Differential expression of miRNAs and related mRNAs during heat stress in buffalo heifers.

The present experiment was aimed to study differential expression of miRNAs and related mRNAs during heat stress (HS) in buffalo heifers. Twelve Murrah buffalo heifers aged between 1.5 and 2.0 years, weighting between 250 and 300 Kg were randomly assigned into two equal groups. The animals were kept in the psychrometric chamber under Thermo-neutral (TN; THI = 72) and HS (THI = 87-90) conditions for 6 h every day between 1000 and 1600 h for 21 days. The blood sampling was done at 1500 h on 15th day of the experiment and physiological parameters viz. pulse rate (PR), respiratory rate (RR) and rectal temperature (RT) were recorded at 1500 h on day -5, -3, -1, 0, +1, +3, +5 with respect to blood sampling. PBMCs were used for extraction of miRNAs and total RNA; and first strand cDNA was synthesized. qPCR was performed for relative gene expression studies. Physiological, hematological (erythrocytic indices), biochemical (triglycerides, urea, ALT, AST, LDH), redox (SOD, ROS) and endocrine parameters (T4) altered significantly (P < 0.05) during HS as compared to TN. Out of eight targeted miRNAs only four were expressed in buffalo heifers. The relative expression of bta-mir-142, bta-mir-1248 and bta-mir-2332 was significantly (P < 0.05) up-regulated whereas expression of bta-mir-2478 was significantly (P < 0.05) down-regulated during HS as compared to TN. The relative expression of the predicted target genes i.e. HSF1, HSP60, HSP70, HSPA8 and HSP90 were significantly (P < 0.05) up-regulated whereas HSF4 expression was significantly (P < 0.05) down-regulated during HS as compared to TN. It can be concluded that a THI of 87-90 could lead to a moderate HS in buffalo heifers. Differential expression studies of miRNAs and related mRNAs in present study deciphers the role of miRNAs in the heat tolerance in buffalo heifers.

Appropriate THI model and its threshold for goats in semi-arid regions of India.

The present study was attempted to identify an appropriate THI model and threshold THI for goats of semi-arid regions of India. Sixty non-pregnant goats each from Jamunapari and Barbari breeds were selected for the study. The study was conducted from last week of February to first week of June, during which average THI ranged between 53 and 92. Pulse rate (PR), respiration rate (RR) and rectal temperature (RT) were recorded at 1430 h on alternate days from six goats of each breed randomly during the experiment. Nine THI models were used to calculate THI. An appropriate THI model was predicted on the basis of correlation between THIs calculated from each model and physiological responses. The data of physiological parameters were linked to the THI calculated from identified THI model and threshold THI for each parameter was determined using segmented regression analysis (SegReg Software). The THI models; THI1{(1.8 × Tdb+32)-[(0.55-0.0055 × RH) × (1.8 × Tdb-26.8)]} and THI8{(0.8 × Tdb)+[(RH/100) × (Tdb-14.4)]+46.4)} were found to be equally appropriate for assessing environmental heat stress. Threshold THIs with respect to PR, RR and RT in Jamunapari goat were 71.78, 75.14 and 85.94, respectively and in Barbari goats, threshold THIs for PR and RR were 79.48 and 84.40, respectively. A threshold THI could not be identified for RT in Barbari goats. It can be concluded that THI1 and THI8 were the appropriate THI models for measuring environmental heat stress in goats. Results suggested that PR is the first physiological parameter which alters after the onset of heat stress and is followed by changes in RR and RT. On the basis of differential threshold THIs, it can be concluded that Barbari is better adapted than Jamunapari goats in semi-arid regions of India.

Usability of daily SF36 questionnaires to capture the QALD variation experienced after vaccination with AS03A-adjuvanted monovalent influenza A (H5N1) vaccine in a safety and tolerability study.

