Adnexal torsion recurrence-is the adnexal twist degree a risk factor? A retrospective cohort study.

OBJECTIVE: To evaluate whether the adnexal twist degree is related to torsion recurrence and whether there is a dose-dependent correlation. DESIGN: A retrospective cohort study. SETTING: Single tertiary medical centre. POPULATION: The study includes non-pregnant patients operated, for the first time, for adnexal torsion, between 2011 and 2018. METHODS: Information regarding the degree of adnexal twist was collected from surgical reports. Recurrence was identified using a computerised database and ascertained via telephone with a response rate of 87.2% (253/290). MAIN OUTCOME MEASURES: Adnexal torsion recurrence rate. RESULTS: A total of 182 women who had undergone laparoscopic detorsion met the inclusion criteria. Twenty-two had torsion recurrence (12.1%). Adnexal twist degree in the primary event was associated with a higher recurrence risk: 4.3% of women with twist degree ≤360 (n = 3/70), 14.5% of women with twist degree of 361-720 (n = 9/62) and 20% of women with twist degree >720 (n = 10/50) (P = 0.03). The median twist degree was 540 (interquartile range [IQR] 360-855) and 720 (IQR 675-1080) degrees in the control and study groups, respectively (P = 0.005). Additional possibly associated factors for recurrence were evaluated. Age emerged as a possible risk factor, with a median age of 19 years in the recurrence group (IQR 14-27 years) versus 28.5 (IQR 19-36 years) in the non-recurrence group (P < 0.01). Logistic regression analysis revealed that together with age, adnexal twist degree remained significantly associated with torsion recurrence (odds ratio [OR] 1.98, 95% CI 1.09-3.61; P = 0.02). CONCLUSION: Adnexal twist degree was found to be positively associated with the risk of torsion recurrence. TWEETABLE ABSTRACT: Adnexal twist degree was found to be positively associated with the risk of torsion recurrence.

A systematic review of colorectal multidisciplinary team meetings: an international comparison.

BACKGROUND: Colorectal multidisciplinary teams (CR MDTs) were introduced to enhance the cancer care pathway and allow for early investigation and treatment of cancer. However, there are no 'gold standards' set for this process. The aim of this study was to review the literature systematically and provide a qualitative analysis on the principles, organization, structure and output of CR MDTs internationally. METHODS: Literature on the role of CR MDTs published between January 1999 and March 2020 in the UK, USA and continental Europe was evaluated. Historical background, structure, core members, education, frequency, patient-selection criteria, quality assurance, clinical output and outcomes were extracted from data from the UK, USA and continental Europe. RESULTS: Forty-eight studies were identified that specifically met the inclusion criteria. The majority of hospitals held CR MDTs at least fortnightly in the UK and Europe by 2002 and 2005 respectively. In the USA, monthly MDTs became a mandatory element of cancer programmes by 2013. In the UK, USA and in several European countries, the lead of the MDT meeting is a surgeon and core members include the oncologist, specialist nurse, histopathologist, radiologist and gastroenterologist. There were differences observed in patient-selection criteria, in the use of information technology, MDT databases and quality assurance internationally. CONCLUSION: CR MDTs are essential in improving the patient care pathway and should express clear recommendations for each patient. However, a form of quality assurance should be implemented across all MDTs.

Patterns of referral for fractured nose during major sporting events: a 10-year follow up.

INTRODUCTION: Nasal fracture is a common form of ear, nose and throat (ENT) trauma with prompt referral required for assessment and potentially manipulation of nasal bones. The aetiology of nasal fracture is multifactorial, and injury occurs across all ages. Previous study has suggested a temporal relationship between nasal injury and major sporting events. METHODS: A total of 1966 adult patients with nasal injuries referred to emergency clinics across three London ENT centres between September 2016 and August 2019 were analysed. RESULTS: The majority of those referred were male (66.58%). Mean age at referral was 36.29±18.38 in males and 49.14±21.43 in females; 10.27% were 75 years and over. Incidence was highest during April-September 2018 (p=0.02). Mean incidence was higher in this period in the male 16-35 subgroup (p=0.039), with 53.1% of their injuries concentrated between Friday and Sunday. CONCLUSIONS: Most nasal injuries occurred in young males. Mean age at referral was higher in females, and there was slightly increased incidence in over-75s, predominantly females. This incidence could be due to increased longevity or greater tendency to injury in females of this age. The injury patterns across the week also differed, with males injured proportionately more at the weekend. Nasal injury referrals of young men increased around the 2018 summer period, coinciding with the 2018 FIFA World Cup. This lends support to the association between major sporting events and the incidence of nasal injury, particularly in young males.

