastinal lymph nodes, its role in the evaluation of intra-abdominal lymphadenopathy is not clear., Aim: To assess the role of EUS-FNA/B in the evaluation of intra-abdominal lymphadenopathy due to TB., Methods: This was a retrospective study where patients with intra-abdominal lymphadenopathy who underwent evaluation with EUS-FNA/B were included. TB was diagnosed if the patient had any one of the following: (1) Positive acid fast bacilli (AFB) stain/TB GeneXpert/TB-polymerase chain reaction/AFB culture of tissue sample; and (2) Positive Mantoux test and response to anti-tubercular therapy. EUS-FNA reports, clinical reports and imaging characteristics of patients were recorded for a detailed analysis of patients with TB., Results: A total of 149 patients underwent an EUS-FNA/B from lymph nodes (mean age 51 ± 17 years, M:F = 1.2). Benign inflammatory reactive changes were seen in 45 patients (30.2%), while 54 patients (36.2%) showed granulomatous inflammation with/without caseation. Among these, 51 patients (94.4%) were confirmed to have TB as per pre-defined criteria. Patients with TB were more likely to have hypoechoic and matted nodes [40 patients (67.7%)]. EUS-FNA/B was found to have a sensitivity and specificity of 86% and 93% respectively, with a diagnostic accuracy of 88% in the evaluation of intra-abdominal lymphadenopathy due to TB., Conclusion: EUS-FNA/B has a high diagnostic yield with a good sensitivity and specificity in the evaluation of intra-abdominal lymphadenopathy due to TB. However, the validity of these findings in populations with low prevalence of TB needs further evaluation., Competing Interests: Conflict-of-interest statement: There are no conflicts of interest to report., (©The Author(s) 2021. Published by Baishideng Publishing Group Inc. All rights reserved.)

Background: The diagnosis of intestinal TB (ITB) is challenging because of its overlapping features with Crohn's disease. This outcome-based study evaluated the combination of colonoscopy, histopathology, Xpert MTB/RIF and TB culture for best sensitivity and specificity., Method: This was a four-year retrospective, observational study of 426 clinically suspected patients who underwent colonoscopy with biopsies for histopathology, Xpert MTB/RIF and TB culture. ITB was diagnosed using the composite reference standard (CRS), which comprised either histological features or culture or Xpert MTB/RIF positivity, and positive response to anti-tuberculous treatment on follow up., Results: 35 (8.2%) patients were diagnosed with ITB. Histopathology had the highest sensitivity (91.4%) and negative predictive value (99.2%), MTB/RIF had the highest specificity (100%) and positive predictive value (100%). A combinatorial approach with Xpert MTB/RIF and histopathology had optimal diagnostic value (97%), approaching 100% sensitivity with culture. 40% of cases were diagnosed within 12 hours with Xpert MTB/RIF and 97% cases within three days., Conclusion: This combinatorial diagnostic model provides rapid and reliable diagnosis of ITB which may be useful in endemic areas., Competing Interests: No conflict of interests declared

Background: Biliary strictures following living donor liver transplantation (LDLT) are usually managed by endoscopic retrograde cholangiography (ERC) with stricture dilation and stent placement. While current endoscopic techniques are successful in most cases, high-grade biliary strictures (HGBS) pose a challenge using currently employed techniques which have a low rate of technical success., Aims: In this study, we have explored the safety and efficacy of Soehendra stent retrievers (SSR) for the dilation of HGBS complicating LDLT., Methods: This was a prospective cohort study where all patients with anastomotic biliary strictures following LDLT from January 2016 till February 2018 were included. Patients with HGBS defined as the exclusive passage of 0.018-inch guidewire, were included in Group 1. In these patients, 5 Fr Soehendra stent retrievers were used to dilate HGBS over guidewire, using torsional movements. Technical success, safety and clinical response was compared with patients who required Per-cutaneous transhepatic cholangiography (PTC) with rendezvous procedure due to a failed ERC, before the commencement of the study (Group 2)., Results: Ten patients with HGBS were included into Group 1. Technical success defined as successful placement of a biliary stent across the stricture was achieved in all the patients in group 1. Favorable response to endotherapy was higher in group 1(8/10 patients (80%)) as compared to group 2(6/14 patients (42.8%)). There were no post procedure complications in patients of group 1, while 3 patients developed cholangitis in group 2., Conclusions: HGBS can be successfully treated with SSR for stricture dilation. It is safe with no significant complications and requires fewer procedures.

