Influence of Obstructive Sleep Apnea on the Risk of Dental Caries: Insights from a 13-Year Population-Based Retrospective Study.

KNOWLEDGE TRANSFER STATEMENT: Obstructive sleep apnea has been proven to have a great negative impact on patients, and the relationship between sleep apnea and dental caries is still inconclusive. Our study shows that patients with sleep apnea and those older than 45 y have a significant risk of dental caries.

Synthesis of Fluorinated Nucleosides/Nucleotides and Their Antiviral Properties.

The FDA has approved several drugs based on the fluorinated nucleoside pharmacophore, and numerous drugs are currently in clinical trials. Fluorine-containing nucleos(t)ides offer significant antiviral and anticancer activity. The insertion of a fluorine atom, either in the base or sugar of nucleos(t)ides, alters its electronic and steric parameters and transforms the lipophilicity, pharmacodynamic, and pharmacokinetic properties of these moieties. The fluorine atom restricts the oxidative metabolism of drugs and provides enzymatic metabolic stability towards the glycosidic bond of the nucleos(t)ide. The incorporation of fluorine also demonstrates additional hydrogen bonding interactions in receptors with enhanced biological profiles. The present article discusses the synthetic methodology and antiviral activities of FDA-approved drugs and ongoing fluoro-containing nucleos(t)ide drug candidates in clinical trials.

Real Gas Effects in High-Pressure Ignition of n-Dodecane/Air Mixtures.

This work studies the real gas effects on the autoignition of hydrocarbon fuels under high pressures, using normal dodecane (n-dodecane) as the representative fuel and the Redlich-Kwong equation of state (EoS) as the real gas description. It is demonstrated that the real gas description yields a shorter ignition delay time (IDT) compared with the ideal gas description, especially in low-temperature regimes which could encompass the negative temperature coefficient (NTC) phenomena and has a stronger dependence on the molecular volume than the attractive potential. The study further shows that high pressure facilitates low-temperature reaction pathways, where the compressibility factors of key reactants contribute to real gas effects. Moreover, the results suggest that accounting for real gas behavior leads to an increase in the formation of polycyclic aromatic hydrocarbons (PAHs), which, in turn, promotes soot generation.

Metabolic pathways in immune senescence and inflammaging: Novel therapeutic strategy for chronic inflammatory lung diseases. An EAACI position paper from the Task Force for Immunopharmacology.

The accumulation of senescent cells drives inflammaging and increases morbidity of chronic inflammatory lung diseases. Immune responses are built upon dynamic changes in cell metabolism that supply energy and substrates for cell proliferation, differentiation, and activation. Metabolic changes imposed by environmental stress and inflammation on immune cells and tissue microenvironment are thus chiefly involved in the pathophysiology of allergic and other immune-driven diseases. Altered cell metabolism is also a hallmark of cell senescence, a condition characterized by loss of proliferative activity in cells that remain metabolically active. Accelerated senescence can be triggered by acute or chronic stress and inflammatory responses. In contrast, replicative senescence occurs as part of the physiological aging process and has protective roles in cancer surveillance and wound healing. Importantly, cell senescence can also change or hamper response to diverse therapeutic treatments. Understanding the metabolic pathways of senescence in immune and structural cells is therefore critical to detect, prevent, or revert detrimental aspects of senescence-related immunopathology, by developing specific diagnostics and targeted therapies. In this paper, we review the main changes and metabolic alterations occurring in senescent immune cells (macrophages, B cells, T cells). Subsequently, we present the metabolic footprints described in translational studies in patients with chronic asthma and chronic obstructive pulmonary disease (COPD), and review the ongoing preclinical studies and clinical trials of therapeutic approaches aiming at targeting metabolic pathways to antagonize pathological senescence. Because this is a recently emerging field in allergy and clinical immunology, a better understanding of the metabolic profile of the complex landscape of cell senescence is needed. The progress achieved so far is already providing opportunities for new therapies, as well as for strategies aimed at disease prevention and supporting healthy aging.

Multi-locus sequence typing and phylogenetics of Cryptococcus neoformans AD hybrids.