BACKGROUND: This study aims to describe the short-term reactogenicity of the AS03-adjuvanted H5N1 vaccine expressed through adverse events (AEs) and quality-adjusted life-day (QALD) scores. The AEs are likely to be short-term and therefore the quality of life (QoL) questionnaire, SF-36v2, was administered daily to record changes over seven days. A more sensitive application of this instrument should allow for a better understanding of short-term tolerability of adjuvanted vaccines. METHODS: Participants (N = 50) received a 2-dose vaccination schedule. Solicited (collected daily: days 0 to 7 [post dose 1] and 21 to 28 [post dose 2]) and unsolicited (collected weekly until day 21) AEs were collected via diary cards. The QoL questionnaires were completed daily (days 0-6) and weekly (days 0, 6, 21, 27) after dose one. Questionnaire data were transformed into SF-6D scores to report QALDs. It was hypothesized post-hoc that the QALD and daily AEs scores should correlate if discrete QoL-changes were captured. RESULTS: Pain (92%) and muscle ache (66%) were the most commonly reported solicited local and general AEs respectively, neither increased in intensity nor in frequency after dose 2. No safety concerns were identified during the study. A correlation between the daily AEs and QALD scores existed (correlation coefficient, - 0.97 (p < 0.001)). The impact of the AEs scores on the QALD was marginal (- 0.02 max for one day). CONCLUSION: Similarly with other H5N1 studies, no safety concern was identified throughout the study. Some time-limited variations in QALD-scores were reported. Our results imply that daily administration of the SF-36v2 captures changes in QALD-scores. TRIAL REGISTRATION: ClinicalTrials.gov . NCT01788228. Registered 11 February 2013.

Insula and amygdala resting-state functional connectivity differentiate bipolar from unipolar depression.

OBJECTIVE: Distinguishing depressive episodes due to bipolar disorder (BD) or major depressive disorder (MDD) solely on clinical grounds is challenging. We aimed at comparing resting-state functional connectivity (rsFC) of regions subserving emotional regulation in similarly depressed BD and MDD. METHOD: We enrolled 76 in-patients (BD, n = 36; MDD, n = 40) and 40 healthy controls (HC). A seed-based approach was used to identify regions showing different rsFC with the insula and the amygdala. Insular and amygdalar parcellations were then performed along with diagnostic accuracy of the main findings. RESULTS: Lower rsFC between the left insula and the left mid-dorsolateral prefrontal cortex and between bilateral insula and right frontopolar prefrontal cortex (FPPFC) was observed in BD compared to MDD and HC. These results were driven by the dorsal anterior and posterior insula (PI). Lower rsFC between the right amygdala and the left anterior hippocampus was observed in MDD compared to BD and HC. These results were driven by the centromedial and laterobasal amygdala. Left PI/right FPPC rsFC showed 78% accuracy differentiating BD and MDD. CONCLUSION: rsFC of amygdala and insula distinguished between depressed BD and MDD. The observed differences suggest the possibility of differential pathophysiological mechanisms of emotional dysfunction in bipolar and unipolar depression.

Unusual Presentation of Necrotic Erythema Nodosum Leprosum on Scalp: A Case Report.

Lepra reactions are acute episodes occurring during the disease process of leprosy and are of 2 types: type 1 or reversal reaction and type 2 reaction or erythema odosumleprosum (ENL). In the episodes of lepra reaction several parts are affected including face and extremities like oral cavity. In the present case report we reported a rare case of lepromatous leprosy with necrotic ENL involving scalp apart from the usual sites. A 58 year old married male presented to us with complaints of spontaneous onset, recurrent eruption of multiple reddish raised painful lesions. Biopsy from the infiltrated skin over the back showed atrophic epidermis, free Grenz zone, diffuse and periadnexal macrophage granulomas with predominant mononuclear infiltrate, appandageal atrophy, fibrosis around the neural structures and leukocytoclastic vasculitis. Fites stain showed strong positivity for M. leprae. His routine blood investigations showed anemia (Hb = 7.8 gm%), neutrophil leukocytosis (TLC = 17,600, DLC = P66L28M4E2) and raised ESR (80 mm in the first hour). These bullous and necrotic lesions in leprosy may be a manifestation of severe type II reactions in patients with very high bacillary load.