Aim: Validation of new metrics to identify functionally significant obstruction (FSO), to better define biliary strictures complicating living donor liver transplantation (LDLT)., Methods: All LDLT recipients who presented with cholestasis were studied. Novel metrics for FSO are as follows: (1) magnetic resonance cholangiopancreatography (MRCP) ductal ratio (MDR): The ratio between hepatic duct and recipient duct diameter on the MRCP taken at presentation; (2) endoscopic retrograde cholangiography (ERC) ductal ratio (EDR): The ratio between hepatic duct and recipient duct diameter on the first ERC done for suspected biliary strictures; (3) delayed contrast drainage (DCD): > 50% contrast retained above the anastomotic site, in more than three consecutive fluoroscopic images taken at least 15 min after contrast instillation. Association between these metrics and endotherapy response was analyzed along with patient demographics, intraoperative variables (cold ischemia time, blood transfusions, biliary anastomosis) and perioperative complications (hepatic artery thrombosis [HAT], bile leak). Favorable response to endotherapy was defined as symptomatic relief with ≥ 80% reduction in total bilirubin/alkaline phosphatase., Results: A total of 83 LDLT recipients presented with altered liver function tests. Favorable response was seen in 18/39 patients (46.2%). On univariate analysis, HAT, multiple biliary anastomoses, graft-to-recipient weight ratio (GRWR), MDR, EDR and DCD were significant (p value ≤ 0.05). On multivariate analysis, only MDR ≥ 1.15 was an independent predictor of favorable response to endotherapy (OR 48 [95% CI 7.096-324.71])., Conclusion: A paradigm shift in the approach to management of biliary strictures complicating LDLT is proposed whereby a multidimensional definition of FSO can help in reliable patient selection for endotherapy and improve patient outcome as a whole.

Introduction: Chronic calcific pancreatitis (CCP) is a major risk factor for pancreatic ductal adenocarcinoma (PDAC) and is common in southern India. Endoscopic ultrasound fine-needle aspiration (EUS-FNA) is useful for tissue acquisition in patients with solid pancreatic lesions. Multiple factors may affect the diagnostic yield of FNA samples. The present study was performed to assess the impact of pancreatic calcifications on the diagnostic yield of EUS-FNA in PDAC., Methods: All patients with confirmed PDAC from January 2013 to December 2017 were included. CCP was diagnosed based on typical imaging characteristics with or without evidence of pancreatic insufficiency along with surgical histopathology reports showing features of chronic pancreatitis. The diagnostic yield and adequacy of cellularity were  assessed by a pathologist who was blinded and were compared between the two groups: group 1: PDAC patients with no evidence of CCP and, group 2: PDAC patients with CCP., Results: A total of 122 patients were included in the study. The diagnostic yield was lower in patients in group 2 (n = 42, 25 [59.52%]) as compared to those in group 1 (n = 80, 63 [78.75%]) (p-value = 0.01). On multivariate analysis, only the presence of calcifications was found to have an independent association with diagnostic yield (odds ratio 3.83 [95% confidence interval 1.22-11.9])., Conclusions: CCP had a significant impact on the diagnostic yield of EUS-FNA for pancreatic adenocarcinoma. Novel techniques and newer technology that may mitigate the negative effect of calcification on diagnostic yield of EUS-FNA in patients with CCP.

