Early enteral nutrition after surgical treatment of gut perforations: A prospective randomised study

BACKGROUND: Withholding enteral feeds after an elective gastrointestinal surgery is based on the hypothesis that this period of "nil by mouth" provides rest to the gut and promotes healing. AIMS: To assess whether early postoperative naso-gastric tube feeding in the form of a balanced diet formula is safe in and beneficial to patients who have undergone surgical intervention for perforation of the gut. SETTING: A surgical unit of a Medical College Hospital. DESIGN AND SUBJECTS: Prospective randomised open control study. METHODS AND MATERIAL: Patients undergoing surgical intervention for peritonitis following perforation of the gut were randomised to the study group receiving feedings of a balanced diet formula through a naso-gastric tube from the second postoperative day, or the control group in which patients were managed with the conventional regimen of intravenous fluid administration. The groups were compared for incidence and duration of complications, biochemical measurements and other characteristics like weight loss/gain. STATISTICAL ANALYSIS: Chi square test and 'T' test. RESULTS: One hundred patients were enrolled in each group. 88% subjects in the study group achieved positive nitrogen balance on the eighth postoperative day as compared to none in the conventionally managed group. The relative risks (95% confidence interval) of morbidity from wound infection, wound dehiscence, pneumonia, leakage of anastomoses and septicaemia were 0.66 (0.407-1.091), 0.44 (0.141-1.396), 0.70 (0.431-1.135), 0.54 (0.224-1.293) and 0.66 (0.374-1.503) respectively. Average loss of weight between the first and tenth day was 3.10 kg in the study group as compared to 5.10 kg in the conventionally managed group ('P' value < 0.001, 95% Confidence Interval - 2.46 - 1.54). CONCLUSION: Early enteral nutrition is safe and is associated with beneficial effects such as lower weight loss, early achievement of positive nitrogen balance as compared to the conventional regimen of feeding in operated cases of gut perforation

Characterization of shape and dimensional accuracy of incrementally formed titanium sheet parts with intermediate curvatures between two feature types

Single point incremental forming (SPIF) is a relatively new manufacturing process that has been recently used to form medical grade titanium sheets for implant devices. However, one limitation of the SPIF process may be characterized by dimensional inaccuracies of the final part as compared with the original designed part model. Elimination of these inaccuracies is critical to forming medical implants to meet required tolerances. Prior work on accuracy characterization has shown that feature behavior is important in predicting accuracy. In this study, a set of basic geometric shapes consisting of ruled and freeform features were formed using SPIF to characterize the dimensional inaccuracies of grade 1 titanium sheet parts. Response surface functions using multivariate adaptive regression splines (MARS) are then generated to model the deviations at individual vertices of the STL model of the part as a function of geometric shape parameters such as curvature, depth, distance to feature borders, wall angle, etc. The generated response functions are further used to predict dimensional deviations in a specific clinical implant case where the curvatures in the part lie between that of ruled features and freeform features. It is shown that a mixed-MARS response surface model using a weighted average of the ruled and freeform surface models can be used for such a case to improve the mean prediction accuracy within ±0.5 mm. The predicted deviations show a reasonable match with the actual formed shape for the implant case and are used to generate optimized tool paths for minimized shape and dimensional inaccuracy. Further, an implant part is then made using the accuracy characterization functions for improved accuracy. The results show an improvement in shape and dimensional accuracy of incrementally formed titanium medical implants

Effect of stress relieving heat treatment on surface topography and dimensional accuracy of incrementally formed grade 1 titanium sheet parts

The forming of parts with an optimized surface roughness and high dimensional accuracy is important in many applications of incremental sheet forming (ISF). To realize this, the effect of stress relieving heat treatment of grade-1 Ti parts performed before and after forming on the surface finish and dimensional accuracy was studied. It was found that heat treatment at a temperature of 540 °C for 2 h improves the surface finish of formed parts resulting in a surface with little or no visible tool marks. Additionally, it improves the dimensional accuracy of parts after unclamping from the rig used for forming, in particular, that of parts with shallow wall angles (typically <25°). It was also noted that post-forming heat treatment improves the surface finish of parts. The surface topography of formed parts was studied using interferometry to yield areal surface roughness parameters and subsequently using secondary electron imaging. Back-scatter electron microscopy imaging results coupled with energy-dispersive X-ray (EDX) analysis showed that heat treatment prior to forming leads to tool wear as indicated by the presence of Fe in samples. Furthermore, post-forming heat treatment prevents curling up of formed parts due to compressive stresses if the formed part is trimmed

Contribution of Cystine-Glutamate Antiporters to the Psychotomimetic Effects of Phencyclidine

