Category: Nevin Manimala

Viruses. 2023 May 31;15(6):1303. doi: 10.3390/v15061303.

ABSTRACT

Respiratory viral infections are a leading global cause of disease with multiple viruses detected in 20-30% of cases, and several viruses simultaneously circulating. Some infections with unique viral copathogens result in reduced pathogenicity, while other viral pairings can worsen disease. The mechanisms driving these dichotomous outcomes are likely variable and have only begun to be examined in the laboratory and clinic. To better understand viral-viral coinfections and predict potential mechanisms that result in distinct disease outcomes, we first systematically fit mathematical models to viral load data from ferrets infected with respiratory syncytial virus (RSV), followed by influenza A virus (IAV) after 3 days. The results suggest that IAV reduced the rate of RSV production, while RSV reduced the rate of IAV infected cell clearance. We then explored the realm of possible dynamics for scenarios that had not been examined experimentally, including a different infection order, coinfection timing, interaction mechanisms, and viral pairings. IAV coinfection with rhinovirus (RV) or SARS-CoV-2 (CoV2) was examined by using human viral load data from single infections together with murine weight-loss data from IAV-RV, RV-IAV, and IAV-CoV2 coinfections to guide the interpretation of the model results. Similar to the results with RSV-IAV coinfection, this analysis shows that the increased disease severity observed during murine IAV-RV or IAV-CoV2 coinfection was likely due to the slower clearance of IAV-infected cells by the other viruses. The improved outcome when IAV followed RV, on the other hand, could be replicated when the rate of RV infected cell clearance was reduced by IAV. Simulating viral-viral coinfections in this way provides new insights about how viral-viral interactions can regulate disease severity during coinfection and yields testable hypotheses ripe for experimental evaluation.

PMID:37376603 | DOI:10.3390/v15061303

Viruses. 2023 May 30;15(6):1284. doi: 10.3390/v15061284.

ABSTRACT

BACKGROUND: Over the last two decades, honey bees (Apis mellifera) have suffered high rates of colony losses that have been attributed to a variety of factors, chief among which are viral pathogens, such as deformed wing virus (DWV), whose virulence has increased because of vector-based transmission by the invasive, ectoparasitic varroa mite (Varroa destructor). A shift in the experimental mode of transmission of the black queen cell virus (BQCV) and sacbrood virus (SBV) from fecal/food-oral (direct horizontal) to vector-mediated (indirect horizontal) transmission also results in high virulence and viral titers in pupal and adult honey bees. Agricultural pesticides represent another factor that acts independently or in interaction with pathogens, and they are also thought to cause colony loss. Understanding the molecular mechanisms underlying the higher virulence following a vector-based mode of transmission provides deeper insight into honey bee colony losses, as does determining whether or not host-pathogen interactions are modulated by exposure to pesticides.

METHODS: Through an experimental design with controlled laboratory, we investigated the effects of the modes of transmission of BQCV and SBV (feeding vs. vector-mediated via injection) alone or in combination with chronic exposure to sublethal and field-realistic concentrations of flupyradifurone (FPF), a novel agricultural insecticide, on honey bee survival and transcription responses by using high-throughput RNA sequencing (RNA-seq) analysis.

RESULTS: Co-exposure to viruses via feeding (VF) or injection (VI) and FPF insecticide had no statistically significant interactive effect on their survival compared to, respectively, VF or VI treatments alone. Transcriptomic analysis revealed a distinct difference in the gene expression profiles of bees inoculated with viruses via injection (VI) and exposed to FPF insecticide (VI+FPF). The number of differentially expressed genes (DEGs) at log2 (fold-change) > 2.0 in VI bees (136 genes) or/and VI+FPF insecticide (282 genes) was very high compared to that of VF bees (8 genes) or the VF+FPF insecticide treatment (15 genes). Of these DEGs, the expression in VI and VI+FPF bees of some immune-related genes, such as those for antimicrobial peptides, Ago2, and Dicer, was induced. In short, several genes encoding odorant binding proteins, chemosensory proteins, odor receptors, honey bee venom peptides, and vitellogenin were downregulated in VI and VI+FPF bees.