Hybrid AD strains of the human pathogenic Cryptococcus neoformans species complex have been reported from many parts of the world. However, their origin, diversity, and evolution are incompletely understood. In this study, we analyzed 102 AD hybrid strains representing 21 countries on five continents. For each strain, we obtained its mating type and its allelic sequences at each of the seven loci that have been used for genotyping haploid serotypes A and D strains of the species complex by the Cryptococcus research community. Our results showed that most AD hybrids exhibited loss of heterozygosity at one or more of the seven analyzed loci. Phylogenetic and population genetic analyses of the allelic sequences revealed multiple origins of the hybrids within each continent, dating back to one million years ago in Africa and up to the present in other continents. We found evidence for clonal reproduction and long-distance dispersal of these hybrids in nature. Comparisons with the global haploid serotypes A and D strains identified new alleles and new haploid multi-locus genotypes in AD hybrids, consistent with the presence of yet-to-be discovered genetic diversity in haploid populations of this species complex in nature. Together, our results indicate that AD hybrids can be effectively genotyped using the same multi-locus sequencing type approach as that established for serotypes A and D strains. Our comparisons of the AD hybrids among each other as well as with the global haploid serotypes A and D strains revealed novel genetic diversity as well as evidence for multiple origins and dynamic evolution of these hybrids in nature.

Inbred SJL mice recapitulate human resistance to Cryptococcus infection due to differential immune activation.

IMPORTANCE: Cryptococcosis studies often utilize the common C57BL/6J mouse model. Unfortunately, infection in these mice fails to replicate the basic course of human disease, particularly hampering immunological studies. This work demonstrates that SJL/J mice can recapitulate human infection better than other mouse strains. The immunological response to Cryptococcus infection in SJL/J mice was markedly different from C57BL/6J and much more productive in combating this infection. Characterization of infected mice demonstrated strain-specific genetic linkage and differential regulation of multiple important immune-relevant genes in response to Cryptococcus infection. While our results validate many of the previously identified immunological features of cryptococcosis, we also demonstrate limitations from previous mouse models as they may be less translatable to human disease. We concluded that SJL/J mice more faithfully recapitulate human cryptococcosis serving as an exciting new animal model for immunological and genetic studies.

Interactive effects of Louisiana Sweet Crude (LSC) thin oil sheens and ultraviolet light on mortality and swimming behavior of the larval Eastern oyster, Crassostrea virginica.

The Eastern oyster (Crassostrea virginica) is an important commercial bivalve species which also has numerous ecological roles including biogeochemical cycling, providing habitat for larval fish and crustaceans, and reducing the impacts of coastal storms. Oil may pose a threat to oyster larvae swimming in the water column, leading to potential negative effects on survival, growth, and development. Oil toxicity may be further enhanced by chemical changes in the presence of sunlight. This study determined the toxicity of thin oil sheens with and without ultraviolet (UV) light, then examined the latent effects of the short term exposure on longer term survival and swimming ability. Larval C. virginica were exposed to four different oil sheen thicknesses for 24 h with either no UV light or 2-h UV light. Following the exposure, larvae were transferred to clean seawater and no UV light for 96 h. The presence of a 2-h UV light exposure significantly increased oyster mortality, indicating photo-enhanced toxicity. The LC50 for a 24-h oil sheen exposure without UV was 7.26 µm (23 µg/L PAH50) while a 2 h-UV exposure lowered the sheen toxicity threshold to 2.67 µm (10 µg/L PAH50). A previous 24-h oil sheen exposure (≥0.5 µm) led to latent effects on larval oyster survival, regardless of previous UV exposure. Sublethal impacts to larval oyster swimming behavior were also observed from the previous oil sheen exposure combined with UV exposure. This study provides new data for the toxicity of thin oil sheens to a sensitive early life stage of estuarine bivalve.

Prodrug Strategies for the Development of ß-l-5-((E)-2-Bromovinyl)-1-((2S,4S)-2-(hydroxymethyl)-1,3-(dioxolane-4-yl))uracil (l-BHDU) against Varicella Zoster Virus (VZV).

