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Microbiology Spectrum Jul 2024The increasing prevalence of invasive fungal pathogens is dramatically changing the clinical landscape of infectious diseases, posing an imminent threat to public...
The increasing prevalence of invasive fungal pathogens is dramatically changing the clinical landscape of infectious diseases, posing an imminent threat to public health. Specifically, , the human opportunistic pathogen, expresses elaborate virulence mechanisms and is equipped with sophisticated adaptation strategies to survive in harsh host environments. This study extensively characterizes Wos2, an Hsp90 co-chaperone homolog, featuring bilateral functioning for both cryptococcal adaptation and the resulting virulence response. In this study, we evaluated the proteome and secretome signatures associated with deletion in enriched and infection-mimicking conditions to reveal Wos2-dependent regulation of the oxidative stress response through global translational reprogramming. The Δ strain demonstrates defective intracellular and extracellular antioxidant protection systems, measurable through a decreased abundance of critical antioxidant enzymes and reduced growth in the presence of peroxide stress. Additional Wos2-associated stress phenotypes were observed upon fungal challenge with heat shock, osmotic stress, and cell membrane stressors. We demonstrate the importance of Wos2 for intracellular lifestyle of during macrophage infection and provide evidence for reduced phagosomal replication levels associated with Δ. Accordingly, Δ featured significantly reduced virulence within impacting fungal burden in a murine model of cryptococcosis. Our study highlights a vulnerable point in the fungal chaperone network that offers a therapeutic opportunity to interfere with both fungal virulence and fitness.IMPORTANCEThe global impact of fungal pathogens, both emerging and emerged, is undeniable, and the alarming increase in antifungal resistance rates hampers our ability to protect the global population from deadly infections. For cryptococcal infections, a limited arsenal of antifungals and increasing rates of resistance demand alternative therapeutic strategies, including an anti-virulence approach, which disarms the pathogen of critical virulence factors, empowering the host to remove the pathogens and clear the infection. To this end, we apply state-of-the-art mass spectrometry-based proteomics to evaluate the impact of a recently defined novel co-chaperone, Wos2, toward cryptococcal virulence using and models of infection. We explore global proteome and secretome remodeling driven by the protein and uncover the novel role in modulating the fungal oxidative stress response. Complementation of proteome findings with infectivity assays demonstrated the protective role of Wos2 within the macrophage phagosome, influencing fungal replication and survival. These results underscore differential cryptococcal survivability and weakened patterns of dissemination in the absence of . Overall, our study establishes Wos2 as an important contributor to fungal pathogenesis and warrants further research into critical proteins within global stress response networks as potential druggable targets to reduce fungal virulence and clear infection.
PubMed: 38953322
DOI: 10.1128/spectrum.00152-24 -
Current Research in Parasitology &... 2024Our study rationale was to establish contemporary epidemiological data on malaria and schistosomiasis among school-going children in Chikwawa District before future...
A baseline epidemiological survey for malaria and schistosomiasis reveals an alarming burden in primary schools despite ongoing control in Chikwawa District, southern Malawi.
Our study rationale was to establish contemporary epidemiological data on malaria and schistosomiasis among school-going children in Chikwawa District before future environmental changes associated with the Shire Valley Transformation Programme occurred. Our cross-sectional surveys tested 1134 children from 21 government-owned primary schools (approximately 50 children per school); rapid diagnostic tests for malaria (Humasis Pf/PAN) and intestinal schistosomiasis (urine-Circulating Cathodic Antigen) were used, with urine reagents strips and egg-filtration with microscopy for urogenital schistosomiasis. All infected children were treated with an appropriate dose of Lonart® (for malaria) and/or Cesol® (for schistosomiasis). Across 21 schools the overall prevalence was 9.7% (95% CI: 8.8-10.6%) for malaria, 1.9% (95% CI: 1.4-2.3%) for intestinal schistosomiasis, and 35.0% (95% CI: 33.6-36.5%) for egg-patent urogenital schistosomiasis. The prevalence of co-infection of malaria with urogenital schistosomiasis was 5.5% (95% CI: 4.8-6.2%). In a third of the schools, the prevalence of malaria and urogenital schistosomiasis was above national averages of 10.5% and 40-50%, respectively, with two schools having maxima of 36.8% and 84.5%, respectively. Set against a background of ongoing control, our study has revealed an alarming burden of malaria and schistosomiasis in southern Malawi. These findings call for an immediate mitigating response that significantly bolsters current control interventions to better safeguard children's future health.