CONCLUSIONS: Given the importance of these suppressed genes in honey bees’ innate immunity, eicosanoid biosynthesis, and olfactory associative function, their inhibition because of the change in the mode of infection with BQCV and SBV to vector-mediated transmission (injection into haemocoel) could explain the high virulence observed in these viruses when they were experimentally injected into hosts. These changes may help explain why other viruses, such as DWV, represent such a threat to colony survival when transmitted by varroa mites.

PMID:37376584 | DOI:10.3390/v15061284

Viruses. 2023 May 25;15(6):1245. doi: 10.3390/v15061245.

ABSTRACT

AIM: This study evaluated the relationship between the systemic immune-inflammatory index (SII), neutrophil-to-lymphocyte ratio (NLR), and platelet-to-lymphocyte ratio (PLR) with clinical findings of respiratory syncytial virus (RSV) infection among children with a diagnosis of lower respiratory tract infection (LRTI).

METHODS: The study was conducted between 1 January 2020 and 1 January 2022 in a pediatric clinic. This retrospective study included 286 consecutive patients between 0 and 12 years of age, 138 of whom were RSV (+) (48.25%) and 148 of whom were RSV (-) (51.75%). The detection of the RSV antigen was carried out using the chromatographic immunoassay method on nasopharyngeal swabbing samples.

RESULTS: CRP content was significantly higher in patients with RSV (+) than in children with RSV (-), while NLR, PLR, and SII, as inflammatory parameters, were significantly lower. Fever, coughs, and wheezing were the most common symptoms in the RSV (+) groups (100%). RSV infections were the highest in November, October, and December, in that order. The AUC was statistically significant for parameters in all groups. AUC values were 0.841 (95%: 0.765-0.917) for leukocytes, 0.703 (95%: 0.618-0.788) for lymphocytes, 0.869 (95%: 0.800-0.937) for CRP, 0.706 (95%: 0.636-0.776) for NLR, 0.779 (95%: 0.722-0.836) for PLR, and 0.705 (95%: 0.633-0.776) for SII. CRP was found to have both high sensitivity (80.4%) and high specificity (82.4%) among all parameters. While the ROC analysis results showed similar results for children under two years old, only CRP and NLR were statistically significant in this group.

CONCLUSION: CRP performed better than other blood parameters as a marker. The NLR, PLR, and SII index were significantly lower in LRTI patients with RSV (+) than in those with RSV (-), which implies a higher grade of inflammation. If the cause of the disease can be determined by this method, disease management will be easier, and unnecessary antibiotics could be avoided.

PMID:37376545 | DOI:10.3390/v15061245

Viruses. 2023 May 24;15(6):1232. doi: 10.3390/v15061232.

ABSTRACT

The first case of ASF in a domestic pig population in Serbia was confirmed in 2019 in a backyard population. Today, outbreaks in wild boar and, more importantly, in domestic pigs are still occurring, although the government measures for ASF prevention are in place. The aim of this study was to determine critical risk factors and identify the possible reasons for ASF introduction into different extensive pig farms. The study was conducted on 26 extensive pig farms with confirmed ASF outbreaks, with data collected from beginning of 2020 to the end of 2022. Collected epidemiological data were divided into 21 main categories. After identifying specific values of variables as critical for ASF transmission, we identified nine important ASF transmission indicators as those variables for which at least 2/3 of the observed farms reported values critical for ASF transmission. Among them were type of holding, distance to hunting ground, farm/yard fencing, and home slaughtering; however, the hunting activity of pig holders, swill feeding, and feeding with mowed green mass were not included. We represented the data in the form of contingency tables to study associations between pairs of variables using Fisher’s exact test. All pairs of variables in the group including type of holding, farm/yard fencing, domestic pig-wild boar contact, and hunting activity were significantly related; hunting activity of pig holders, holding pigs in backyards, unfenced yards, and domestic pig-wild boar contact were observed on the same farms. Free-range pig farming led to observed domestic pig-wild boar contact on all farms. The identified critical risk factors need to be strictly addressed to prevent the further spread of ASF to extensive farms and backyards in Serbia and elsewhere.

