Anticancer actions of carnosine in cellular models of prostate cancer.

Treatments for organ-confined prostate cancer include external beam radiation therapy, radical prostatectomy, radiotherapy/brachytherapy, cryoablation and high-intensity focused ultrasound. None of these are cancer-specific and are commonly accompanied by side effects, including urinary incontinence and erectile dysfunction. Moreover, subsequent surgical treatments following biochemical recurrence after these interventions are either limited or affected by the scarring present in the surrounding tissue. Carnosine (ß-alanyl-L-histidine) is a histidine-containing naturally occurring dipeptide which has been shown to have an anti-tumorigenic role without any detrimental effect on healthy cells; however, its effect on prostate cancer cells has never been investigated. In this study, we investigated the effect of carnosine on cell proliferation and metabolism in both a primary cultured androgen-resistant human prostate cancer cell line, PC346Flu1 and murine TRAMP-C1 cells. Our results show that carnosine has a significant dose-dependent inhibitory effect in vitro on the proliferation of both human (PC346Flu1) and murine (TRAMP-C1) prostate cancer cells, which was confirmed in 3D-models of the same cells. Carnosine was also shown to decrease adenosine triphosphate content and reactive species which might have been caused in part by the increase in SIRT3 also shown after carnosine treatment. These encouraging results support the need for further human in vivo work to determine the potential use of carnosine, either alone or, most likely, as an adjunct therapy to surgical or other conventional treatments.

Health of singleton neonates in Switzerland through time and crises: a cross-sectional study at the population level, 2007-2022.

BACKGROUND: Being exposed to crises during pregnancy can affect maternal health through stress exposure, which can in return impact neonatal health. We investigated temporal trends in neonatal outcomes in Switzerland between 2007 and 2022 and their variations depending on exposure to the economic crisis of 2008, the flu pandemic of 2009, heatwaves (2015 and 2018) and the COVID-19 pandemic. METHODS: Using individual cross-sectional data encompassing all births occurring in Switzerland at the monthly level (2007-2022), we analysed changes in birth weight and in the rates of preterm birth (PTB) and stillbirth through time with generalized additive models. We assessed whether the intensity or length of crisis exposure was associated with variations in these outcomes. Furthermore, we explored effects of exposure depending on trimesters of pregnancy. RESULTS: Over 1.2 million singleton births were included in our analyses. While birth weight and the rate of stillbirth have remained stable since 2007, the rate of PTB has declined by one percentage point. Exposure to the crises led to different results, but effect sizes were overall small. Exposure to COVID-19, irrespective of the pregnancy trimester, was associated with a higher birth weight (+12 grams [95% confidence interval (CI) 5.5 to 17.9 grams]). Being exposed to COVID-19 during the last trimester was associated with an increased risk of stillbirth (odds ratio 1.24 [95%CI 1.02 to 1.50]). Exposure to the 2008 economic crisis during pregnancy was not associated with any changes in neonatal health outcomes, while heatwave effect was difficult to interpret. CONCLUSION: Overall, maternal and neonatal health demonstrated resilience to the economic crisis and to the COVID-19 pandemic in a high-income country like Switzerland. However, the effect of exposure to the COVID-19 pandemic is dual, and the negative impact of maternal infection on pregnancy is well-documented. Stress exposure and economic constraint may also have had adverse effects among the most vulnerable subgroups of Switzerland. To investigate better the impact of heatwave exposure on neonatal health, weekly or daily-level data is needed, instead of monthly-level data.

Evaluating the Concept of Brain Sparing in a High Income Setting, Using Historical Records of Maternal Influenza or Syphilis Infection.

