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In research and engineering, short laser pulses are fundamental for metrology and communication. The generation of pulses by passive mode-locking is especially desirable due to the compact setup dimensions, without the need for active modulation requiring dedicated external circuitry. However, well-established models do not cover regular self-pulsing in gain media that recover faster than the cavity round trip time. For quantum cascade lasers (QCLs), this marked a significant limitation in their operation, as they exhibit picosecond gain dynamics associated with intersubband transitions. We present a model that gives detailed insights into the pulse dynamics of the first passively mode-locked QCL that was recently demonstrated. The presence of an incoherent saturable absorber, exemplarily realized by multilayer graphene distributed along the cavity, drives the laser into a pulsed state by exhibiting a similarly fast recovery time as the gain medium. This previously unstudied state of laser operation reveals a remarkable response of the gain medium on unevenly distributed intracavity intensity. We show that in presence of strong spatial hole burning in the laser gain medium, the pulse stabilizes itself by suppressing counter-propagating light and getting shortened again at the cavity facets. Finally, we study the robustness of passive mode-locking with respect to the saturable absorber properties and identify strategies for generating even shorter pulses. The obtained results may also have implications for other nanostructured mode-locked laser sources, for example, based on quantum dots.

Background Ectopic pregnancy (EP) is a significant cause of maternal morbidity and mortality. Accurate and timely diagnosis is crucial, particularly in women of reproductive age presenting with acute abdominal pain. This audit aimed to assess the completeness and accuracy of gynecological history documentation, including pregnancy status, in female patients admitted for emergency surgery due to abdominal pain. Methods A retrospective audit was conducted within a single NHS Trust, analyzing the surgical assessment documents of 50 female patients aged 12-50 years admitted for emergency surgery. Data collected included documentation of pregnancy status, gynecological history, last menstrual period, sexual activity, and contraceptive use. A subsequent audit cycle assessed the impact of an educational intervention on documentation practices. Results Initial findings revealed significant deficiencies in the documentation of key gynecological parameters. Pregnancy status was documented in only 14% of cases, and contraceptive use in 20%. A substantial proportion of cases lacked documentation of gynecological history 50% and sexual history 56%. An educational intervention resulted in a significant improvement in the documentation of sexual history, contraceptive use, and pregnancy status. Conclusion This audit revealed significant deficiencies in the initial gynecological assessment of female patients with acute abdominal pain, particularly regarding the documentation of pregnancy status, menstrual history, and contraceptive use. The study highlights the need for improved clinical practices, including enhanced medical education, standardized assessment protocols, and electronic documentation of pregnancy status. Continued research is crucial to address these deficiencies and optimize patient care within the NHS., Competing Interests: Human subjects: Consent for treatment and open access publication was obtained or waived by all participants in this study. Audit and Research Department, Wrightington, Wigan and Leigh NHS Foundation Trust issued approval GenSurg/CA/2021-22/09. Animal subjects: All authors have confirmed that this study did not involve animal subjects or tissue. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2025, Siddiqui et al.)

