Effects of pubic hair grooming on women's sexual health: a systematic review and meta-analysis.

BACKGROUND: Pubic hair grooming involves the partial or complete removal of pubic hair, and it is a common practice among men and women. Grooming is more prevalent in women, who employ various methods such as shaving, waxing and laser removal. However, it is associated with variable rates of post-grooming adverse outcomes including lacerations and sexually transmitted infections (STIs). To the best of our knowledge, this is the first systematic review and meta-analysis comparing women's sexual health outcomes between those who groom and those who don't. METHODS: We followed the MOOSE guidelines and conducted a computerized-based search using (PubMed, Web of Science, Scopus, and Ovid Medline), till June 20th, 2022, for eligible studies using the relevant keywords; (pubic hair grooming) OR (pubic hair removal OR Genital hairless OR Bikini hair removal OR pubic hair depilation). Cross-sectional studies included which compared grooming practices among women in terms of motivation and health outcomes. Women's satisfaction and incidence of STIs were pooled as standardized mean difference (SMD) and odds ratio (OR) respectively. RESULTS: Twenty-Two cross-sectional studies were included in our review with 73,091 participant.The odds of having gram-negative gonorrheal and chlamydial infection in Pubic hair groomers were found to be statistically significant (OR = 1.55, 95% CI [1.31, 1.84], P < 0.001) (OR = 1.56, 95% CI [1.32, 1.85], P < 0.001] respectively. There was no difference between groomer and non-groomer women regarding viral infections such as genital herpes (OR = 1.40, 95% CI [0.56, 3.50], P = 0.47) and Condyloma acuminata (OR = 1.75, 95% CI [0.51, 6.01], P = 0.37). The most common grooming side effect is genital itching (prevalence = 26.9%, P < 0.001). Non-electrical razor (prevalence = 69.3%, P < 0.001) is the most common grooming method. White women (prevalence = 80.2%, P < 0.001) remove pubic hair more frequently compared to black women (prevalence = 12.2%, P < 0.001). Women practice complete grooming (50.3%, P < 0.001) of the pubic hair more frequently than partial grooming (33.1%, P < 0.001). There are no differences in women's satisfaction between the two groups (SMD = 0.12, 95% CI [-0.16, 0.40], P = 0.39). CONCLUSION: This review aligns with previous observational studies regarding sexual health outcomes of pubic hair grooming. There is a need to raise awareness among women regarding the safe practice of pubic hair grooming, emphasizing the clarification of hazards and benefits.

Accuracy of oscillometric noninvasive blood pressure at the ankle in the lateral position during general anesthesia.

BACKGROUND: This study aimed to evaluate the accuracy of ankle blood pressure measurements in relation to invasive blood pressure in the lateral position. METHODS: This prospective observational study included adult patients scheduled for elective non-cardiac surgery under general anesthesia in the lateral position. Paired radial artery invasive and ankle noninvasive blood pressure readings were recorded in the lateral position using GE Carescape B650 monitor. The primary outcome was the ability of ankle mean arterial pressure (MAP) to detect hypotension (MAP < 70 mmHg) using area under the receiver operating characteristic curve (AUC) analysis. The secondary outcomes were the ability of ankle systolic blood pressure (SBP) to detect hypertension (SBP > 140 mmHg) as well as bias (invasive measurement - noninvasive measurement), and agreement between the two methods using the Bland-Altman analysis. RESULTS: We analyzed 415 paired readings from 30 patients. The AUC (95% confidence interval [CI]) of ankle MAP for detecting hypotension was 0.88 (0.83-0.93). An ankle MAP of ≤ 86 mmHg had negative and positive predictive values (95% CI) of 99 (97-100)% and 21 (15-29)%, respectively, for detecting hypotension. The AUC (95% CI) of ankle SBP to detect hypertension was 0.83 (0.79-0.86) with negative and positive predictive values (95% CI) of 95 (92-97)% and 36 (26-46)%, respectively, at a cutoff value of > 144 mmHg. The mean bias between the two methods was - 12 ± 17, 3 ± 12, and - 1 ± 11 mmHg for the SBP, diastolic blood pressure, and MAP, respectively. CONCLUSION: In patients under general anesthesia in the lateral position, ankle blood pressure measurements are not interchangeable with the corresponding invasive measurements. However, an ankle MAP > 86 mmHg can exclude hypotension with 99% accuracy, and an ankle SBP < 144 mmHg can exclude hypertension with 95% accuracy.