INTRODUCTION: In the context of adverse in utero environments, the fetal brain might be preserved at the expense of other tissues. This trade-off, brain sparing, has not been studied in the context of maternal infection. We investigated cases of maternal syphilis in the early 20th century and influenza during the 1918-1920 pandemic, in the Swiss city of Lausanne, a relatively high-income setting. We tested the brain sparing hypothesis, that head circumference is protected at the expense of birth weight. METHODS: A total of 8530 individual birth records from 1911 to 1922 from the University Maternity Hospital of Lausanne were used. We fitted generalized linear and additive linear models to explain how neonatal size varies under disease exposure. RESULTS: Influenza reduced head circumference and birth weight among livebirths similarly, by -0.11 and -0.14 standard deviation (SD) units respectively. Conversely, for syphilis-exposed infants, head circumference was affected more than birth weight (-0.61 SD vs. -0.46 SD). Stillborn infants exposed to syphilis experienced a much greater reduction in head circumference (-1.92 SD) than liveborn infants. After adjustment for gestational age, these findings persisted in the case of influenza, but the effects of syphilis were reduced. Furthermore, half of syphilis-exposed infants were born before term, suggesting that lower infant size was partly mediated by shorter gestation. Nevertheless, head circumference among stillbirths exposed to syphilis was still substantially reduced, even after adjustment for gestational age (-1.26 SD). CONCLUSION: Our findings do not support the brain sparing hypothesis. Moreover, the substantial reduction in head circumference among syphilis-exposed fetuses might help explain why a quarter of them were stillborn.

Temperature-related emergency injury visits in Hanoi, Vietnam.

BACKGROUND: The short-term association between increasing temperatures and injury has been described in high-income countries, but less is known for low-income and-middle-income countries, including Vietnam. METHODS: We used emergency injury visits (EIV) data for 2017-2019 from 733 hospitals and clinics in Hanoi, Vietnam to examine the effects of daily temperature on EIV. Time-series analysis with quasi-Poisson models was used to estimate a linear relative risk increase (RRI) for overall populations and ones stratified by age and sex. Exposure-response curves estimated non-linear associations as an RR between daily temperature and injury. Models were adjusted for the day of week, holidays, daily relative humidity, daily particulate matter, and long-term and seasonal trends. RESULTS AND CONCLUSIONS: A total of 39 313 EIV were recorded averaging 36 injuries daily. Injuries more likely occurred in males and those aged 15-44, and aged 44-60. For linear effects, a 5°C increase in same day mean temperature was associated with an overall increased EIV (RRI 4.8; 95% CI 2.3 to 7.3) with males (RRI 5.9; 95% CI 3.0 to 8.9) experiencing a greater effect than females (RRI 3.0; 95% CI -0.5 to 6.5). Non-linear effects showed an increase in EIV at higher temperatures compared with the threshold temperature of 15°C, with the greatest effect at 33°C (RR 1.3; 95% CI 1.2 to 1.6). Further research to investigate temperature-injury among different populations and by the cause of injury is warranted.

Acute invasive fungal rhinosinusitis in post-COVID-19 patients in Vietnam.

BACKGROUND: Acute invasive fungal rhinosinusitis (AIFR) is a potentially lethal infection commonly found in immunocompromised patients. It is considered the most aggressive subtype of fungal sinusitis and can lead to severe morbidity and mortality. There was a significant increase in the incidence of AIFR in post-COVID-19 patients compared to AIFR cases before the COVID-19 pandemic. This study aimed to describe the clinical presentation of AIFR associated with COVID-19 illness. METHODS: A retrospective study included 22 patients diagnosed with AIFR with a recent COVID-19 infection. RESULTS: The most frequent disease associated with AIFR was diabetes mellitus (95.5%). The mycological analysis identified infection caused by Aspergillus species in 72.7% of patients. Along with stabilizing hemodynamic parameters and controlling any comorbidities, all patients in the present study underwent combined surgical debridement followed by antifungal medications. The overall survival rate was 72.7%. The chance of developing a fatal outcome was significantly higher if meningitis presented initially (odds ratio 35.63, p < 0.05). CONCLUSION: The presence of meningitis upon initial diagnosis is related to a significantly higher chance of developing a fatal outcome and should be considered, especially in AIFR patients previously treated for COVID-19 infections. Early diagnosis, early use of antifungal agents, aggressive surgical debridement, and control of comorbid conditions remain crucial in managing AIFR.

