Nevin Manimala

Trop Biomed. 2023 Sep 1;40(3):337-343. doi: 10.47665/tb.40.3.010.

ABSTRACT

Antibody cross-reactivity among flaviviruses is a major limitation in understanding the prevalence without vector control measures. In this study, we investigated the presence of Zika virus (ZIKV)-specific antibodies and the significance of their cross-reactivity with other flaviviruses, which could affect the serological specificity in both symptomatic and asymptomatic pregnant women. Among the results obtained from 217 serum samples tested for ZIKV-specific IgM and IgG, no specific predictions regarding seropositivity or exposure due to extensive cross-reactivity with dengue virus (DENV) serology could be made. Clear-cut positivity was observed in 1.8% (n = 4) and 1.0% (n = 2) for ZIKV IgM and IgG, respectively. The same samples assessed for DENV showed 1.3% (n = 3) seropositivity each for IgM and IgG levels. None of the samples were positive for ZIKV and DENV IgM or IgG. However, one sample (0.4%) tested positive for ZIKV and DENV IgM. No significant correlation was observed between DENV IgM and IgG when comparing the overlapped serotiters. On the other hand, the ZIKV IgG-positive sample showed higher serotiters for DENV IgG, indicating cross-reactivity with ZIKV but without statistical significance. Therefore, screening for the incidence of ZIKV becomes particularly challenging in a population where the presence or pre-exposure to DENV is observed. Our observations further suggest that unless flavivirus prevalence is properly addressed, determining the prevalence of ZIKV antibodies, which may be confounded with other uninvestigated flaviviruses, will be complicated.

PMID:37897167 | DOI:10.47665/tb.40.3.010

Trop Biomed. 2023 Sep 1;40(3):281-289. doi: 10.47665/tb.40.3.002.

ABSTRACT

The intake of food and water containing the Sarcocystis parasite has been linked to a number of outbreaks worldwide, including Malaysia. Nevertheless, the lack of surveys and epidemiological data on Sarcocystis infections in Malaysia makes it difficult to estimate its occurrence in humans and animals. A cross-sectional study was conducted to determine the prevalence of Sarcocystis and the risk factors associated with infection among village chickens and pigs reared under different farm managements in Peninsular Malaysia. Phylogenetic trees were constructed using partial fragments of the 18S rRNA gene and ITS1 sequences. In the present study, 680 sera samples were collected from village chickens (n=250) and commercial pigs (n=433) and anti-Sarcocystis antibodies were screened using the enzymelinked immunosorbent assays (ELISA) kit. At the animal level, the prevalence of Sarcocystis was 9.2% (95% CI: 5.92-13.48) and at the farm level, it was 64.0% (95% CI: 42.52-82.03) in village chickens. The animal-level seroprevalence of Sarcocystis for pigs was 3.7% (95% CI: 2.13-5.93) and 36.8% (95% CI: 16.29-61.64) at the farm-level. Polymerase Chain Reaction (PCR) was conducted on meat samples from various parts of village chickens (n=250) consisting of brain, heart, lung, and pectoralis muscle tissues, and pork (n=121) consisting of intercostal muscle, diaphragm, and tongue. Sarcocystis DNA was detected in 6.4% (95% CI: 4.60-11.60) of village chicken samples but zero in pork samples. A total of 11 unique Sarcocystis haplotypes were isolated from these tissue samples. Multivariable logistic regression analysis of the putative risk factors showed a statistically significant association between Sarcocystis infection in pigs and uncovered storage of feed. Although no zoonotic Sarcocystis was isolated in this study, we reported the first discovery of S. wenzeli in Malaysia.

PMID:37897159 | DOI:10.47665/tb.40.3.002

J Hepatobiliary Pancreat Sci. 2023 Oct 27. doi: 10.1002/jhbp.1389. Online ahead of print.

ABSTRACT

PURPOSE: To investigate the prognostic impact of RAS mutations on the Japanese Society of Hepatobiliary and Pancreatic Surgeons (JSHBPS) nomogram score in patients with colorectal cancer liver metastasis (CRLM) following hepatectomy.