PMID:37376532 | DOI:10.3390/v15061232

Front Biosci (Elite Ed). 2023 May 5;15(2):11. doi: 10.31083/j.fbe1502011.

ABSTRACT

BACKGROUND: Nylon 11 is a synthetic plastic widely used in commercial products such as tubing for automobiles, offshore oilfields, and medical devices. An increasing amount of nylon and other plastic wastes have been released into various environments, posing ecological threats. The biodegradation of bundled nylon polymers has been considered impossible due to their crystalline structures.

METHODS: Nylon 11 film was created and incubated with adult mealworms. The mass, as well as structures, of nylon 11 films at pre- and post-incubation with beetles were compared. The number of nylon 11 monomer degrading bacteria in feces were determined by culture-dependent approach. The t-test was utilized to examine the statistical significance.

RESULTS: We discovered that adult mealworm (Tenebrio molitor) beetle can ingest nylon 11 when stretched thin. The microscopic observation of their feces did not identify the presence of large fragments of nylon 11. The analysis of fecal bacteria revealed that while the total number of culturable bacteria did not change significantly, the number of 11-aminoundecanoic acid-metabolizing bacteria increased by 10,000-fold.

CONCLUSIONS: Our results suggest that bundled nylon 11 polymers were fragmented into smaller pieces, including monomeric units (11-aminoundecanoic acid) by adult mealworm. The monomers seem to have supported the proliferation of gut microbial communities capable of utilizing 11-aminoundecanoic acid as a carbon and nitrogen source. Our work implies the potential use of the mealworm beetle as a means to fragment nylon polymers for remediation applications.

PMID:37369567 | DOI:10.31083/j.fbe1502011

Emerg Med J. 2023 Jun 27:emermed-2023-213142. doi: 10.1136/emermed-2023-213142. Online ahead of print.

ABSTRACT

BACKGROUND: Time-based targets are used to improve patient flow and quality of care within EDs. While previous research often highlighted the benefits of these targets, some studies found negative consequences of their implementation. We study the consequences of removing the 4-hour access standard.

METHODS: We conducted a before and after, retrospective, observational study using anonymised, routinely collected, patient-level data from a single English NHS ED between April 2018 and December 2019. The primary outcomes of interest were the proportion of admitted patients, that is, the admission rate, the length of stay in the ED and ambulance handover times. We used interrupted time series models to study and estimate the impact of removing the 4-hour access standard.

RESULTS: A total of 169 916 attendances were included in the analysis. The interrupted time series models for the average daily admission rate indicate a drop from an estimated 35% to an estimated 31% (95% CI -4.1 to -3.9). This drop is only statistically significant for Majors (Ambulant) patients (from an estimated 38.3% to an estimated 31.4%) and, particularly, for short-stay admissions (from an estimated 18.1% to an estimated 12.8%). The models also show an increase in the average daily length of stay for admitted patients from an estimated 316 min to an estimated 387 min (95% CI 33.5 to 108.9), and an increase in the average daily length of stay for discharged patients from an estimated 222 min to an estimated 262 min (95% CI 6.9 to 40.4).

CONCLUSION: Lifting the 4-hour access standard reporting was associated with a drop in short-stay admissions to the hospital. However, it was also associated with an increase in the average length of stay in the ED. Our study also suggests that the removal of the 4-hour standard does not impact all patients equally. While certain patient groups such as those Majors (Ambulant) patients with less severe issues might have benefited from the removal of the 4-hour access standard by avoiding short-stay hospital admissions, the average length of stay in the ED seemed to have increased across all groups, particularly for older and admitted patients.