Long-Term Prognosis of Patients With Myocarditis Attributed to COVID-19 mRNA Vaccination, SARS-CoV-2 Infection, or Conventional Etiologies.

Importance: Although patients with myocarditis after COVID-19 mRNA vaccination appear to have a good prognosis near hospital discharge, their longer-term prognosis and management remain unknown. Objective: To study the cardiovascular complications of post-COVID-19 mRNA vaccination myocarditis and other types of myocarditis during an 18-month follow-up, as well as disease management based on a study of the frequency of medical procedures and drug prescriptions. Design, Setting, and Participants: In this cohort study based on the French National Health Data System, all individuals aged 12 to 49 years hospitalized for myocarditis in France between December 27, 2020, and June 30, 2022, were identified. Exposure: Individuals were categorized as having postvaccine myocarditis (within 7 days after COVID-19 mRNA vaccine), post-COVID-19 myocarditis (within 30 days of SARS-CoV-2 infection), or conventional myocarditis. Main Outcomes and Measures: The occurrence of clinical outcomes (hospital readmission for myopericarditis, other cardiovascular events, all-cause death, and a composite outcome of these events) over the 18 months following hospital admission were analyzed using weighted Cox models to standardize the comparisons with the conventional myocarditis group. Also, medical management after hospital discharge was longitudinally assessed using generalized estimated equation models. Results: In total, 4635 individuals were hospitalized for myocarditis: 558 with postvaccine myocarditis, 298 with post-COVID-19 myocarditis, and 3779 with conventional myocarditis. Patients with postvaccine myocarditis were younger than those with post-COVID-19 and conventional myocarditis (mean [SD] age of 25.9 [8.6], 31.0 [10.9], and 28.3 [9.4] years, respectively) and were more frequently men (84%, 67%, and 79%). Patients with postvaccine myocarditis had a lower standardized incidence of the composite clinical outcome than those with conventional myocarditis (32/558 vs 497/3779 events; weighted hazard ratio, 0.55 [95% CI, 0.36-0.86]), whereas individuals with post-COVID-19 myocarditis had similar results (36/298 events; weighted hazard ratio, 1.04 [95% CI, 0.70-1.52]). The standardized frequency of medical procedures and drugs prescribed in patients with postvaccine myocarditis or post-COVID-19 myocarditis followed a similar trend in the 18 months following hospital discharge to that of patients with conventional myocarditis. Conclusions and Relevance: Patients with post-COVID-19 mRNA vaccination myocarditis, contrary to those with post-COVID-19 myocarditis, show a lower frequency of cardiovascular complications than those with conventional myocarditis at 18 months. However, affected patients, mainly healthy young men, may require medical management up to several months after hospital discharge.

Mapping Studies of Alcohol Use Among People Living with HIV/AIDS During 1990-2019 (GAPRESEARCH).

Alcohol drinking has long been reported to be common in people living with HIV/AIDS, having biological and behavioral impacts on the transmission, progression, and prevention of HIV/AIDS. A total of 7059 eligible articles and reviews published in English from 1990 to 2019 were extracted from the WOS. Results show an increase in publication volume, while citations peak for papers published in 2006. Content analysis reveals a wide-ranging coverage of topics, with the most popular being effects of alcohol consumption on ART adherence and outcomes, alcohol-related sexual behaviors, TB co-infection, and psycho-socio-cultural considerations in examining and designing measures targeting alcohol use and interventions to reduce alcohol dependence in PLWHA. This calls for more active engagement of governments in research and in designing and implementing interventions, as well as collaborations and knowledge transfer from high-income countries to developing counterparts, to effectively address alcohol use-related issues in PLWHA, moving toward the HIV/AIDS eradication target.

Preference and willingness to pay for reproductive health services among adults in Urban-Rural transition settings of a developing country: evidence from a cross-sectional study in a rural district of Hanoi, Vietnam.

