Safety of robotic cholecystectomy as index training procedure: the UK experience.

AIMS: To evaluate the safety profile of robotic cholecystectomy performed within the United Kingdom (UK) Robotic Hepatopancreatobiliary (HPB) training programme. METHODS: A retrospective evaluation of prospectively collected data from eleven centres participating in the UK Robotic HPB training programme was conducted. All adult patients undergoing robotic cholecystectomy for symptomatic gallstone disease or gallbladder polyp were considered. Bile duct injury, conversion to open procedure, conversion to subtotal cholecystectomy, length of hospital stay, 30-day re-admission, and post-operative complications were the evaluated outcome parameters. RESULTS: A total of 600 patients were included. The median age was 53 (IQR 65-41) years and the majority (72.7%; 436/600) were female. The main indications for robotic cholecystectomy were biliary colic (55.5%, 333/600), cholecystitis (18.8%, 113/600), gallbladder polyps (7.7%, 46/600), and pancreatitis (6.2%, 37/600). The median length of stay was 0 (IQR 0-1) days. Of the included patients, 88.5% (531/600) were discharged on the day of procedure with 30-day re-admission rate of 5.5% (33/600). There were no bile duct injuries and the rate of conversion to open was 0.8% (5/600) with subtotal cholecystectomy rate of 0.8% (5/600). CONCLUSION: The current study confirms that robotic cholecystectomy can be safely implemented to routine practice with a low risk of bile duct injury, low bile leak rate, low conversion to open surgery, and low need for subtotal cholecystectomy.

In-vitro and in-vivo antidiabetic activity of aerial parts of Aitchisonia rosea supported by phytochemical and GC-MS analysis.

Medicinal plants contain a wide variety of bioactive phytoconstituents which can serve as new therapeutic agents for several diseases. This study examines the antidiabetic potential of Aitchisonia rosea in alloxan-induced diabetic rats and identifies its bioactive phytoconstituents using GC-MS. In vitro, antidiabetic potential was established using the α-amylase inhibition assay. In vivo, antidiabetic potential was investigated by employing the oral glucose tolerance test (OGTT). GC-MS analysis was used to identify the bioactive phytoconstituents. The in vitro and in vivo tests showed that the aqueous extract of A. rosea possesses better antidiabetic potential. The α-amylase inhibition assay highlighted an IC50 value of 134.87µg/ml. In an oral glucose tolerance test, rats given an aqueous A. rosea extract significantly lowered their blood sugar levels significant reduction in the blood glucose concentration was observed in the oral glucose tolerance test in rats treated with the aqueous A. rosea extract. GC-MS investigation revealed many phytoconstituents, with serverogenin acetate and cycloheptasiloxane tetradecamethyl being important antidiabetic agents. This study found anti-diabetic properties in A. rosea extract. The phytochemical and GC-MS investigation also found serverogenin acetate and cycloheptasiloxane tetradecamethyl, which could be used to develop new antidiabetic drugs.

Presenilin Is Essential for ApoE Secretion, a Novel Role of Presenilin Involved in Alzheimer's Disease Pathogenesis.