Varicella zoster virus (VZV) establishes lifelong infection after primary disease and can reactivate. Several drugs are approved to treat VZV diseases, but new antivirals with greater potency are needed. Previously, we identified ß-l-5-((E)-2-bromovinyl)-1-((2S,4S)-2-(hydroxymethyl)-1,3-(dioxolane-4-yl))uracil (l-BHDU, 1), which had significant anti-VZV activity. In this communication, we report the synthesis and evaluation of numerous l-BHDU prodrugs: amino acid esters (14-26), phosphoramidates (33-34), long-chain lipids (ODE-l-BHDU-MP, 38, and HDP-l-BHDU-MP, 39), and phosphate ester prodrugs (POM-l-BHDU-MP, 41, and POC-l-BHDU-MP, 47). The amino acid ester l-BHDU prodrugs (l-phenylalanine, 16, and l-valine, 17) had a potent antiviral activity with EC50 values of 0.028 and 0.030 µM, respectively. The phosphate ester prodrugs POM-l-BHDU-MP and POC-l-BHDU-MP had a significant anti-VZV activity with EC50 values of 0.035 and 0.034 µM, respectively, and no cellular toxicity (CC50 > 100 µM) was detected. Out of these prodrugs, ODE-l-BHDU-MP (38) and POM-l-BHDU-MP (41) were selected for further evaluation in future studies.

Acute traumatic dural arteriovenous fistula of the superior sagittal sinus: illustrative case.

BACKGROUND: Dural arteriovenous fistulas (dAVFs) are aberrant vascular communications between meningeal arteries and venous sinuses or cortical veins. dAVF pathogenesis is incompletely understood; however, formation likely occurs as a result of angioneogensis. OBSERVATIONS: A 78-year-old man presented after trauma with basal and cortical subarachnoid hemorrhage (SAH). Computed tomography revealed a parietal bone fracture overlying the superior sagittal sinus (SSS). Catheter angiography performed within 24 hours of the injury demonstrated an SSS dAVF supplied by the middle meningeal artery, adjacent to the fracture. LESSONS: The authors present the case of an acute traumatic dAVF adjacent to a calvarial fracture. In this case, the authors proprose that the underlying pathogenesis is suggestive of direct vessel injury rather than the pathway commonly associated with this pathology.

Novel modification of Marcy operation for indirect inguinal hernia reconstituting deep inguinal ring shutter action.

PURPOSE: The two most frequent and significant complications after inguinal hernia repair are hernia recurrence and post-herniorrhaphy chronic pain. To add anatomic and physiologic strength to the tissue repair, especially in indirect inguinal herniorrhaphy, we devised a modification of Marcy operation that can reconstitute inguinal shutter action more efficiently by changing the direction of the sutures vertical to horizontal. METHODS: During 36 months from 1st Jan. 2019, 148cases of 140 patients were operated for Indirect inguinal hernia or Pantaloon hernia (11 cases). 145 indirect inguinal herniorrhaphy were performed exclusively with author's modification of Marcy operation. Hernia recurrence during the follow-up period (3 months-36 months), and postoperative chronic pain at 3 months after herniorrhaphy were analyzed. RESULTS: 104 cases among the 145 indirect inguinal hernia (71.7%) were operated with only deep inguinal ring (DIR) reconstruction as author modified. In 41 cases (28.3%), posterior wall reconstruction was done simultaneously. There was no recurrence or reoperation case during the follow-up period. The incidence of postoperative chronic pain at postoperative 3 months of VAS greater than 3.0 was 2.2% (3 cases). CONCLUSIONS: Author's modification of Marcy operation was feasible anatomically in all indirect inguinal hernia repair, which is theoretically superior to classic Marcy operation in that repositioning the DIR more laterally and securing the obliquity and shutter action of the DIR. Result is at least not inferior in the aspect of short-term recurrence and chronic post-herniorrhaphy pain.

Strains Associated with Two 2020 Welder Anthrax Cases in the United States Belong to Separate Lineages within Bacillus cereus sensu lato.