Enhancement of Amplified Spontaneous Emission by Electric Field in CsPbBr3 Perovskites.

Perovskite gain materials can sustain continuous-wave lasing at room-temperature. A first step toward the unachieved goal of electrically excited lasing would be an improvement in gain when electrical stimulation is added to the optical. However, to date, electrical stimulation supplementing optical has reduced gain performance. We find that amplified spontaneous emission (ASE) in a CsPbBr3 perovskite light-emitting diode (LED) held under invariant subthreshold optical excitation can be turned on/off by the addition/removal of an electric field. A positive bias voltage leads to a factor of 3 reduction in the optical ASE threshold, the cause of which can be attributed to an enhancement of the radiative rate. The slow components (10 s time scale) of the modulation in the photoluminescence and ASE when the voltage is changed suggest that the relocation of mobile ions trigger the increased radiative rate and observed lowering of ASE thresholds.

Porphyrin-Based Brain Tumor-Targeting Agents: [64Cu]Cu-porphyrin and [64Cu]Cu-TDAP.

The aim of this study is to evaluate a radioactive metal complex platform for brain tumor targeting. Herein, we introduce a new porphyrin derivative, 5,10,15,20-(tetra-N,N-dimethyl-4-aminophenyl)porphyrin (TDAP), in which four N,N-dimethyl-4-p-phenylenediamine (DMPD) moieties are conjugated to the porphyrin labeled with the radiometal 64Cu. DMPD affected the pharmacokinetics of porphyrin in terms of retention time in vivo and tumor-targeting ability relative to those of unmodified porphyrin. [64Cu]Cu-TDAP showed stronger enhancement than [64Cu]Cu-porphyrin in U87MG glioblastoma cells, especially in the cytoplasm and nucleus, indicating its tumor-targeting properties and potential use as a therapeutic agent. In the subcutaneous and orthotopic models of brain-tumor-bearing mice, [64Cu]Cu-TDAP was clearly visualized in the tumor site via positron emission tomography imaging and showed a tumor-to-brain ratio as high as 13. [64Cu]Cu-TDAP deserves attention as a new diagnostic agent that is suitable for the early diagnosis and treatment of brain tumors.

Liver Inclusion Appears to Be Protective Against Graft Loss-Due-to Chronic But Not Acute Rejection Following Intestinal Transplantation.

In intestinal transplantation, while other centers have shown that liver-including allografts have significantly more favorable graft survival and graft loss-due-to chronic rejection (CHR) rates, our center has consistently shown that modified multivisceral (MMV) and full multivisceral (MV) allografts have significantly more favorable acute cellular rejection (ACR) and severe ACR rates compared with isolated intestine (I) and liver-intestine (LI) allografts. In the attempt to resolve this apparent discrepancy, we performed stepwise Cox multivariable analyses of the hazard rates of developing graft loss-due-to acute rejection (AR) vs. CHR among 350 consecutive intestinal transplants at our center with long-term follow-up (median: 13.5 years post-transplant). Observed percentages developing graft loss-due-to AR and CHR were 14.3% (50/350) and 6.6% (23/350), respectively. Only one baseline variable was selected into the Cox model indicating a significantly lower hazard rate of developing graft loss-due-to AR: Transplant Type MMV or MV (p < 0.000001). Conversely, two baseline variables were selected into the Cox model indicating a significantly lower hazard rate of developing graft loss-due-to CHR: Received Donor Liver (LI or MV) (p = 0.002) and Received Induction (p = 0.007). In summary, while MMV/MV transplants (who receive extensive native lymphoid tissue removal) offered protection against graft loss-due-to AR, liver-containing grafts appeared to offer protection against graft loss-due-to CHR, supporting the results of other studies.

Fluorescence Naphthalene Cationic Schiff Base Reusable Paper as a Sensitive and Selective for Heavy Metals Cations Sensor: RSM, Optimization, and DFT Modelling.

