Post-mastectomy surveillance of BRCA1/BRCA2 mutation carriers: Outcomes from a specialized clinic for high-risk breast cancer patients.

Female BRCA1/BRCA2 mutation carriers may elect bilateral risk-reducing mastectomy. There is a paucity of data on yield of imaging surveillance after risk-reducing mastectomy. This retrospective study focused on female BRCA1/BRCA2 mutation carriers who underwent bilateral mastectomy either as primary preventative, or as secondary preventative, after breast cancer diagnosis. All participants underwent breast imaging at 6- to 12-month intervals after mastectomy. Data on subsequent breast cancer diagnosis and timing were collected and compared between the groups. Overall, 184 female mutation carriers (134 BRCA1, 45 BRCA2, 5 both BRCA genes) underwent bilateral mastectomy after initial breast cancer diagnosis, between April 1, 2009 and August 31, 2018. During a mean follow-up of 6.2 ± 4.2 years, 13 (7.06%) were diagnosed with breast cancer; 12 ipsilateral (range: 0.4-28.8 years) and 1 contralateral breast cancer, 15.9 years after surgery. On the contrary, among asymptomatic BRCA1 (n = 40) and BRCA2 (n = 13) mutation carriers who underwent primary risk-reducing mastectomy (mean age at surgery 39.5 ± 8.4 years); none has developed breast cancer after a mean follow-up of 5.4 ± 3.4 years. BRCA1/BRCA2 mutation carriers with prior disease who underwent risk-reducing mastectomy after breast cancer diagnosis are still prone for developing ipsi or contralateral breast cancer, and therefore may benefit from continues clinical and imaging surveillance, unlike BRCA1/BRCA2 mutation carriers who undergo primary preventative bilateral mastectomy.

Upregulation of PD-1 follows tumour development in the AOM/DSS model of inflammation-induced colorectal cancer in mice.

Chronic inflammation may drive development of cancer as observed in inflammation-induced colorectal cancer (CRC). Though immune cells can infiltrate the tumour microenvironment, cancer cells seem to evade anti-tumour responses, which is one of the established hallmarks of cancer. Targeting the programmed cell death protein-1 (PD-1)/PD-L1 signalling pathway is currently at the forefront in the development of anti-tumour immunity-based therapies for multiple malignancies. By blocking the immune-checkpoint of activated T-cells, it is possible to rewire the adaptive resistance induced by the PD-1 ligands expressed in the tumour microenvironment. However, adverse immunotherapy-modulated events could complicate the treatment of individuals with preexisting chronic inflammatory conditions. In this study, we investigated the expression of different systemic and mucosal T-cell subsets during the course of azoxymethane (AOM)/dextran sulphate sodium (DSS)-induced colitis and colitis-associated CRC. In addition, we examined the expression of PD-1 and its ligands PD-L1 and PD-L2 as well as other molecular targets related to T-cell exhaustion. We found a significant increase in PD-1 expression on all examined mucosal T-cell subsets of the colon and the ileum, which correlated with disease progression. We also observed an upregulation of PD-L1 and PD-L2 mRNA expression throughout the AOM/DSS regime. Blocking PD-1 signalling with an anti-PD1 antibody did not affect the tumour burden in the AOM/DSS-treated mice, but did potentiate the weight loss in the third DSS cycle, indicating possible immune-mediated toxicity. This raises a concern for patients with colitis-associated CRCs and should be further investigated.

Diabetic foot ulcer in Southern Jordan: A cross-sectional Study of Clinical and Microbiological Aspects.

Background: Diabetes mellitus (DM) is a common metabolic disorder that significantly affects public health. Diabetic foot ulcer (DFU) is one of the serious complications of diabetes. DFU has a wide spectrum of bacterial isolates comprising Gram-positive, Gram-negative, aerobic bacteria and anaerobes. In the last two decades there has been an increase in the multidrug-resistant isolates (MDR). Materials and methods: This cross-sectional prospective observational study was conducted in southern Jordan among patients with DFU. The included variables are sociodemographic and clinical information. Isolates from swab culture of ulcers and antimicrobial susceptibility pattern are also recorded. Results: A total of 64 diabetic patients with DFU were included in this study. Most patients included in the study were males with male-to-female ratio of (2.2:1). The mean age was 54 years (SD ± 10.7). The mean duration of DM was 16.4 years (SD ± 7.5) and the mean HbA1c was 9.9% (SD ± 2.1). Neuropathy and anemia were noted in 72% and 44% of patients, respectively. The most frequent bacterial isolates were gram negative bacteria accounts for 29 isolates (45.3%). About 37.5% (24) of bacterial isolates showed MDR pattern. Previous antibiotic use in the last 30 days showed significant association with MDR bacteria (p-value <0.05). Previous history of amputations, presence of neuropathy, renal impairment, retinopathy, presence of anemia, limited joint mobility and presence of foot deformity were significantly associated with Wagner's grade ≥ three. Conclusion: Many factors affect and increase the risk of having high grade diabetic foot ulcer. The most frequent bacterial isolates from diabetic foot ulcers were gram negative bacteria. High rates of MDR in this study reflect the loose implementation of regulations in Jordan regarding antibiotics dispensing.