Beyond rose colored glasses: the adaptive role of depressive and anxious symptoms among individuals with heart failure who were evaluated for transplantation.

The prospect of and the evaluative period for transplantation can be stressful for individuals with heart failure (HF). Little is known about the impact of psychosocial factors on service utilization and health outcomes. The current study examined the impact of depression, dysthymia, and anxiety on two-yr hospitalization and mortality among 96 individuals with HF who were evaluated for transplantation. Results revealed that only a small percentage of individuals endorsed sufficient symptomatology to meet criteria for a psychiatric, Axis I disorder (3.1% = anxiety; 2.1% = depression; 1.0% = dysthymia) although a significant proportion of the sample was prescribed an antidepressant or an anxiolytic (37%). Multivariable regression analysis was conducted to examine the association between significant independent demographic, medical, and psychiatric predictors and total duration of hospitalizations; logistic regression analysis was used to examine the relation between predictors and mortality. An increase in anxious symptoms was associated with a decrease in total number of days hospitalized during the two-yr period following the initial evaluation. Similarly, as depressive symptoms increased, risk of two-yr mortality decreased. Future research should assess communication between the patient and providers to further elucidate the potential relationship between psychiatric symptoms, service utilization/hospitalization, and mortality in this patient population.

Models for anti-tumor activity of bisphosphonates using refined topochemical descriptors.

An in silico approach comprising of decision tree (DT), random forest (RF) and moving average analysis (MAA) was successfully employed for development of models for prediction of anti-tumor activity of bisphosphonates. A dataset consisting of 65 analogues of both nitrogen-containing and non-nitrogen-containing bisphosphonates was selected for the present study. Four refinements of eccentric distance sum topochemical index termed as augmented eccentric distance sum topochemical indices 1-4 [formula: see text] have been proposed so as to significantly augment discriminating power. Proposed topological indices (TIs) along with the exiting TIs (>1,400) were subsequently utilized for development of models for prediction of anti-tumor activity of bisphosphonates. A total of 43 descriptors of diverse nature, from a large pool of molecular descriptors, calculated through E-Dragon software (version 1.0) and an in-house computer program were selected for development of suitable models by employing DT, RF and MAA. DT identified two TIs as most important and classified the analogues of the dataset with an accuracy of 97% in training set and 90.7% in tenfold cross-validated set. Random forest correctly classified the analogues with an accuracy of 89.2%. Four independent models developed through MAA predicted the activity of analogues of the dataset with an accuracy of 87.6% to 89%. The statistical significance of proposed models was assessed through intercorrelation analysis, specificity, sensitivity and Matthew's correlation coefficient. The proposed models offer a vast potential for providing lead structures for development of potent anti-tumor agents for treatment of cancer that has spread to the bone.

Models for cannabinoid-1 receptor antagonistic activity of substituted 2-(3-pyrazolyl)-1,3,4-oxadiazoles.

Antagonism of cannabinoid receptor-1 has emerged as a most promising therapeutic target for the development of anti-obesity drugs. In the present study, an in silico approach using decision tree, random forest and moving average analysis has been applied to a data set comprising of 76 analogues of substituted 2-(3-pyrazolyl)-1,3,4-oxadiazoles for development of models for prediction of antagonistic activity of cannabinoid receptor-1. A total of 46 2D and 3D molecular descriptors of diverse nature were employed for decision tree and random forest analysis. The values of majority of these descriptors for each analogue involved in the dataset were computed using E-Dragon software (version 1.0). Random forest correctly classified the analogues into active and inactive with an accuracy of 95%. A decision tree was also utilized for determining the importance of molecular descriptors. The decision tree learned the information from the input data with an accuracy of 99% and correctly predicted the cross-validated (10 fold) data with an accuracy up to 90%. Finally, three molecular descriptors of diverse nature (including best descriptor identified by decision tree analysis) were subsequently used to build suitable models using moving average analysis. These models resulted in the prediction of cannabinoid receptor-1 antagonistic activity with an accuracy of 95-96%. High predictability of proposed models offer vast potential for providing lead structures for the development of potent cannabinoid receptor-1 antagonists for the treatment of obesity.