Production of Brucella lumazine Synthase Recombinant Protein to Design a Subunit Vaccine against Undulant Fever.

Brucella bacterium causes Brucellosis, an infectious disease spreading from animals to human. Brucella lumazine synthase (BLS) is a highly immunogenic protein with adjuvant properties, which has been introduced as an effective protein carrier for vaccine development. This protein also plays a significant role in inducing immune system. This study aimed to clone, express, and purify the BLS gene from Brucella melitensis Rev1. The BLS gene was amplified by particular primers with the restriction enzyme sites as a linker and it was inserted into pTZ57R/T vector. Subsequently, it was ligated into pET32(a)+ expression vector. Recombinant expression vector containing coding sequence of BLS was transformed into E. coli BL21 (DE3) host gene expression and stimulated by 0.1mM IPTG. The results of sequencing showed that there were not any mutations in BLS encoding sequence. The expression results were set by sequencing and endorsed using sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) analyses and western blotting that showed 35 kDa protein band appropriately.

Association of serum ghrelin with weight gain during pregnancy in overweight and normal women.

PURPOSE: Despite the fact that the ghrelin hormone plays pivotal role in the process of weight gain, its correlation with weighing during pregnancy has not been elucidated. Hence, the present study was conducted to evaluate the correlation between plasma ghrelin levels and gestational weight gain in overweight and normal women. METHODS: This prospective cohort study was conducted in 27 overweight and 18 normal body mass index (BMI) pregnant women referring to Tehran health care centers. Weight gain during all trimesters of pregnancy was measured and the blood samples were collected at 8-12 (first trimester) and 16-20 weeks (second trimester) of pregnancy. The plasma total ghrelin concentration was measured by ELISA method. RESULTS: The overweight pregnant women exhibited significantly lower weight gain at the second (p = 0.002), third trimesters (p = 0.005) as well as total weighing during pregnancy (p = 0.001) compared to the normal BMI pregnant women. There was no significant difference in plasma ghrelin levels between the groups from the first to the second trimesters of pregnancy (p > 0.05). Moreover, no correlation was found between ghrelin levels and gestational weight gain in the overweight and normal groups. CONCLUSIONS: Our results indicate that the increased level of serum ghrelin could not be considered as a key mediator for weight gain difference during pregnancy of overweight women.

Pentoxifylline mitigates detrimental impact of chronic nonbacterial prostatitis on sperm characteristics, reproductive hormones and histopathology in rats.

The protective role of pentoxifylline (PTX) on sperm characteristics, reproductive hormones and histopathology following carrageenan-induced chronic nonbacterial prostatitis (CNP) was investigated in male Wistar rats. Thirty-six rats were grouped into six rats per group. Group 1 (control) received saline normal. Group 2 received a single intraprostatic dose of 3% carrageenan (50 µl) on day 1 (CNP). Groups 3 and 5 received cernilton (standard drug) and PTX orally at 100 and 50 mg/kg for 14 consecutive days respectively. Groups 4 and 6 received a single dose of 3% carrageenan (50 µl) intraprostatically on day 1 followed by cernilton and PTX orally at 100 and 50 mg/kg on the eighth day for 14 consecutive days respectively. Prostatic index, serum prostatic specific antigen, malondialdehyde, testosterone and luteinising hormone levels were significantly increased (p < .05), whereas serum follicle-stimulating hormone, sperm count, motility and viability were significantly decreased (p < .05) in CNP group. Histopathology of prostate revealed leucocyte infiltration, large involutions and projection into the lumen in CNP group and these aberrations were improved by PTX. According to these findings, we concluded that PTX effectively mitigated detrimental impact of CNP on sperm characteristics, reproductive hormones and histopathology in rats.

Monocytes enhance neutrophil-induced blister formation in an ex vivo model of bullous pemphigoid.

