Stage-specific exposure of Caenorhabditis elegans to cadmium identifies unique transcriptomic response cascades and an uncharacterized cadmium responsive transcript.

Age/stage sensitivity is considered a significant factor in toxicity assessments. Previous studies investigated cadmium (Cd) toxicosis in Caenorhabditis elegans, and a plethora of metal-responsive genes/proteins have been identified and characterized in fine detail; however, most of these studies neglected age sensitivity and stage-specific response to toxicants at the molecular level. This present study compared the transcriptome response between C. elegans L3 vs L4 larvae exposed to 20 µM Cd to explore the transcriptional hallmarks of stage sensitivity. The results showed that the transcriptome of the L3 stage, despite being exposed to Cd for a shorter period, was more affected than the L4 stage, as demonstrated by differences in transcriptional changes and magnitude of induction. Additionally, T08G5.1, a hitherto uncharacterized gene located upstream of metallothionein (mtl-2), was transcriptionally hyperresponsive to Cd exposure. Deletion of one or both metallothioneins (mtl-1 and/or mtl-2) increased T08G5.1 expression, suggesting that its expression is linked to the loss of metallothionein. The generation of an extrachromosomal transgene (PT08G5.1:: GFP) revealed that T08G5.1 is constitutively expressed in the head neurons and induced in gut cells upon Cd exposure, not unlike mtl-1 and mtl-2. The low abundance of cysteine residues in T08G5.1 suggests, however, that it may not be involved directly in Cd sequestration to limit its toxicity like metallothionein, but might be associated with a parallel pathway, possibly an oxidative stress response.

Juggling cadmium detoxification and zinc homeostasis: A division of labour between the two C. elegans metallothioneins.

The chemical properties of toxic cadmium and essential zinc are very similar, and organisms require intricate mechanisms that drive selective handling of metals. Previously regarded as unspecific "metal sponges", metallothioneins (MTLs) are emerging as metal selectivity filters. By utilizing C. elegans mtl-1 and mtl-2 knockout strains, metal accumulation in single worms, single copy fluorescent-tagged transgenes, isoform specific qPCR and lifespan studies it was possible to demonstrate that the handling of cadmium and zinc by the two C. elegans metallothioneins differs fundamentally: the MTL-2 protein can handle both zinc and cadmium, but when it becomes unavailable, either via a knockout or by elevated cadmium exposure, MTL-1 takes over zinc handling, leaving MTL-2 to sequester cadmium. This division of labour is reflected in the folding behaviour of the proteins: MTL-1 folded well in presence of zinc but not cadmium, the reverse was the case for MTL-2. These differences are in part mediated by a zinc-specific mononuclear His3Cys site in the C-terminal insertion of MTL-1; its removal affected the entire C-terminal domain and may shift its metal selectivity towards zinc. Overall, we uncover how metallothionein isoform-specific responses and protein properties allow C. elegans to differentiate between toxic cadmium and essential zinc.

Prevalence, Microbiological Profile, and Risk Factors of Surgical Site Infections in Saudi Patients with Colorectal Cancer.

Background: Resection surgery in patients with colorectal cancer (CRC) patients is associated with potential complications, including surgical site infection (SSI). Objectives: To estimate the prevalence rate of SSI, identify the common pathogens responsible for SSI, and determine potential risk factors for SSI development in a cohort from Saudi Arabia. Materials and Methods: Patients with CRC who underwent bowel resection surgery at King Abdulaziz Medical City, Riyadh, between January 01, 2016, and December 31, 2019, were retrospectively included. Demographics, comorbidities, surgical procedure data, and the results of preoperative laboratory tests were retrospectively collected from medical records through the health information system. The study population was divided into two groups: those who developed SSI and those who did not. Results: A total of 92 patients with CRC who underwent resection surgery were included, of which 54 (58.7%) were males. The median age was 65 (IQR 55.5-75.0) years. SSI was observed in 25 (27.2%) patients. The most frequently isolated organisms were Escherichia coli and Pseudomonas aeruginosa, followed by Klebsiella pneumoniae, vancomycin-sensitive Enterococcus faecium, and methicillin-resistant Staphylococcus aureus. Three E. coli isolates were producers of extended-spectrum beta-lactamases, and two K. pneumoniae isolates exhibited a multidrug resistance profile. Low preoperative serum albumin level was identified as a significant independent risk factor for developing SSI (AOR = 0.853, 95% CI = 0.748-0.973, P = 0.0181). Conclusion: The study found a notable prevalence of SSI among the included patients. Gram-negative bacteria were more involved in SSI events and were also associated with drug-resistance patterns. Gut microbiota bacteria were most commonly involved in SSIs. Low preoperative serum albumin levels predicted the development of postoperative SSI, and thus its close monitoring and management before surgery could reduce the SSIs.