Models for prediction of (V)600(E)BRAF and melanoma cells growth inhibitory activities of pyridoimidazolones.

Targeted inhibition of activated BRAF mutation has emerged as a most promising and putative therapeutic approach for the anticancer drug development. In the present study, an in-silico approach using decision tree and moving average analysis has been applied to a data set comprising of 43 analogues of pyridoimidazolones for development of models for prediction of both (V)600(E)BRAF and melanoma cells (BRAF WM266.4) growth inhibitory activities. A decision tree was mainly employed for determining the importance of molecular descriptors (n=46). The value of majority of these descriptors for each analogue in the dataset was computed using E-Dragon software (version 1.0). The decision tree learned the information from the input data with an accuracy of 98% and correctly predicted the cross-validated (10-fold) data with accuracy up to 79%. A total of three non-correlating descriptors, identified best by the decision tree analysis, were subsequently utilized for development of suitable models using moving average analysis. These proposed models resulted in the prediction of (V)600(E)BRAF inhibitory activity (IC50) and melanoma cells growth (SRB GI50) inhibitory activity with an overall accuracy of ≥90%. The statistical significance of models/descriptors was assessed through intercorrelation analysis, sensitivity, specificity and Matthew's correlation coefficient.

The gut microbiota is associated with psychiatric symptom severity and treatment outcome among individuals with serious mental illness.

BACKGROUND: Emerging evidence implicates the gut microbiota in central nervous system functioning via its effects on inflammation, the hypothalamic-pituitary axis, and/or neurotransmission. Our understanding of the cellular underpinnings of the brain-gut relationship is based almost exclusively on animal models with some small-scale human studies. This study examined the relationship between the gut microbiota and psychiatric symptom severity and treatment response among inpatients with serious mental illness. METHOD: We collected data from adult inpatients (N = 111). Measures of diagnoses, suicide severity, trauma, depression, and anxiety were collected shortly after admission, while self-collected fecal swabs were collected early in the course of hospitalization and processed using 16S rRNA gene sequencing and whole genome shotgun sequencing methods. RESULTS: Results indicate that depression and anxiety severity shortly after admission were negatively associated with bacterial richness and alpha diversity. Additional analyses revealed a number of bacterial taxa associated with depression and anxiety severity. Gut microbiota richness and alpha diversity early in the course of hospitalization was a significant predictor of depression remission at discharge. CONCLUSIONS: This study is among the first to demonstrate a gut microbiota relationship with symptom severity among psychiatric inpatients as well as a relationship to remission of depression post-treatment. These findings are consistent with animal models and limited human studies as well as with the broader literature implicating inflammation in the pathophysiology of depression. These findings offer the foundation for further studies of novel therapeutic approaches to the treatment, prevention of, or recurrence of serious mental illness.

Vascular endothelial growth factor in eye disease.

Collectively, angiogenic ocular conditions represent the leading cause of irreversible vision loss in developed countries. In the US, for example, retinopathy of prematurity, diabetic retinopathy and age-related macular degeneration are the principal causes of blindness in the infant, working age and elderly populations, respectively. Evidence suggests that vascular endothelial growth factor (VEGF), a 40kDa dimeric glycoprotein, promotes angiogenesis in each of these conditions, making it a highly significant therapeutic target. However, VEGF is pleiotropic, affecting a broad spectrum of endothelial, neuronal and glial behaviors, and confounding the validity of anti-VEGF strategies, particularly under chronic disease conditions. In fact, among other functions VEGF can influence cell proliferation, cell migration, proteolysis, cell survival and vessel permeability in a wide variety of biological contexts. This article will describe the roles played by VEGF in the pathogenesis of retinopathy of prematurity, diabetic retinopathy and age-related macular degeneration. The potential disadvantages of inhibiting VEGF will be discussed, as will the rationales for targeting other VEGF-related modulators of angiogenesis.

Genetic evaluation of suspected cases of transient HIV-1 infection of infants.