BACKGROUND: Since the introduction of fee-for-service models in public hospitals and the legalization of private health services in Vietnam in 1989, the price of reproductive health services has risen. These changes have exacerbated inequities in accessing reproductive health services. This study examines potential disparities in willingness to pay for reproductive health services among adults in a rural district of Hanoi. METHODS: A cross-sectional study was conducted at 9 communes in Thanh Oai district, a rural district of Hanoi, Vietnam, in July 2019. Face-to-face interviews were conducted using a structured questionnaire to collect self-reported data. The contingent valuation was used to examine willingness to pay for reproductive health services with a starting price of 2 million VND (~ US$86.2, July 2019 exchange rate), which is the average price of all RHS in public facilities in Vietnam. Multiple Logistic regression and Multiple Interval regression models were used to identify factors associated with willingness to pay and the amount that people were willing to pay for reproductive health services. RESULTS: Among 883 participants, this study found 59.1% of them willing to pay for reproductive health services at an average maximum amount of US$36.2, significantly less than the current average price of US$86.2. Occupation, number of sex partners, perception towards the necessity of reproductive health services, and prior use of reproductive health services were found to significantly influence willingness to pay for reproductive health services, while age, income level, gender, occupation, perception towards the necessity of reproductive health services and prior use of reproductive health services were reportedly correlated with the amount participants were willing to pay for reproductive health services. CONCLUSION: Lower willingness to pay for reproductive health services compared to the current prices (US$36.2 vs. US$86.2) is likely related to an overall low awareness of the necessity of reproductive health services, and future education campaigns should specifically target those from lower-income backgrounds. Financial subsidization should also be provided, especially for those from the low-income group, to ensure equitable access to reproductive health services. Given the heterogeneity of reproductive health services, further studies should examine the willingness to pay for each type of service independently.

Risk for Myocardial Infarction, Stroke, and Pulmonary Embolism Following COVID-19 Vaccines in Adults Younger Than 75 Years in France.

BACKGROUND: The BNT162b2 (Pfizer-BioNTech) vaccine has been shown to be safe with regard to risk for severe cardiovascular events (such as myocardial infarction [MI], pulmonary embolism [PE], and stroke) in persons aged 75 years or older. Less is known about the safety of other COVID-19 vaccines or outcomes in younger populations. OBJECTIVE: To assess short-term risk for severe cardiovascular events (excluding myocarditis and pericarditis) after COVID-19 vaccination in France's 46.5 million adults younger than 75 years. DESIGN: Self-controlled case series method adapted to event-dependent exposure and high event-related mortality. SETTING: France, 27 December 2020 to 20 July 2021. PATIENTS: All adults younger than 75 years hospitalized for PE, acute MI, hemorrhagic stroke, or ischemic stroke (n = 73 325 total events). MEASUREMENTS: Linkage between the French National Health Data System and COVID-19 vaccine databases enabled identification of hospitalizations for cardiovascular events (MI, PE, or stroke) and receipt of a first or second dose of the Pfizer-BioNTech, mRNA-1273 (Moderna), Ad26.COV2.S (Janssen), or ChAdOx1 nCoV-19 (Oxford-AstraZeneca) vaccine. The relative incidence (RI) of each cardiovascular event was estimated in the 3 weeks after vaccination compared with other periods, with adjustment for temporality (7-day periods). RESULTS: No association was found between the Pfizer-BioNTech or Moderna vaccine and severe cardiovascular events. The first dose of the Oxford-AstraZeneca vaccine was associated with acute MI and PE in the second week after vaccination (RI, 1.29 [95% CI, 1.11 to 1.51] and 1.41 [CI, 1.13 to 1.75], respectively). An association with MI in the second week after a single dose of the Janssen vaccine could not be ruled out (RI, 1.75 [CI, 1.16 to 2.62]). LIMITATIONS: It was not possible to ascertain the relative timing of injection and cardiovascular events on the day of vaccination. Outpatient deaths related to cardiovascular events were not included. CONCLUSION: In persons aged 18 to 74 years, adenoviral-based vaccines may be associated with increased incidence of MI and PE. No association between mRNA-based vaccines and the cardiovascular events studied was observed. PRIMARY FUNDING SOURCE: None.