A Comprehensive Review on Monkeypox Viral Disease with Potential Diagnostics and Therapeutic Options.

The purpose of this review is to give an up-to-date, thorough, and timely overview of monkeypox (Mpox), a severe infectious viral disease. Furthermore, this review provides an up-to-date treatment option for Mpox. The monkeypox virus (MPXV) has remained the most virulent poxvirus for humans since the elimination of smallpox approximately 41 years ago, with distribution mainly in central and west Africa. Mpox in humans is a zoonotically transferred disease that results in symptoms like those of smallpox. It had spread throughout west and central Africa when it was first diagnosed in the Republic of Congo in 1970. Mpox has become a major threat to global health security, necessitating a quick response by virologists, veterinarians, public health professionals, doctors, and researchers to create high-efficiency diagnostic tests, vaccinations, antivirals, and other infection control techniques. The emergence of epidemics outside of Africa emphasizes the disease's global significance. A better understanding of Mpox's dynamic epidemiology may be attained by increased surveillance and identification of cases.

Knowledge and use of the International Classification of Functioning, disability and health (ICF) and ICF Core Sets for musculoskeletal conditions among saudi physical therapists.

BACKGROUND: The International Classification of Functioning, Disability, and Health (ICF) provides a coherent biopsychosocial view of health states. The ICF Core Sets were developed to facilitate and encourage the use of the ICF in clinical practice and research. OBJECTIVE: To examine the level of knowledge and use of the ICF and ICF Core Sets for musculoskeletal conditions among Saudi physical therapists. DESIGN: Cross-sectional study. METHOD: We approached Saudi physical therapists (PTs) involved in managing patients with musculoskeletal conditions. Data were collected through an electronic survey consisting of multiple-choice questions related to the knowledge of the ICF, general ICF Core Sets and ICF Core Sets for musculoskeletal conditions. RESULTS: A total of 203 PTs participated in this study. Seventy percent of PTs knew about the meaning of ICF, but only 33% recognized aspects of the ICF. For the osteoarthritis (OA) ICF Core Set, 71.9% had poor knowledge, and for the low back pain (LBP) ICF Core Set, 61.8% had poor knowledge. CONCLUSIONS: The Saudi PTs surveyed in this study had a good level of knowledge about the meaning of the ICF; however, this knowledge appeared to be limited when they were asked about aspects of the ICF. They had poor knowledge of musculoskeletal ICF Core Sets but seemed to be more familiar with the LBP ICF Core Set compared to the OA ICF Core Set.

Lightsheet fluorescence lifetime imaging microscopy with wide-field time-correlated single photon counting.

We report on wide-field time-correlated single photon counting (TCSPC)-based fluorescence lifetime imaging microscopy (FLIM) with lightsheet illumination. A pulsed diode laser is used for excitation, and a crossed delay line anode image intensifier, effectively a single-photon sensitive camera, is used to record the position and arrival time of the photons with picosecond time resolution, combining low illumination intensity of microwatts with wide-field data collection. We pair this detector with the lightsheet illumination technique, and apply it to 3D FLIM imaging of dye gradients in human cancer cell spheroids, and C. elegans.