From Neck Pain to Sarcoidosis: The Interesting Association.

We report the case of a 31-year-old male patient, presenting to the emergency department (ED) with a 6-week history of left-sided lateral neck pain, along with a minor localized swelling. A few weeks after the beginning of his complaints, he contracted a mild coronavirus disease 2019 (COVID-19). Upon examination, his aches were defined as carotidynia; thus, proper radiologic evaluation was carried out. While ultrasound (US) and magnetic resonance imaging (MRI) scans showed evident signs of left common carotid (LCC) vasculitis, computed tomography angiography (CTA) and positron emission tomography-CT (PET-CT) scans revealed no vascular findings. Unexpected hypermetabolic hilar and mediastinal lymphadenopathy was found on PET-CT, necessitating lymph node biopsy. Pathology results displayed noncaseating granulomas. Besides, angiotensin-converting enzyme (ACE) levels in blood were high. Sarcoidosis, with concurrent LCC vasculitis, was diagnosed, and corticosteroid therapy was started. Shortly thereafter, remarkable recovery ensued.

Intestinal Growth in Glucagon Receptor Knockout Mice Is Not Associated With the Formation of AOM/DSS-Induced Tumors.

Treatment with exogenous GLP-2 has been shown to accelerate the growth of intestinal adenomas and adenocarcinomas in experimental models of colonic neoplasia, however, the role of endogenous GLP-2 in tumor promotion is less well known. Mice with a global deletion of the glucagon receptor (Gcgr-/-) display an increase in circulating GLP-1 and GLP-2. Due to the intestinotrophic nature of GLP-2, we hypothesized that Gcgr-/- mice would be more susceptible to colonic dysplasia in a model of inflammation-induced colonic carcinogenesis. Female Gcgr-/- mice were first characterized for GLP-2 secretion and in a subsequent study they were given a single injection with the carcinogen azoxymethane (7.5 mg/kg) and treated with dextran sodium sulfate (DSS) (3%) for six days (n=19 and 9). A cohort of animals (n=4) received a colonoscopy 12 days following DSS treatment and all animals were sacrificed after six weeks. Disruption of glucagon receptor signaling led to increased GLP-2 secretion (p<0.0001) and an increased concentration of GLP-2 in the pancreas of Gcgr-/- mice, coinciding with an increase in small intestinal (p<0.0001) and colonic (p<0.05) weight. Increased villus height was recorded in the duodenum (p<0.001) and crypt depth was increased in the duodenum and jejunum (p<0.05 and p<0.05). Disruption of glucagon receptor signaling did not affect body weight during AOM/DSS treatment, neither did it affect the inflammatory score assessed during colonoscopy or the number of large and small adenomas present at the end of the study period. In conclusion, despite the increased endogenous GLP-2 secretion Gcgr-/- mice were not more susceptible to AOM/DSS-induced tumors.

Short-term tissue permeability actions of dextran sulfate sodium studied in a colon organ culture system.

Dextran sulfate sodium (DSS)-induced colitis is the most commonly used animal model for inflammatory bowel diseases. However, the precise molecular action of DSS, in particular its initial effect on the epithelial tissue permeability, is still poorly understood. In the present work, organ culture of mouse - and pig colon explants were performed for 1-2 h in the presence/absence of 2% DSS together with polar- and lipophilic fluorescent probes. Probe permeability was subsequently assessed by fluorescence microscopy. DSS rapidly increased paracellular permeability of 70-kDa dextran without otherwise affecting the overall epithelial integrity. FITC-conjugated DSS likewise permeated the epithelial barrier and strongly accumulated in nuclei of cells scattered in the lamina propria. By immunolabeling, plasma cells, T cells, macrophages, mast cells, and fibroblasts were identified as possible targets for DSS, indicating that accumulation of the polyanion in nuclei was not confined to a particular type of cell in the lamina propria. In contrast, colonocytes were rarely targeted by DSS, but as visualized by transmission electron microscopy, it induced the formation of vacuole-like structures in the intercellular space between adjacent epithelial cells. Nuclei of various cell types in the lamina propria, including both cells of the innate and adaptive immune system, are novel targets for a rapid action of DSS, and from previous in vitro studies, polyanions like DSS are known to disrupt nucleosomes by binding to the histones. We therefore propose that nuclear targeting is one way whereby DSS exerts its inflammatory action as a colitogen in animal models of inflammatory bowel diseases.