Real-Time Detection of Sleep Apnea Based on Breathing Sounds and Prediction Reinforcement Using Home Noises: Algorithm Development and Validation.

BACKGROUND: Multinight monitoring can be helpful for the diagnosis and management of obstructive sleep apnea (OSA). For this purpose, it is necessary to be able to detect OSA in real time in a noisy home environment. Sound-based OSA assessment holds great potential since it can be integrated with smartphones to provide full noncontact monitoring of OSA at home. OBJECTIVE: The purpose of this study is to develop a predictive model that can detect OSA in real time, even in a home environment where various noises exist. METHODS: This study included 1018 polysomnography (PSG) audio data sets, 297 smartphone audio data sets synced with PSG, and a home noise data set containing 22,500 noises to train the model to predict breathing events, such as apneas and hypopneas, based on breathing sounds that occur during sleep. The whole breathing sound of each night was divided into 30-second epochs and labeled as "apnea," "hypopnea," or "no-event," and the home noises were used to make the model robust to a noisy home environment. The performance of the prediction model was assessed using epoch-by-epoch prediction accuracy and OSA severity classification based on the apnea-hypopnea index (AHI). RESULTS: Epoch-by-epoch OSA event detection showed an accuracy of 86% and a macro F1-score of 0.75 for the 3-class OSA event detection task. The model had an accuracy of 92% for "no-event," 84% for "apnea," and 51% for "hypopnea." Most misclassifications were made for "hypopnea," with 15% and 34% of "hypopnea" being wrongly predicted as "apnea" and "no-event," respectively. The sensitivity and specificity of the OSA severity classification (AHI≥15) were 0.85 and 0.84, respectively. CONCLUSIONS: Our study presents a real-time epoch-by-epoch OSA detector that works in a variety of noisy home environments. Based on this, additional research is needed to verify the usefulness of various multinight monitoring and real-time diagnostic technologies in the home environment.

Yeast vacuolar enzymes as novel hatching inhibitors for aquatic organisms, Daphnia magna and Danio rerio eggs.

Concerns over the spread of non-native species in aquatic environments have led to the need for effective methods to prevent and control their spread while protecting native species. This study investigated the potential of yeast vacuolar enzymes as a natural hatching inhibitor for controlling aquatic organisms. Hatching experiments with Daphnia magna eggs demonstrated that exposure to yeast vacuole enzymes inhibited hatching in a concentration-dependent manner, suggesting their potential as an effective inhibitor of egg hatching in aquatic organisms. Interestingly, the protease used for comparative purposes did not inhibit hatching, but instead increased the mortality of hatched D. magna. Additionally, chorionic changes were observed in non-hatched D. magna eggs and zebrafish eggs exposed to yeast vacuole enzymes, suggesting that the enzyme can alter the chorion and interfere with hatching. These findings suggest that yeast vacuolar enzymes may be a promising and natural management tool for controlling the spread of harmful aquatic organisms, and further research is warranted to explore their potential for species-specific control.

Natural Phosphodiesterase-4 Inhibitors with Potential Anti-Inflammatory Activities from Millettia dielsiana.