BACKGROUND: Lesions of bullous pemphigoid (BP), an autoimmune subepidermal blistering disease characterized by the presence of tissue-bound and circulating autoantibodies to hemidesmosomal antigens, harbor a mixed inflammatory cellular infiltrate. In various models, neutrophils, eosinophils, mast cells, monocytes as well as B and T cells have been shown to be involved in the pathogenesis of BP. However, their interactions with and effective role in blister formation remain uncertain. This study was aimed at investigating the effect of monocyte/neutrophil interaction on blister formation in an ex vivo BP model. METHODS: Skin cryosections were incubated with purified human neutrophils and monocytes, in the presence or absence of BP autoantibodies. Production of reactive oxygen species (ROS), degranulation, mediator release (neutrophil elastase [NE], myeloperoxidase [MPO], matrix metalloproteinase-9 [MMP-9]), binding of Fcγ receptor (CD16, CD32, CD64), and cell adhesion (CD18, ICAM-1) was investigated using appropriate inhibitors. Dermal-epidermal separation (DES) was assessed by light microscopy and quantified by Fiji software. RESULTS: Monocytes and neutrophils synergistically interact resulting in a significantly higher DES compared to either monocytes or neutrophils separately (P < .0001). Monocyte/neutrophil-induced DES was associated with increased ROS production and was dependent on adhesion and FcγRIII binding. Upon stimulation by the granule-poor fraction of monocyte supernatants, neutrophils increased their release of MMP-9, thereby also DES at the dermal-epidermal junction of skin cryosections. CONCLUSION: Our observations suggest that the interaction of cells, as shown here for monocytes and neutrophils, enhances mediator release resulting in an increased subepidermal blister formation. Thus, blocking intercellular cross talk promises a new therapeutic approach for blocking tissue damage in BP.

Pathogen control at the intestinal mucosa - H2O2 to the rescue.

Intestinal infections are a global challenge, connected to malnutrition and inadequate hygiene in developing countries, and to expanding antibiotic resistance in developed countries. In general, a healthy host is capable of fighting off gut pathogens or at least to recover from infections quickly. The underlying protective mechanism, termed colonization resistance, is provided by indigenous commensal communities (microbiota) that are shaped and aided by the host's epithelial and innate immune system. Commensal-pathogen interactions are governed by competition for a suitable niche for replication and stable colonization, nutrient availability, species-specific alterations of the metabolic environment, changes in oxygen tension and release of chemicals and proteinaceous toxins (bacteriocins). This protective intestinal milieu is further reinforced by antimicrobial factors and chemicals secreted by the epithelial barrier, by dendritic cell sensing and by homeostasis between T-cell subsets (Treg/Th17) in the lamina propria. The 3 players (host-microbiota-pathogen) communicate via direct interactions or secreted factors. Our recent manuscript illustrates that reactive oxygen species (ROS) are an integral part of colonization resistance and should be considered an interkingdom antivirulence strategy.

Evidence for a role of eosinophils in blister formation in bullous pemphigoid.

BACKGROUND: Bullous pemphigoid (BP) is an autoimmune bullous disease of the skin characterized by subepidermal blister formation due to tissue-bound and circulating autoantibodies to the hemidesmosomal antigens BP180 and BP230. Although eosinophils and their toxic mediators are found abundantly in BP lesions, their role in blister formation has remained unclear. OBJECTIVE: To investigate the role of eosinophils in the pathogenesis of BP with a specific focus on blister formation and to define conditions inducing dermal-epidermal separation (DES). METHODS: In an ex vivo human model of BP, normal human skin cryosections were incubated with purified human peripheral blood eosinophils with or without activation in the presence or absence of BP autoantibodies, brefeldin A, diphenyleneiodonium, DNase or blocking F(ab')2 fragments to CD16, CD18, CD32 and CD64. Dermal-epidermal separation was assessed by light microscopy studies and quantified using Fiji software. RESULTS: Following activation with IL-5 and in the presence of BP autoantibodies, eosinophils induced separation along the dermal-epidermal junction of ex vivo skin. Dermal-epidermal separation was significantly reduced by blocking any of the following: Fcγ receptor binding (P = 0.048), eosinophil adhesion (P = 0.046), reactive oxygen species (ROS) production (P = 0.002), degranulation (P < 0.0001) or eosinophil extracellular trap (EET) formation (P = 0.048). CONCLUSIONS: Our results provide evidence that IL-5-activated eosinophils directly contribute to BP blister formation in the presence of BP autoantibodies. Dermal-epidermal separation by IL-5-activated eosinophils depends on adhesion and Fcγ receptor activation, requires elevated ROS production and degranulation and involves EET formation. Thus, targeting eosinophils may be a promising therapeutic approach for BP.