Background: Rubella is a contagious viral illness that can be prevented by vaccination. Currently, vaccination is being offered to children and adolescents. Since an infection in pregnancy can have teratogenic effects, identification of susceptive women and vaccination before conception would be ideal., Aims: The aim of this study is to estimate the deficiency in immunity against Rubella in women planning conception., Settings and Design: Retrospective data collected from all women who attended a private assisted reproduction center for evaluation of infertility or for pre-pregnancy counseling between January 2012 and October 2017., Materials and Methods: Women underwent measurement of the rubella-specific immunoglobulin G using enzyme-linked fluorescent assay., Statistical Analysis: Data between age groups were compared using the Chi-squared test. P < 0.05 was considered statistically significant., Results: Of the 1671 cases analyzed, 418 lacked sufficient immunity and therefore needed vaccination., Conclusions: One in four women was at risk of developing rubella during pregnancy. It is important to screen and vaccinate susceptible women to reduce the risk of congenital rubella syndrome., Competing Interests: There are no conflicts of interest.

Introduction: Renal artery embolization (RAE) is an important treatment option for patients with acute renal haemorrhage. Many types of embolic agents are presently available. We describe here the use of gel foam embolization for the treatment of acute renal haemorrhage., Material and Methods: A total of 12 patients (10 males and 2 females) underwent RAE. The indications in all cases were persistent renal haemorrhage which was secondary to renal biopsy (10 cases), blunt trauma to abdomen (1 case) and percutaneous nephrostomy (1 case). Embolic agent used was gel foam in all but one case. Embolization was done by selective catheterization of the feeding segmental / lobar renal artery branches., Results: Successful obliteration of the vascular malformation with no post-procedure complications were achieved in all cases., Conclusion: RAE with gel foam is a relatively inexpensive, safe, effective and minimally invasive procedure for the treatment of life-threatening renal haemorrhage, preserving healthy renal parenchyma and renal function.

The hemicholinium-3 (HC-3) sensitive, high-affinity choline transporter (CHT) sustains cholinergic signaling via the presynaptic uptake of choline derived from dietary sources or from acetylcholinesterase (AChE)-mediated hydrolysis of acetylcholine (ACh). Loss of cholinergic signaling capacity is associated with cognitive and motor deficits in humans and in animal models. Whereas genetic elimination of CHT has revealed the critical nature of CHT in maintaining ACh stores and sustaining cholinergic signaling, the consequences of elevating CHT expression have yet to be studied. Using bacterial artificial chromosome (BAC)-mediated transgenic methods, we generated mice with integrated additional copies of the mouse Slc5a7 gene. BAC-CHT mice are viable, appear to develop normally, and breed at wild-type (WT) rates. Biochemical studies revealed a 2 to 3-fold elevation in CHT protein levels in the CNS and periphery, paralleled by significant increases in [(3)H]HC-3 binding and synaptosomal choline transport activity. Elevations of ACh in the BAC-CHT mice occurred without compensatory changes in the activity of either choline acetyltransferase (ChAT) or AChE. Immunohistochemistry for CHT in BAC-CHT brain sections revealed markedly elevated CHT expression in the cell bodies of cholinergic neurons and in axons projecting to regions known to receive cholinergic innervation. Behaviorally, BAC-CHT mice exhibited diminished fatigue and increased speeds on the treadmill test without evidence of increased strength. Finally, BAC-CHT mice displayed elevated horizontal activity in the open field test, diminished spontaneous alteration in the Y-maze, and reduced time in the open arms of the elevated plus maze. Together, these studies provide biochemical, pharmacological and behavioral evidence that CHT protein expression and activity can be elevated beyond that seen in wild-type animals. BAC-CHT mice thus represent a novel tool to examine both the positive and negative impact of constitutively elevated cholinergic signaling capacity., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

