Phenotypic methods versus PCR-RFLP for the identification of dermatophyte species isolated from patients with dermatophytosis in Egypt

Background: Dermatophytes are major causative agents of cutaneous fungal infections worldwide. Identification of dermatophyte species is based on macroscopic and microscopic morphology on different culture media. Molecular methods such as PCR-RFLP are rapid, reliable and precise identification methods. This local study aimed to identify the spectrum of dermatophyte species among the studied patients population using different phenotypic and genotypic methods.Materials and methods: Hair, skin and nail specimens were collected from 135 patients with clinically suspected cases of dermatophytosis. All specimens were subjected to microscopic examination using KOH and culture on SDA and dermasel agar. Phenotypic identification was done by colony and microscopic morphology, and subculture on malt, PDA, lactrimel and urea agar plates. Molecular identification was done by PCR-RFLP using MvaI.Results: Out of 135 patients included in the study, 78 (57.8%) were positive by culture for dermatophytes. Five different species were identified, the most commonly isolated species was M. canis (51.3%) followed by T. violaceum (42.3%). PCR-RFLP correctly identified the isolated dermatophyte species, producing unique restriction patterns.Conclusion: Dermatophytosis is common in Egypt where humid hot climate and animal contact play important role in the spread of these fungi. The use of PCR-RFLP directly on clinical specimens rather than its use in the identification of dermatophytes from culture media is recommended.Keywords: Dermatophytosis, Dermasel agar, SDA, Sporulation media, PCR-RFL

Norovirus: an overview of virology and preventative measures

Norovirus (NoV) is an enteric non-enveloped virus which is the leading cause of gastroenteritis across all age groups. It is responsible for around 200,000 deaths annually and outbreaks are common in small communities such as educational and care facilities. 40% of all NoV outbreaks occur in long-term and acute-care facilities, forming the majority of outbreaks. Nosocomial settings set ideal environments for ease of transmission, especially due to the presence of immunocompromised groups. It is estimated to cost global economies around £48 billion a year, making it a global issue. NoV is transmitted via the faecal-oral route and infection with it results in asymptomatic cases or gastrointestinal disease. It has high mutational rates and this allows for new variants to emerge and be more resistant. The classification system available divides NoV into 10 genogroups and 49 genotypes based on whole amino acid sequencing of VP1 capsid protein and partial sequencing of RdRp, respectively. The most predominant genotypes which cause gastroenteritis in humans include GI.1 and GII.4, where GII.4 is responsible for more extreme clinical implications such as hospitalisation. In addition, GII.4 has been responsible for 6 pandemic strains, the last of which is the GII.4 Sydney (2012) variant. In recent years, the successful cultivation of HuNoV was reported in stem cell-derived human intestinal enteroids (HIEs), which promises to assist in giving a deeper understanding of its underlying mechanisms of infection and the development of more personalized control measures. There are no specific control measures against NoV, therefore common practices are used against it such as hand washing. No vaccine is available, but the HIL-214 candidate passed clinical phase 2b and shows promise

Are mild cleansers appropriate for hand hygiene in the COVID era? An in vitro investigation of the antiviral efficacy of different hand hygiene products

Background: Washing hands with soap and lukewarm water for 20 s is a fundamental measure advocated especially within the UK to help control the spread of viral disease. However, these practices can induce irritant contact dermatitis, particularly in healthcare professionals (HCPs). HCPs typically manage their condition by replacing soap or alcohol-based hand sanitizers with cleansers containing mild surfactants and/or emollient ingredients [skin-friendly cleansers (SFCs)] to mitigate skin damage and/or using topical emollients after washing for repair. Despite this widespread practice, there is very limited evidence supporting the efficacy of these interventions in the prevention of viral propagation. Methodology: Within this study a range of viruses comprising human coronavirus (HCoV), herpes simplex virus (HSV)-1, influenza (IVA), adenovirus (Ad), and murine norovirus (MNV) were tested against multiple hand wash products, including SFCs. In vitro analysis using plaque assays and tissue culture infectious dose 50 (TCID50) were used to assess virus infectability after incubation with the test products (soaps and SFCs) over a range of concentrations and time points. Transmission electron microscopy (TEM) was used to determine virus architecture and size, while viral replication genes were measured by reverse transcription-polymerase chain reaction (RT-PCR). Results/conclusions: Enveloped viruses demonstrated greater susceptibility over a range of test products, suggesting some SFCs are a suitable alternative to soap (depending on the presence of a viral envelope). However, no virucidal activity was observed for non-enveloped viruses. Water type (i.e., soft/hard) and pre-exposed hand hygiene conditions (i.e., clean/dirty) made little difference to the effectiveness of both soaps and SFCs. Therefore, new hand hygiene regimens should be implemented based on trying to encompass all viruses with varying structures, with specific emphasis on the absence of a viral envelope

Posttranscriptional Upregulation of IDH1 by HuR Establishes a Powerful Survival Phenotype in Pancreatic Cancer Cells.