Heavy metals are particularly damaging contaminants in the environment, and even trace concentrations represent a risk to human health due to their toxicity. To detect the heavy metals of Mn2+ and Co2+ ions, a novel selective reusable paper-based Fluorescence naked-eye sensor based on naphthalene cationic Schiff base (NCSB) was synthesized and confirmed using FT-IR, 1 H-NMR, and MS tools. Based on a blue to colorless color change in the aqueous solution, the NCSB sensor is utilized to Mn2+ and Co2+ cations selectively among other metal ions (Fe2+, Cu2+, Mg2+, Ni2+, Zn2+, Cd2+, Hg2+, Pb2+, Sn2+ and Cr3+). In the aqueous medium, the NCSB sensor displayed high sensitivity, with limits of detection (LOD) values of 0.014 µM (14.08 nM) and 0.041 µM (41.47 nM) for Mn2+ and Co2+ cations, respectively. The paper-based sensor naked-eye detected Mn2+ and Co2+ cations in water at concentrations as low as 0.65 µM (65 nM) and 0.086 µM (86 nM), respectively. It was discovered that 5 min of incubation time and a pH range of 7 to 11 were optimal for the complexation reaction between the Mn2+ and Co2+ ions and the NCSB sensor. Through a static quenching process, the interaction of the different metal ions with the Schiff base group in the NCSB molecule results in the development of a ground-state non-fluorescent complex. NCSB sensor was also successfully applied in analysis of Mn2+ and Co2+ in environmental water with good recoveries of 94.8-105.9%. The theoretical calculations based on density functional theory (DFT) studies are in support of experimental interpretations. The links between the input factors and the anticipated response were evaluated using the quadratic model of the response surface methodology (RSM) modeling.

Endoscopic management of refractory leak and gastro-cutaneous fistula after laparoscopic sleeve gastrectomy: a randomized controlled trial.

BACKGROUND: Gastro-cutaneous fistula is a rare complication after laparoscopic sleeve gastrectomy (LSG) with incidence of occurrence 1-2%. Most of gastro-cutaneous fistulae do not respond to conservative management and need intervention either surgically or endoscopically. METHODS: This prospective randomized clinical study included referred patients who had LSG performed at our department or other centers, and complicated with post-LSG leak or gastro-cutaneous fistula between December/2019 and March/2021. Included patients were ASA Physical status I-II. Primary and secondary outcomes were recurrence of the fistula and mortality in each group after the intervention during the 18 months follow-up period, respectively. RESULTS: Thirty patients were randomized into two groups: Surgery Group (SG, n = 15) and Endoscopy Group (EG, n = 15). Mean age of patients was 42.3 ± 8.7 and 42.6 ± 8.3 years-old in SG and EG, respectively. Females constituted 73.3% and 80% in SG and EG, respectively. Median time-to-gastric leak post LSG was six (range: 4-7) days in both groups. SG patients were surgically managed with primary repair of the gastric fistula and gastrojejunostomy in 13 patients or converting SG into Roux-en-Y gastric bypass in two patients, while EG patients were endoscopically managed with stitching, stenting, stenting and dilation, and clipping and dilation in 5, 4, 4 and 2 patients, respectively. Incidence of recurrent leak during 1st week was significantly higher in SG than EG (p < 0.001). No mortality reported in EG, while 2 patients died in SG (p = 0.48). CONCLUSION: Endoscopic intervention may offer a successful modality in managing post-LSG gastric leak and gastro-cutaneous fistula that do not respond to conservative measures in stable patients.

Endoscopic management of low output recurrent colonic fistula or leak after anterior resection for rectal cancer: a randomized controlled trial.