Anthrax-causing members of Bacillus cereus sensu lato (s.l.) pose a serious threat to public health. While most anthrax-causing strains resemble B. anthracis phenotypically, rare cases of anthrax-like illness caused by strains resembling "B. cereus" have been reported. Here, whole-genome sequencing was used to characterize three B. cereus s.l. isolates associated with two 2020 welder anthrax cases in the United States, which resembled "B. cereus" phenotypically. Comparison of the three genomes sequenced here to all publicly available, high-quality B. cereus s.l. genomes (n = 2890 total genomes) demonstrated that genomes associated with each case effectively belonged to separate species at the conventional 95% average nucleotide identity prokaryotic species threshold. Two PubMLST sequence type 78 (ST78) genomes affiliated with a case in Louisiana were most closely related to B. tropicus and possessed genes encoding the Bps exopolysaccharide capsule, as well as hemolysin BL (Hbl) and cytotoxin K (CytK). Comparatively, a ST108 genome associated with a case in Texas was most closely related to B. anthracis; however, like other anthrax-causing strains most closely related to B. anthracis, this genome did not possess Bps-, Hbl-, or CytK-encoding genes. Overall, results presented here provide insights into the evolution of anthrax-causing B. cereus s.l.

Outbreak of cutaneous anthrax associated with handling meat of dead cows in Southwestern Uganda, May 2018.

BACKGROUND: Anthrax is a zoonotic infection caused by the bacteria Bacillus anthracis. Humans acquire cutaneous infection through contact with infected animals or animal products. On May 6, 2018, three cows suddenly died on a farm in Kiruhura District. Shortly afterwards, a sub-county chief in Kiruhura District received reports of humans with suspected cutaneous anthrax in the same district. The patients had reportedly participated in the butchery and consumption of meat from the dead cows. We investigated to determine the magnitude of the outbreak, identify exposures associated with illness, and suggest evidence-based control measures. METHODS: We conducted a retrospective cohort study among persons whose households received any of the cow meat. We defined a suspected human cutaneous anthrax case as new skin lesions (e.g., papule, vesicle, or eschar) in a resident of Kiruhura District from 1 to 26 May 2018. A confirmed case was a suspected case with a lesion testing positive for B. anthracis by polymerase chain reaction (PCR). We identified cases through medical record review at Engari Health Centre and active case finding in the community. RESULTS: Of the 95 persons in the cohort, 22 were case-patients (2 confirmed and 20 suspected, 0 fatal cases) and 73 were non-case household members. The epidemic curve indicated multiple point-source exposures starting on May 6, when the dead cows were butchered. Among households receiving cow meat, participating in slaughtering (RR = 5.3, 95% CI 3.2-8.3), skinning (RR = 4.7, 95% CI = 3.1-7.0), cleaning waste (RR = 4.5, 95% CI = 3.1-6.6), and carrying meat (RR = 3.9, 95% CI = 2.2-7.1) increased the risk of infection. CONCLUSIONS: This cutaneous anthrax outbreak was caused by handling infected animal carcasses. We suggested to the Ministry of Agriculture, Animal Industry and Fisheries to strengthen surveillance for possible veterinary anthrax and ensure that communities do not consume carcasses of livestock that died suddenly. We also suggested that the Ministry of Health equip health facilities with first-line antibiotics for community members during outbreaks.

Epidemiologic Investigation of Two Welder's Anthrax Cases Caused by Bacillus Cereus Group Bacteria: Occupational Link Established by Environmental Detection.

Abstract Bacillus cereus group bacteria containing the anthrax toxin genes can cause fatal anthrax pneumonia in welders. Two welder's anthrax cases identified in 2020 were investigated to determine the source of each patient's exposure. Environmental sampling was performed at locations where each patient had recent exposure to soil and dust. Samples were tested for the anthrax toxin genes by real-time PCR, and culture was performed on positive samples to identify whether any environmental isolates matched the patient's clinical isolate. A total of 185 environmental samples were collected in investigation A for patient A and 108 samples in investigation B for patient B. All samples from investigation B were real-time PCR-negative, but 14 (8%) samples from investigation A were positive, including 10 from patient A's worksite and 4 from his work-related clothing and gear. An isolate genetically matching the one recovered from patient A was successfully cultured from a worksite soil sample. All welder's anthrax cases should be investigated to determine the source of exposure, which may be linked to their worksite. Welding and metalworking employers should consider conducting a workplace hazard assessment and implementing controls to reduce the risk of occupationally associated illnesses including welder's anthrax.