The results of in silico screening of the 50 isolated compounds from Millettia dielsiana against the target proteins PDE4 (PDE4A, PDE4B, and PDE4D) showed binding affinity ranges from -5.81 to -11.56, -5.27 to -13.01, and -5.80 to -12.12 kcal mol-1, respectively, with median values of -8.83, -8.84, and -8.645 kcal mol-1, respectively. Among these compounds, Millesianin F was identified as the most promising PDE4A inhibitor due to its strongest binding affinity with the target protein PDE4A. (-11.56 kcal mol-1). This was followed by the compound 5,7,4'-trihydroxyisoflavone 7-O-ß-d-apiofuranosyl-(1→6)-ß-d-glucopyranoside (D50) with the binding affinity value of -11.35 kcal mol-1. For the target protein PDE4B, compound D50 exhibited the strongest binding affinity value of -13.01 kcal mol-1, while showing poorer inhibition ability for PDE4D. The 100 ns MD simulation examination (radius of gyration, Solvent Accessible Surface Area (SASA), Root-Mean-Square Deviation (RMSD), Root-Mean-Square Fluctuation (RMSF), and hydrogen bonding) was carried out to examine the overall stability and binding efficiency of the protein-ligand complex between compounds (Millesianin F, Millesianin G, Claclrastin-7-O-ß-d-glucopyranoside, 7-hydroxy-4',6 dimethoxyisoflavone-7-O-ß-d-apiofuranosyl-(1→6)-ß-d-glucopyranoside, 7-hydroxy-4',8-dimethoxyisoflavone 7-O-ß-d-apiofuranosyl-(1→6)-ß-d-glucopyranoside, Odoratin-7-O-ß-d-glucopyranoside, and 5,7,4'-trihydroxyisoflavone 7-O-ß-d-apiofuranosyl-(1→6)-ß-d-glucopyranoside) and PDE4 (A, B) subtype proteins. Compound D50 has shown strong anti-inflammatory activity, as evidenced by experimental results. It effectively inhibits PDE4B and PDE4D, with IC50 values of 6.56 ± 0.7 µM and 11.74 ± 1.3 µM, respectively. Additionally, it reduces NO production, with an IC50 value of 5.40 ± 0.9 µM. Based on these findings, it is promising and considered a potential novel anti-inflammatory drug for future development.

Spectrum of HBB gene mutations among 696 ß-thalassemia patients and carriers in Southern Vietnam.

BACKGROUND: Thalassemias are common inherited blood disorders that have been extensively studied in Asia. Thus far, data on mutations of the HBB gene in Vietnamese patients with ß-thalassemia are limited to small studies. METHODS: We recruited 696 ß-thalassemia patients and carriers in southern Vietnam and analyzed for the HBB gene mutations using Sanger sequencing technology. RESULTS: We documented 27 types of known mutations and 10 types of novel variants on 737 alleles out of 1392 surveyed alleles. The three most common mutations, which account for more than ¾ of all mutant alleles, were c.79G > A (HbE), c.124_127delTTCT, and c.52A > T. The novel variants were mainly located in 5' untranslated region (c.-92delC and c.-67A > G) and 3' untranslated region (c.*4C > T, c.*116_*117insA, c.*142 T > C, c.*156G > C, c.*176_*177insA, and c.*247 T > C), except for one in intron 2 (c.316-99 T > G) and one in exon 3 (c.385delG). CONCLUSION: We provide here a comprehensive mutation spectrum of the HBB gene in Southern Vietnam, which is crucial for carrier screening and prenatal diagnosis in the future.

Hepatoprotective Effect of Millettia dielsiana: In Vitro and In Silico Study.