Introduction Bariatric surgery is increasingly employed to address the global burden of morbid obesity, with Roux-en-Y gastric bypass (RYGB) representing the predominant procedure. However, some patients, particularly those with extreme obesity (BMI >50 kg/m²), may experience unsatisfactory weight-related outcomes following RYGB. While biliopancreatic diversion with duodenal switch (BPD-DS) offers superior weight reduction for this population, its complexity and associated risks limit its widespread use. Single anastomosis duodeno-ileal bypass with sleeve gastrectomy (SADI-S) was developed as a simpler substitue to BPD-DS, aiming to gain equivalent weight loss with improved safety profile. This analysis examined the efficacy of SADI-S in facilitating weight loss and ameliorating concomitant conditions (type 2 diabetes mellitus, hypertension, and obstructive sleep apnea) at various time points up to nine years post-procedure. Additionally, the study assessed the incidence of nutritional deficiencies following SADI-S. Material and methods This retrospective analysis utilized data obtained from patients undergoing SADI-S at a high-volume specialized bariatric centre between January 2016 and December 2022. Inclusion criteria encompassed individuals with high BMI and uncontrolled obesity-related comorbidities who had experienced insufficient weight-related outcomes following a previous bariatric surgery and demonstrated good compliance within a Tier 3 weight management program. Patients were excluded if they were non-compliant, unfit for surgery, or under 18 years old. Participants were followed up quarterly in the first year, every four months in the second year, and yearly thereafter. Nutritional assessments were performed in accordance with British Obesity and Metabolic Surgery Society (BOMSS) guidelines. Relevant data were extracted from patient clinical records and institutional electronic databases and analyzed using Microsoft Excel. Results There were 4000+ bariatric procedures conducted during this time. Seventeen patients were deemed as suitable candidates for SADI-S after multidisciplinary team discussion. The surgeries were performed by various surgeons. Most participants were women, with an age range of 23 to 64 years. The median BMI was 63.4 kg/m² (range: 35 kg/m² to 96.2 kg/m²). Mean percentage excess weight loss (%EWL) was 32% (range: 15% to 53%) at six months, 69.6% (range: 34% to 90%) at one year, and 86.2% (range: 43% to 109%) at two years post-procedure. Extended follow-up data (six to nine years) were available for 16 patients, with one patient lost to subsequent assessments. At this stage, the mean %EWL was 76% (range: 62% to 96%). No patients developed protein-energy malnutrition. However, micronutrient deficiencies were observed, with four patients (23.53%) exhibiting zinc deficiency and three (17.65%) presenting with calcium deficiency. All deficiencies were successfully managed with oral supplementation. Conclusion SADI-S effectively achieves substantial and sustained weight loss with high comorbidity resolution in individuals with high BMI. While micronutrient deficiencies require proactive management, SADI-S appears safe and yields favourable outcomes comparable to, or exceeding, those reported in larger studies. Long-term weight maintenance is promising. This study contributes valuable real-world evidence supporting the efficacy and safety of SADI-S, though larger studies are needed for further validation., Competing Interests: Human subjects: Consent for treatment and open access publication was obtained or waived by all participants in this study. Animal subjects: All authors have confirmed that this study did not involve animal subjects or tissue. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Haider et al.)

Narrow-bandgap (NBG) perovskite solar cells based on tin-lead mixed perovskite absorbers suffer from significant open-circuit voltage ( V OC ) losses due primarily to a high defect density and charge carrier recombination at the device interfaces. In this study, the V OC losses in NBG perovskite single junction cells ( E g = 1.21 eV) are addressed. The optimized NBG subcell is then used to fabricate highly efficient all-perovskite tandem solar cells (TSCs). The improvement in the V OC is achieved via the addition of a thin poly(triarylamine) interlayer between the poly(3,4-ethylenedioxythiophene) poly(styrenesulfonate) (PEDOT:PSS)-based hole transport layer (HTL) and the NBG perovskite. The optimal bilayer HTL results in a champion power conversion efficiency (PCE) of 20.3%, compared to 17.8% of the PEDOT:PSS-based control device. The V OC improvement of the single-junction NBG cell is also successfully transferred to all-perovskite TSC, resulting in a high V OC of 2.00 V and a PCE of 25.1%., Competing Interests: The authors declare no competing financial interest., (© 2024 The Authors. Published by American Chemical Society.)

Introduction Acute pancreatitis (AP), characterized by the inflammation of the pancreas, is a common acute surgical condition accounting for approximately 3% of all surgical admissions with abdominal pain and has an incidence of approximately 56 cases per 100,000 population every year. The General Medical Council (GMC), National Institute for Health and Care Excellence (NICE), and Royal College of Nursing best practice guidelines recommend that such patients and their family members should be provided with both verbal and written information about acute pancreatitis and its management in a way that they can understand. The aim of this audit cycle was to find out the compliance with information provided to patients with acute pancreatitis as per the GMC good medical practice and NICE guidelines and assess their satisfaction. Method A closed-loop audit consisting of two cycles was carried out. Thirty patients who were admitted to the department of general surgery with acute pancreatitis were provided with a questionnaire containing 11 questions asking about the information provided to them about their condition by healthcare professionals; then, interventions were carried out in the form of developing patient information leaflets (PILs) and encouraging healthcare professionals to distribute them and provide information to the patients and their family members. Results Overall, improvements were seen in all aspects of the information being provided to patients, and particularly, more than 100% improvement was seen in patient satisfaction related to the information provided to them in the second cycle after the implementation of interventions. Conclusions This study concludes that patients should be given all the information they require in accordance with their right to information, in line with GMC best practice, NICE, and Royal College of Nursing best practice guidelines. A very effective way to improve the health outcomes and satisfaction of patients is to give them access to a patient information leaflet, which can allow patients to consider their options and understand what can happen during treatment, especially when doctors have limited time to carry out detailed discussions with the patient., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2023, Jamal et al.)