Alzheimer's disease (AD) is a debilitating dementia characterized by progressive memory loss and aggregation of amyloid-ß (Aß) protein into amyloid plaques in patient brains. Mutations in presenilin (PS) lead to abnormal generation of Aß, which is the major cause of familial AD (FAD), and apolipoprotein E4 (ApoE4) is the major genetic risk factor for sporadic AD (SAD) onset. However, whether dysfunction of PS is involved in the pathogenesis of SAD is largely unknown. We found that ApoE secretion was completely abolished in PS-deficient cells and markedly decreased by inhibition of γ-secretase activity. Blockade of γ-secretase activity by a γ-secretase inhibitor, DAPT, decreased ApoE secretion, suggesting an important role of γ-secretase activity in ApoE secretion. Reduced ApoE secretion is also observed in nicastrin-deficient cells with reduced γ-secretase activity. PS deficiency enhanced nuclear translocation of ApoE and binding of ApoE to importin α4, a nuclear transport receptor. Moreover, the expression of PS mutants in PS-deficient cells suppressed the restoration effects on ApoE secretion compared with the expression of wild-type PS. Plasma ApoE levels were lower in FAD patients carrying PS1 mutations compared with normal control subjects. Our findings suggest a novel role of PS contributing to the pathogenesis of SAD by regulating ApoE secretion.SIGNIFICANCE STATEMENT Familial AD (FAD) typically results from mutations in the genes encoding amyloid precursor protein, presenilin 1 (PS1), or PS2. Many PS mutants have been found to exert impaired γ-secretase activity and increased amyloid-ß 42 (Aß42)/Aß40 ratio, which induce early amyloid deposition and FAD. On the other hand, apolipoprotein E4 (ApoE4) is the major genetic risk factor for sporadic AD (SAD) and contributes to AD pathogenesis because it has reduced Aß clearance capability compared with ApoE3 and ApoE2. FAD and SAD have long been considered to be caused by these two independent mechanisms; however, for the first time, we demonstrated that PS is essential for ApoE secretion and PS mutants affected ApoE secretion in vitro and in human samples, suggesting a novel mechanism by which PS is also involved in SAD pathogenesis.

A direct examination of microbial specialized metabolites associated with ocean sediments from Baffin Bay and the Gulf of Maine.

Specialized metabolites produced by microorganisms found in ocean sediments display a wide range of clinically relevant bioactivities, including antimicrobial, anticancer, antiviral, and anti-inflammatory. Due to limitations in our ability to culture many benthic microorganisms under laboratory conditions, their potential to produce bioactive compounds remains underexplored. However, the advent of modern mass spectrometry technologies and data analysis methods for chemical structure prediction has aided in the discovery of such metabolites from complex mixtures. In this study, ocean sediments were collected from Baffin Bay (Canadian Arctic) and the Gulf of Maine for untargeted metabolomics using mass spectrometry. A direct examination of prepared organic extracts identified 1468 spectra, of which ∼45% could be annotated using in silico analysis methods. A comparable number of spectral features were detected in sediments collected from both locations, but 16S rRNA gene sequencing revealed a significantly more diverse bacterial community in samples from Baffin Bay. Based on spectral abundance, 12 specialized metabolites known to be associated with bacteria were selected for discussion. The application of metabolomics directly on marine sediments provides an avenue for culture-independent detection of metabolites produced under natural settings. The strategy can help prioritize samples for novel bioactive metabolite discovery using traditional workflows.

Perioperative interventions to reduce pancreatic fistula following pancreatoduodenectomy: meta-analysis.

BACKGROUND: Data on interventions to reduce postoperative pancreatic fistula (POPF) following pancreatoduodenectomy (PD) are conflicting. The aim of this study was to assimilate data from RCTs. METHODS: MEDLINE and Embase databases were searched systematically for RCTs evaluating interventions to reduce all grades of POPF or clinically relevant (CR) POPF after PD. Meta-analysis was undertaken for interventions investigated in multiple studies. A post hoc analysis of negative RCTs assessed whether these had appropriate statistical power. RESULTS: Among 22 interventions (7512 patients, 55 studies), 12 were assessed by multiple studies, and subjected to meta-analysis. Of these, external pancreatic duct drainage was the only intervention associated with reduced rates of both CR-POPF (odds ratio (OR) 0.40, 95 per cent c.i. 0.20 to 0.80) and all-POPF (OR 0.42, 0.25 to 0.70). Ulinastatin was associated with reduced rates of CR-POPF (OR 0.24, 0.06 to 0.93). Invagination (versus duct-to-mucosa) pancreatojejunostomy was associated with reduced rates of all-POPF (OR 0.60, 0.40 to 0.90). Most negative RCTs were found to be underpowered, with post hoc power calculations indicating that interventions would need to reduce the POPF rate to 1 per cent or less in order to achieve 80 per cent power in 16 of 34 (all-POPF) and 19 of 25 (CR-POPF) studies respectively. CONCLUSION: This meta-analysis supports a role for several interventions to reduce POPF after PD. RCTs in this field were often relatively small and underpowered, especially those evaluating CR-POPF.

Recent advancements in engineered biopolymeric-nanohybrids: A greener approach for adsorptive-remediation of noxious metals from aqueous matrices.