PubMed: 38952689
DOI: 10.1016/j.crpvbd.2024.100183 -
Scientific Reports Jul 2024This study was performed to analyze fingertip capillary blood sampling in pediatric patients using microcapillary blood collection tubes and microhematocrit tubes and to...
This study was performed to analyze fingertip capillary blood sampling in pediatric patients using microcapillary blood collection tubes and microhematocrit tubes and to compare the blood cell analysis results obtained via these two blood collection methods. Finger capillary blood was collected from 110 outpatients using microcapillary blood collection tubes and microhematocrit tubes and complete blood count analysis was performed with a Sysmex XS-900i hematology analyzer and manual microscopy for blood cell morphology. Paired data was evaluated for agreement and bias using the microhematocrit samples as the reference group and the samples from the microcapillary blood collection tubes as the observation group. The two blood collection methods demonstrated good agreement for measuring red blood cell (RBC) parameters (i.e., RBC, Hb, Hct, MCV, MCH and MCHC), wherein the relative bias was > allowable total error (TEa) in 0.91%, 1.82%, 11.82%, 1.82%, 0.91% and 8.18% of the parameter measures, respectively. According to industry requirements, the proportion of samples meeting the acceptable bias level should be > 80%. Additionally, the estimated biases at each medical decision level were within clinically acceptable levels for RBC, Hb, Hct, and MCV. However, the proportion of WBC and PLT counts with relative bias > TEa was 25.45% and 35.45%, respectively. Furthermore, the relative bias of the WBC count at the medical decision level of 0.5 × 10/L and that of the PLT counts at the medical decision levels of 10 × 10/L and 50 × 10/L were clinically significant. Bland-Altman analysis further showed a mean bias of 0.66 × 10/L (95% LoA, - 0.79 to 2.11) for the WBC count and 39 × 10/L (95% LoA, - 46 to 124) for the PLT count from the blood samples collected in the microcapillary blood collection tubes compared with the counts of those collected in the microhematocrit tubes. Neutrophil, monocyte, lymphocyte, eosinophil, and PLT counts increased significantly in the microcapillary blood collection tubes compared with those in the microhematocrit tubes, along with an elevated number of instrument false alarms (P < 0.05). The two capillary blood collection devices exhibit performance differences. Therefore, clinicians should pay attention to the variation in results caused by different blood collection methods.
Topics: Humans; Blood Specimen Collection; Female; Child; Male; Blood Cell Count; Child, Preschool; Fingers; Infant; Adolescent; Capillaries; Leukocyte Count
PubMed: 38951565
DOI: 10.1038/s41598-024-64448-z -
The British Journal of General Practice... Jul 2024Diagnostic testing is prevalent among children with persistent non-specific symptoms (PNS), and both undertesting and overtesting have negative consequences for child...
BACKGROUND
Diagnostic testing is prevalent among children with persistent non-specific symptoms (PNS), and both undertesting and overtesting have negative consequences for child and society. Research in adults with PNS has shown that general practitioners (GPs) use diagnostic testing for reasons other than diagnosis, but comparable research has not been conducted in children. Understanding GPs' perspectives of testing decisions in children could provide insights into mechanisms of undertesting and overtesting.
AIM
To investigate GPs' perspectives of conducting or refraining from diagnostic testing in children with PNS, and differences with motives in adults.
DESIGN AND SETTING
Qualitative study using semi-structured interviews with Dutch GPs.
METHOD
We purposively sampled GPs until data saturation. Reasons for conducting or refraining from diagnostic tests were explored using two real-life cases from daily practice. Online video interviews were transcribed verbatim. Data were collected and analyzed concurrently by thematic content analysis.
FINDINGS
Twelve GPs participated. Their decision-making involved a complex trade-off among four themes: medical (e.g., alarm symptoms), psychosocial (e.g., doctor-patient relationship), consultation management (e.g., 'quick fix'), and efficient resource utilization (e.g., sustainability). Compared to adults, GPs were more hesitant to conduct diagnostic testing in children due to their higher vulnerability to fearing invasive procedures, lower probability of organic disease, and reduced autonomy.
CONCLUSION
As in adults, GPs' decisions to conduct diagnostic tests in children were motivated by reasons beyond diagnostic uncertainty. Educational programs, interventions, and guidelines that aim to change the testing behaviors of GPs in children with PNS should target these reasons as well.