Restorative proctocolectomy with ileal pouch-anal anastomosis (IPAA) has become standard surgical treatment of choice in patients with ulcerative colitis (UC) and familial adenomatous polyposis (FAP) in which the medical management fails. Despite the wide use of laparoscopic method, the enhanced and innovative features that come with the robotic platform, such as endo-wrist technology, 3D visualization, surgeon-controlled camera and motion scaling, make it an appealing choice. This study aims to investigate the feasibility and safety of robotic approach for proctectomy or proctocolectomy with IPAA as compared to conventional laparoscopic approach. A systematic review was completed for studies done between 2010 and 2022 comparing the robotic approach with the laparoscopic approach. Nine studies were found to be feasible to be included in this review. In terms of the outcomes, although the mean operating time was slightly higher than the laparoscopic approach, the other outcomes, such as mean blood loss, return of the bowel movement, mean hospital stay, and conversion to open, were found to be significantly lower in the robotic approach as compared to both laparoscopic and conventional open techniques. Despite the overall increased rate of complications combined from all the studies, the rate of significant complications such as anastomotic leaks requiring readmission and return to theater was also found to be substantially less. This study concludes that although robotic approach is in its initial stages for pelvic surgeries, it can be safely employed due to improved dexterity and visibility., (© 2022. Crown.)

Self-healing materials have the potential to create a paradigm shift in the life cycle design of engineered structures, by changing the relation between material damage and structural failure, affecting structures' lifetime, safety, and reliability. However, the knowledge of self-healing capabilities in metallic materials is still in its infancy compared to other material systems because of challenges in the synthesis of organized and complex structures. This paper presents a study of a metal matrix composite system that was synthesized with an off-eutectic Tin (Sn)-Bismuth (Bi) alloy matrix, reinforced with Nickel-Titanium (NiTi) shape memory alloy (SMA) wires. The ability to close cracks, recover bulk geometry, and regenerate strength upon the application of heat was investigated. NiTi wires were etched and coated in flux before being incorporated into the matrix to prevent disbonding with the matrix. Samples were subjected to large deformations in a three-point bending setup. Subsequent thermo-mechanical testing of the composites confirmed the materials' ability to restore their geometry and recover strength, without using any consumable components. Self-healing was accomplished through a combination of activation of the shape memory effect in the NiTi to recover the samples' original macroscopic geometry, closing cracks, and melting of the eutectic material in the matrix alloy, which resealed the cracks. Subsequent testing indicated a 92% strength recovery.

Autoimmune diseases are driven largely by a pathogenic cytokine milieu produced by aberrantly activated lymphocytes. Many cytokines, including interferon gamma (IFN-γ), utilize the JAK/STAT pathway for signal propagation. Suppressor of Cytokine Signaling-1 (SOCS1) is an inducible, intracellular protein that regulates IFN-γ signaling by dampening JAK/STAT signaling. Using Fas deficient, MRL/MpJ-Fas lpr /J (MRL/lpr) mice, which develop lupus-like disease spontaneously, we tested the hypothesis that a peptide mimic of the SOCS1 kinase inhibitory region (SOCS1-KIR) would inhibit lymphocyte activation and modulate lupus-associated pathologies. Consistent with in vitro studies, SOCS1-KIR intraperitoneal administration reduced the frequency, activation, and cytokine production of memory CD8 + and CD4 + T lymphocytes within the peripheral blood, spleen, and lymph nodes. In addition, SOCS1-KIR administration reduced lymphadenopathy, severity of skin lesions, autoantibody production, and modestly reduced kidney pathology. On a cellular level, peritoneal SOCS1-KIR administration enhanced Foxp3 expression in total splenic and follicular regulatory T cells, reduced the effector memory/naïve T lymphocyte ratio for both CD4 + and CD8 + cells, and reduced the frequency of GL7 + germinal center enriched B cells. Together, these data show that SOCS1-KIR treatment reduced auto-reactive lymphocyte effector functions and suggest that therapeutic targeting of the SOCS1 pathway through peptide administration may have efficacy in mitigating autoimmune pathologies.