Background: Non-communicable diseases are the leading causes of death globally, killing more people each year than all other causes combined. As many other developing countries, Nepal is also facing double burden of diseases. The aim of present study was to assess gender wise differences on prevalence of risk factors of non-communicable diseases., Methods: This was a community based cross sectional study which was based on WHO's STEP approach for surveillance risk factors of non-communicable diseases among males and females. Multi-staged sampling technique was used to get required study sample. Descriptive and inferential statistics were applied to compare the risk factors between two genders., Results: More than two-fifth of male and one-fifth of female respondents were currently using tobacco. The proportion of current alcohol users was found higher among the male respondents (28.6%) than their female counterparts (13.6%) (P<0.001). Only 35 (5.3%) of males and 13 (2.3%) of females were found consuming adequate (≥5 serving) intake of fruits per day. Study revealed that hypertension was slightly higher in male 165 (24.8%) than their female counterparts 111 (19.3%) but differences between two genders were statistically not significant., Conclusions: The findings of present study suggest that there is high prevalence of risk factors of non-communicable diseases among both sexes in central Nepal. The finding emphasises the need for a focused national strategies targeting to tackle this modern epidemic of non-communicable diseases by incorporating primordial prevention activities to all adult population irrespective to gender.

Nerve cell metabolic activity is monitored in multiple brain regions, including the hypothalamus and hindbrain dorsal vagal complex (DVC), but it is unclear if individual metabolosensory loci operate autonomously or interact to coordinate central nervous system (CNS) reactivity to energy imbalance. This research addressed the hypothesis that hypoglycemia-associated DVC lactoprivation stimulates hypothalamic AMPK activity and metabolic neurotransmitter expression. As DVC catecholaminergic neurons express biomarkers for metabolic monitoring, we investigated whether these cells are a source of lactate deficit signaling to the hypothalamus. Caudal fourth ventricle (CV4) infusion of the glucose metabolite l-lactate during insulin-induced hypoglycemia reversed changes in DVC A2 noradrenergic, arcuate neuropeptide Y (NPY) and pro-opiomelanocortin (POMC), and lateral hypothalamic orexin-A (ORX) neuronal AMPK activity, coincident with exacerbation of hypoglycemia. Hindbrain lactate repletion also blunted hypoglycemic upregulation of arcuate NPY mRNA and protein. This treatment did not alter hypoglycemic paraventricular oxytocin (OT) and lateral hypothalamic ORX mRNA profiles, but exacerbated or reversed adjustments in OT and ORX neuropeptide synthesis, respectively. CV4 delivery of the monocarboxylate transporter inhibitor, 4-CIN, increased A2 phosphoAMPK (pAMPK), elevated circulating glucose, and stimulated feeding, responses that were attenuated by 6-hydroxydopamine pretreatment. 4-CIN-infused rats exhibited increased (NPY, ORX neurons) or decreased (POMC neurons) pAMPK concurrent with hyperglycemia. These data show that hindbrain lactoprivic signaling regulates hypothalamic AMPK and key effector neurotransmitter responses to hypoglycemia. Evidence that A2 AMPK activity is lactate-dependent, and that DVC catecholamine cells are critical for lactoprivic control of glucose, feeding, and hypothalamic AMPK, implies A2 derivation of this metabolic regulatory stimulus.

Reductions in the capacity of the human choline transporter (SLC5A7, CHT) have been hypothesized to diminish cortical cholinergic neurotransmission, leading to risk for cognitive and mood disorders. To determine the acetylcholine (ACh) release capacity of cortical cholinergic projections in a mouse model of cholinergic hypofunction, the CHT+/- mouse, we assessed extracellular ACh levels while mice performed an operant sustained attention task (SAT). We found that whereas SAT-performance-associated increases in extracellular ACh levels of CHT+/- mice were significantly attenuated relative to wildtype littermates, performance on the SAT was normal. Tetrodotoxin-induced blockade of neuronal excitability reduced both dialysate ACh levels and SAT performance similarly in both genotypes. Likewise, lesions of cholinergic neurons abolished SAT performance in both genotypes. However, cholinergic activation remained more vulnerable to the reverse-dialyzed muscarinic antagonist atropine in CHT+/- mice. Additionally, CHT+/- mice displayed greater SAT-disrupting effects of reverse dialysis of the nAChR antagonist mecamylamine. Receptor binding assays revealed a higher density of α4β2* nAChRs in the cortex of CHT+/- mice compared to controls. These findings reveal compensatory mechanisms that, in the context of moderate cognitive challenges, can overcome the performance deficits expected from the significantly reduced ACh capacity of CHT+/- cholinergic terminals. Further analyses of molecular and functional compensations in the CHT+/- model may provide insights into both risk and resiliency factors involved in cognitive and mood disorders., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