In silico docking studies of 50 selected compounds from Millettia dielsiana Harms ex Diels (family Leguminosae) were docked into the binding pocket of the PI3K/mTOR protein. In there, compounds trans-3-O-p-hydroxycinnamoyl ursolic acid (1) and 5,7,4'-trihydroxyisoflavone 7-O-ß-D-apiofuranosyl-(1→6)-ß-D-glucopyranoside (2) are predicted to be very promising inhibitors against PI3K/mTOR. They direct their cytotoxic activity against Hepatocellular carcinoma with binding affinity (BA) values, the pulling work spent to the co-crystallized ligand from the binding site of PI3K/mTOR (W and Fmax), and the non-equilibrium binding free energy (∆GneqJar) as BA values = -9.237 and -9.083 kcal/mol, W = 83.5 ± 10.6 kcal/mol with Fmax = 336.2 ± 45.3 pN and 126.6 ± 21.7 kcal/mol with Fmax = 430.3 ± 84.0 pN, and ∆GneqJar = -69.86074 and -101.2317 kcal/mol, respectively. In molecular dynamic simulation, the RMSD value of the PI3K/mTOR complex with compounds (1 and 2) was in the range of 0.3 nm to the end of the simulation. Therefore, the compounds (1 and 2) are predicted to be very promising inhibitors against PI3K/mTOR. The crude extract, ethyl acetate fraction and compounds (1 and 2) from Millettia dielsiana exhibited moderate to potent in vitro cytotoxicity on Hepatocellular carcinoma cell line with IC50 values of 81.2 µg/mL, 60.4 µg/mL, 23.1 µM, and 16.3 µM, respectively, and showed relatively potent to potent in vitro antioxidant activity on mouse hepatocytes with ED50 values of 24.4 µg/mL, 19.3 µg/mL, 30.7 µM, and 20.5 µM, respectively. In conclusion, Millettia dielsiana and compounds (1 and 2) are predicted to have very promising cytotoxic activity against Hepatocellular carcinoma and have a hepatoprotective effect.

COVID-19 hotspots through clusters analysis in France (may-October 2020): where should we track the virus to mitigate the spread?

BACKGROUND: In France, the lifting of the lockdown implemented to control the COVID-19 first wave in 2020 was followed by a reinforced contact-tracing (CT) strategy for the early detection of cases and transmission chains. We developed a reporting system of clusters defined as at least three COVID-19 cases, within seven days and belonging to the same community or having participated in the same gathering, whether they know each other or not. The aim of this study was to describe the typology and criticality of clusters reported between the two lockdowns in France to guide future action prioritisation. METHODS: In this study we describe the typology and criticality of COVID-19 clusters between the two lockdowns implemented in France (between May and end of October 2020). Clusters were registered in a national database named "MONIC" (MONItoring des Clusters), established in May 2020. This surveillance system identified the most affected communities in a timely manner. A level of criticality was defined for each cluster to take into consideration the risk of spreading within and outside the community of occurrence, and the health impact within the community. We compared the level of criticality according to the type of community in which the cluster occurred using Pearson's chi-square tests. RESULTS: A total of 7236 clusters were reported over the study period, particularly in occupational environment (25.1%, n = 1813), elderly care structures (21.9%, n = 1586), and educational establishments (15.9%, n = 1154). We show a shift over time of the most affected communities in terms of number of clusters. Clusters reported in occupational environment and the personal sphere had increased during summer while clusters reported in educational environment increased after the start of the school year. This trend mirrors change of transmission pattern overtime according to social contacts. Among all reported clusters, 43.1% had a high level of criticality with significant differences between communities (p < 0.0001). A majority of clusters had a high level of criticality in elderly care structures (82.2%), in disability care centres (56.6%), and health care facilities (51.7%). CONCLUSION: These results highlight the importance of targeting public health action based on timely sustained investigations, testing capacity and targeted awareness campaigns. The emergence of new SARS-CoV-2 variants strengthen these public health recommendations and the need for rapid and prioritise vaccination campaigns.

Sterilization Modality Selection: Role of Sterility Assurance Subject Matter Expert.

Selection of a sterilization modality for a medical device is a critical decision that requires sterility assurance subject matter experts (SME)s to work collaboratively with various company functions. The sterility assurance SME is responsible and accountable for the sterilization modality decision for a product. The modality selection process starts with the sterility assurance SME partnering with research and development to ensure that the sterilization modality allows the device to deliver its intended function in patient care. After the sterilization modality is selected, the sterility assurance SME needs to work with other partners, including quality, supply chain/logistics, operations, and regulatory, to ensure that the selected sterilization modality is appropriately integrated into the end-to-end process. Collaborative partnerships between sterility assurance experts and key partners regarding sterilization modality selection reduce the potential for negative impacts within the end-to-end sterility assurance process, including impacts on product functionality, increased regulatory approval timelines, and inefficiencies and risks throughout the supply chain. This article describes aspects of a comprehensive approach to sterilization modality selection, including critical information necessary to address each of the key considerations.