Industrial wastewater is causing serious health problems due to presence of large concentrations of toxic metals. Removal of these metals is still a big challenge using pristine natural biopolymers due to their low surface area, water solubility, and poor recovery. Developing biopolymeric composites with other materials has attained attention because they possess a high surface area and structural porosity, high reactivity, and less water solubility. In simple words, biopolymeric nanohybrids have great adsorption capacity for heavy metals. Biopolymeric materials are abundant, low cost, biodegradable, and possess different functional moieties (carboxyl, amine, hydroxyl, and carbonyl) which play a vital role to adsorb metal ions through various inter-linkages (i.e., electrostatic, hydrogen bonding, ion exchange, chelation, etc.). Biopolymeric nanohybrids have been proven a potent tool in environmental remediation such as the abatement of heavy metal ions from polluted water. Herein, we have reported the adsorption potential of various biopolymers (cellulose, chitosan, pectin, gelatin, and silk proteins) for the removal of heavy metals. This review discusses the suitability of biopolymeric nanohybrids as an adsorbent for heavy metals, their synthesis, modification, adsorption potential, and adsorption mechanism along with best fitted thermodynamic and kinetic models. The influence of pH, contact time, and adsorbent dose on adsorption potential has also been discussed in detail. Lastly, the challenges, research gaps and recommendations have been presented. This review concludes that biopolymers in combination with other materials such as metal-based nanoparticles, clay, and carbon-based materials are excellent materials to remove metallic ions from wastewater. Significant adsorption of heavy metals was obtained at a moderate pH (5-6). Contact time and adsorbent dose also affect the adsorption of heavy metals in certain ways. The Pseudo-first order model fits the data for the initial period of the first step of the reaction. Kinetic studies of different adsorption processes of various biopolymeric nanohybrids described that for majority of bionanohybrids, Pseudo-second order fitted the experimental data very well. Functionalized biopolymeric nanohybrids being biodegradable, environment friendly, cost-effective materials have great potential to adsorb heavy metal ions. These may be the future materials for environmental remediation.

Knowledge, attitude, and practice regarding treatment of group a beta haemolytic tonsillo pharyngitis and prevention of rheumatic fever among doctors in Karachi, Pakistan: A perspective study.

OBJECTIVE: To assess knowledge and practices associated with rheumatic fever among medical practitioners in an urban setting. METHODS: The cross-sectional study was conducted at five major hospitals in Karachi from August to November 2019, and comprised house officers, postgraduate trainees, and general physicians of either gender. The subjects were given a questionnaire assessing their knowledge and perception regarding acute rheumatic fever as well as prophylaxis. Data was analysed using SPSS 25. RESULTS: Of the 247 respondents, 173(70%) were house officers, 31(13%) were postgraduate trainees and 43(17%) were general physicians. Overall, 202(82%) subjects were associated with some teaching hospital. Significantly more postgraduate trainees and general physicians answered correctly when asked to identify clinical and laboratory findings suggestive of Group A streptococcal throat infection than house officers (p<0.001). Among the house officers 49(28.3%), and among the postgraduate trainees 11(35.4%) knew the correct way to prescribe penicillin to prevent rheumatic fever. Among the general physicians, 20(46.5%) had accurate knowledge regarding the prescription. CONCLUSIONS: Knowledge and practices of medical practitioners regarding rheumatic fever were less than ideal and may play a part in misdiagnoses of Group A streptococcal infections and, hence, prophylaxis.

External validation of postoperative pancreatic fistula prediction scores in pancreatoduodenectomy: a systematic review and meta-analysis.