Objective: To evaluate the etiology, presentation, complications and management of chronic pancreatitis in children., Design: Retrospective chart review., Setting: Gastroenterology department at Christian Medical College and Hospital, Vellore, India between January 2005 and December 2010., Participants: 99 Children (>18 yrs) diagnosed with chronic pancreatitis based on clinical and imaging features., Main Outcome Measures: Etiology, clinical presentation, complications and management of chronic pancreatitis in children., Results: Of 3887 children who attended the Gastroenterology department, 99(2.5%) had chronic pancreatitis, of which 60 (60.6%) were males. In 95(95.9%) patients no definite cause was detected and they were labeled as Idiopathic chronic pancreatitis. All patients had abdominal pain, while 9(9.1%) had diabetes mellitus. Of the 22 children tested for stool fat, 10(45.5%) had steatorrhea. Pancreatic calcification was seen in 69 (69.7%). 68 (71.6%) patients with idiopathic chronic pancreatitis had calcification. Calcific idiopathic chronic pancreatitis was more frequent in males (67.6% vs. 48.1%, P=0.07), and was more commonly associated with diabetes mellitus (13.2% vs. none, P=0.047) and steatorrhea (61.5% vs. 16.7%, P=0.069). Pseudocyst (17.1%) and ascites (9.1%) were the most common complications. All children were treated with pancreatic enzyme supplements for pain relief. 57 patients were followed up. With enzyme supplementation, pain relief was present in 32 (56.1%) patients. Of those who did not improve, 10 underwent endotherapy and 15 underwent surgery. Follow up of 8 patients who underwent endotherapy, showed that 5 (62.5%) had relief. Follow up of 11 patients who underwent surgery showed that only 3 (27%) had pain relief. There was no death., Conclusions: Idiopathic chronic pancreatitis is the predominant form of chronic pancreatitis in children and adolescents. It can present with or without calcification. The calcific variety is an aggressive disease characterized by early morphological and functional damage to the pancreas.

This study investigated the hypothesis that estrogen controls hindbrain AMP-activated protein kinase (AMPK) activity and regulation of blood glucose, counterregulatory hormone secretion, and hypothalamic nerve cell transcriptional status. Dorsal vagal complex A2 noradrenergic neurons were laser microdissected from estradiol benzoate (E)- or oil (O)-implanted ovariectomized female rats after caudal fourth ventricular (CV4) delivery of the AMPK activator 5-aminoimidazole-4-carboxamide-riboside (AICAR), for Western blot analysis. E advanced AICAR-induced increases in A2 phospho-AMPK (pAMPK) expression and in blood glucose levels and was required for augmentation of Fos, estrogen receptor-α (ERα), monocarboxylate transporter-2, and glucose transporter-3 protein in A2 neurons and enhancement of corticosterone secretion by this treatment paradigm. CV4 AICAR also resulted in site-specific modifications in Fos immunolabeling of hypothalamic metabolic structures, including the paraventricular, ventromedial, and arcuate nuclei. The current studies demonstrate that estrogen regulates AMPK activation in caudal hindbrain A2 noradrenergic neurons during pharmacological replication of energy shortage in this area of the brain, and that this sensor is involved in neural regulation of glucostasis, in part, through control of corticosterone secretion. The data provide unique evidence that A2 neurons express both ERα and -β proteins and that AMPK upregulates cellular sensitivity to ERα-mediated signaling during simulated energy insufficiency. The results also imply that estrogen promotes glucose and lactate uptake by these cells under those conditions. Evidence for correlation between hindbrain AMPK and hypothalamic nerve cell genomic activation provides novel proof for functional connectivity between this hindbrain sensor and higher order metabolic brain loci while demonstrating a modulatory role for estrogen in this interaction., (Copyright © 2013 Wiley Periodicals, Inc.)