BACKGROUND: Colonic anastomotic leak and fistula following anterior resection surgery for rectal cancer are associated with high mortality rates. The incidence of occurrence varies from 2 to 25% and it is difficult to accurately calculate the incidence of fistula and leak post anterior resection, as most of them are asymptomatic. Endoscopic management of fistula and leak has become the first line of management after conservative management in many gastrointestinal surgical centers with the advantages of being less invasive, shorter length of post-operative hospital stay, effective and rapid recovery in comparison to revision surgery. Effective endoscopic management for colonic fistula or leak depends on the clinical status of the patient and fistula characters (time-to-occur and size and site of defect), and device availability. METHODS: This prospective randomized controlled clinical trial included all patients who developed the manifestations of low output recurrent colonic fistula or leak after colonic anterior resection for rectal cancer at Zagazig University Hospital between (December 2020 and August 2022). Sample size was 78 patients divided into two equal groups. Endoscopic group (EG): included 39 patients who underwent endoscopic management. Surgical group (SG): included 39 patients who underwent surgical management. RESULTS: The investigators randomized eligible 78 patients into two groups: 39 patients in SG and 39 patients in EG. The median size of the fistula or leak was nine (range: 7-14) mm in EG, versus ten (range: 7-12) mm in SG. Clipping and Endo-stitch device were used in 24 patients versus 15 patients, respectively, in EG while primary repair with ileostomy, and resection & anastomosis were used in 15 patients versus 24 patients, respectively, in SG. Recurrence, abdominal collection, and mortality were the post procedure's complications with incidence of occurrence of 10.3, 7.7 and 0%, respectively, in EG versus 20.5, 20.5 and 2.6%, respectively, in SG. Excellent, good, and poor were the parameters for quality of life with incidence of occurrence of 43.6, 54.6 and 0%, respectively, in EG versus 28.2, 33.3 and 38.5%, respectively, in SG. Median hospital stay was one (range: 1-2) day in endoscopic group, and seven (range: 6-8) days in SG. CONCLUSION: Endoscopic intervention may offer a successful modality in managing low output recurrent colonic fistula or leak after anterior resection for rectal cancer that did not respond to conservative measures in stable patients. CLINICALTRIALS: gov ID: NCT05659446.

Endoscopic management of acute sigmoid volvulus in high risk surgical elderly patients: a randomized controlled trial.

BACKGROUND: Most patients with sigmoid volvulus are of old age with multiple comorbidities. So, the risk of surgery for those elderly patients is usually associated with increased rates of morbidity and mortality. Early intervention is required for managing sigmoid volvulus to avoid its serious complications; therefore, early endoscopic untwist of sigmoid colon can be performed followed by endoscopic fixation of sigmoid colon under sedation in this category of the patients to avoid development of high risk surgical complications following surgical fixation of sigmoid colon or sigmoidectomy after initial simple loop colostomy procedure to relieve obstruction. METHODS: This prospective randomized controlled clinical trial included all patients who developed acute sigmoid volvulus and were referred to the Zagazig University Hospital Emergency Department between December 2020 and August 2022. The study was prospectively approved by Zagazig University Faculty of Medicine Institutional Review Board (Approval Number: 9989/23-10-2022) and was retrospectively submitted in http://clinicaltrials.gov in November 2022 ( http://clinicaltrials.gov ID: NCT05620446). Included eligible patients were simply randomized at a 1:1 ratio to "Endoscopic Group (EG)" or "Surgical Group (SG)" via drawing of sealed envelopes containing computer-generated random numbers prepared by a third party before start of intervention. RESULTS: Sample size included 18 patients divided into 2 equal groups. (1) Endoscopic group included 9 patients who were subjected to endoscopic untwist of sigmoid colon followed by endoscopic fixation of sigmoid colon under sedation; (2) Surgical group included 9 patients who were subjected to surgical fixation of sigmoid colon or sigmoidectomy after initial simple loop colostomy under general anesthesia. In comparison between both groups, there were statistically significant differences regarding length of hospital stay and procedure time. Unfortunately, there were no statistically significant differences regarding postoperative complications and co-morbidities. Eight patients in the endoscopy group demonstrated excellent quality of life, and one demonstrated good quality of life; unlike the surgical group, there were 3 patients with excellent quality of life, 5 patients with good quality of life, and 1 patient with poor quality of life. So there was statistically significant difference regarding quality of life between both groups. During the 9-month follow-up period, both groups demonstrated no cases of recurrence post-fixation. CONCLUSION: Endoscopic management of acute sigmoid volvulus is effective and safe in elderly high risk surgical patients (either in managing the intestinal obstruction caused by volvulus or in definitive treatment of volvulus).