[Management of complications after revascularization due to peripheral arterial occlusive disease : Prophylaxis and consistent adequate therapy after timely diagnostics]. / Management von Komplikationen nach Revaskularisation wegen peripherer arterieller Verschlusskrankheit : Prophylaxe und konsequente adäquate Therapie nach zeitgerechter Diagnostik.

BACKGROUND: Complications are a threat to successful revascularization for treatment of perpheral arterial occlusive disease (PAOD) and must, therefore, be either primarily prevented or effectively treated after having occurred. OBJECTIVES: The aim of this article is to give a survey of possible complications after revascularization for treatment of PAOD and their management. MATERIAL AND METHODS: A systematic literature review was performed in PubMed and Medline. The analysis mainly considered recent publications with a higher level of evidence. RESULTS: Revascularization for treatment of PAOD can basically be performed by an open surgical approach, an endovascular approach or as a combination of both methods (hybrid operation). The spectrum of possible complications varies accordingly. A differentiation can be made between bleeding, ischemic and systemic complications as well as between vascular and non-vascular complications. Optimal management of complications begins with primary prophylaxis and further includes a timely diagnosis and treatment of established complications. The best prophylaxis consists of a high quality of indications and performance of revascularization. CONCLUSION: Optimal management of complications is essential and of utmost importance for successful revascularization to treat PAOD.

Basophils exhibit antibacterial activity through extracellular trap formation.

Basophils are primarily associated with immunomodulatory functions in allergic diseases and parasitic infections. Recently, it has been demonstrated that both activated human and mouse basophils can form extracellular DNA traps (BETs) containing mitochondrial DNA and granule proteins. In this report, we provide evidence that, in spite of an apparent lack of phagocytic activity, basophils can kill bacteria through BET formation.

CFD convective flow simulation of the varying properties of CO2-H2O mixtures in geothermal systems.

Numerical simulation of a geothermal reservoir, modelled as a bottom-heated square box, filled with water-CO2 mixture is presented in this work. Furthermore, results for two limiting cases of a reservoir filled with either pure water or CO2 are presented. Effects of different parameters including CO2 concentration as well as reservoir pressure and temperature on the overall performance of the system are investigated. It has been noted that, with a fixed reservoir pressure and temperature, any increase in CO2 concentration leads to better performance, that is, stronger convection and higher heat transfer rates. With a fixed CO2 concentration, however, the reservoir pressure and temperature can significantly affect the overall heat transfer and flow rate from the reservoir. Details of such variations are documented and discussed in the present paper.

Active eosinophilic esophagitis is characterized by epithelial barrier defects and eosinophil extracellular trap formation.

BACKGROUND: Eosinophilic esophagitis (EoE) exhibits esophageal dysfunction owing to an eosinophil-predominant inflammation. Activated eosinophils generate eosinophil extracellular traps (EETs) able to kill bacteria. There is evidence of an impaired barrier function in EoE that might allow pathogens to invade the esophagus. This study aimed to investigate the presence and distribution of EETs in esophageal tissues from EoE patients and their association with possible epithelial barrier defects. METHODS: Anonymized tissue samples from 18 patients with active EoE were analyzed. The presence of DNA nets associated with eosinophil granule proteins forming EETs and the expression of filaggrin, the protease inhibitor lympho-epithelial Kazal-type-related inhibitor (LEKTI), antimicrobial peptides, and cytokines were evaluated by confocal microscopy following immune fluorescence staining techniques. RESULTS: Eosinophil extracellular trap formation occurred frequently and was detected in all EoE samples correlating with the numbers of infiltrating eosinophils. While the expression of both filaggrin and LEKTI was reduced, epithelial antimicrobial peptides (human beta-defensin-2, human beta-defensin-3, cathelicidin LL-37, psoriasin) and cytokines (TSLP, IL-25, IL-32, IL-33) were elevated in EoE as compared to normal esophageal tissues. There was a significant correlation between EET formation and TSLP expression (P = 0.02) as well as psoriasin expression (P = 0.016). On the other hand, a significant negative correlation was found between EET formation and LEKTI expression (P = 0.016). CONCLUSION: Active EoE exhibits the presence of EETs. Indications of epithelial barrier defects in association with epithelial cytokines are also present which may have contributed to the activation of eosinophils. The formation of EETs could serve as a firewall against the invasion of pathogens.