Although serum anti-Müllerian hormone (AMH) is considered a good predictor of ovarian response during in vitro fertilisation (IVF), pregnancies have been reported with low values, questioning its usefulness as a predictor of treatment outcome. A retrospective study was therefore carried out to assess the IVF treatment outcomes in women with AMH below the tenth percentile of the study population. In all, 134 women with AMH ≤ 3 pmol/L underwent 180 IVF cycles. The mean age at the time of treatment was 37 ± 5 years. Fifty-three (29.4%) cycles were abandoned because of poor response to gonadotrophins, 12 (6.7%) due to absence of eggs at oocyte retrieval and 18 (10%) due to fertilisation failure. Seven (3.8%) had a biochemical pregnancy, 4 (2.2%) had a missed miscarriage and 8 (4.4%) had a live birth. When stratified by age, women older than 42 years had less number of follicles (p < 0.05) and those older than 39 years had less oocytes (p < 0.01) compared to those 35 years and younger. Live births declined with increasing age, when age was assessed as a continuous variable (p = 0.023). Women with low AMH levels have a high probability of treatment cancellation, failure to proceed to embryo transfer and a low chance of achieving a viable pregnancy.

Choledochal cysts are rare cystic transformations of the biliary tree that are increasingly diagnosed in adult patients. We report here a case of spontaneous rupture of a choledochal cyst in a pregnant young lady with chronic pancreatitis.

CNS neurons exhibit sustained activation by recurring hypoglycemia in the presence of estrogen. We investigated the impact of estradiol on fuel uptake and detection of energy imbalance by hindbrain A2 metabolosensory neurons during acute vs. chronic hypoglycemia. A2 neurons were laser dissected from estradiol benzoate (EB)- and oil (O)-implanted ovariectomized rats after single or serial injection of neutral protamine Hagedorn (NPH) insulin for single-cell qPCR or high-sensitivity Western blotting. Acute NPH increased A2 GLUT3 mRNA but not protein in EB, but decreased both profiles in O rats. Single insulin dosing did not alter monocarboxylate transporter-2 (MCT2) mRNAs in EB or O, but increased MCT2 protein in EB. Preceding hypoglycemia augmented baseline transporter mRNA and protein in O, but decreased GLUT4 and increased MCT2 proteins in EB. Chronic NPH increased A2 MCT2 and GLUT3 proteins in EB, but elevated GLUT4 protein in O. A2 phospho-AMPK (pAMPK) protein was progressively diminished by acute and chronic hypoglycemia in EB, but elevated in O after serial NPH. Dopamine-β-hydroxylase (DβH) transcripts were decreased in EB during acute and chronic hypoglycemia, but unaltered by serial NPH dosing in O. These results suggest that estrogen enhances A2 lactate utilization during acute hypoglycemia, thereby lessening AMPK activation relative to euglycemic controls. Cellular adaptation to chronic hypoglycemia may involve estrogen-dependent augmentation of lactate and GLUT3-mediated glucose uptake and hormone-independent increases in GLUT4 expression, coincident with diminished pAMPK-mediated signaling of energy deficiency. The data also imply that increased lactate and glucose uptake during recurring hypoglycemia may be required for sustained DβH transcriptional reactivity to this metabolic stress., (Copyright © 2012 Wiley Periodicals, Inc.)