PubMed: 38950942
DOI: 10.3399/BJGP.2023.0683 -
The Journal of Urology Jul 2024Nocturnal urine volume and bladder reservoir function are key pathogenic factors behind monosymptomatic nocturnal enuresis (MNE). We investigated the predictive value of...
Development of a Novel Prediction Tool for Response to First-Line Treatments of Monosymptomatic Nocturnal Enuresis-A Randomized, Controlled International Multicenter Study (DRYCHILD).
PURPOSE
Nocturnal urine volume and bladder reservoir function are key pathogenic factors behind monosymptomatic nocturnal enuresis (MNE). We investigated the predictive value of these together with other demographic and clinical variables for response to first-line treatments in children with MNE.
MATERIALS AND METHODS
A randomized, controlled, international multicenter study was conducted in 324 treatment-naïve children (6-14 years) with primary MNE. The children were randomized to treatment with or without prior consideration of voiding diaries. In the group where treatment choice was based on voiding diaries, children with nocturnal polyuria and normal maximum voided volume (MVV) received desmopressin (dDAVP) treatment and children with reduced MVV and no nocturnal polyuria received an enuresis alarm. In the other group, treatment with dDAVP or alarm was randomly allocated.
RESULTS
A total of 281 children (72% males) were qualified for statistical analysis. The change of responding to treatment was 21% higher in children where treatment was individualized compared to children where treatment was randomly selected (RR = 1.21 (1.02-1.45), = .032). In children with reduced MVV and no nocturnal polyuria (35% of all children), individualized treatment was associated with a 46% improvement in response compared to random treatment selection (RR = 1.46 (1.14-1.87), = .003). Furthermore, we developed a clinically relevant prediction model for response to dDAVP treatment (ROC 0.85).
CONCLUSIONS
The present study demonstrates that treatment selection based on voiding diaries improve response to first line treatment, particularly in specific subtypes. Information from voiding diaries together with clinical and demographic information provides the basis for predicting response.
PubMed: 38950376
DOI: 10.1097/JU.0000000000004129 -
PLoS Neglected Tropical Diseases Jul 2024Giardiasis and zinc deficiency have been identified as serious health problems worldwide. Although Zn depletion is known to occur in giardiasis, no work has investigated...
BACKGROUND
Giardiasis and zinc deficiency have been identified as serious health problems worldwide. Although Zn depletion is known to occur in giardiasis, no work has investigated whether changes occur in brain structures.
METHODS
Three groups of gerbils were used: control (1), orogastrically inoculated on day 3 after birth with trophozoites of two isolates of Giardia intestinalis (HGINV/WB) group (2 and 3). Estimates were made at five ages covering: establishment of infection, Giardia population growth, natural parasite clearance and a post-infection age. QuantiChrome zinc assay kit, cresyl violet staining and TUNEL technique were used.
RESULTS
A significant decrease (p<0.01) in tissue zinc was observed and persisted after infection. Cytoarchitectural changes were observed in 75% of gerbils in the HGINV or WB groups. Ectopic pyramidal neurons were found in the cornus ammonis (CA1-CA3). At 60 and 90 days of age loss of lamination was clearly visible in CA1. In the dentate gyrus (DG), thinning of the dorsal lamina and abnormal thickening of the ventral lamina were observed from 30 days of age. In the cerebellum, we found an increase (p<0.01) in the thickness of the external granular layer (EGL) at 14 days of age that persisted until day 21 (C 3 ± 0.3 μm; HGINV 37 ± 5 μm; WB 28 ± 3 μm); Purkinje cell population estimation showed a significant decrease; a large number of apoptotic somas were observed scattered in the molecular layer; in 60 and 90 days old gerbils we found granular cell heterotopia and Purkinje cell ectopia. The pattern of apoptosis was different in the cerebellum and hippocampus of parasitized gerbils.
CONCLUSION
The morphological changes found suggest that neuronal migration is affected by zinc depletion caused by giardiasis in early postnatal life; for the first time, the link between giardiasis-zinc depletion and damaged brain structures is shown. This damage may explain the psychomotor/cognitive delay associated with giardiasis. These findings are alarming. Alterations in zinc metabolism and signalling are known to be involved in many brain disorders, including autism.
PubMed: 38950061
DOI: 10.1371/journal.pntd.0012302 -
Journal of Chemical Ecology Jun 2024Plant responses to damage by insectivorous herbivores are well-documented in mature leaves. The resulting herbivore-induced plant volatiles (HIPVs) protect the plant by...