Detection of human immunodeficiency virus-type 1 (HIV-1) on only one or a few occasions in infants born to infected mothers has been interpreted to indicate that infection may be transient rather than persistent. Forty-two cases of suspected transient HIV-1 viremia among 1562 perinatally exposed seroreverting infants and one mother were reanalyzed. HIV-1 env sequences were not found in specimens from 20; in specimens from 6, somatic genetic analysis revealed that specimens were mistakenly attributed to an infant; and in specimens from 17, phylogenetic analysis failed to demonstrate the expected linkage between the infant's and the mother's virus. These findings argue that transient HIV-1 infection, if it exists, will only rarely be satisfactorily documented.

Regulation of adiponectin release and demonstration of adiponectin mRNA as well as release by the non-fat cells of human omental adipose tissue.

OBJECTIVE: Adiponectin is an adipokine produced by adipose tissue. The present studies examined the in vitro release of adiponectin by human omental adipose tissue explants as well as the mRNA content of freshly isolated non-fat cells and adipocytes plus cultured preadipocytes and adipocytes derived from omental fat. RESULTS: The release of adiponectin was reduced while that of interleukin-8 (IL-8) was enhanced in tissue explants from morbidly obese women. The release of adiponectin was also reduced by one-third in explants from morbidly obese diabetic women while that of IL-8 was unaffected by diabetes. The release of adiponectin was enhanced by insulin and by inhibition of endogenous tumor necrosis factor (TNFalpha) using etancercept. Adiponectin was released in appreciable amounts by the undigested matrix obtained by collagenase digestion of adipose tissue. The release of adiponectin by non-fat cells (matrix+SV cells) was comparable to that by the adipocytes derived from the same amount of tissue while the adiponectin mRNA content of the pooled matrix and SV cell fractions was 40% of that in intact tissue. The adiponectin mRNA content was 48-fold greater in isolated adipocytes than in non-fat cells derived from adipose tissue. In contrast, the amount of adiponectin mRNA in vitro differentiated omental adipocytes was 1 x l0(6)-fold greater than that in cultured preadipocytes while that of leptin was 3 x 10(4)-fold greater. CONCLUSION: Adiponectin mRNA is present in the non-fat cells of freshly isolated adipose tissue and release by the non-fat cells derived from a gram of adipose tissue is comparable to that by adipocytes isolated from the same amount of tissue. While leptin is only released by mature adipocytes, adiponectin is released by both the non-fat cells and the fat cells derived from human omental adipose tissue.

Identification of omentin mRNA in human epicardial adipose tissue: comparison to omentin in subcutaneous, internal mammary artery periadventitial and visceral abdominal depots.

OBJECTIVE: The purpose of this study was to determine the relative distribution of omentin and visfatin mRNA in human epicardial, peri-internal mammary, upper thoracic, upper abdominal and leg vein subcutaneous adipose tissue as well as the distribution of omentin in the nonfat cells and adipocytes of human omental adipose tissue. BACKGROUND: Omentin is found in human omentum but not subcutaneous fat. Omentin and visfatin are considered markers of visceral abdominal fat. RESEARCH DESIGN AND METHODS: The mRNA content of omentin and visfatin was measured by qRT-PCR analysis of fat samples removed from humans undergoing cardiac or bariatric surgery. RESULTS: Omentin mRNA in internal mammary fat was 3.5%, that in the upper thoracic subcutaneous fat was 4.7% while that in the other subcutaneous fat depots was less than 1% of omentin in epicardial fat. The distribution of visfatin mRNA did not vary between the five depots. Omentin mRNA was preferentially expressed in the nonfat cells of omental adipose tissue since the omentin mRNA content of isolated adipocytes was 9% of that in nonfat cells, and similar results were seen for visfatin. The amount of omentin mRNA in differentiated adipocytes was 0.3% and that of visfatin 4% of that in nonfat cells. The amount of omentin mRNA in preadipocytes was virtually undetectable while that of visfatin was 3% of that in freshly isolated nonfat cells from omental adipose tissue. CONCLUSION: Omentin mRNA is predominantly found in epicardial and omental human fat whereas visfatin mRNA is found to the same extent in epicardial, subcutaneous and omental fat.