BACKGROUND: Multiple risk scores claim to predict the probability of postoperative pancreatic fistula (POPF) after pancreatoduodenectomy. It is unclear which scores have undergone external validation and are the most accurate. The aim of this study was to identify risk scores for POPF, and assess the clinical validity of these scores. METHODS: Areas under receiving operator characteristic curve (AUROCs) were extracted from studies that performed external validation of POPF risk scores. These were pooled for each risk score, using intercept-only random-effects meta-regression models. RESULTS: Systematic review identified 34 risk scores, of which six had been subjected to external validation, and so included in the meta-analysis, (Tokyo (N=2 validation studies), Birmingham (N=5), FRS (N=19), a-FRS (N=12), m-FRS (N=3) and ua-FRS (N=3) scores). Overall predictive accuracies were similar for all six scores, with pooled AUROCs of 0.61, 0.70, 0.71, 0.70, 0.70 and 0.72, respectively. Considerably heterogeneity was observed, with I2 statistics ranging from 52.1-88.6%. CONCLUSION: Most risk scores lack external validation; where this was performed, risk scores were found to have limited predictive accuracy. . Consensus is needed for which score to use in clinical practice. Due to the limited predictive accuracy, future studies to derive a more accurate risk score are warranted.

High temperature promotes amyloid ß-protein production and γ-secretase complex formation via Hsp90.

Alzheimer's disease (AD) is characterized by neuronal loss and accumulation of ß-amyloid-protein (Aß) in the brain parenchyma. Sleep impairment is associated with AD and affects about 25-40% of patients in the mild-to-moderate stages of the disease. Sleep deprivation leads to increased Aß production; however, its mechanism remains largely unknown. We hypothesized that the increase in core body temperature induced by sleep deprivation may promote Aß production. Here, we report temperature-dependent regulation of Aß production. We found that an increase in temperature, from 37 °C to 39 °C, significantly increased Aß production in amyloid precursor protein-overexpressing cells. We also found that high temperature (39 °C) significantly increased the expression levels of heat shock protein 90 (Hsp90) and the C-terminal fragment of presenilin 1 (PS1-CTF) and promoted γ-secretase complex formation. Interestingly, Hsp90 was associated with the components of the premature γ-secretase complex, anterior pharynx-defective-1 (APH-1), and nicastrin (NCT) but was not associated with PS1-CTF or presenilin enhancer-2. Hsp90 knockdown abolished the increased level of Aß production and the increased formation of the γ-secretase complex at high temperature in culture. Furthermore, with in vivo experiments, we observed increases in the levels of Hsp90, PS1-CTF, NCT, and the γ-secretase complex in the cortex of mice housed at higher room temperature (30 °C) compared with those housed at standard room temperature (23 °C). Our results suggest that high temperature regulates Aß production by modulating γ-secretase complex formation through the binding of Hsp90 to NCT/APH-1.

Reduction-Sensitive Dextran-Paclitaxel Polymer-Drug Conjugate: Synthesis, Self-Assembly into Nanoparticles, and In Vitro Anticancer Efficacy.

Delivery systems that can encapsulate a precise amount of drug and offer a spatiotemporally controlled drug release are being actively sought for safe yet effective cancer therapy. Compared to polymer nanoparticle (NP)-based delivery systems that rely on physical drug encapsulation, NPs derived from stimuli-sensitive covalent polymer-drug conjugates (PDCs) have emerged as promising alternatives offering precise control over drug dosage and spatiotemporal drug release. Herein, we report a reduction-sensitive PDC "Dex-SS-PTXL" synthesized by conjugating dextran and paclitaxel (PTXL) through a disulfide bond-bearing linker. The synthesized Dex-SS-PTXL PDC with a precise degree of substitution in terms of the percentage of repeat units of dextran covalently conjugated to PTXL (27 ± 0.6%) and the amount of drug carried by the PDC (39 ± 1.4 wt %) was found to self-assemble into spherical NPs with an average size of 110 ± 34 nm and a ζ-potential of -14.09 ± 8 mV. The reduction-sensitive Dex-SS-PTXL NPs were found to release PTXL exclusively in response to the reducing agent concentration reflective of the intracellular reducing environment of the tumor cells. Challenging BT-549 and MCF-7 cells with Dex-SS-PTXL NPs revealed significant cytotoxicity, while the IC50 values and the mode of action (mitotic arrest) of Dex-SS-PTXL NPs were found to be comparable to those of free PTXL, highlighting the active nature of the intracellularly released drug. The developed PDC with its unique ability to self-assemble into NPs and stimuli-responsive drug release can enhance the success of the NP-based drug delivery systems during clinical translation.