Organic solar cells based on nonfullerene acceptors have recently witnessed a significant rise in their power conversion efficiency values. However, they still suffer from severe instability issues, especially in an inverted device architecture based on the zinc oxide bottom electron transport layers. In this work, we insert a pyrene-bodipy donor-acceptor dye as a thin interlayer at the photoactive layer/zinc oxide interface to suppress the degradation reaction of the nonfullerene acceptor caused by the photocatalytic activity of zinc oxide. In particular, the pyrene-bodipy-based interlayer inhibits the direct contact between the nonfullerene acceptor and zinc oxide hence preventing the decomposition of the former by zinc oxide under illumination with UV light. As a result, the device photostability was significantly improved. The  π-π interaction between the nonfullerene acceptor and the bodipy part of the interlayer facilitates charge transfer from the nonfullerene acceptor toward pyrene, which is followed by intramolecular charge transfer to bodipy part and then to zinc oxide. The bodipy-pyrene modified zinc oxide also increased the degree of crystallization of the photoactive blend and the face-on stacking of the polymer donor molecules within the blend hence contributing to both enhanced charge transport and increased absorption of the incident light. Furthermore, it decreased the surface work function as well as surface energy of the zinc oxide film all impacting in improved power conversion efficiency values of the fabricated cells with champion devices reaching values up to 9.86 and 11.80% for the fullerene and nonfullerene-based devices, respectively.

Introduction Metacarpal and phalangeal fractures are common upper limb fractures due to direct blows, axial loading, and torsional loading injuries. The universal goal in treating all fractures for the patient to achieve normal motion, but the ideal technique for stabilization is still debated. For internal fixation, Kirschner wires (K-wires) or miniplates can be used, and each carries certain advantages. No previous study has compared K-wire use to miniplate use in treating metacarpal and phalangeal fractures. Therefore, we conducted this randomized control trial to evaluate the outcomes of K-wire and miniplate use in treating metacarpal and phalangeal fractures. Materials and methods This randomized controlled trial was conducted in the Department of Orthopaedic Surgery, Bahawal Victoria Hospital, from February 2017 to February 2018. Seventy-five patients were included in this study and randomly assigned into two groups. One group was treated with K-wire fixation, and the other group was treated with miniplate fixation. We assessed total active motion (TAM), range of motion (ROM), duration of injury, and complication rate. Data were analyzed using IBM SPSS Statistics for Windows, Version 23.0 (Armonk, NY: IBM Corp). P values ≤ 0.05 were considered significant. Results Mean surgical time, pain scale, and time of union of K-wire treated patients was 38.63±3.64 minutes, 4.17±1.11, and 12.95±3.38 weeks, respectively. The success of the union was noted in 38 K-wire patients (95%). Total active ROM was greater in miniplate fixation patients compared with K-wire treated patients, but this difference was statistically significant. Similarly, TAM was also greater in the miniplate fixation patients compared to the K-wire treated patients, but this difference was also not statistically significant. Conclusion Both K-wire fixation and miniplate fixation are equally effective in terms of TAM, ROM, and complications when used to treat metacarpal and phalangeal fractures., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2020, Ahmed et al.)