Altered glutamate signaling contributes to a myriad of neural disorders, including schizophrenia. While synaptic levels are intensely studied, nonvesicular release mechanisms, including cystine–glutamate exchange, maintain high steady-state glutamate levels in the extrasynaptic space. The existence of extrasynaptic receptors, including metabotropic group II glutamate receptors (mGluR), pose nonvesicular release mechanisms as unrecognized targets capable of contributing to pathological glutamate signaling. We tested the hypothesis that activation of cystine–glutamate antiporters using the cysteine prodrug N-acetylcysteine would blunt psychotomimetic effects in the rodent phencyclidine (PCP) model of schizophrenia. First, we demonstrate that PCP elevates extracellular glutamate in the prefrontal cortex, an effect that is blocked by N-acetylcysteine pretreatment. To determine the relevance of the above finding, we assessed social interaction and found that N-acetylcysteine reverses social withdrawal produced by repeated PCP. In a separate paradigm, acute PCP resulted in working memory deficits assessed using a discrete trial t-maze task, and this effect was also reversed by N-acetylcysteine pretreatment. The capacity of N-acetylcysteine to restore working memory was blocked by infusion of the cystine–glutamate antiporter inhibitor (S)-4-carboxyphenylglycine into the prefrontal cortex or systemic administration of the group II mGluR antagonist LY341495 indicating that the effects of N-acetylcysteine requires cystine–glutamate exchange and group II mGluR activation. Finally, protein levels from postmortem tissue obtained from schizophrenic patients revealed significant changes in the level of xCT, the active subunit for cystine–glutamate exchange, in the dorsolateral prefrontal cortex. These data advance cystine–glutamate antiporters as novel targets capable of reversing the psychotomimetic effects of PCP

Subanesthetic ketamine treatment promotes abnormal interactions between neural subsystems and alters the properties of functional brain networks

Acute treatment with subanesthetic ketamine, a non-competitive N-methyl-D-aspartic acid (NMDA) receptor antagonist, is widely utilized as a translational model for schizophrenia. However, how acute NMDA receptor blockade impacts on brain functioning at a systems level, to elicit translationally relevant symptomatology and behavioral deficits, has not yet been determined. Here, for the first time, we apply established and recently validated topological measures from network science to brain imaging data gained from ketamine-treated mice to elucidate how acute NMDA receptor blockade impacts on the properties of functional brain networks. We show that the effects of acute ketamine treatment on the global properties of these networks are divergent from those widely reported in schizophrenia. Where acute NMDA receptor blockade promotes hyperconnectivity in functional brain networks, pronounced dysconnectivity is found in schizophrenia. We also show that acute ketamine treatment increases the connectivity and importance of prefrontal and thalamic brain regions in brain networks, a finding also divergent to alterations seen in schizophrenia. In addition, we characterize how ketamine impacts on bipartite functional interactions between neural subsystems. A key feature includes the enhancement of prefrontal cortex (PFC)-neuromodulatory subsystem connectivity in ketamine-treated animals, a finding consistent with the known effects of ketamine on PFC neurotransmitter levels. Overall, our data suggest that, at a systems level, acute ketamine-induced alterations in brain network connectivity do not parallel those seen in chronic schizophrenia. Hence, the mechanisms through which acute ketamine treatment induces translationally relevant symptomatology may differ from those in chronic schizophrenia. Future effort should therefore be dedicated to resolve the conflicting observations between this putative translational model and schizophrenia

PARP16 is a tail-anchored endoplasmic reticulum protein required for the PERK- and IRE1α-mediated unfolded protein response

Poly(ADP-ribose) polymerases (PARPs; also known as ADP-ribosyl transferase D proteins) modify acceptor proteins with ADP-ribose modifications of varying length (reviewed in refs 1, 2, 3). PARPs regulate key stress response pathways, including DNA damage repair and the cytoplasmic stress response. Here, we show that PARPs also regulate the unfolded protein response (UPR) of the endoplasmic reticulum (ER). Human PARP16 (also known as ARTD15) is a tail-anchored ER transmembrane protein required for activation of the functionally related ER stress sensors PERK and IRE1α during the UPR. The third identified ER stress sensor, ATF6, is not regulated by PARP16. As is the case for other PARPs that function during stress, the enzymatic activity of PARP16 is upregulated during ER stress when it ADP-ribosylates itself, PERK and IRE1α. ADP-ribosylation by PARP16 is sufficient for activating PERK and IRE1α in the absence of ER stress, and is required for PERK and IRE1α activation during the UPR. Modification of PERK and IRE1α by PARP16 increases their kinase activities and the endonuclease activity of IRE1α. Interestingly, the carboxy-terminal luminal tail of PARP16 is required for PARP16 function during ER stress, suggesting that it transduces stress signals to the cytoplasmic PARP catalytic domain.National Cancer Institute (U.S.) (Cancer Center Support Core Grant P30-CA14051)National Institutes of Health (U.S.) (Grant 5R01 GM087465-02)Kathy and Curt Marble Cancer Research FundJeptha H. and Emily V. Wade FundVirginia and D.K. Ludwig Fund for Cancer Researc

Development of multivariable models to predict change in Body Mass Index within a clinical trial population of psychotic individuals

Many antipsychotics promote weight gain, which can lead to non-compliance and relapse of psychosis. By developing models that accurately identify individuals at greater risk of weight gain, clinicians can make informed treatment decisions and target intervention measures. We examined clinical, genetic and expression data for 284 individuals with psychosis derived from a previously published randomised controlled trial (IMPACT). These data were used to develop regression and classification models predicting change in Body Mass Index (BMI) over one year. Clinical predictors included demographics, anthropometrics, cardiac and blood measures, diet and exercise, physical and mental health, medication and BMI outcome measures. We included genetic polygenic risk scores (PRS) for schizophrenia, bipolar disorder, BMI, waist-hip-ratio, insulin resistance and height, as well as gene co-expression modules generated by Weighted Gene Co-expression Network Analysis (WGCNA). The best performing predictive models for BMI and BMI gain after one year used clinical data only, which suggests expression and genetic data do not improve prediction in this cohort