METHODS: We included 218 consecutive patients undergoing hepatectomy for CRLM between 2004 and 2020. The JSHBPS nomogram score was calculated using six preoperative clinical factors. The score ranged from 0 to 25, and higher scores indicated greater tumor burden. Associations of RAS mutations with disease-free survival (DFS) and overall survival (OS) by the JSHBPS nomogram score were examined. Multivariable Cox proportional hazard regression models were used to estimate adjusted hazard ratios (HRs) and confidence intervals (CIs).

RESULTS: RAS mutations were detected in 72 (33%) of the 218 patients. Multivariate analyses revealed that RAS mutations were independently associated with poor DFS (HR, 1.93; 95% CI: 1.20-3.10; p = .007) and OS (HR, 2.65; 95% CI: 1.59-4.71; p = .001) compared with wild-type RAS with JSHBPS nomogram scores ≤ 10. However, in patients with scores ≥ 11, the association of RAS mutations with DFS or OS was not statistically significant (p > .08).

CONCLUSION: RAS mutation status in combination with the JSHBPS nomogram may be useful for preoperatively identifying CRLM with high risk of recurrence and mortality after hepatectomy.

PMID:37897144 | DOI:10.1002/jhbp.1389

Nurs Crit Care. 2023 Oct 27. doi: 10.1111/nicc.12991. Online ahead of print.

ABSTRACT

BACKGROUND: The incidence of coagulation of continuous renal replacement therapy circuits remains high. To the best of our knowledge, no scholar has published a protocol to avoid management errors when different types of citrates coexist in the same Intensive Care Unit.

AIM: To assess the safety and efficacy of the unification of two protocols with different concentrations of citrate solution.

STUDY DESING: A prospective, quasi-experimental study was carried out in the intensive care unit of a tertiary referral hospital (in Barcelona, Spain), over 3 years. Consecutive adult patients requiring continuous renal replacement therapy with citrate were included. The sample was divided into two groups, a control group (concentrated citrate) and an intervention group (diluted citrate). The decision to initiate anticoagulation with diluted (18 mmol/L) or concentrated (136 mmol/L) citrate was made based on the machine available and the decision of the doctor responsible for the patient. It was not possible to randomize the sample. Both protocols were matched with a starting citrate dose of 3.5 mmol/L, and a dialysis solution was used. Post-filter replacement was not used, and the citrate solution was the only fluid administered pre-filter.

RESULTS: The analysis included 59 circuits in the concentrated citrate group and 40 circuits in the diluted citrate group. An increased need for electrolyte replacement was observed in the diluted group (p < .001). The concentrated citrate group had a longer filter life (p < .05), and there was a slight trend toward alkalosis.

CONCLUSION: The diluted citrate group had a higher incidence of electrolyte replacement. The concentrated citrate group had longer circuit lifespan and a trend toward metabolic alkalosis, although this was not statistically significant. If these conclusions are considered, the protocol can be unified.

RELEVANCE TO CLINICAL PRACTICE: The present work aims to provide information on the differences in the use of regional anticoagulation with diluted or concentrated citrate. The objective is to pay special attention to aspects that can lead to complications. The unified protocol proposed in this paper could be extrapolated to any machine on the market that uses either of these two types of citrate concentration.

PMID:37897131 | DOI:10.1111/nicc.12991

Nutr Bull. 2023 Oct 28. doi: 10.1111/nbu.12640. Online ahead of print.

ABSTRACT

We investigated the extent of alignment between ‘healthiness’ defined by a food classification system that classifies foods and beverages primarily by their nutrient composition, the Health Star Rating (HSR) and a system that considers only the degree of processing of the product, the NOVA classification system. We used data for 25 486 products contained within the George Institute for Global Health’s Australian 2022 FoodSwitch Dataset. Agreement between the two systems in the proportion of products classified as ‘healthier’ (HSR ≥3.5 or NOVA group 1-3) or ‘less healthy’ (HSR <3.5 or NOVA group 4) was assessed using the κ statistic. There was ‘fair’ agreement (κ = 0.30, 95%CI: 0.29-0.31) between both systems in the proportion of all products classified as healthier or less healthy. Approximately one-third (n = 8729) of all products were defined as ‘discordant’, including 34.3% (n = 5620) of NOVA group 4 products with HSR ≥3.5 (commonly convenience foods, sports/diet foods, meat alternatives, as well as products containing non-sugar sweeteners) and 34.1% (n = 3109) of NOVA group 1-3 products with HSR <3.5 (commonly single-ingredient foods such as sugars/syrups, full-fat dairy and products specially produced to contain no ultra-processed ingredients). Our analysis strengthens the evidence for the similarities and differences in product healthiness according to a nutrient-based classification system and a processing-based classification system. Although the systems’ classifications align for the majority of food and beverage products, the discordance found for some product categories indicates potential for confusion if systems are deployed alongside each other within food policies.