Cancer aggressiveness may result from the selective pressure of a harsh nutrient-deprived microenvironment. Here we illustrate how such conditions promote chemotherapy resistance in pancreatic ductal adenocarcinoma (PDAC). Glucose or glutamine withdrawal resulted in a 5- to 10-fold protective effect with chemotherapy treatment. PDAC xenografts were less sensitive to gemcitabine in hypoglycemic mice compared with hyperglycemic mice. Consistent with this observation, patients receiving adjuvant gemcitabine (n = 107) with elevated serum glucose levels (HgbA1C \u3e 6.5%) exhibited improved survival. We identified enhanced antioxidant defense as a driver of chemoresistance in this setting. ROS levels were doubled in vitro by either nutrient withdrawal or gemcitabine treatment, but depriving PDAC cells of nutrients before gemcitabine treatment attenuated this effect. Mechanistic investigations based on RNAi or CRISPR approaches implicated the RNA binding protein HuR in preserving survival under nutrient withdrawal, with or without gemcitabine. Notably, RNA deep sequencing and functional analyses in HuR-deficient PDAC cell lines identified isocitrate dehydrogenase 1 (IDH1) as the sole antioxidant enzyme under HuR regulation. HuR-deficient PDAC cells lacked the ability to engraft successfully in immunocompromised mice, but IDH1 overexpression in these cells was sufficient to fully restore chemoresistance under low nutrient conditions. Overall, our findings highlight the HuR–IDH1 regulatory axis as a critical, actionable therapeutic target in pancreatic cancer

Boundary Conditions for Elastohydrodynamics of Circular Point Contacts

The paper presents the solution of an elastohydrodynamic point contact condition using inlet and outlet lubricant entrainment with partial counter-flow. The inlet and outlet boundaries are determined using potential flow analysis for the pure rolling of contiguous surfaces. This shows that Swift–Stieber boundary conditions best conform to the observed partial counter-flow at the inlet conjunction, satisfying the compatibility condition. For the outlet region, the same is true when Prandtl–Hopkins boundary conditions are employed. Using these boundary conditions, the predictions conform closely to the measured pressure distribution using a deposited pressure-sensitive micro-transducer in a ball-to-flat race contact. Furthermore, the predicted conjunctional shape closely conforms to the often observed characteristic keyhole conjunction through optical interferometry. The combined numerical–experimental analysis with realistic boundary conditions described here has not hitherto been reported in the literature

G protein-coupled estrogen receptor 1 regulates renal endothelin-1 signaling system in a sex-specific manner

Demographic studies reveal lower prevalence of hypertension among premenopausal females compared to age-matched males. The kidney plays a central role in the maintenance of sodium (Na+) homeostasis and consequently blood pressure. Renal endothelin-1 (ET-1) is a pro-natriuretic peptide that contributes to sex differences in blood pressure regulation and Na+ homeostasis. We recently showed that activation of renal medullary G protein-coupled estrogen receptor 1 (GPER1) promotes ET-1-dependent natriuresis in female, but not male, rats. We hypothesized that GPER1 upregulates the renal ET-1 signaling system in females, but not males. To test our hypothesis, we determined the effect of GPER1 deletion on ET-1 and its downstream effectors in the renal cortex, outer and inner medulla obtained from 12–16-week-old female and male mice. GPER1 knockout (KO) mice and wildtype (WT) littermates were implanted with telemetry transmitters for blood pressure assessment, and we used metabolic cages to determine urinary Na+ excretion. GPER1 deletion did not significantly affect 24-h mean arterial pressure (MAP) nor urinary Na+ excretion. However, GPER1 deletion decreased urinary ET-1 excretion in females but not males. Of note, female WT mice had greater urinary ET-1 excretion than male WT littermates, whereas no sex differences were observed in GPER1 KO mice. GPER1 deletion increased inner medullary ET-1 peptide content in both sexes but increased outer medullary ET-1 content in females only. Cortical ET-1 content increased in response to GPER1 deletion in both sexes. Furthermore, GPER1 deletion notably increased inner medullary ET receptor A (ETA) and decreased outer medullary ET receptor B (ETB) mRNA expression in male, but not female, mice. We conclude that GPER1 is required for greater ET-1 excretion in females. Our data suggest that GPER1 is an upstream regulator of renal medullary ET-1 production and ET receptor expression in a sex-specific manner. Overall, our study identifies the role of GPER1 as a sex-specific upstream regulator of the renal ET-1 system

A transient tribodynamic approach for the calculation of internal combustion engine piston slap noise

An analytical/numerical methodology is presented to calculate the radiated noise due to internal combustion engine piston impacts on the cylinder liner through a film of lubricant. Both quasi-static and transient dynamic analyses coupled with impact elasto-hydrodynamics are reported. The local impact impedance is calculated, as well as the transferred energy onto the cylinder liner. The simulations are verified against experimental results for different engine operating conditions and for noise levels calculated in the vicinity of the engine block. Continuous wavelet signal processing is performed to identify the occurrence of piston slap noise events and their spectral content, showing good conformance between the predictions and experimentally acquired signals

Adjusting 1.5 degree C climate change mitigation pathways in light of adverse new information

Understanding how 1.5 °C pathways could adjust in light of new adverse information, such as a reduced 1.5 °C carbon budget, or slower-than-expected low-carbon technology deployment, is critical for planning resilient pathways. We use an integrated assessment model to explore potential pathway adjustments starting in 2025 and 2030, following the arrival of new information. The 1.5 °C target remains achievable in the model, in light of some adverse information, provided a broad portfolio of technologies and measures is still available. If multiple pieces of adverse information arrive simultaneously, average annual emissions reductions near 3 GtCO2/yr for the first five years following the pathway adjustment, compared to 2 GtCO2/yr in 2020 when the Covid-19 pandemic began. Moreover, in these scenarios of multiple simultaneous adverse information, by 2050 mitigation costs are 4-5 times as high as a no adverse information scenario, highlighting the criticality of developing a wide range of mitigation options, including energy demand reduction options