In vivo assessment of pathogens toxicity on Daphnia magna using fluorescent dye staining.

Daphnia has been widely used as an indicator species in aquatic biomonitoring for decades. Traditional toxicity assays based on lethality take a long time to assess, and the effect mode of contaminants is not clear. Because of the translucency of the Daphnia body and the application of fluorescent probes in cell staining, different intoxicated parts can be visualized. In this study, a double-staining method using two fluorescent dyes, Calcein AM (cell-permeant dye) and Propidium Iodide (cell-impermeant dye), was carried out on Daphnia magna exposed to six pathogens: Salmonella spp. (four strains) and Shigella spp. (two strains). The results showed that those bacteria caused different infections on daphnia depending on the age of this organism and bacterial concentrations. In detail, S. dublin and S. sonnei are the most harmful to Daphnia when they cause damage at smaller concentrations at the younger stage (3 weeks old). Interestingly, older Daphnia can give responses to nearly 10 CFU/ml to less than 100 CFU/ml of some bacteria strains. In another experiment, S. sonnei disturbed Daphnia after just 10 min of exposure, and Daphnia adapted to S. choleraesuis, S. typhi, and S. flexneri at the early stage (3 weeks old) after 1 h of exposure. Moreover, the damaged areas of the daphnia body were directly observed via a microscope, contributing to the understanding and the prediction of toxicity mechanisms.

Successful fifth metatarsal bulk autograft reconstruction of thermal necrosis post intramedullary fixation.

Reamed intramedullary (IM) screw fixation for proximal fifth metatarsal fractures is technically challenging with potentially devastating complications if basic principles are not followed. A case of an iatrogenic fourth-degree burn after elective reamed IM screw fixation of a proximal fifth metatarsal fracture in a high-level athlete is reported. The case was complicated by postoperative osteomyelitis with third-degree soft-tissue defect. This was successfully treated with staged autologous bone graft reconstruction, tendon reconstruction, and local bi-pedicle flap coverage. The patient returned to competitive-level sports, avoiding the need for fifth ray amputation. Critical points of the IM screw technique and definitive reconstruction are discussed. Bulk autograft reconstruction is a safe and effective alternative to ray amputation in segmental defects of the fifth metatarsal.Level of evidence V.

An Elite Hybrid Particle Swarm Optimization for Solving Minimal Exposure Path Problem in Mobile Wireless Sensor Networks.

Mobile wireless sensor networks (MWSNs), a sub-class of wireless sensor networks (WSNs), have recently been a growing concern among the academic community. MWSNs can improve network coverage quality which reflects how well a region of interest is monitored or tracked by sensors. To evaluate the coverage quality of WSNs, we frequently use the minimal exposure path (MEP) in the sensing field as an effective measurement. MEP refers to the worst covered path along which an intruder can go through the sensor network with the lowest possibility of being detected. It is greatly valuable for network designers to recognize the vulnerabilities of WSNs and to make necessary improvements. Most prior studies focused on this problem under a static sensor network, which may suffer from several drawbacks; i.e., failure in sensor position causes coverage holes in the network. This paper investigates the problem of finding the minimal exposure paths in MWSNs (hereinafter MMEP). First, we formulate the MMEP problem. Then the MMEP problem is converted into a numerical functional extreme problem with high dimensionality, non-differentiation and non-linearity. To efficiently cope with these characteristics, we propose HPSO-MMEP algorithm, which is an integration of genetic algorithm into particle swarm optimization. Besides, we also create a variety of custom-made topologies of MWSNs for experimental simulations. The experimental results indicate that HPSO-MMEP is suitable for the converted MMEP problem and performs much better than existing algorithms.