Pulmonary Surface Irregularity Score as a New Quantitative CT Marker for Idiopathic Pulmonary Fibrosis-a Pilot Study.

The purpose of this study is to evaluate the accuracy and inter-observer agreement of a quantitative pulmonary surface irregularity (PSI) score on high-resolution chest CT (HRCT) for predicting transplant-free survival in patients with IPF. For this IRB-approved HIPAA-compliant retrospective single-center study, adult patients with IPF and HRCT imaging (N = 50) and an age- and gender-matched negative control group with normal HRCT imaging (N = 50) were identified. Four independent readers measured the PSI score in the midlungs on HRCT images using dedicated software while blinded to clinical data. A t-test was used to compare the PSI scores between negative control and IPF cohorts. In the IPF cohort, multivariate cox regression analysis was used to associate PSI score and clinical parameters with transplant-free survival. Inter-observer agreement for the PSI score was assessed by intraclass correlation coefficient (ICC). The technical failure rate of the midlung PSI score was 0% (0/100). The mean PSI score of 5.38 in the IPF cohort was significantly higher than 3.14 in the negative control cohort (p < .001). In the IPF cohort, patients with a high PSI score (≥ median) were 8 times more likely to die than patients with a low PSI score (HR: 8.36; 95%CI: 2.91-24.03; p < .001). In a multivariate model including age, gender, FVC, DLCO, and PSI score, only the PSI score was associated with transplant-free survival (HR:2.11 per unit increase; 95%CI: 0.26-3.51; p = .004). Inter-observer agreement for the PSI score among 4 readers was good (ICC: 0.88; 95%CI: 0.84-0.91). The PSI score had high accuracy and good inter-observer agreement on HRCT for predicting transplant-free survival in patients with IPF.

The Functional Luminal Imaging Probe (FLIP): A Good Tool for Adjustment of anal Canal Dimensions During Operative Management of Fecal Incontinence.

PURPOSE: Fecal incontinence is a troublesome problem in the field of colorectal surgery. The main aim of this study was to adjust the anal canal resistance during operative management of anal incontinence using Endo-FLIP. METHODS: This was a prospective cohort study held at Cairo university hospital. Hundred forty-eight incontinent patients treated by different surgical procedures were included. During the procedure the Endo-FLIP was applied to adjust the anal canal dimensions (ACL and ACD) so the ACR could be adjusted based on the flow equation. These were also assessed pre-operatively with Endo-FLIP system and the flow equation calculator. The clinical severity of the disease and outcome after surgical procedures were assessed and correlated to the physiologic parameters. RESULTS: ACL, ACD and ACR had had significant correlations to the degree of incontinence (P < .001). ACL, ACD and ACR showed statistically significant change with primary repair and gluteus maximus transposition operations. After treatment of fecal incontinence, in good responders' group, the mean resting anal canal resistance increased significantly to 4649.05 ± 1161.49 (postoperative) while in poor responders' group it was 1919.9 ± 1077.73. CONCLUSIONS: The Endo-flip can be used to measure the anal canal geometric parameters (ACL and ACD) and then anal canal resistance could be calculated by the flow equation - pre-and post-operatively- which help the adjustment of the surgical repair of sphincter injury in fecal incontinence patients which may improve the surgical outcome.

Does pericapsular nerve group block have limited analgesia at the initial post-operative period? Systematic review and meta-analysis.

Perioperative pain management related to hip surgical procedures is challenging. Pericapsular nerve group (PENG) block is a novel technique that is assumed to provide better analgesia in addition to its post-operative motor-sparing effect. In this review, we aim to assess the safety and efficacy of PENG block on pain management in patients undergoing hip surgeries. Fifteen clinical trials with a total of 837 patients were included. Pain scores favored PENG group when compared to FICB group (fascia iliaca compartment block) or analgesics-only group, but the difference could only be detected in the early post-operative period. Afterward, it seems to lose its superiority, and no difference could be detected. In addition, cumulative opioid consumption favored PENG group at 24 h but not at 48 h. Regarding patients' satisfaction, our analysis showed results favoring PENG group, but there was no difference in time to first opioid or length of hospital stay. The incidence of vomiting was lower in PENG, but there was no difference in the incidence of nausea, pruritis, and dizziness. PENG provides better analgesia and lower opioid consumption in the initial post-operative period. Current evidence is not enough, and further high-quality randomized controlled trials with larger sample sizes are required.