Adverse roles of mast cell chymase-1 in COPD.

BACKGROUND: COPD is the third leading cause of death worldwide. Cigarette smoke (CS)-induced chronic inflammation inducing airway remodelling, emphysema and impaired lung function is the primary cause. Effective therapies are urgently needed. Human chymase (hCMA)1 and its orthologue mCMA1/mouse mast cell protease (mMCP)5 are exocytosed from activated mast cells and have adverse roles in numerous disorders, but their role in COPD is unknown. METHODS: We evaluated hCMA1 levels in lung tissues of COPD patients. We used mmcp5-deficient (-/-) mice to evaluate this protease's role and potential for therapeutic targeting in CS-induced experimental COPD. In addition, we used ex vivo/in vitro studies to define mechanisms. RESULTS: The levels of hCMA1 mRNA and CMA1+ mast cells were increased in lung tissues from severe compared to early/mild COPD patients, non-COPD smokers and healthy controls. Degranulated mast cell numbers and mMCP5 protein were increased in lung tissues of wild-type mice with experimental COPD. mmcp5 -/- mice were protected against CS-induced inflammation and macrophage accumulation, airway remodelling, emphysema and impaired lung function in experimental COPD. CS extract challenge of co-cultures of mast cells from wild-type, but not mmcp5 -/- mice with wild-type lung macrophages increased in tumour necrosis factor (TNF)-α release. It also caused the release of CMA1 from human mast cells, and recombinant hCMA-1 induced TNF-α release from human macrophages. Treatment with CMA1 inhibitor potently suppressed these hallmark features of experimental COPD. CONCLUSION: CMA1/mMCP5 promotes the pathogenesis of COPD, in part, by inducing TNF-α expression and release from lung macrophages. Inhibiting hCMA1 may be a novel treatment for COPD.

The association of ABO and Rhesus blood type with the risks of developing SARS-CoV-2 infection: A meta-analysis.

Coronavirus Disease 2019 (COVID-19) has been spreading like a wildfire everywhere in the globe. It has been challenging the global health care system ever since the end of 2019, with its virulence and pathogenicity. Recent studies have shown the association between ABO blood group, Rhesus blood type and susceptibility to COVID-19 infection. Various studies and few meta-analyses have been done and some might be inconsistent; therefore, this meta-analysis was done to assess the relationship between different ABO and Rhesus blood types on the susceptibility to COVID-19 infections. This meta-analysis assessed the odds ratio of COVID-19 infection of different ABO and Rhesus blood types. Subgroup analyses according to (1) age and gender matched; (2) different blood group antigens; (3) Rhesus positive and negative of each blood group were carried out. Publication bias and Quality Assessment of Diagnostic Accuracy Studies-2 (QUADAS-2) were also done to assess the risk of bias in these publications. It was found that blood group A showed significant difference in odds ratio of COVID-19 infection (OR, 1.16; 95% CI, 1.08-1.24). Blood group AB showed significant difference in odds ratio when studies with lower QUADAS-2 score were removed. This means that populations with blood group A and AB are more likely to be infected with COVID-19. As there is a higher tendency that blood group A and AB to be infected with COVID- 19, precautious care should be taken by these populations.

Welder's Anthrax: A Review of an Occupational Disease.

Since 1997, nine cases of severe pneumonia, caused by species within the B. cereus group and with a presentation similar to that of inhalation anthrax, were reported in seemingly immunocompetent metalworkers, with most being welders. In seven of the cases, isolates were found to harbor a plasmid similar to the B. anthracis pXO1 that encodes anthrax toxins. In this paper, we review the literature on the B. cereus group spp. pneumonia among welders and other metalworkers, which we term welder's anthrax. We describe the epidemiology, including more information on two cases of welder's anthrax in 2020. We also describe the health risks associated with welding, potential mechanisms of infection and pathological damage, prevention measures according to the hierarchy of controls, and clinical and public health considerations. Considering occupational risk factors and controlling exposure to welding fumes and gases among workers, according to the hierarchy of controls, should help prevent disease transmission in the workplace.