Plant responses to damage by insectivorous herbivores are well-documented in mature leaves. The resulting herbivore-induced plant volatiles (HIPVs) protect the plant by attracting carnivorous arthropods and even some insectivorous vertebrates, to parasitize or consume the plant invaders. However, very little is known about plant production of HIPVs in developing buds, particularly when herbivorous insects are too small to be considered a prey item. It is additionally unclear whether plants respond differently to generalist and specialist chewing insects that overlap in distribution. Therefore, we compared HIPV production of Downy oak (Quercus pubescens Willd.) buds infested with freshly hatched caterpillars of Tortrix viridana (specialist) and Operophtera brumata (generalist), against uninfested buds. Of the compounds identified in both years of the experiment, we found that (Z)-hex-3-enyl acetate, (E)-β-ocimene, acetophenone, linalool, (E)-4,8-dimethyl-1,3,7-nonatriene (DMNT), methyl salicylate, α-copaene, α-humulene, (E)-caryophyllene, and (E,E)-α-farnesene appeared to be higher in infested buds compared to controls. We found no difference in HIPV production between the specialist and the generalist herbivores. Production of HIPVs was also associated with leaf damage, with higher HIPV production in more severely attacked buds. Thus, our study shows that oak trees already start responding to insect herbivory before leaves are developed, by producing compounds similar to those found in damaged mature leaves. Future work should focus on how Downy oak may benefit from initiating alarm cues at a time when carnivorous arthropods and insectivorous vertebrates are unable to use herbivorous insects as host or food.
PubMed: 38949747
DOI: 10.1007/s10886-024-01520-y -
International Maritime Health 2024In confined waters, ships run a high risk of groundings, contact, sinkings and near misses. In such waters the maritime traffic is dense, the waterway is narrow, the...
BACKGROUND
In confined waters, ships run a high risk of groundings, contact, sinkings and near misses. In such waters the maritime traffic is dense, the waterway is narrow, the depth is limited, and tides and currents are constantly changing.
MATERIALS AND METHODS
From 2009-2019, 75 accidents were investigated in the estuary of the Seine. Weather conditions and perceived fatigue were studied. From May to June 2020, 114 seafarers, 34 pilots and 80 captains, responded to a questionnaire focusing on the use of Pilot Portable Units (PPU) and Electronic Chart Display Information Systems (ECDIS).
RESULTS
The 75 accidents corresponded to an average of 6.8 ± 3.2 accidents per year. Groundings were the most frequent accidents (35%, n = 26) followed by contact accidents with the quayside (25%, n = 19), between ships or tugs while manoeuvring (8%, n = 6) or while sailing (1%, n = 1). There was no loss of vessels nor fatalities of crew members. In poor weather conditions, there were 76% more accidents than in normal conditions (4.4 ± 2.5 accidents/10,000 movements versus 2.5 ± 1.9 accidents/10,000 movements, p < 0.03). Almost all the accidents (96%) were related to human errors of judgment (81%), or negligence (53%), or both (39). Perceived fatigue was probably in cause in 6 accidents. Only 3 accidents were related to mechanical causes. Through the questionnaires, 69% of the pilots complained of difficulties in mastering the devices and software. They felt distracted by alarms which affected their attention while navigating. They requested training on a simulator. Concerning ship captains, 83% felt comfortable with ECDIS devices yet only 20% were able to configure the ECDIS correctly.
CONCLUSIONS
In the Seine estuary, 75 accidents occurred within the 11 year-study. Risk factors were poor weather conditions and human error. PPU and ECDIS were considered as useful tools in the prevention of accidents. However, pilots and captains requested more thorough training in their use.
Topics: Humans; Ships; Accidents, Occupational; France; Adult; Surveys and Questionnaires; Weather; Male; Estuaries; Pilots; Naval Medicine; Fatigue; Female; Middle Aged
PubMed: 38949220
DOI: 10.5603/imh.99407 -
International Maritime Health 2024In a working environment that is predominantly male, very tough physically, with a difficult working environment, occupational exposures and working, verbal and physical... (Observational Study)
Observational Study
BACKGROUND
In a working environment that is predominantly male, very tough physically, with a difficult working environment, occupational exposures and working, verbal and physical aggression can be more frequent than in other sectors. Fishing, merchant shipping and yachting are all sectors where fitness to sail is reassessed every year by doctors in the Seafarers' Health Service. Seafarers are increasingly reporting insulting, violent or sexist behaviour. The main types of abuse seen on board can be verbal and/or physical aggression, humiliation, whether in private or in front of others. Sexual harassment of women is a very worrying subject.