Photovoltaic devices based on organic semiconductors and organo-metal halide perovskites have not yet reached the theoretically predicted power conversion efficiencies while they still exhibit poor environmental stability. Interfacial engineering using suitable materials has been recognized as an attractive approach to tackle the above issues. We introduce here a zinc porphyrin-triazine-bodipy donor-π bridge-acceptor dye as a universal electron transfer mediator in both organic and perovskite solar cells. Thanks to its "push-pull" character, this dye enhances electron transfer from the absorber layer toward the electron-selective contact, thus improving the device's photocurrent and efficiency. The direct result is more than 10% average power conversion efficiency enhancement in both fullerene-based (from 8.65 to 9.80%) and non-fullerene-based (from 7.71 to 8.73%) organic solar cells as well as in perovskite ones (from 14.56 to 15.67%), proving the universality of our approach. Concurrently, by forming a hydrophobic network on the surface of metal oxide substrates, it improves the nanomorphology of the photoactive overlayer and contributes to efficiency stabilization. The fabricated devices of both kinds preserved more than 85% of their efficiency upon exposure to ambient conditions for more than 600 h without any encapsulation.

The adhesion strength of thin films is critical to the durability of micro and nanofabricated devices. However, current testing methods are imprecise and do not produce quantitative results necessary for design specifications. The most common testing methods involve the manual application and removal of unspecified tape. This overcome many of the challenges of connecting to thin films to test their adhesion properties but different tapes, variation in manual application, and poorly controlled removal of tape can result in wide variation in resultant forces. Furthermore, the most common tests result in a qualitative ranking of film survival, not a measurement with scientific units. This paper presents a study into application and peeling parameters that can cause variation in the peeling force generated by tapes. The results of this study were then used to design a test methodology that would control the key parameters and produced repeatable quantitative measurements. Testing using the resulting method showed significant improvement over more standard methods, producing measured results with reduced variation. The new method was tested on peeling a layer of paint from a PTFE backing and was found to be sensitive enough to register variation in force due to differing peeling mechanisms within a single test.

Introduction The currently available literature suggests a wide range of conversion (4.9-20%) from laparoscopic cholecystectomy (LC) to open cholecystectomy (OC) despite the increase in surgical expertise. Open cholecystectomy is important as the last resort for safe surgical practice in complicated cases. Increased number of pre-operative and perioperative risk factors need to be identified to pre-empt conversion. However, there has been a significant decrease in conversion rates over the past few decades. This study was conducted to determine conversion rates in our population and to identify any significant risks for conversion. Methods This prospective study was conducted at the Shifa International Hospital, Islamabad, Pakistan, including 1081 cholecystectomies, performed over a two-year period from January 2017 to January 2019. Comparison of risk factors between the two groups; laparoscopic cholecystectomy (LC) group and conversion to open cholecystectomy (OC) group was done. Statistical analysis was done using SPSS 24.0.1. P<0.05 were considered significant. Results In our study, the overall conversion rate was 7.78%. Factors of conversion to open cholecystectomy (OC) included age ≥65, morbid obesity, diabetes mellitus, and previous abdominal surgery. Deranged alkaline phosphatase (ALP), increased total bilirubin, increased common bile duct (CBD) diameter, and multiple stones in ultrasonography showed a statistically significant association with the conversion. Per-operative findings of increased adhesions >50%, empyema gallbladder (GB), perforated GB, and scleroatrophic GB showed a higher risk of conversion too (p <0.05). However, there was no statistical association with preoperative endoscopic retrograde cholangiopancreatography (ERCP) to OC in our population. Conclusion An open cholecystectomy is a safe approach for patients with complicated gallbladder disease. No doubt laparoscopic cholecystectomy is the gold standard having its outstanding benefits. This study identifies predictors of choice for OC in addition to the decision to convert to OC. In view of the raised morbidity and mortality associated with open cholecystectomy, distinguishing these predictors will serve to decrease the rate of OC and to address these factors preoperatively., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2019, Amin et al.)