Advances in mouse genetic technology have spurred increasing interest in the development of cognitive tasks for mice. Here, we describe and discuss the modifications necessary to adapt a task for the assessment of sustained attention performance for use in mice, including for taxing the top-down control of such performance. The validity of the Sustained Attention Task (SAT), including the distractor version (dSAT), has previously been demonstrated in rats and humans. This task requires moveable or retractable operanda; insertion of operanda into the operant chambers cues animals to respond to a prior signal or non-signal event, reporting either a hit or a miss, or a correct rejection or false alarm, respectively. Retractable levers did not support sufficiently high and stable levels of performance in mice. Given the widespread use of static nose-poke devices for testing operant performance in mice, we therefore designed and fabricated a retractable nose-poke device. As this device extends into chambers, a hole for nose-poking is slowly opened and closed again as the device retracts (termed the "Michigan Controlled Access Response Port", MICARP). Results describe the effects of variation of signal duration and event rate, trial outcome and trial type probability, effects of mice deprivation levels, and the reliability of SAT and dSAT performance. Mice perform the SAT and dSAT at levels comparable to those observed in rats. This task will be of assistance in expanding the translational usefulness of the SAT and dSAT., (Copyright © 2011 Elsevier B.V. All rights reserved.)

Cellular metabolic stasis is monitored in discrete brain sites, including the dorsal vagal complex (DVC), where A2 noradrenergic neurons perform this sensory function. Single-cell qPCR and high-sensitivity immunoblotting were used to determine if A2 neurons adapt to chronic hypoglycemia by increasing substrate fuel transporter expression, and whether such adjustments coincide with decreased cellular energy instability during this systemic metabolic stress. Tyrosine hydroxylase-immunolabeled neurons were laser-microdissected from the caudal DVC 2 hr after single or serial neutral protamine Hagedorn insulin (NPH) dosing. Preceding hypoglycemia suppressed basal A2 MCT2, GLUT3, and GLUT4 profiles and diminished MCT2, GLUT4, and glucokinase responses to recurring hypoglycemia. Acute NPH caused a robust increase in A2 phospho-AMPK protein levels; baseline phospho-AMPK expression was elevated after 3 days of insulin treatment but only slight augmented after a fourth NPH injection. Transcripts encoding the catecholamine biosynthetic enzyme dopamine-β-hydroxylase were unaffected by acute NPH but were diminished by serial insulin dosing. This evidence for diminished basal A2 glucose and lactate uptake and attenuated phospho-AMPK-mediated detection of hypoglycemia-associated energy deficits suggests that these cells acclimate to chronic hypoglycemia by adopting a new metabolic steady state characterized by energy paucity and reduced sensitivity to hypoglycemia. Because dopamine-β-hydroxylase mRNA was reduced after serial, but not single NPH dosing, A2 neurotransmitter biosynthesis may be impervious to acute hypoglycemia but inhibited when posthypoglycemic metabolic deficiency is exacerbated by recurring hypoglycemia. This research suggests that chronic hypoglycemia-associated adjustments in A2-sensory neurotransmission may reflect cellular energetic debilitation rather than adaptive attenuation of cellular metabolic imbalance., (Copyright © 2011 Wiley-Liss, Inc.)

