Objectives
Occurrence of invasive fungal respiratory superinfections in patients with COVID‐19 has gained increasing attention in the latest studies. Yet, description of acute invasive fungal ...sinusitis with its management in those patients is still scarce. This study aims to describe this recently increasing clinical entity in relation to COVID‐19 patients.
Study Design
Longitudinal prospective study.
Methods
Prospective longitudinal study included patients diagnosed with acute invasive fungal rhinosinusitis after a recent COVID‐19 infection. Antifungal agents given included amphotericin B, voriconazole, and/or posaconazole. Surgical treatment was restricted to patients with PCR negative results for COVID‐19. Endoscopic, open, and combined approaches were utilized to eradicate infection. Follow‐up for survived patients was maintained regularly for the first postoperative month.
Results
A total of 36 patients with a mean age of 52.92 ± 11.30 years old were included. Most common associated disease was diabetes mellitus (27.8%). Mycological analysis revealed infection with Mucor and Aspergillus species in 77.8% and 30.6% of patients, respectively. Sino‐nasal, orbital, cerebral, and palatine involvement was found in 100%, 80.6%, 27.8%, and 33.3% of patients, respectively. The most common reported symptoms and signs are facial pain (75%), facial numbness (66.7%), ophthalmoplegia, and visual loss (63.9%). All patients were treated simultaneously by surgical debridement with antifungal medications except for two patients with PCR‐positive swab for COVID‐19. These two patients received antifungal therapy alone. Overall survival rate was 63.89% (23/36).
Conclusion
Clinical suspicion of acute invasive fungal sinusitis among COVID‐19 patients and early management with antifungal therapy and surgical debridement is essential for better outcomes and higher survival.
Level of Evidence
4 Laryngoscope, 131:2652–2658, 2021
Automated nucleus segmentation is considered the gold standard for diagnosing some severe diseases. Accurate instance segmentation of nuclei is still very challenging because of the large number of ...clustered nuclei, and the different appearance of nuclei for different tissue types. In this paper, a neural network is proposed for fast and accurate instance segmentation of nuclei in histopathology images. The network is inspired by the Unet and residual nets. The main contribution of the proposed model is enhancing the classification accuracy of nuclear boundaries by moderately preserving the spatial features by relatively d the size of feature maps. Then, a proposed 2D convolution layer is used instead of the conventional 3D convolution layer, the core of CNN-based architectures, where the feature maps are first compacted before being convolved by 2D kernel filters. This significantly reduces the processing time and avoids the out of memory problem of the GPU. Also, more features are extracted when getting deeper into the network without degrading the spatial features dramatically. Hence, the number of layers, required to compensate the loss of spatial features, is reduced that also reduces the processing time. The proposed approach is applied to two multi-organ datasets and evaluated by the Aggregated Jaccard Index (AJI), F1-score and the number of frames per second. Also, the formula of AJI is modified to reflect the object- and pixel-level errors more accurately. The proposed model is compared to some state-of-the-art architectures, and it shows better performance in terms of the segmentation speed and accuracy.
Mitochondrial dysfunction is one of the hallmarks of aging. Changes in sebaceous gland (SG) function and sebum production have been reported during aging. This study shows the direct effects of ...mitochondrial dysfunction on SG morphology and function. A mitochondrial DNA (mtDNA) depleter mouse was used as a model for introducing mitochondrial dysfunction in the whole animal. The effects on skin SGs and modified SGs of the eyelid, lip, clitoral, and preputial glands were characterized. The mtDNA depleter mice showed gross morphologic and histopathologic changes in SGs associated with increased infiltration by mast cells, neutrophils, and polarized macrophages. Consistently, there was increased expression of proinflammatory cytokines. The inflammatory changes were associated with abnormal sebocyte accumulation of lipid, defective sebum delivery at the skin surface, and the up-regulation of key lipogenesis-regulating genes and androgen receptor. The mtDNA depleter mice expressed aging-associated senescent marker. Increased sebocyte proliferation and aberrant expression of stem cell markers were observed. These studies provide, for the first time, a causal link between mitochondrial dysfunction and abnormal sebocyte function within sebaceous and modified SGs throughout the whole body of the animal. They suggest that mtDNA depleter mouse may serve as a novel tool to develop targeted therapeutics to address SG disorders in aging humans.