Introduction The American Society of Metabolic and Bariatric Surgery has stated that bariatric surgery is indicated in Class I obesity patients with one or more comorbidities. However, other weight loss options, such as diet plus exercise, are available to patients with a body mass index (BMI) ranging from 30 to 35 kg/m 2 . This study aimed to prospectively compare the results of Class I obesity patients undergoing laparoscopic sleeve gastrectomy (LSG) or using a weight control program (WCP). Methods A prospective analysis was conducted of patients with Class I obesity and comorbid diabetes and hypertension, with follow-ups at 6, 12, and 18 months. Subjects were divided into two groups: the LSG group of patients who had undergone LSG, and the WCP group who adhered to a WCP. The percentage of excess BMI loss (%EBMIL) and comorbidity remission (diabetes mellitus and hypertension) were tracked with measurements of hemoglobin A1C (HBA1C) levels and systolic blood pressure. Self-esteem was also tracked using the Rosenberg Self-Esteem Scale (SES) at 0 and 18 months. The overall patient satisfaction score was calculated using a visual analogue scale. Results Of the 150 patients enrolled in the study, 106 were included in the LSG group, and 103 were included in the WCP group. The reduction in HBA1C was more pronounced in the LSG group, and the differences between the two were statistically significant after 6, 12, and 18 months (LSG 5.6 ± 0.47 vs. WCP 6.5 ± 0.64, CI 1.04-0.73, P < 0.05). At 12 and 18 months, there were statistically significant reductions in systolic blood pressure after LSG (LSG 134.2 ± 7.16 vs. WCP 145.63 ± 5.94, CI 13.2-9.6, P < 0.05). Self-esteem levels measured by the Rosenberg SES increased for all participants, while patient satisfaction score was higher in the LSG group than that in the WCP group (P < 0.05). The %EBMIL at 6 months in the LSG group was 35.48%, compared to the WCP group at only 7.23%. At 12 months, the %EBMIL had increased twofold in the LSG group, at 68.19%, compared to 14.53% in the WCP group. At the final 18-month follow-up, the %EBMIL in the LSG group was 99.60% but was only 25.70% in the WCP group (P < 0.05). Conclusion Our study elucidates a clear superiority of LSG over any structured WCP with regard to weight reduction, improvement in glycemic control, and reduction in blood pressure in Class I obesity patients. Additionally, patients having LSG reported markedly improved self-esteem and satisfaction when compared with those who undertook a WCP., Competing Interests: The authors have declared that no competing interests exist.

Solar cells based on organic-inorganic halide perovskites are now leading the photovoltaic technologies because of their high power conversion efficiency. Recently, there have been debates on the microstructure-related defects in metal halide perovskites (grain size, grain boundaries, etc.) and a widespread view is that large grains are a prerequisite to suppress nonradiative recombination and improve photovoltaic performance, although opinions against it also exist. Herein, we employ blends of methylammonium lead iodide perovskites with an insulating polymer (polyvinylpyrrolidone) that offer the possibility to tune the grain size in order to obtain a fundamental understanding of the photoresponse at the microscopic level. We provide, for the first time, spatially resolved details of the microstructures in such blend systems via Raman mapping, light beam-induced current imaging, and conductive atomic force microscopy. Although the polymer blend systems systematically alter the morphology by creating small grains (more grain boundaries), they reduce nonradiative recombination within the film and enhance its spatial homogeneity of radiative recombination. We attribute this to a reduction in the density of bulk trap states, as evidenced by an order of magnitude higher photoluminescence intensity and a significantly higher open-circuit voltage when the polymer is incorporated into the perovskite films. The solar cells employing blend systems also show nearly hysteresis-free power conversion efficiency ∼17.5%, as well as a remarkable shelf-life stability over 100 days.

Objective To assess the outcome and safety of staple line over-sewing for patients undergoing laparoscopic sleeve gastrectomy (LSG). Study design and location Retrospective descriptive analysis conducted at Shifa International Hospital Islamabad. Materials and methods Consecutive patients undergoing LSG as a treatment for morbid obesity from October 2013 to December 2016 were included in the study after approval from the ethical review board. Patients were divided into two groups: group A who underwent reinforcement using Vicryl 2.0 and group B where no reinforcement was done. Results A total of 225 patients underwent LSG between October 2013 and December 2016, including 147 females (65.4%) and 78 males (34.6%). Both groups were comparable in terms of age, body mass index (BMI) and gender distribution (p-value more than 0.05). There was one leak in group A (1.36%), none in group B. The bleeding rate was 4.3% in group A and 2.7% in group B. Conclusion This was a retrospective analysis of all the patients who underwent LSG, and it was observed that there was no added benefit of sewing the staple line in terms of rate of bleeding and leak., Competing Interests: The authors have declared that no competing interests exist.