PMID:37369563 | DOI:10.1136/emermed-2023-213142

BMJ Open Respir Res. 2023 Jun;10(1):e001662. doi: 10.1136/bmjresp-2023-001662.

ABSTRACT

BACKGROUND: A close relationship exists between obstructive sleep apnoea (OSA) and hypertension. However, the impact of hypertension on the prognostic significance of OSA in patients with acute coronary syndrome (ACS) remains unclear.

METHODS: This is a post hoc analysis of the OSA-ACS project, which consecutively included patients with ACS and receiving overnight sleep study from June 2015 to January 2020. OSA was defined as AHI ≥15 events/hour. The primary outcome was major adverse cardiovascular and cerebrovascular events (MACCE), including a composite of cardiovascular death, myocardial infarction, stroke, ischemia-driven revascularisation or hospitalisation for unstable angina or heart failure.

RESULTS: A total of 1927 patients with ACS were finally enrolled in this study. The mean patient age was 56.4±10.5 years. Among them, 1247 (64.7%) patients had hypertension, and 1014 (52.6%) patients had OSA. During 2.9 (1.5, 3.6) years of follow-up, OSA was associated with an increased risk of MACCE among patients with hypertension (HR=1.35, 95% CI 1.04 to 1.75, p=0.02), but not in patients without hypertension (HR=1.15, 95% CI 0.79 to 1.68, p=0.47). The interaction between OSA and hypertension for MACCE was not statistically significant (interaction p=0.29). For patients with pre-existing hypertension, OSA was associated with an increased risk of MACCE only among those with grade 3 hypertension (HR 1.54, 95% CI 1.12 to 2.13, p=0.008), but not those with grade 1 or 2 hypertension.

CONCLUSIONS: OSA was associated with an increased risk of MACCE following ACS in patients with hypertension, especially in patients with pre-existing severe hypertension. These findings highlight the importance of identifying OSA in ACS patients with hypertension.

TRIAL REGISTRATION NUMBER: NCT03362385.

PMID:37369551 | DOI:10.1136/bmjresp-2023-001662

BMJ Open Diabetes Res Care. 2023 Jun;11(3):e003327. doi: 10.1136/bmjdrc-2023-003327.

ABSTRACT

INTRODUCTION: Hypoglycemia is a major limiting factor in achieving recommended glycemic targets for people with type 1 diabetes. Exposure to recurrent hypoglycemia results in blunted hormonal counter-regulatory and symptomatic responses to hypoglycemia. Limited data on metabolic adaptation to recurrent hypoglycemia are available. This study examined the acute metabolic responses to hypoglycemia and the effect of antecedent hypoglycemia on these responses in type 1 diabetes.

RESEARCH DESIGN AND METHODS: Twenty-one outpatients with type 1 diabetes with normal or impaired awareness of hypoglycemia participated in a study assessing the response to hypoglycemia on 2 consecutive days by a hyperinsulinemic glucose clamp. Participants underwent a period of normoglycemia and a period of hypoglycemia during the hyperinsulinemic glucose clamp. Plasma samples were taken during normoglycemia and at the beginning and the end of the hypoglycemic period. Metabolomic analysis of the plasma samples was conducted using comprehensive two-dimensional gas chromatography with time-of-flight mass spectrometry.

RESULTS: In total, 68 metabolites were studied. On day 1, concentrations of the branched-chain amino acids, leucine (p=3.8×10^-3) and isoleucine (p=2.2×10^-3), decreased during hypoglycemia. On day 2, during hypoglycemia, five amino acids (including leucine and isoleucine) significantly decreased, and two fatty acids (tetradecanoic and oleic acids) significantly increased (p<0.05). Although more metabolites responded to hypoglycemia on day 2, the responses of the single metabolites were not statistically significant between the 2 days.