Diseases of the colon are a big health burden in both men and women worldwide ranging from acute infection to cancer. Environmental and genetic factors influence disease onset and outcome in multiple ...colonic pathologies. The importance of inflammation in the onset, progression and outcome of multiple colonic pathologies is gaining more traction as the evidence from recent research is considered. In this review, we provide an update on the literature to understand how genetics, diet, and the gut microbiota influence the crosstalk between immune and non‑immune cells resulting in inflammation observed in multiple colonic pathologies. Specifically, we focus on four colonic diseases two of which have a more established association with inflammation (inflammatory bowel disease and colorectal cancer) while the other two have a less understood relationship with inflammation (diverticular disease and irritable bowel syndrome).
Flavonoids, the main class of polyphenols, are characterized by the presence of 2-phenyl-benzo-pyrane nucleus. They are found in rich quantities in citrus fruits. Citrus flavonoids are classified ...into flavanones, flavones, flavonols, polymethoxyflavones and anthocyanins (found only in blood oranges). Flavanones are the most abundant flavonoids in citrus fruits. In many situations, there are structure-function relationships. Due to their especial structures and presence of many hydroxyls, polymethoxies and glycoside moiety, the flavonoids have an array of multiple biological and pharmacological activities. This article provides an updated overview of the differences in chemical structures of the classes and members of citrus flavonoids and their benefits in health and diseases. The review article also sheds light on the mechanisms of actions of citrus flavonoids in the treatment of different diseases, including arthritis, diabetes mellitus, cancer and neurodegenerative disorders as well as liver, kidney and heart diseases. The accumulated and updated knowledge in this review may provide useful information and ideas in the discovery of new strategies for the use of citrus flavonoids in the protection, prevention and therapy of diseases.
The gut microbiota is considered a rich source for potential novel probiotics. Enterococcus genus is a normal component of a healthy gut microbiota, suggesting its vital role. Nosocomial infections ...caused mainly by E. facalis and E. faecium have been attributed to the plasticity of the Enterococcus genomes. In this study, we assessed the probiotic and safety characteristics of two E. lactis strains isolated from the human gut microbiota using in-vitro and in silico approaches. Additionally, the safety of the E. lactis species was evaluated using comparative genomics analysis. The two E. lactis strains 10NA and 50NA showed resistance to bile salts and acid tolerance with antibacterial activity against Escherichia coli, Salmonella typhi, and Clostridioides difficile. For safety assays, the two strains did not display any type of hemolysis on blood agar, and the survival of Caco-2 cells was not significantly different (P-value > 0.05) compared to the control using cell free supernatants at 100% (v/v), 50% (v/v), 10% (v/v), and 5% (v/v) concentrations. Regarding antibiotic susceptibility, both strains were sensitive to vancomycin, tetracycline, and chloramphenicol. Comprehensive whole-genome analysis revealed no concerning associations between virulence or antibiotic resistance genes and any of the identified mobile genetic elements. Comparative genome analysis with closely related E. faecium species genomes revealed the distinctive genomic safety of the E. lactis species. Our two E. lactis strains showed promising probiotic properties in-vitro. Their genomes were devoid of any transferable antibiotic resistance genes. In silico comparative analysis confirmed the safety of the E. lactis species. These results suggest that E. lactis species could be a potential source for safer Enterococcus probiotic supplements.
Unconventional S-adenosyl-L-methionine (SAM) mimics with enhanced hydrophobicity are an adaptable building block to develop cell-potent inhibitors for SAM-dependent methyltransferases as targeted ...therapeutics. We recently discovered cell-potent bisubstrate inhibitors for nicotinamide N-methyltransferase (NNMT) by using an unconventional SAM mimic. To delve into the selectivity implications of the unconventional SAM mimic, we employed a chemoproteomic approach to assess two potent NNMT inhibitors LL320 (K i, app = 6.8 nM) and II399 (containing an unconventional SAM mimic, K i, app = 5.9 nM) within endogenous proteomes. Our work began with the rational design and synthesis of immobilized probes 1 and 2, utilizing LL320 and II399 as parent compounds. Systematic analysis of protein networks associated with these probes revealed a comprehensive landscape. Notably, NNMT emerged as the top-ranking hit, substantiating the high selectivity of both inhibitors. Meanwhile, we identified additional interacting proteins for LL320 (38) and II399 (17), showcasing the intricate selectivity profiles associated with these compounds. Subsequent experiments confirmed LL320’s interactions with RNMT, DPH5, and SAHH, while II399 exhibited interactions with SHMT2 and MEPCE. Importantly, incorporating the unconventional SAM mimic in II399 led to improved selectivity compared to LL320. Our findings underscore the importance of selectivity profiling and validate the utilization of the unconventional SAM mimic as a viable strategy to create highly selective and cell-permeable inhibitors for SAM-dependent methyltransferases.