Impact of SARS-CoV-2 pandemic on pancreatic cancer services and treatment pathways: United Kingdom experience.

INTRODUCTION: The SARS-CoV-2 pandemic presented healthcare providers with an extreme challenge to provide cancer services. The impact upon the diagnostic and treatment capacity to treat pancreatic cancer is unclear. This study aimed to identify national variation in treatment pathways during the pandemic. METHODS: A survey was distributed to all United Kingdom pancreatic specialist centres, to assess diagnostic, therapeutic and interventional services availability, and alterations in treatment pathways. A repeating methodology enabled assessment over time as the pandemic evolved. RESULTS: Responses were received from all 29 centres. Over the first six weeks of the pandemic, less than a quarter of centres had normal availability of diagnostic pathways and a fifth of centres had no capacity whatsoever to undertake surgery. As the pandemic progressed services have gradually improved though most centres remain constrained to some degree. One third of centres changed their standard resectable pathway from surgery-first to neoadjuvant chemotherapy. Elderly patients, and those with COPD were less likely to be offered treatment during the pandemic. CONCLUSION: The COVID-19 pandemic has affected the capacity of the NHS to provide diagnostic and staging investigations for pancreatic cancer. The impact of revised treatment pathways has yet to be realised.

Function and regulation annotation of up-regulated long non-coding RNA LINC01234 in gastric cancer.

BACKGROUND: Accumulated evidences indicate that long non-coding RNAs (lncRNAs) participate in many biological mechanisms. Moreover, it acts as an essential regulator in various human diseases such as gastric cancer (GC). Nevertheless, the comprehensive regulatory roles and clinical significance of most lncRNAs in GC are not fully understood. METHODS: In this research, our aim was to investigate the underlying mechanism of lncRNA LINC01234 in GC. Firstly, the usage of qRT-PCR helped to establish expression pattern of LINC01234 in GC tissues. Following this, appropriate statistical tests were applied to analyze the relation between expression level and clinicopathological factors. Ultimately, potential functions and regulatory network of LINC01234 were concluded via GSEA and a series of bioinformatics tools or databases, respectively. RESULTS: Consequently, at the end of research we found LINC01234 is up-regulated in GC tissues in comparison with adjacent normal tissues. Furthermore, its expression level is correlated with differentiation of patients with GC. It is also important to highlight bioinformatics analysis revealed that LINC01234 is involved in cancer-associated pathways such as cell cycle and mismatch repair. Also, regulatory network of LINC01234 presented a probability in the involvement of tumorigenesis through regulating cancer-associated genes. CONCLUSION: Overall, our results suggested that LINC01234 may play a crucial role in GC.

The optimal CO2 concentrations for the growth of three perennial grass species.

BACKGROUND: Grasslands are one of the most representative vegetation types accounting for about 20% of the global land area and thus the response of grasslands to climate change plays a pivotal role in terrestrial carbon balance. However, many current climate change models, based on earlier results of the doubling-CO2 experiments, may overestimate the CO2 fertilization effect, and as a result underestimate the potentially effects of future climate change on global grasslands when the atmospheric CO2 concentration goes beyond the optimal level. Here, we examined the optimal atmospheric CO2 concentration effect on CO2 fertilization and further on the growth of three perennial grasses in growth chambers with the CO2 concentration at 400, 600, 800, 1000, and 1200 ppm, respectively. RESULTS: All three perennial grasses featured an apparent optimal CO2 concentration for growth. Initial increases in atmospheric CO2 concentration substantially enhanced the plant biomass of the three perennial grasses through the CO2 fertilization effect, but this CO2 fertilization effect was dramatically compromised with further rising atmospheric CO2 concentration beyond the optimum. The optimal CO2 concentration for the growth of tall fescue was lower than those of perennial ryegrass and Kentucky bluegrass, and thus the CO2 fertilization effect on tall fescue disappeared earlier than the other two species. By contrast, the weaker CO2 fertilization effect on the growth of perennial ryegrass and Kentucky bluegrass was sustained for a longer period due to their higher optimal CO2 concentrations than tall fescue. The limiting effects of excessively high CO2 concentrations may not only associate with changes in the biochemical and photochemical processes of photosynthesis, but also attribute to the declines in stomatal conductance and nitrogen availability. CONCLUSIONS: In this study, we found apparent differences in the optimal CO2 concentrations for the growth of three grasses. These results suggest that the growth of different types of grasses may respond differently to future elevated CO2 concentrations through the CO2 fertilization effect, and thus potentially alter the community composition and structure of grasslands. Meanwhile, our results may also be helpful for improving current process-based ecological models to more accurately predict the structure and function of grassland ecosystems under future rising atmospheric CO2 concentration and climate change scenarios.