It has been reported that adrenalectomy (ADX) and the potent type II glucocorticoid receptor agonist, dexamethasone, exert opposing effects on glucose utilization in specific brain regions, including the hypothalamus. The present study investigated the hypothesis that ADX alters neuronal substrate fuel transporter mRNA levels in characterized hypothalamic and hindbrain metabolic monitoring structures, and adjustments in these gene profiles are correlated with modified transcription of genes encoding the glucose sensor, glucokinase (GCK), and the energy-dependent, inwardly-rectifying potassium channel, K(ATP). The lateral hypothalamic area (LHA), ventromedial hypothalamic nucleus (VMN), and dorsal vagal complex (DVC) were microdissected from ADX and sham-operated male rats 2 h after neutral protamine Hagedorn insulin or vehicle injection, and evaluated by quantitative real-time RT-PCR for neuronal glucose (GLUT3, GLUT4), monocarboxylate (MCT2) transporter, GCK, and sulfonylurea receptor-1 (SUR1) mRNA content. ADX modified basal fuel transporter and energy transducer gene expression in a site-specific manner since this manipulation decreased MCT2 and GLUT3 transcription in the DVC only; increased or decreased GCK mRNA in the LHA and VMN, respectively; and decreased SUR1 gene profiles in the DVC and LHA. Adrenal removal did not alter baseline GLUT4 mRNA in any structure examined. ADX also prevented the following transcriptional responses to insulin-induced hypoglycemia: downregulated DVC MCT2, downregulated DVC and upregulated LHA and VMN GLUT3, upregulated LHA GLUT4, upregulated LHA GCK, and upregulated VMN SUR1. These results show that the adrenals regulate basal GLUT3 gene profiles in the DVC alone; during hypoglycemia, these glands suppress (DVC) or increase GLUT3 (LHA and VMH) mRNA, and selectively elevate GLUT4 transcripts in the LHA. The data demonstrate divergent adrenal control of DVC neuronal monocarboxylate transporter gene expression under basal (stimulatory) versus hypoglycemic (inhibitory) conditions. The current work also reveals contrasting adrenal regulation of baseline GCK mRNA in the LHA (inhibitory) and VMN (stimulatory), as well as adrenal-dependent hypoglycemic enhancement of LHA GCK and VMN SUR1 gene profiles. Additional research is required to characterize the impact of adrenal-sensitive substrate transporter and metabolic transducer function on fuel uptake and metabolic regulatory signaling in these brain sites., (Copyright 2009 S. Karger AG, Basel.)

Context: Women with primary infertility and no obvious pelvic pathology on clinical evaluation and imaging are either treated empirically or further investigated by laparoscopy., Aims: The role of diagnostic laparoscopy in women who fail to conceive after empirical treatment with ovulation induction and intrauterine insemination was evaluated., Settings and Design: Retrospective study at a private infertility center., Materials and Methods: A study of patients who underwent diagnostic laparoscopy between 1(st) January 2001 and 31(st) December 2008 was performed. Those patients who had no detectable pathology based on history, physical examination, and ultrasound and had treatment for three or more cycles in the form of ovulation induction and IUI were included in the study. Moderate and severe male factor infertility and history of any previous surgery were exclusion criteria., Statistical Analysis Used: Data were statistically analyzed using Statistics Package for Social Sciences (ver. 16.0; SPSS Inc., Chicago)., Results: Of the 127 women who underwent diagnostic laparoscopy and hysteroscopy, 87.4% (n = 111) of patients had positive findings. Significant pelvic pathology (moderate endometriosis, pelvic inflammatory disease, and tubal pathology) was seen in 26.8% of cases., Conclusion: One in four women had significant pelvic pathology where treatment could possibly improve future fertility. Diagnostic laparoscopy has a role in infertile women with no obvious abnormality before they proceed to more aggressive treatments.

Uterine malignancies are not uncommonly misdiagnosed for the more ubiquitous leiomyoma. A case of endometrial stromal sarcoma with ultrasound and color Doppler imaging is described.

Background: To evaluate pregnancy outcomes following laparoscopic myomectomy and single-layer myometrial closure., Methods: This study conducted at a private advanced endoscopy and assisted reproductive technology centre retrospectively evaluated outcomes of 115 women who had pregnancies subsequent to laparoscopic myomectomy., Results: Of the 217 women followed up, 115 had pregnancies subsequent to a laparoscopic myomectomy. Of 141 pregnancies, there were 87 Caesarean sections, 19 vaginal deliveries, 29 abortions and 6 ectopic pregnancies. There were no incidents of uterine scar rupture in any of these pregnancies., Conclusions: Uterine rupture during pregnancies following laparoscopic myomectomy is rare following single-layer myometrial closure.

We describe multiple parasitic myomas visualized on laparoscopy in a woman who had a previous laparoscopic myomectomy. Location of the myomas suggests morcellation as a contributing factor.