Sleeve gastrectomy prior to liver transplantation is superior to medical weight loss in reducing posttransplant metabolic complications

Strategies to optimize the management of obesity-related metabolic complications after liver transplantation (LT) are needed. We examined the effect of pre-LT sleeve gastrectomy (SG), as compared to medical weight loss (MWL), on post-LT outcomes. This is a cohort study of adults (≥18 years) with medically complicated obesity who were eligible for pre-LT SG and underwent LT from January 1, 2006 to June 1, 2016. Logistic regression models evaluated the association of SG on post-LT diabetes and hypertension, defined as new-onset or progressive disease post-LT. Cox regression models evaluated the association of SG on recurrent and de novo nonalcoholic fatty liver disease (NAFLD). Among 70 LT recipients who were eligible for pre-LT SG, 14 (20%) underwent SG and 56 (80%) underwent MWL only. Mean follow-up was 5.2 years post-LT. The SG cohort sustained higher % total body weight loss at 3 years post-LT (28.9% vs. 5.4%, p < .001). In multivariable analyses, SG was associated with significantly lower risk of post-LT diabetes (OR 0.04, 95% CI 0.00–0.41, p = .01), hypertension (OR 0.15, 95% CI 0.04–0.67, p = .01), and recurrent and de novo NAFLD (HR 0.19, 95% CI 0.04–0.91, p = .04). When compared to MWL, SG resulted in sustained weight loss and significantly lower risk of diabetes, hypertension, and recurrent and de novo NAFLD post-LT.     

An inventory-location optimization model for equitable influenza vaccine distribution in developing countries during the COVID-19 pandemic

The addition of other respiratory illnesses such as flu could cripple the healthcare system during the coronavirus disease 2019 (COVID-19) pandemic. An annual seasonal influenza vaccine is the best way to help protect against flu. Fears of coronavirus have intensified the shortage of influenza shots in developing countries that hope to vaccinate many populations to reduce stress on their health services. We present an inventory-location mixed-integer linear programming model for equitable influenza vaccine distribution in developing countries during the pandemic. The proposed model utilizes an equitable objective function to distribute vaccines to critical healthcare providers and first responders, elderly, pregnant women, and those with underlying health conditions. We present a case study in a developing country to exhibit efficacy and demonstrate the optimization model’s applicability.     

Congenital lens coloboma and associated pathologies

Coloboma of the lens is characterized by notching of the equator of the lens. The cause of the condition is faulty development of the zonule. The lens deprived of its normal pull in the defective region is thicker and more spherical as if there were no loss of its substance. We report five cases of lens coloboma and localized zonular defect without any associated systemic anomalies. One case included retinal detachment; another included an iris coloboma; and a third included iris, choroid and optic disk colobomas and retinal detachment with lens coloboma. The remaining two cases were without associated ocular anomalies. The pathogenic mechanisms and relationship of this defect with the differentiation of the tertiary vitreous and development of the zonule is discussed. The defect most likely occurs in the third to fourth months of gestation during differentiation of the tertiary vitreous in response to toxic, inflammatory or genetic factors.     

Release and actions of adenosine in the central nervous system

Adenosine is released from active neurons into the extracellular fluid at a concentration of about 1mol/l. Neither the precise cellular origin nor the biochemical form of release has been firmly established, though the nucleotide is probably released partly directly, as a result of raised intracellular levels, and partly as nucleotides, which are subsequently hydrolysed. Once in the extracellular medium, adenosine markedly inhibits the release of excitatory neurotransmitters and modulatory peptides and has direct inhibitory effects on postsynaptic excitability via A₁ receptors. A population of A₂ receptors may mediate depolarization and enhanced transmitter release. Adenosine also modulates neuronal sensitivity to acetylcholine and catecholarnines, all these effects probably contributing to the behavioural changes observed in conscious animals. As a result of their many actions, adenosine analogues are being intensively investigated for use as anticonvulsant, anxiolytic, and neuroprotective agents.     

Urethro-vesical function during spinal shock

Summary Twenty spinal shock patients were investigated with simultaneous urethrovesical, anal and rectal pressure recordings and EMG of the external urethral and anal sphincters. Dynamic and static urethral pressure profiles (UPP) were carried out with empty and full bladder. Baldder filling was accompanied by an increased resistance in the internal sphincter zone, which in turn was paralleled in the majority of cases by an elevation of pressure in the membranous urethra without concomitant increase of its EMG activity. This is suggestive of an increased sympathetic activity in the bladder neck area and in the smooth muscle component of the external urethral sphincter. Dynamic pullthrough UPP's displayed higher resistances in the membranous urethra than static interrupted UPP's pointing to the role played by the urethral muscosal receptors in eliciting artefactual results. Higher pressures were recorded in the juxtabulbar portion of the membranous urethra than in its mid portion pointing to a gradient of pressure within the external urethral sphincter itself. The amount of EMG activity recorded in the anal and urethral sphincters at rest was somewhat decreased; high pressures and distinct reflex activity were recorded in both sphincters showing that they escape spinal shock characterized primarily by areflexia. After defining spinal shock a rational explanation based upon neuroanatomical and neurophysiological findings is offered as to why somatic activity of the sacral segments escapes it as evidenced by clincial, urodynamic, and electromyographic recordings.     

Draize rabbit eye test compatibility with eye irritation thresholds in humans: a quantitative structure-activity relationship analysis.