PMID:37897130 | DOI:10.1111/nbu.12640

Water Environ Res. 2023 Oct 27:e10945. doi: 10.1002/wer.10945. Online ahead of print.

ABSTRACT

This is the first study that describes ammonium oxidizing bacterial populations and correlations of these populations with a range of criteria in activated sludge wastewater treatment plants in South Africa. In this study, not only the influent, but also the activated sludge chemistry was comprehensively characterized. Multivariate statistical analyses were used to determine the relative significances of the geographical location (factor: site), wastewater treatment plant process (factor: configuration), seasonality (factor: season), and environmental parameters on the ammonium oxidizing bacterial genera in six municipal activated sludge wastewater treatments plants from two sites (the Cities of Cape Town and Ekurhuleni). The geographical location (site) was significant for selection of the ammonium oxidizing genera (Global ANOSIM R value=0.538, p=0.001). It was established that the inter-site differences were not climatic in origin, nor related to the composition of the influent, but were rather driven by the activated sludge chemistry. It was found using BEST analysis that the activated sludge ammonia, activated sludge total phosphate and activated sludge total chemical oxygen demand were the most significant (p<0.001) drivers for ammonium oxidizing bacterial selection (ANOSIM Global R value 0.419), and were significantly higher in the activated sludge from the City of Cape Town wastewater treatment plants. Nitrosospira was the most abundant ammonium oxidizing bacterial genus, with notably higher relative and estimated actual abundances in the City of Cape Town wastewater treatment plants than the City of Ekurhuleni wastewater treatment plants. The strong selection of Nitrosospira in the City of Cape Town wastewater treatment plants with higher nutrient concentrations strongly suggests that high concentrations of activated sludge ammonia, activated sludge total phosphate and activated sludge total chemical oxygen demand are key selective drivers for this genus.

PMID:37897128 | DOI:10.1002/wer.10945

J Evol Biol. 2023 Oct 28. doi: 10.1111/jeb.14238. Online ahead of print.

ABSTRACT

Anthropogenic change exposes populations to environments that have been rare or entirely absent from their evolutionary past. Such novel environments are hypothesized to release cryptic genetic variation, a hidden store of variance that can fuel evolution. However, support for this hypothesis is mixed. One possible reason is a lack of clarity in what is meant by ‘novel environment’, an umbrella term encompassing conditions with potentially contrasting effects on the exposure or concealment of cryptic variation. Here, we use a meta-analysis approach to investigate changes in the total genetic variance of multivariate traits in ancestral versus novel environments. To determine whether the definition of a novel environment could explain the mixed support for a release of cryptic genetic variation, we compared absolute novel environments, those not represented in a population’s evolutionary past, to extreme novel environments, those involving frequency or magnitude changes to environments present in a population’s ancestry. Despite sufficient statistical power, we detected no broad-scale pattern of increased genetic variance in novel environments, and finding the type of novel environment did not explain any significant variation in effect sizes. When effect sizes were partitioned by experimental design, we found increased genetic variation in studies based on broad-sense measures of variance, and decreased variation in narrow-sense studies, in support of previous research. Therefore, the source of genetic variance, not the definition of a novel environment, was key to understanding environment-dependant genetic variation, highlighting non-additive genetic variance as an important component of cryptic genetic variation and avenue for future research.

PMID:37897127 | DOI:10.1111/jeb.14238

J Natl Cancer Inst. 2023 Oct 27:djad201. doi: 10.1093/jnci/djad201. Online ahead of print.