The generation of neutrophils in the bone marrow is controlled by autophagy.

Autophagy has been demonstrated to have an essential function in several cellular hematopoietic differentiation processes, for example, the differentiation of reticulocytes. To investigate the role of autophagy in neutrophil granulopoiesis, we studied neutrophils lacking autophagy-related (Atg) 5, a gene encoding a protein essential for autophagosome formation. Using Cre-recombinase mediated gene deletion, Atg5-deficient neutrophils showed no evidence of abnormalities in morphology, granule protein content, apoptosis regulation, migration, or effector functions. In such mice, however, we observed an increased proliferation rate in the neutrophil precursor cells of the bone marrow as well as an accelerated process of neutrophil differentiation, resulting in an accumulation of mature neutrophils in the bone marrow, blood, spleen, and lymph nodes. To directly study the role of autophagy in neutrophils, we employed an in vitro model of differentiating neutrophils that allowed modulating the levels of ATG5 expression, or, alternatively, intervening pharmacologically with autophagy-regulating drugs. We could show that autophagic activity correlated inversely with the rate of neutrophil differentiation. Moreover, pharmacological inhibition of p38 MAPK or mTORC1 induced autophagy in neutrophilic precursor cells and blocked their differentiation, suggesting that autophagy is negatively controlled by the p38 MAPK-mTORC1 signaling pathway. On the other hand, we obtained no evidence for an involvement of the PI3K-AKT or ERK1/2 signaling pathways in the regulation of neutrophil differentiation. Taken together, these findings show that, in contrast to erythropoiesis, autophagy is not essential for neutrophil granulopoiesis, having instead a negative impact on the generation of neutrophils. Thus, autophagy and differentiation exhibit a reciprocal regulation by the p38-mTORC1 axis.

[Aneurysms of the abdominal aorta and iliac arteries: paradigm shift - operative therapy, if possible endovascular?]. / Aneurysmen der Bauchaorta und der Beckenarterien: Paradigmenwechsel - operative Therapie, wenn möglich endovaskulär?

BACKGROUND: Therapy of abdominal aortic aneurysms (AAA) is currently based on a high level of evidence. This is not true in the same manner for iliac artery aneurysms (IAA) which are frequently associated with AAAs and occur only rarely as isolated lesions. The therapeutic principles apply in the same way to both aneurysm locations. OBJECTIVES: New findings, improved perioperative care and the rapid development of minimally invasive techniques require a constant update which is the aim of this article concerning the therapy of AAAs and IAAs. MATERIAL AND METHODS: A systematic literature review was performed in PubMed and Medline and priority was given to recent publications with a high level of evidence. RESULTS: Endovascular aneurysm repair (EVAR) and open aneurysm repair (OAR) result in a similar long-term survival. The perioperative survival advantage with EVAR persists only during medium-term postoperative courses. The reintervention rate after EVAR is substantially higher compared to OAR. For older patients and those who are considered unfit for OAR the expected benefits from EVAR has not been proven to date. Aneurysmal ruptures after EVAR demonstrate that a life-long surveillance of these patients is necessary. CONCLUSION: Therapy of AAAs and IAAs is increasingly being performed by EVAR. Even the majority of complex aneurysms are amenable to minimally invasive treatment. Nevertheless, indications for OAR continue to exist. Screening for AAAs results in a decrease of aneurysmal ruptures for which EVAR is also gaining importance.

Evaluating Similarity Measures for Brain Image Registration.