Volatile Anesthetics versus Total Intravenous Anesthesia for Cardiac Surgery.

BACKGROUND: Volatile (inhaled) anesthetic agents have cardioprotective effects, which might improve clinical outcomes in patients undergoing coronary-artery bypass grafting (CABG). METHODS: We conducted a pragmatic, multicenter, single-blind, controlled trial at 36 centers in 13 countries. Patients scheduled to undergo elective CABG were randomly assigned to an intraoperative anesthetic regimen that included a volatile anesthetic (desflurane, isoflurane, or sevoflurane) or to total intravenous anesthesia. The primary outcome was death from any cause at 1 year. RESULTS: A total of 5400 patients were randomly assigned: 2709 to the volatile anesthetics group and 2691 to the total intravenous anesthesia group. On-pump CABG was performed in 64% of patients, with a mean duration of cardiopulmonary bypass of 79 minutes. The two groups were similar with respect to demographic and clinical characteristics at baseline, the duration of cardiopulmonary bypass, and the number of grafts. At the time of the second interim analysis, the data and safety monitoring board advised that the trial should be stopped for futility. No significant difference between the groups with respect to deaths from any cause was seen at 1 year (2.8% in the volatile anesthetics group and 3.0% in the total intravenous anesthesia group; relative risk, 0.94; 95% confidence interval [CI], 0.69 to 1.29; P = 0.71), with data available for 5353 patients (99.1%), or at 30 days (1.4% and 1.3%, respectively; relative risk, 1.11; 95% CI, 0.70 to 1.76), with data available for 5398 patients (99.9%). There were no significant differences between the groups in any of the secondary outcomes or in the incidence of prespecified adverse events, including myocardial infarction. CONCLUSIONS: Among patients undergoing elective CABG, anesthesia with a volatile agent did not result in significantly fewer deaths at 1 year than total intravenous anesthesia. (Funded by the Italian Ministry of Health; MYRIAD ClinicalTrials.gov number, NCT02105610.).

Energy yield modelling of textured perovskite/silicon tandem photovoltaics with thick perovskite top cells.

Recent advances in solution processing of micrometer-thick perovskite solar cells over textured silicon bottom solar cells allowed a new promising approach for the fabrication of 2T perovskite/silicon tandem photovoltaics, combining optimal light management in the textured bottom cell with the ease of solution processing. Detailed simulations are needed to assess the performances of this morphology configuration (thick perovskite configuration). In this work, in-depth optical and energy yield (EY) simulations are performed to compare the thick perovskite configuration with other relevant morphology configurations for 2T perovskite/silicon tandem photovoltaics. Under standard test conditions, the total photogenerated current of the thick perovskite configuration is 1.3 mA cm-2 lower (-3.4% relative) than the one of the conformal perovskite on textured silicon configuration for non-encapsulated cells and only 0.8 mA cm-2 (-2.1% relative) for encapsulated cells. Under realistic outdoor conditions, EY modelling for a wide range of locations shows that, while conformal perovskite on textured silicon configuration remains the optimal configuration, thick perovskite configuration exhibits a mere ∼2.5% lower annual EY. Finally, intermediate scenarios are investigated with the angle of the perovskite front-side texture differing from the silicon texture and critical angles for efficient light management in these configurations are identified.

T-cell receptor sequencing specifies psoriasis as a systemic and atopic dermatitis as a skin-focused, allergen-driven disease.