Draize rabbit eye test scores, as modified maximum average score (MMAS), for 68 pure bulk liquids were adjusted by the liquid-saturated vapor pressure P. These 68 adjusted scores, as log (MMAS/P), were shown to be completely equivalent to eye irritation thresholds (EIT), expressed as log (1/EIT), for 23 compounds in humans. Thus, for the first time the Draize eye test in rabbits for pure bulk liquids is shown to be perfectly compatible with eye irritation thresholds in humans. The total data set for 91 compounds was analyzed by the general solvation equation of Abraham. Values of log (MMAS/P) or log (1/EIT) could be fitted to a five-parameter equation with R2 = 0.936, SD = 0.433, AD = 0.000, and AAD = 0.340 over a range of 9.6 log units. When divided into a training set of 45 compounds, the corresponding equation could be used to predict the remaining 46 compounds in a test set with AD = -0.037 and AAD = 0.345 log units. Thus, the 91-compound equation can now be used to predict further EIT values to around 0.4 log units. It is suggested that the mechanism of action in the Draize test and in the human EIT involves passive transfer of the compound to a biophase that is quite polar, is a strong hydrogen bond base, a moderate hydrogen bond acid, and quite hydrophobic. The biophase does not resemble water or plasma, but resembles an organic solvent such as N-methylformamide.     

Therapeutic targeting of the survivin pathway in cancer: initiation of mitochondrial apoptosis and suppression of tumor-associated angiogenesis.

PURPOSE: Molecular antagonists of the inhibitor of apoptosis protein survivin have shown promise as novel anticancer strategies for triggering tumor cell apoptosis, dysregulating mitotic progression, and inhibiting tumor growth in preclinical models. However, how survivin couples to the cell death machinery has remained elusive, and the relevant cellular targets of survivin antagonists have not been completely elucidated. Experimental Design: Human umbilical vein and dermal microvascular endothelial cells were infected with replication-deficient adenoviruses encoding survivin (pAd-Survivin), green fluorescent protein (pAd-GFP), or a phosphorylation-defective survivin Thr(34)-->Ala (pAd-T34A) dominant negative mutant. The effect of wild-type or mutant survivin was investigated on capillary network stability, endothelial cell viability, and caspase activation in vitro and on kinetics of tumor growth and development of angiogenesis in a breast cancer xenograft model in vivo. The cell death pathway initiated by survivin targeting was mapped with respect to cytochrome c release, changes in mitochondrial transmembrane potential, and apoptosome requirements using mouse embryonic fibroblasts deficient in Apaf-1 or caspase-9. RESULTS: Adenoviral transduction of endothelial cells with pAd-Survivin inhibited growth factor deprivation- or ceramide-induced apoptosis, reduced caspase-3 and -7 generation, and stabilized three-dimensional capillary networks in vitro. Conversely, expression of pAd-T34A caused apoptosis in umbilical vein and dermal microvascular endothelial cells and resulted in caspase-3 activity. Cell death induced by survivin targeting exhibited the hallmarks of mitochondrial-dependent apoptosis with release of cytochrome c and loss of mitochondrial transmembrane potential and was suppressed in Apaf-1 or caspase-9 knockout mouse embryonic fibroblasts. When injected in human breast cancer xenografts, pAd-T34A inhibited growth of established tumors and triggered tumor cell apoptosis in vivo. This was associated with a approximately 60% reduction in tumor-derived blood vessels by quantitative morphometry of CD31-stained tumor areas, and appearance of endothelial cell apoptosis by internucleosomal DNA fragmentation in vivo. CONCLUSIONS: Survivin functions as a novel upstream regulator of mitochondrial-dependent apoptosis, and molecular targeting of this pathway results in anticancer activity via a dual mechanism of induction of tumor cell apoptosis and suppression of angiogenesis.     

Pyloric volume: an important factor in the surgeon’s ability to palpate the pyloric “olive” in hypertrophic pyloric stenosis

Objective. The objective of this study was to determine whether the size of the pyloric mass is one of the factors in the surgeon's ability to palpate the pyloric “olive”. Materials and methods. The ultrasonographic images and medical records of 60 infants with surgically confirmed hypertrophic pyloric stenosis (HPS) were reviewed. The pyloric diameter (PD) and pyloric length (PL) were measured and the pyloric volume (PV) was calculated using the equation PV = 1/4π× (PD)²× PL. Based on the pediatric surgeon's physical examination the infants were divided into two groups: those with and those without palpable pyloric masses. Results. Infants with a palpable pyloric mass had an average pyloric volume of 3.33 ± 1.76 mm³, which was statistically larger than those whose hypertrophied pylorus could not be palpated (average volume 2.59 ± 2.07 mm³, P < 0.01). There was no statistically significant age difference between the two groups. Conclusion. Clinical skill of the examiner and other clinical aspects (patient cooperation, etc.) determine palpability of the pylorus in HPS. The size of the hypertrophied pylorus is also an important factor affecting the clinican's ability to palpate the pyloric mass. Received: 29 December 1995 Accepted: 7 June 1996     

The association between social support and the mental health of social workers and police officers who work with unaccompanied asylum-seeking refugee children’s forced repatriation: A Swedish experience

This study aims to contribute to the knowledge of social support and its association with mental health amongst social workers and police officers in forced repatriation work of unaccompanied asylum-seeking refugee children. Nationally distributed surveys to social workers and police officers with and without experience of forced repatriation were used, measured by an abbreviated version of the Interview Schedule for Social Interaction (ISSI), and analyzed by univariate and multivariable regression models. Social workers in forced repatriation showed significantly poorer mental health than other social workers, but simultaneously relatively high access to social support. Irrespective of working with forced repatriation, police officers reported relatively high access to social support, but no difference in mental health. Furthermore, low levels of satisfaction with social interaction and close emotional support increased the odds of psychological disturbances for police officers in forced repatriation. Findings are discussed with special regard to the complexity of forced repatriation, particularly when children are the focus.