Resident physicians in Sudan face a variety of physical and psychological stressors. Nevertheless, the prevalence of burnout syndrome among this critical population remains unknown. The purpose of ...this study was to estimate the prevalence rate of burnout and its associated factors in a sample of resident physicians in Sudan.
A cross-sectional design was used to assess the burnout syndrome among resident physicians at the teaching hospitals of Wad-Medani in Gezira state, east-central Sudan. Three hundred resident physicians at the dermatology, general surgery, pediatrics, obstetrics and gynecology, psychiatry, ear, nose and throat (ENT), oncology, urology, and internal medicine departments, were approached and invited to participate in the study. The Arabic version of the Maslach Burnout Inventory was distributed to respondents from July to October 2021.
From the 300 resident physicians, 208 (69.3%) responded. The average age of the study population was 29.99 ± 3.01 years, with more than half were females (56.7%), single (59.6%), and with more than three years of residency experience (50.5%). In total, 86.1% met the criteria for burnout in at least one dimension and 13.9% in all three dimensions. On the dimension of emotional exhaustion (EE), 70.7% reported high levels of burnout. While, 44.2% reported high levels of depersonalization (DP), and 73.1% experienced a sense of decreased professional accomplishment (PA). There were significant differences in burnout, EE, and DP levels among different specialties, with the pediatrics-specialty trainees reported higher levels. Burnout syndrome was associated with the working hours per single duty; participants who reported working for more than 24 hours had experienced higher levels of burnout, EE, and DP.
Large-scale studies are required to assess the determinants of burnout syndrome among resident physicians in Sudan. In addition, Stakeholders should urgently implement effective remedies to protect the mental health of resident physicians.
Display omitted
•Ovarian aging is one of the etiological factors in infertile women.•Mitochondrial dysfunction drives ovarian aging.•Rejuvenating mitochondria with nutrient therapy may improve ...fertility.•Optimizing mitochondria by lifestyle or environment prolongs reproductive longevity.•Mitochondrial replacement therapy for in vitro fertilization is being investigated.
Mitochondrial dysfunction is one of the hallmarks of aging. Consistently mitochondrial DNA (mtDNA) copy number and function decline with age in various tissues. There is increasing evidence to support that mitochondrial dysfunction drives ovarian aging. A decreased mtDNA copy number is also reported during ovarian aging. However, the mitochondrial mechanisms contributing to ovarian aging and infertility are not fully understood. Additionally, investigations into mitochondrial therapies to rejuvenate oocyte quality, select viable embryos and improve mitochondrial function may help enhance fertility or extend reproductive longevity in the future. These therapies include the use of mitochondrial replacement techniques, quantification of mtDNA copy number, and various pharmacologic and lifestyle measures. This review aims to describe the key evidence and current knowledge of the role of mitochondria in ovarian aging and identify the emerging potential options for therapy to extend reproductive longevity and improve fertility.
Milk fat globule epidermal growth factor-factor 8 (MFG-E8) is a peripheral glycoprotein that acts as a bridging molecule between the macrophage and apoptotic cells, thus executing a pivotal role in ...the scavenging of apoptotic cells from affected tissue. We have previously reported that apoptotic cell clearance activity or efferocytosis is compromised in diabetic wound macrophages. In this work, we test the hypothesis that MFG-E8 helps resolve inflammation, supports angiogenesis, and accelerates wound closure. MFG-E8(-/-) mice displayed impaired efferocytosis associated with exaggerated inflammatory response, poor angiogenesis, and wound closure. Wound macrophage-derived MFG-E8 was recognized as a critical driver of wound angiogenesis. Transplantation of MFG-E8(-/-) bone marrow to MFG-E8(+/+) mice resulted in impaired wound closure and compromised wound vascularization. In contrast, MFG-E8(-/-) mice that received wild-type bone marrow showed improved wound closure and improved wound vascularization. Hyperglycemia and exposure to advanced glycated end products inactivated MFG-E8, recognizing a key mechanism that complicates diabetic wound healing. Diabetic db/db mice suffered from impaired efferocytosis accompanied with persistent inflammation and slow wound closure. Topical recombinant MFG-E8 induced resolution of wound inflammation, improvements in angiogenesis, and acceleration of closure, upholding the potential of MFG-E8-directed therapeutics in diabetic wound care.
PDF