BACKGROUND: Atopic dermatitis (AD) and psoriasis represent two of the most common inflammatory skin diseases in developed countries. A hallmark of both diseases is T-cell infiltration into the skin. However, it is still not clarified to what extent these infiltrating T cells are antigen-specific skin-homing T cells or unspecific heterogeneous bystander cells. METHODS: To elucidate this, T cells from lesional skin and from blood of 9 AD and 10 psoriasis patients were compared by receptor (TCR) sequencing. Therefore, peripheral blood mononuclear cells (PBMC) were cell-sorted according to expression of the cutaneous leukocyte antigen (CLA) into skin-homing (CLA+ ) and non-skin-homing (CLA- ) subfractions. Aeroallergen-specific T-cell lines were grown from AD patients' PBMC in parallel. RESULTS: Intra-individual comparison of TCRB CDR3 regions revealed that clonally expanded T cells in skin lesions of both AD and psoriasis patients corresponded to skin-homing circulating T cells. However, in psoriasis patients, these T-cell clones were also detectable to a larger extent among CLA- circulating T cells. Up to 28% of infiltrating cells in AD skin were identified as allergen-specific by overlapping TCR sequences. CONCLUSIONS: Our data show that in line with the systemic nature of psoriasis, T-cell clones that infiltrate psoriatic skin lesions do not exclusively possess skin-homing ability and are therefore most probably specific to antigens that are not exclusively expressed or located in the skin. T cells driving AD skin inflammation appear to home nearly exclusively to the skin and are, to a certain extent, specific to aeroallergens.

Specific T cells targeting Staphylococcus aureus fibronectin-binding protein 1 induce a type 2/type 1 inflammatory response in sensitized atopic dermatitis patients.

BACKGROUND: Atopic dermatitis (AD) is one of the most common inflammatory skin diseases worldwide and Staphylococcus aureus colonization and secondary infections occur in the majority of AD patients. Allergic sensitizations against microbial antigens have been discussed as possible trigger factors of AD. Recently, we reported IgE sensitization against fibronectin-binding protein 1 (FBP1), an essential virulence component in S. aureus, in a subgroup of patients suffering from AD. To expand these findings by investigating delayed-type immune reactions, the objective of this study was to detect and phenotypically characterize FBP1-specific T cells as possible trigger factors in AD. METHODS: Immunodominant T-cell epitopes were mapped by proliferation testing of patient-derived FBP1-specific T-cell lines after stimulation with single 15mer peptides, which were derived from different functional domains of the FBP1 sequence. Major histocompatibility complex class II tetramers carrying immunodominant epitopes successfully stained T helper cells in 8 out of 8 HLA-matched, IgE-sensitized AD patients. RESULTS: Cytokine profiling of multimer-sorted cells revealed that predominantly the type 2 cytokines IL-13 and IL-4 were secreted by these cells. In contrast, IL-17, the marker cytokine for response to extracellular pathogens, was scarcely detectable. CONCLUSIONS: We demonstrate that FBP1 contains immunodominant peptides that induce a specific pro-inflammatory T helper cell response with increased Th2 levels that can drive an allergic inflammation in sensitized AD patients.

Association of TNF-α G-308 a Promoter Polymorphism with the Course and Outcome of COVID-19 Patients.

BACKGROUND: Tumor necrosis factor-ɑ (TNF-ɑ) is one of the most important cytokines that manage the host defense mechanism, which may play a role in the pathogenesis of COVID-19 patients. The work aims to study the association of TNF-ɑ G-308 A gene polymorphism with the course and outcome of COVID-19 patients in Mansoura University Hospital. METHODS: 900 patients with COVID-19 infection and 184 controls were tested for TNF-ɑ G-308 A promoter polymorphism. Different genotypes of TNF-ɑ G-308 A were compared as regards the severity and prognosis of the disease. RESULTS: No statistically significant difference was found between patients and controls as regards the demographic data. The AA genotype of TNF-ɑ showed a higher incidence of the disease in comparison to the other genotypes. As regards the demographic and laboratory characters, no statistically significant difference was found between the different genotypes except for age, lymphopenia, CRP, and serum ferritin levels. In 336(80.0%) cases of the AA genotype, the disease was severe in comparison to 90(41.7%) cases in the GA genotype and no cases in the GG genotype with P = .001. CONCLUSION: People who carry the A allele of TNF-ɑ polymorphism are more prone to COVID-19 infection. The AA genotype of TNF-ɑ is associated with a more aggressive pattern of the disease. In those patients, the use of anti - TNF therapy may be promising.

Design, synthesis, and biological evaluation of pseudo-bicyclic pyrimidine-based compounds as potential EGFR inhibitors.