Predicting anti-HIV-1 activity of 6-arylbenzonitriles: computational approach using superaugmented eccentric connectivity topochemical indices.

Highly discriminating adjacency-cum-distance based topochemical indices termed as superaugmented eccentric connectivity topochemical indices for quantitative structure-activity and structure-property relationships (QSAR/QSPR) have been conceptualized in the present study. These indices were found to exhibit high sensitivity towards the presence and relative position of heteroatom(s), exceptionally high discriminating power and negligible degeneracy for all possible structures of five vertices containing one heteroatom. Utility of these indices was investigated for development of models for prediction of anti-human immunodeficiency virus (HIV)-1 activity using a data set comprising 81 differently substituted 6-arylbenzonitriles. The values of the superaugmented eccentric connectivity topochemical indices of all the analogues comprising the data set were computed using an in-house computer program. The resultant data was analyzed and suitable models were developed after identification of the active ranges. Subsequently, a biological activity was assigned to each analogue using these models which was then compared with the reported anti-HIV-1 activity. The accuracy of prediction was found to be approximately 81% for all the three topochemical models. High sensitivity towards presence and relative position of heteroatom(s), exceptionally high discriminating power amalgamated with low degeneracy offer proposed topochemical indices vast potential for isomer discrimination, similarity/dissimilarity, drug design, quantitative structure-activity/structure-property relationships, lead optimization and combinatorial library design.

Adduction of amiloride hydrochloride in urea through a modified technique for the dissolution enhancement.

Amiloride hydrochloride is a potassium-sparing diuretic since it favors sodium excretion and potassium reabsorption. In the present study, urea, a well-known adductor for linear compounds was successfully employed for inclusion of amiloride hydrochloride-a substituted cyclic organic compound through a modified technique. Formation of urea inclusion compounds was confirmed by FTIR, DSC and XRD. The minimum amount of rapidly adductible endocyte (RAE) required for adduction of amiloride hydrochloride in urea was estimated by a modified Zimmerschied calorimetric method. Urea-AH-RAE inclusion compounds containing varying proportions of guests were prepared and their thermal behavior studied by DSC. The inclusion compounds were also found to exhibit high content uniformity and markedly improved dissolution profile as demonstrated by increased dissolution efficiency. Studies reveal the possibility of exploiting co-inclusion of the drug in urea host lattice for the dissolution enhancement.

Minimally invasive surgery fellows would perform a wider variety of cases in their "ideal" fellowship.

BACKGROUND: With the increase in minimally invasive surgery (MIS) fellowships, the concept of the ideal and standardized training curriculum is emerging in importance. The authors hypothesize that the procedure mix in current MIS training is different from what current MIS fellows would expect for their "ideal" fellowship. METHODS: An anonymous survey of current MIS fellows examined their perceptions of the case diversity and volume they expect to perform in their fellowships as compared with an ideal fellowship. Differences between expected and ideal case volume were analyzed using Wilcoxon tests. RESULTS: A total of 32 questionnaires were returned. Current MIS fellows believe their expected training will exceed the ideal volume of laparoscopic cholecystectomies (p = 0.002). They believe their expected training is equivalent to ideal training in laparoscopic gastric bypass, ventral herniorraphy, inguinal herniorraphy, antireflux procedures, appendectomy, and diagnostic endoscopy (nonsignificant difference). However, current expected training falls short of their "ideal" case volume in laparoscopic gastric banding, colectomy, common bile duct exploration, gastrectomy, esophagectomy, splenectomy, adrenalectomy, hepatectomy, nephrectomy, and pancreatectomy (p < 0.05). The current MIS fellows also expect that their thoracoscopic, therapeutic endoscopy, and robotic procedure volume will be less than "ideal" (p < 0.05). CONCLUSION: In 13 of 20 procedure types, current MIS fellows expect to perform a smaller case volume than in an "ideal" fellowship. The ideal case volume in the MIS fellowship curriculum needs to be defined better.