Objective: To investigate the outcomes of laparoscopic sleeve gastrectomy (LSG) in terms of weight loss., Study Design: Descriptive cohort study., Place and Duration of Study: Department of Surgery, Shifa International Hospital, Islamabad, from January 2009 to January 2015., Methodology: A total of 100 consecutive patients were included in the study through retrospective chart review. A5-port technique was utilized with the gastric sleeve being created using endostapler. Postoperatively, patients gradually progressed from clear liquid diet and oral rehydration salts to nutritional supplements over three days. By two weeks postoperatively, patients had progressed to a solid diet. SPSS was used for data entry and analysis. Body mass index (BMI) and weight in kg were determined., Results: From 100 patients, 17 were lost to follow-up less than a week into the postoperative period. Of the remaining, average age of the patients was 34.7 ±11.3 years at the time of surgery. The majority of patients were females (72%). Mean preoperative and postoperative BMI was 45.3 ±10.4 kg/m2 and 35.0 ±10 kg/m2, respectively. Of the 83 patients, 62 were followed-up for longer than 1 month (average 419 days). For patients in this category, mean reduction in BMI was 10.3 ±6.5 kg/m2 with average weight loss of 34.3 ±18.2 kg. There were no mortalities associated with LSG., Conclusion: Laparoscopic sleeve gastrectomy is a safe and effective intervention in young Pakistani females with encouraging outcomes at a mean follow-up of over one year.

Suppressor of cytokine signaling 1-deficient (SOCS1(-/-)) mice, which are lymphopenic, die <3 wk after birth of a T cell-mediated autoimmune inflammatory disease characterized by leukocyte infiltration and destruction of vital organs. Notably, Foxp3(+) regulatory T cells (Tregs) have been shown to be particularly potent in inhibiting inflammation-associated autoimmune diseases. We observed that SOCS1(-/-) mice were deficient in peripheral Tregs despite enhanced thymic development. The adoptive transfer of SOCS1-sufficient Tregs, CD4(+) T lymphocytes, or administration of SOCS1 kinase inhibitory region (KIR), a peptide that partially restores SOCS1 function, mediated a statistically significant but short-term survival of SOCS1(-/-) mice. However, the adoptive transfer of SOCS1-sufficient CD4(+) T lymphocytes, combined with the administration of SOCS1-KIR, resulted in a significant increase in the survival of SOCS1(-/-) mice both short and long term, where 100% death occurred by day 18 in the absence of treatment. Moreover, the CD4(+)/SOCS1-KIR combined therapy resulted in decreased leukocytic organ infiltration, reduction of serum IFN-γ, and enhanced peripheral accumulation of Foxp3(+) Tregs in treated mice. These data show that CD4(+)/SOCS1-KIR combined treatment can synergistically promote the long-term survival of perinatal lethal SOCS1(-/-) mice. In addition, these results strongly suggest that SOCS1 contributes to the stability of the Foxp3(+) Treg peripheral population under conditions of strong proinflammatory environments.