CONCLUSIONS: In individuals with type 1 diabetes, one episode of hypoglycemia decreases leucine and isoleucine concentrations. Antecedent hypoglycemia results in the decrement of five amino acids and increases the concentrations of two fatty acids, suggesting an alteration between the two hypoglycemic episodes, which could indicate a possible adaptation. However, more studies are needed to gain a comprehensive understanding of the consequences of these alterations.

TRIAL REGISTRATION NUMBER: NCT01337362.

PMID:37369531 | DOI:10.1136/bmjdrc-2023-003327

CMAJ Open. 2023 Jun 27;11(3):E569-E578. doi: 10.9778/cmajo.20210291. Print 2023 May-Jun.

ABSTRACT

BACKGROUND: Previous research has shown that cocaine-associated deaths occur more frequently in hot weather, which has not been described for other illicit drugs or combinations of drugs. The study objective was to evaluate the relation between temperature and risk of death related to cocaine, opioids and amphetamines in British Columbia, Canada.

METHODS: We extracted data on all deaths with cocaine, opioid or amphetamine toxicity recorded as an underlying or contributing cause from BC vital statistics for 1998-2017. We used a time-stratified case-crossover design to estimate the effect of temperature on the risk of death associated with acute drug toxicity during the warmer months (May through September). Odds ratios (ORs) and 95% confidence intervals (CIs) were estimated for each 10°C increase in the 2-day average maximum temperature at the residential location.

RESULTS: We included 4913 deaths in the analyses. A 10°C increase in the 2-day average maximum temperature was associated with an OR of 1.43 (95% CI 1.11-1.86) for deaths with only cocaine toxicity recorded (n = 561), an OR of 1.15 (95% CI 0.99-1.33) for deaths with opioids only (n = 1682) and an OR of 1.11 (95% CI 0.60-2.04) for deaths with amphetamines only (n = 133). There were also elevated effects when toxicity from multiple drugs was recorded. Sensitivity analyses showed differences in the ORs by sex, by climatic region, and when the location of death was used instead of the location of residence.

INTERPRETATION: Increasing temperatures were associated with higher odds of death due to drug toxicity, especially for cocaine alone and combined with other drugs. Targeted interventions are necessary to prevent death associated with toxic drug use during hot weather.

PMID:37369523 | DOI:10.9778/cmajo.20210291

In Vivo. 2023 Jul-Aug;37(4):1703-1713. doi: 10.21873/invivo.13257.

ABSTRACT

BACKGROUND/AIM: Lung percutaneous needle biopsy (PNB) under CT guidance can be performed with a single-needle or with a coaxial (CX) technique. This study evaluated the CX technique in a large cohort of patients who underwent to CT-guided lung PNB in our Institute over a period of 7 years.

PATIENTS AND METHODS: We retrospectively collected and analyzed data relative to 700 CT-guided lung PNBs performed from August 2012 to August 2019 in 700 patients (M:F=436:264; mean age=69 years, range=6-93 years) with normal coagulation and pulmonary function. PNB was considered diagnostic if at least one of the collected tissue specimens allowed for histological diagnosis. Pulmonary hemorrhage (PH) and pneumothorax (PNX) were evaluated as present or absent. Statistical analysis was made by Chi-square test of Pearson, Fisher’s exact test and Wilcoxon test.

RESULTS: The CX technique showed a high diagnostic accuracy (93.0%) and allowed the collection of a great number of appropriate tissue specimens with a single pleural puncture (≥3 specimens in 77.4% of cases). PH was the complication more frequent (55.4%), without significant clinical impact. Global PNXs incidence was high (42.9%), but the introducer allowed to aspirate the PNX with a lower percentage of chest tube placement vs. PNXs not aspirated (6.3% and 13.3%, respectively).

CONCLUSION: This large retrospective study confirmed the high diagnostic accuracy of lung PNB with the CX technique and allowed identification of significant factors to achieve a greater diagnostic power and decrease complication rates.

PMID:37369512 | DOI:10.21873/invivo.13257