Cancer is one of the most dangerous diseases harvesting millions of lives every year globally, which mandates the development of new therapies. In this report, we designed and synthesized a novel series of compounds based on the structure of lapatinib and AF8c, a compound we developed and reported previously, to target EGFR kinase. The series was assayed against a panel of 60 cancer cell lines at the National Cancer Institute (NCI). Compounds 4a, 4f, 4 g, and 4 l showed high efficacy against melanoma, colon, and blood cancers, with 4a being the most effective. The evaluation of the potency of 4a against the 60 cell lines in a five-dose assay revealed a significant potency compared to lapatinib against melanoma, colon, and blood cancers. In vitro enzyme assay over 30 kinases showed significant potency against EGFR and high selectivity to EGFR among the tested kinases. A molecular modeling study of 4a and lapatinib inside the pockets of EGFR revealed that both compounds bind strongly inside the ATP-binding pocket of the EGFR kinase domain. Therefore, we present 4a as a novel EGFR kinase inhibitor with potent in vitro cellular activity against diverse types of cancer cells.

Design, synthesis, and biological evaluation of novel pyrido-dipyrimidines as dual topoisomerase II/FLT3 inhibitors in leukemia cells.

Dual inhibition of topoisomerase (topo) II and FLT3 kinase, as in the case of C-1311, was shown to overcome the shortcomings of using topo II inhibitors solely. In the present study, we designed and synthesized two series of pyrido-dipyrimidine- and pseudo-pyrido-acridone-containing compounds. The two series were evaluated against topo II and FLT3 as well as the HL-60 promyelocytic leukemia cell line in vitro. Compounds 6, 7, and 20 showed higher potency against topo II than the standard amsacrine (AMSA), whereas compounds 19 and 20 were stronger FLT3 inhibitors than the standard DACA. Compounds 19 and 20 showed to be dual inhibitors of both enzymes. Compounds 6, 7, 19, and 20 were more potent inhibitors of the HL-60 cell line than the standard AMSA. The results of the in vitro DNA flow cytometry analysis assay and Annexin V-FITC apoptosis analysis showed that 19 and 20 induced cell cycle arrest at the G2/M phase, significantly higher total percentage of apoptosis, and late-stage apoptosis in HL-60 cell lines than AMSA. Furthermore, 19 and 20 upregulated several apoptosis biomarkers such as p53, TNFα, caspase 3/7 and increased the Bax/Bcl-2 ratio. These results showed that 19 and 20 deserve further evaluation of their antiproliferative activities, particularly in leukemia. Molecular docking studies were performed for selected compounds against topo II and FLT3 enzymes to investigate their binding patterns. Compound 19 exerted dual fitting inside the active site of both enzymes.

The short-term outcome of distal mesogastric fixation after laparoscopic sleeve gastrectomy: a randomized controlled trial.

PURPOSE: The proposed etiology of leakage after laparoscopic sleeve gastrectomy may be the axial rotation of the stomach owing to the loss of abdominal ligament fixation along the greater curvature of the stomach. The mechanism of increased intra-gastric pressure due to axial gastric rotation may place a great deal of stress on the staple lines, leading to an increased incidence of leakage. Other complications may occur, including vomiting, food intolerance or persistent reflux. METHODS: This study was registered in ClinicalTrials.gov (ID: NCT04834323). This study included patients who were admitted to our center to undergo laparoscopic sleeve gastrectomy. Cases were collected in the period from December 2019 to December 2020. The study population included 83 patients, who were divided into the following two groups: Group 1 included 42 patients who received distal mesogastric fixation after laparoscopic sleeve gastrectomy; Group 2 included 41 patients who received laparoscopic sleeve gastrectomy alone without distal mesogastric fixation. RESULTS: No leakage or axial rotation occurs after laparoscopic sleeve gastrectomy with distal fixation, while in patients without distal fixation, leakage and axial rotation occurred with no statistically significant differences between the two groups. Leakage and axial rotation occurred two times more frequently among patients who received laparoscopic sleeve gastrectomy without distal fixations. CONCLUSION: Distal mesogastric fixation after laparoscopic sleeve gastrectomy decreased the axial gastric rotation and subsequently decreased gastric leakage.