Suppressor of cytokine signaling (SOCS)-1 protein modulates signaling by IFN-gamma by binding to the autophosphorylation site of JAK2 and by targeting bound JAK2 to the proteosome for degradation. We have developed a small tyrosine kinase inhibitor peptide (Tkip) that is a SOCS-1 mimetic. Tkip is compared in this study with the kinase inhibitory region (KIR) of SOCS-1 for JAK2 recognition, inhibition of kinase activity, and regulation of IFN-gamma-induced biological activity. Tkip and a peptide corresponding to the KIR of SOCS-1, ((53))DTHFRTFRSHSDYRRI((68)) (SOCS1-KIR), both bound similarly to the autophosphorylation site of JAK2, JAK2(1001-1013). The peptides also bound to JAK2 peptide phosphorylated at Tyr(1007), pJAK2(1001-1013). Dose-response competitions suggest that Tkip and SOCS1-KIR similarly recognize the autophosphorylation site of JAK2, but probably not precisely the same way. Although Tkip inhibited JAK2 autophosphorylation as well as IFN-gamma-induced STAT1-alpha phosphorylation, SOCS1-KIR, like SOCS-1, did not inhibit JAK2 autophosphorylation but inhibited STAT1-alpha activation. Both Tkip and SOCS1-KIR inhibited IFN-gamma activation of Raw 264.7 murine macrophages and inhibited Ag-specific splenocyte proliferation. The fact that SOCS1-KIR binds to pJAK2(1001-1013) suggests that the JAK2 peptide could function as an antagonist of SOCS-1. Thus, pJAK2(1001-1013) enhanced suboptimal IFN-gamma activity, blocked SOCS-1-induced inhibition of STAT3 phosphorylation in IL-6-treated cells, enhanced IFN-gamma activation site promoter activity, and enhanced Ag-specific proliferation. Furthermore, SOCS-1 competed with SOCS1-KIR for pJAK2(1001-1013). Thus, the KIR region of SOCS-1 binds directly to the autophosphorylation site of JAK2 and a peptide corresponding to this site can function as an antagonist of SOCS-1.

We have demonstrated previously that the C-terminal gamma interferon (IFN-gamma) mimetic peptide consisting of residues 95 to 133 [IFN-gamma(95-133)], which contains the crucial IFN-gamma nuclear localization sequence (NLS), has antiviral activity in tissue culture. Here we evaluate the efficacy of this peptide and its derivatives first in vitro and then in an animal model of lethal viral infection with the encephalomyocarditis (EMC) virus. Deletion of the NLS region from the IFN-gamma mimetic peptide IFN-gamma(95-133) resulted in loss of antiviral activity. However, the NLS region does not have antiviral activity in itself. Replacing the NLS region of IFN-gamma(95-133) with the NLS region of the simian virus 40 large T antigen retains the antiviral activity in tissue culture. IFN-gamma(95-133) prevented EMC virus-induced lethality in mice in a dose-dependent manner compared to controls. Mice treated with IFN-gamma(95-133) had no or low EMC virus titers in their internal organs, whereas control mice had consistently high viral titers, especially in the heart tissues. Injection of B8R protein, which is encoded by poxviruses as a defense mechanism to neutralize host IFN-gamma, did not inhibit IFN-gamma(95-133) protection against a lethal dose of EMC virus, whereas mice treated with rat IFN-gamma were not protected. The data presented here show that the IFN-gamma mimetic peptide IFN-gamma(95-133) prevents EMC virus infection in vivo and in vitro and may have potential against other lethal viruses, such as the smallpox virus, which encodes the B8R protein.

We have previously characterized a novel tyrosine kinase inhibitor peptide (Tkip) that is a mimetic of suppressor of cytokine signaling 1 (SOCS-1) and inhibits JAK2 phosphorylation of the transcription factor STAT1alpha. We show in this study that Tkip protects mice against experimental allergic encephalomyelitis (EAE), an animal model for multiple sclerosis. Mice are immunized with myelin basic protein (MBP) for induction of disease. Tkip (63 mug) administered every other day suppressed the development of acute EAE in 75% of New Zealand White (NZW) mice. Furthermore, Tkip completely protected SJL/J mice, which where induced to get the relapsing/remitting form of EAE, against relapses compared with control groups in which >70% of the mice relapsed after primary incidence of disease. Protection of mice by Tkip was similar to that seen with the type I IFN, IFN-tau. Protection of mice correlated with lower MBP Ab titers in Tkip-treated groups as well as suppression of MBP-induced proliferation of splenocytes taken from EAE-afflicted mice. Cessation of Tkip and IFN-tau administration resulted in SJL/J mice relapsing back into disease. Prolonged treatment of mice with Tkip produced no evidence of cellular toxicity or weight loss. Consistent with its JAK2 inhibitory function, Tkip also inhibited the activity of the inflammatory cytokine TNF-alpha, which uses the STAT1alpha transcription factor. The data presented in this study show that Tkip, like the type I IFN, IFN-tau, inhibits both the autoreactive cellular and humoral responses in EAE and ameliorates both the acute and chronic relapsing/remitting forms of EAE.