MATERIALS AND METHODS
It was a retrospective observational study which is part of the professional monitoring of seafarers. The target population was adult seafarers coming for a fitness to sail visit. The group was recruited from seafarers aged over 18 who were being monitored by one of the seafarers' health services (or local centres). The inclusion period was 4 months between January and April 2023. All the information was collected using a self-questionnaire developed from the questionnaires of the Surveillance Médicale des Expositions des Salariés au Risques Professionnels (SUMER) for health status, job satisfaction and the European mini-module, verbal and physical aggression and psychological violence at work (based on the Leymann questionnaire), sexual violence and aggression based on the sexual harassment questionnaire and the PCLS-5 scale validated and translated into French to assess post-traumatic stress. The population studied was therefore 788 sailors.
RESULTS
The study population was predominantly male (82.3%). The average age was 41.4 years (standard deviation = 11.7). 46.7% of seafarers estimate being in very good health. During the past 12 months, overall, 24.5% of seafarers disclaimed having been victim in work-related context of a verbal aggression, with a significant difference according to the gender (21.1% for men and 41.0% for women). During the last 12 months, overall, 3.2% of seafarers have been victim in work-related context of a physical aggression (2.6% for men and 5.8% for women, NS), whereas 10.9% of seafarers reported hostile behaviour at present. Twenty per cent of seafarers reported sexual harassment in the last 12 months. During the entire working life of seafarers, 65.5% of women and 38.2% of men reported sexual harassment, and 38.8% of seafarers stated that they had experienced at least one traumatic event in the last 12 months.
DISCUSSION
A quarter of seafarers say they have been the victim of verbal or physical aggression at work in the last twelve months. These figures are high, and higher than those of the global survey on violence and harassment at work carried out by the International Labour Organization. One of the most alarming results of our study is the overexposure of women working in the maritime industry to the risk of physical, verbal or sexual assault of any kind. Indeed, in all the questions concerning the experience of verbal and physical aggression, the number of women victims is twice as high as that of their male colleagues, and this difference is statistically significant. As far as prevention is concerned, it seems that an effort is needed in terms of information, since only one seafarer in two knows the procedure to follow in the event of aggression within their shipyard. Communication between shipowners and seafarers needs to be stepped up to ensure that everyone is familiar with the procedures.
Topics: Humans; Adult; Sexual Harassment; Female; Male; France; Aggression; Retrospective Studies; Middle Aged; Naval Medicine; Surveys and Questionnaires; Workplace Violence; Ships
PubMed: 38949216
DOI: 10.5603/imh.99382 -
Journal of Family Medicine and Primary... May 2024Telephobia is a kind of anxiety disorder in which the individual is afraid of either answering or making telephone calls. This study was conducted to determine the...
BACKGROUND
Telephobia is a kind of anxiety disorder in which the individual is afraid of either answering or making telephone calls. This study was conducted to determine the prevalence of telephobia among medical students and to determine the association of socio-demographic and other factors with this disorder.
METHODS
A total of 320 undergraduate medical students were enrolled at a tertiary medical college in Western India, of which 300 (93.75%) responded to the survey. A stratified sampling strategy with the proportional allocation method was used in which 40 males and 20 females were selected from each year of students, spanning 5 years. A specially designed semi-structured questionnaire was used for the study, consisting of demographic data, purpose of using the internet, gadget used, and a 10-item telephobia questionnaire modified from the Severity Measure for Agoraphobia-Adult (SMA-A) Questionnaire to measure student's avoidance of telephone calling and receiving.
RESULTS
The mean age of the study participants was 21.91 (±1.84) years, and most of the students were urban residents (184, 61.3%). The prevalence of mild, moderate, and severe telephobia was 33.0%, 7.67%, and 1.33%, respectively, giving an overall prevalence of 42%. Univariate analysis revealed that male gender (χ = 9.822, df = 3, = 0.0201), higher duration of internet usage (χ = 41.15, df = 9, value < 0.000), and viewing porn (χ = 15.94, df = 3, = 0.0011) had significant association with higher severity of telephobia. Viewing of porn sites was reported by 65 (21.7%) medical students, exclusively among males.
CONCLUSION
A prevalence of 9% moderate to severe telephobia among medical students is much alarming, which may aggravate further as the students move from academic to clinical settings. The phenomenon of telephobia needs further exploration, to find its determinants and predictors, especially among vulnerable populations.
PubMed: 38948634
DOI: 10.4103/jfmpc.jfmpc_1673_23