Urea co-inclusion compounds of 13 cis-retinoic acid for simultaneous improvement of dissolution profile, photostability and safe handling characteristics.

13-cis Retinoic acid (cis-RA), a synthetic retinoid used in the treatment of severe acne, is known to exhibit extremely low aqueous solubility and high photosensitivity. In this study, urea, a well-known adductor for linear compounds, was successfully employed for the adduction of cis-RA - a substituted cyclic organic compound. Formation of urea inclusion compounds was confirmed by FTIR, DSC and XRD. A modified Zimmerschied calorimetric method was employed for the estimation of the minimum amount of rapidly adductible endocyte (RAE) required for adduction of cis-RA in urea. Urea-cis-RA-RAE inclusion compounds containing varying proportions of guests were prepared and their thermal behaviour studied by DSC. The inclusion compounds were found to have an improved dissolution profile as demonstrated by an overall increase in the dissolution efficiency. An accelerated photostability study, conducted as per Q1B ICH guidelines, revealed that co-inclusion of cis-RA in urea delayed photo-degradation of the drug when compared with that of the pure drug. The results suggest the possibility of exploiting co-inclusion of the drug in a urea host lattice for improved solubility, stability and reduced handling problems for cis-RA.

Prospective randomized controlled trial of laparoscopic trainers for basic laparoscopic skills acquisition.

BACKGROUND: Laparoscopic surgery requires a different set of skills than traditional open surgery. The acquisition of basic laparoscopic skills may help novices when learning laparoscopic procedures. This study tested the hypothesis that the combination of virtual reality and box trainers leads to better basic laparoscopic skill acquisition than either method alone or no training. METHODS: A randomized control trial involving preclinical medical students with no prior operative experience was performed. The students were grouped according to four training methods: virtual reality training, inanimate box training, a combination of both, and no training (control). The pre- and posttraining scores for four skills in the porcine laboratory were the metrics chosen for this study. RESULTS: A total of 65 students participated in this study. There were no differences among any of the pretraining scores (p > 0.05). The posttraining times differed between the four groups. Post hoc analyses showed statistically significant differences (p < 0.05) between the participants trained with both trainers and the control subjects. CONCLUSIONS: Our data demonstrate that the combination of virtual reality training and inanimate box training leads to better laparoscopic skill acquisition than either training method alone or no training at all. Optimal preclinical laparoscopic training should incorporate both virtual reality trainers and inanimate box trainers.

Predictive value of upper gastrointestinal studies versus clinical signs for gastrointestinal leaks after laparoscopic gastric bypass.

BACKGROUND: The utility of routine upper gastrointestinal (UGI) studies after laparoscopic Roux-en-Y gastric bypass (LRYGB) is a matter of great debate. Because the morbidity and mortality rates associated with an unrecognized postoperative leak are high after LRYGB, diagnosis of a postoperative leak earlier would be of benefit. Clinical signs, however, may predict the diagnosis of a postoperative leak more often. This study explored the hypothesis that UGI studies are more predictive than clinical signs for the early diagnosis of a postoperative leak after LRYGB. METHODS: All patients who underwent LRYGB at the authors' institution were included in this study. Charts were reviewed to examine immediate clinical signs (heart rate, temperature, and white blood cell count within the first 24 h), UGI studies, and clinical course. Sensitivity, specificity, positive predictive value, negative predictive value, and efficiency of clinical signs and UGI studies were calculated. RESULTS: This study included 245 patients with a 3% rate of leak. The positive and negative predictive value of UGI studies were 67% and 99%, respectively. Only an elevated white blood count had a better predictive value (100% for negative predictive value). The efficiency of UGI studies (98%) was better than that of heart rate (83%), white blood count (8%), or temperature (95%). CONCLUSIONS: According to our data, UGI studies are the most predictive of an early leak diagnosis. Clinical signs alone may not be as useful in predicting leaks early after laparoscopic gastric bypasses. Routine early postoperative UGI studies are a reasonable approach to predicting leaks after LRYGB.