Cytoglobin affects tumorigenesis and the expression of ulcerative colitis-associated genes under chemically induced colitis in mice.

Cytoglobin (Cygb) is a member of the hemoglobin family and is thought to protect against cellular hypoxia and oxidative stress. These functions may be particularly important in inflammation-induced cancer, e.g., in patients with ulcerative colitis (UC). In this study, we investigated the development of inflammation and tumors in a murine model of inflammation-induced colorectal cancer using a combined treatment of azoxymethane and dextran sulfate sodium. A bioinformatics analysis of genome-wide expression data revealed increased colonic inflammation at the molecular level accompanied by enhanced macroscopic tumor development in Cygb-deficient mice. Moreover, the expression of the UC-associated gene neurexophilin and PC-esterase domain family member 4 (Nxpe4) depended on the presence of Cygb in the inflamed colonic mucosa. Compared to wild type mice, RT-qPCR confirmed a 14-fold (p = 0.0003) decrease in Nxpe4 expression in the inflamed colonic mucosa from Cygb-deficient mice. An analysis of Cygb protein expression suggested that Cygb is expressed in fibroblast-like cells surrounding the colonic crypts. Histological examinations of early induced lesions suggested that the effect of Cygb is primarily at the level of tumor promotion. In conclusion, in this model, Cygb primarily seemed to inhibit the development of established microadenomas.

Rectal Insulin Instillation Inhibits Inflammation and Tumor Development in Chemically Induced Colitis.

BACKGROUND AND AIMS: Epithelial expression of the insulin receptor in the colon has previously been reported to correlate with extent of colonic inflammation. However, the impact of insulin signalling in the intestinal mucosa is still unknown. Here, we investigated the effects of inactivating the epithelial insulin receptor in the intestinal tract, in an experimental model of inflammation-induced colorectal cancer. METHODS: The mice were generated by utilizing the intestinal- and epithelial-specific villin promoter and the Cre-Lox technology. All mice included in the cohorts were generated by crossing [vil-Cre-INSR+/-] × [INSRfl/fl] to obtain [vil-Cre-INSR-/-], and their floxed littermates [INSRfl/fl] served as the control group. For the intervention study, phosphate-buffered saline with or without insulin was instilled rectally in anaesthetized wild-type mice with chemically induced colitis. RESULTS: We found higher endoscopic colitis scores together with potentiated colonic tumorigenesis in the knockout mice. Furthermore, we showed that topically administered insulin in inflamed colons of wild-type mice reduced inflammation-induced weight loss and improved remission in a dose-dependent manner. Mice receiving rectal insulin enemas exhibited lower colitis endoscopic scores and reduced cyclooxygenase 2 mRNA expression, and developed significantly fewer and smaller tumours compared with the control group receiving phosphate-buffered saline only. CONCLUSIONS: Rectal insulin therapy could potentially be a novel treatment, targeting the epithelial layer to enhance mucosal healing in ulcerated areas. Our findings open up new possibilities for combination treatments to synergize with the existing anti-inflammatory therapies.

Mange mites causing scabies in Egyptian buffaloes at Giza Governorate, Egypt.

In the present study, 560 buffaloes from a private animal farm in Giza Governorate were examined over one year for scabies infestation. The results showed that 466 Buffaloes (83.2%) were infested with two mange mites; Psoroptes natalensis and Sarcoptes scabiei. The highest prevalence rate of infestation was during winter (90.4%), and lowest was in summer (71.4%). The infestation on females was 90.4%, while on males was 80.8%. The mites were predominant on the withers, lumber, back, croup and the external angle of ilium. Buffaloes more than five years old were highly infested than smaller ones, but no mite's infestation were detected in those less than one year.

Allergenic Dermatophagoides mites causing asthma among schoolchildren at Ain-Shams District, Cairo, Egypt.

The present study was performed on house dust samples collected from ten homes of schoolchildren suffering from asthma at Ain-Shams district, over a period of two years (2008 & 2009). The data revealed that the total annual density of the two allergenic mites (Dermatophagoides pteronyssinus (Trouessart) & Dermatophagoides farinae (Hughes) was 202 individual mites with 22 asthmatic children in the first year, and individual mites increased to 268 with 36 asthmatic children in the second year. The two house dust mites were more abundant in bedrooms than in living ones (292 & 187 mites, respectively). The prevalence of the house dust mites on the mattresses and furniture were higher in bedrooms and living rooms than on the floors (340 & 140 mite, respectively). Winter season recorded the highest prevalence for both mites in the first and second year (87 & 110, respectively). Summer represented the lowest values (19 & 25, respectively).

Echinochasmus aspinuosa as a new record species in Egyptian heron.

This paper reported a new Egyptian of Echinochasmus aspinuosa in herons trapped in Giza and Sharkia Governorates. The detailed morphology was given and illustrated. The zoonotic importance of this digenetic treamatode was discussed.