Evaluation of similarity measures for image registration is a challenging problem due to its complex interaction with the underlying optimization, regularization, image type and modality. We propose a single performance metric, named robustness, as part of a new evaluation method which quantifies the effectiveness of similarity measures for brain image registration while eliminating the effects of the other parts of the registration process. We show empirically that similarity measures with higher robustness are more effective in registering degraded images and are also more successful in performing intermodal image registration. Further, we introduce a new similarity measure, called normalized spatial mutual information, for 3D brain image registration whose robustness is shown to be much higher than the existing ones. Consequently, it tolerates greater image degradation and provides more consistent outcomes for intermodal brain image registration.

p73 regulates autophagy and hepatocellular lipid metabolism through a transcriptional activation of the ATG5 gene.

p73, a member of the p53 tumor suppressor family, is involved in neurogenesis, sensory pathways, immunity, inflammation, and tumorigenesis. How p73 is able to participate in such a broad spectrum of different biological processes is still largely unknown. Here, we report a novel role of p73 in regulating lipid metabolism by direct transactivation of the promoter of autophagy-related protein 5 (ATG5), a gene whose product is required for autophagosome formation. Following nutrient deprivation, the livers of p73-deficient mice demonstrate a massive accumulation of lipid droplets, together with a low level of autophagy, suggesting that triglyceride hydrolysis into fatty acids is blocked owing to deficient autophagy (macrolipophagy). Compared with wild-type mice, mice functionally deficient in all the p73 isoforms exhibit decreased ATG5 expression and lower levels of autophagy in multiple organs. We further show that the TAp73α is the critical p73 isoform responsible for inducing ATG5 expression in a p53-independent manner and demonstrate that ATG5 gene transfer can correct autophagy and macrolipophagy defects in p73-deficient hepatocytes. These data strongly suggest that the p73-ATG5 axis represents a novel, key pathway for regulating lipid metabolism through autophagy. The identification of p73 as a major regulator of autophagy suggests that it may have an important role in preventing or delaying disease and aging by maintaining a homeostatic control.

Extracellular DNA traps in allergic, infectious, and autoimmune diseases.

Extracellular DNA traps are part of the innate immune response and are seen with many infectious, allergic, and autoimmune diseases. They can be generated by several different leukocytes, including neutrophils, eosinophils, and monocytes, as well as mast cells. Here, we review the composition of these extracellular DNA-containing structures as well as potential mechanisms for their production and function. In general, extracellular DNA traps have been described as binding to and killing pathogens, particularly bacteria, fungi, but also parasites. On the other hand, it is possible that DNA traps contribute to immunopathology in chronic inflammatory diseases, such as bronchial asthma. In addition, it has been demonstrated that they can initiate and/or potentiate autoimmune diseases. Extracellular DNA traps represent a frequently observed phenomenon in inflammatory diseases, and they appear to participate in the cross-talk between different immune cells. These new insights into the pathogenesis of inflammatory diseases may open new avenues for targeted therapies.

Prevalence of metabolic syndrome in adult population from zahedan, southeast iran.

BACKGROUND: The metabolic syndrome (MES) is associated with a high risk of diabetes and cardiovascular disease. The aim of the present study was to determine the prevalence of the metabolic syndrome as well as cut-off points for waist circumference (WC) for diagnosis of MES in Zahedan, southeast Iran. METHODS: Totally, 1802 people (735 men and 1067 women) with metabolic syndrome were surveyed according to National Cholesterol Education Program Adult Treatment Panel III (NCEP ATP III) and the International Diabetes Federation (IDF) criteria as well as obtained WC cut-off points for IDF criteria. RESULTS: The prevalence of metabolic syndrome was higher in women than in men. In both sexes the prevalence increased with age. The prevalence of metabolic syndrome among 1802 individuals aged ≥19 years according to NCEP ATP III, IDF and IDF -AHA/NHLBI were 21.0% (15.4% in male, 24.9% female), 24.8 (20.0% in male, 28.1% in female) and 23.3% (19.7% in male, 25.8% in female), respectively. Low HDL-C (60.6%) and high WC (43.3%) were the most common components of the metabolic syndrome, followed by high triglycerides (32%), elevated glucose (17.1%) and high blood pressure (13%). CONCLUSION: Our data shows a high prevalence of MES in Zahedan, Southeast Iran, therefore, future health prevention strategies are required for the prevention of MES.