Development and validation of a stability-indicating RP-HPLC-FLD method for determination of 5-[(4-chlorophenoxy) methyl]-1, 3, 4-oxadiazole-2-thiol; A novel drug candidate.

The present study describes the development and validation of a simple high performance liquid chromatographic method for the determination of a novel drug candidate, 5-[(4-chlorophenoxy) methyl]-1, 3, 4-oxadiazole-2-thiol. The stability-indicating capacity of the method was evaluated by subjecting the compound's solution to hydrolytic, oxidative, photolytic, transition metal- and thermal- stress. The chromatographic separation was achieved over a C18 column (Promosil, 5 µm, 4.60 × 250 mm), maintained at 25°C, using an isocratic mobile phase comprising a mixture of acetonitrile and acidified water of pH 2.67 (1:1, v/v), at a flow rate of 1.00 mL/min and detection using a fluorescent light detector (excitation at 250 nm and emission at 410 nm). The Beer's law was followed over the concentration range 2.50-50.00 µg/ml. The recovery (98.56-100.19%, SD <5%), intraday accuracy and precision (97.31-100.81%, RSD <5%), inter-day accuracy and precision (97.50-100.75%, RSD <5%) and intermediate accuracy and precision (98.10-99.91%, RSD <5%) indicated that the method was reliable, repeatable, reproducible and rugged. The resolution and selectivity factors of the compound's peak from the nearest resolving peak, particularly in case of dry heat and copper metal stress, were found to be greater than 2 and 1, respectively, which indicated specificity and selectivity. The compound was extensively decomposed in alkaline-hydrolytic, oxidative, metal- and dry heat- stress. However, the compound in acidic and neutral conditions was resistant to photolysis. The results of the present study indicate that the developed method is specific, selective, sensitive and suitable, hence, may be used for quality control, stability testing and preformulation studies.

Effect of half adult dose of oral Rifampicin (300mg) in patients with idiopathic central serous chorioretinopathy.

OBJECTIVES: To evaluate the effect of half adult dose of oral Rifampicin on mean change in best corrected visual acuity and central macular thickness in patients with central serous chorioretinopathy. METHODS: Thirty-eight eyes of 31 patients with idiopathic central serous chorioretinopathy (CSCR) were registered. Unaided Visual acuity, best corrected visual acuity was documented and detailed slit lamp examination along with dilated ophthalmoscopy was performed. All subjects were treated with oral Rifampicin 300 mg (half adult dose) daily for 03 months. Patients underwent a complete ocular and systemic examination as well as central macular thickness (CMT) measurement by optical coherence tomography (OCT) every month after starting treatment until four months. Fundus fluorescein angiography (FFA) was performed in recurrent cases. Liver function tests were carried out prior to the treatment and during follow up period. RESULTS: A total of 38 eyes of 31 patients (24 males, 07 females) were included in the study. Mean age of patients was 36.16±3.19 years (range 30-44). Mean best corrected visual acuity (BCVA) before treatment was 0.56±0.11 and improved to 0.47±0.14 at 04 weeks (P<0.001) of treatment. The mean CMT at the time of presentation was 494.39±96.29 um and was decreased to 306.90±50.71 um after 04 weeks of treatment (P<0.001). The mean induced reduction in CMT was 187.48±122 um (P<0.001) while that in BCVA 0.41±0.16 at 04 weeks of treatment (P<0.001). Liver function tests were within normal range before and after the treatment. CONCLUSION: Half adult dose rifampicin (300mg) is effective and safe in treatment of central serous chorioretinopathy without causing any systemic imbalance.

Development of cetyl dimethicone based water-in-oil emulsion containing botanicals: Physical characteristics and stability.

The aim of current research was to develop a water-in-oil emulsion containing grape seed extract for application in cosmeceuticals. Finally grinded dried grape seeds powder was extracted with hydro alcoholic mixture. Emulsions consisting of different concentrations of cetyl dimethicone (Abile EM90), the nonionic emulsifier, liquid paraffin as oily phase and water as aqueous phase were developed. Color, odor, pH, viscosity, liquefaction, phase separation, centrifugation and thermal stability of the formulated emulsions were observed at various storage temperatures i.e. 8±0.5°C, 25±0.5°C, 40±0.5°C and 40°C±0.5°C with 70% RH. The stable formulation consist of 16% mineral oil, 4% of ABIL EM 90(®), 4% grape seeds extract, 1% rose oil and 75% distilled water. All the results derived from this study showed good stability over the three months study period which indicates w/o emulsion can be used as carrier of 4% grape seeds extract to enhance desired effects when applied topically.

Case report of mannose-binding lectin (MBL) deficiency and postoperative sepsis and coagulopathy in a patient following total pancreatectomy for chronic pancreatitis.

CONTEXT: Complement plays a central role against infection and coordinates the activity of coagulation and fibrinolysis. In this report we present a patient that underwent total pancreatectomy experienced sepsis, coagulopathy and bleeding that endangered the postoperative course. CASE REPORT: A sixty-five-year-old woman underwent total pancreatectomy for intractable pain without islet transplant, this patient was diagnosed as AP and MBL deficient from a blood test performed preoperatively. On the postoperative course she experienced severe haemorrhages and sepsis for 3 weeks postoperatively. An analysis of serial perioperative serum samples conducted which showed further depletion of the alternate and MBL complement pathway without restoration to baseline levels. CONCLUSION: This is the first reported case of alternative and mannose-binding lectin pathways depletion associated with major postoperative bleeding and sepsis following pancreatic surgery. Future research should examine the relationship between complement pathways activity and postoperative complications in order to possibly introduce it as a preoperative screening and possible replacement therapy prior to any major surgical intervention.

Pyoderma Gangrenosum: A Case Highlighting the Importance of Timely Diagnosis.

Pyoderma Gangrenosum (PG) is a distinctive dermatologic condition characterized by recurrent inflammatory ulcers, often manifesting with violaceous borders and undermined edges. We describe a 40-year-old male who presented with acute on chronic necrotic ulcer of the left index finger following foreign body penetration. Despite multiple emergency department visits and treatments for presumed recurrent cellulitis, including various debridements, his condition persisted without symptomatic relief. A high index of clinical suspicion, due to recurrent presentations and potential pathergy, prompted an excision biopsy which confirmed Pyoderma Gangrenosum (PG). Regrettably, due to delays in appropriate management, the patient chose amputation because of intolerable pain, highlighting the critical importance of timely diagnosis for optimal patient outcomes.

The development of a multiorgan ex vivo perfused model: results with the porcine liver-kidney circuit over 24 hours.

We already developed an ex vivo liver-kidney model perfused for 6 h in which the kidney acted as a homeostatic organ to improve the circuit milieu compared to liver alone. In the current study, we extended the multiorgan perfusions to 24 h to evaluate the results and eventual pitfalls manifesting with longer durations. Five livers and kidneys were harvested from female pigs and perfused over 24 h. The extracorporeal circuit included a centrifugal pump, heat exchanger, and oxygenator. The primary end point of the study was the evaluation of the organ functions as gathered from biochemical and acid-base parameters. In the combined liver-kidney circuit, the organs survived and maintained an acceptable homeostasis for different lengths of time, longer for the liver (up to 19-23 h of perfusions) than the kidney (9-13 h of perfusions). Furthermore, glucose and creatinine values decreased significantly over time (from the 5th and 9th hour of perfusion onward). The addition of a kidney to the perfusion circuit improved the biochemical environment by removing excess products from ongoing metabolic processes. The consequence is a more physiological milieu that could improve results from future experimental studies. However, it is likely that long perfusions require some nutritional support over the hours to maintain the organ's vitality and functionality throughout the experiments.