ABSTRACT

BACKGROUND: Examining screening outcomes by breast density for breast magnetic resonance imaging (MRI) with or without mammography could inform discussions about supplemental MRI in women with dense breasts.

METHODS: We evaluated 52 237 women aged 40-79 years who underwent 2611 screening MRIs alone and 6518 supplemental MRI plus mammography pairs propensity score-matched to 65 810 screening mammograms. Rates per 1000 examinations of interval, advanced, and screen-detected early stage invasive cancers and false-positive recall and biopsy recommendation were estimated by breast density (nondense = almost entirely fatty or scattered fibroglandular densities; dense = heterogeneously/extremely dense) adjusting for registry, examination year, age, race and ethnicity, family history of breast cancer, and prior breast biopsy.

RESULTS: Screen-detected early stage cancer rates were statistically higher for MRI plus mammography vs mammography for nondense (9.3 vs 2.9; difference = 6.4, 95% confidence interval [CI] = 2.5 to 10.3) and dense (7.5 vs 3.5; difference = 4.0, 95% CI = 1.4 to 6.7) breasts and for MRI vs MRI plus mammography for dense breasts (19.2 vs 7.5; difference = 11.7, 95% CI = 4.6 to 18.8). Interval rates were not statistically different for MRI plus mammography vs mammography for nondense (0.8 vs 0.5; difference = 0.4, 95% CI = -0.8 to 1.6) or dense breasts (1.5 vs 1.4; difference = 0.0, 95% CI = -1.2 to 1.3), nor were advanced cancer rates. Interval rates were not statistically different for MRI vs MRI plus mammography for nondense (2.6 vs 0.8; difference = 1.8 (95% CI = -2.0 to 5.5) or dense breasts (0.6 vs 1.5; difference = -0.9, 95% CI = -2.5 to 0.7), nor were advanced cancer rates. False-positive recall and biopsy recommendation rates were statistically higher for MRI groups than mammography alone.

CONCLUSION: MRI screening with or without mammography increased rates of screen-detected early stage cancer and false-positives for women with dense breasts without a concomitant decrease in advanced or interval cancers.

PMID:37897090 | DOI:10.1093/jnci/djad201

Clin Pharmacol Ther. 2023 Oct 27. doi: 10.1002/cpt.3087. Online ahead of print.

ABSTRACT

Study sponsors and market authorization holders are required by the FDA and EMA regulatory agencies to enroll patients administered a gene therapy product, whether in a trial setting or post-licensure, in a long term follow-up safety study to continue the safety assessments of their product. These follow-up studies range between 5 to 15 years after dosing. This unprecedented duration of engagement with patients and caregivers raises logistical challenges that will require innovation and collaboration across sponsors and regulators. In this paper we delineate some of the key considerations for designing long term follow-up protocols in the gene therapy setting, with an eye towards platform and master protocol approaches, and offer guidance for innovative operational and statistical methods that can help assess the safety profile and durability of response for these novel therapeutics.

PMID:37897056 | DOI:10.1002/cpt.3087

Br J Clin Pharmacol. 2023 Oct 27. doi: 10.1111/bcp.15943. Online ahead of print.

ABSTRACT

AIMS: This study aimed to evaluate the predictive performance of previously constructed cefazolin pharmacokinetic models and determine whether cefazolin administration via the target-controlled infusion (TCI) method may be possible in clinical practice.

METHODS: Twenty-five gastrectomy patients receiving cefazolin as a prophylactic antibiotic were enrolled. Two grams of cefazolin were dissolved in 50 mL of normal saline to give a concentration of 40 mg mL^-1 . Before skin incision, cefazolin was administered using a TCI syringe pump and its administration continued until the end of surgery. The target total plasma concentration was set to 100 μg mL^-1 . Total and unbound plasma concentrations of cefazolin were measured in three arterial blood samples collected at 30, 60, and 120 min after the start of cefazolin administration. The predictive performance of the TCI system was evaluated using four measures: inaccuracy, divergence, bias, and wobble.

RESULTS: Total (n = 75) and unbound (n = 75) plasma concentration measurements from 25 patients were included in the analysis. The pooled median (95% confidence interval) biases and inaccuracies were 6.3 (4.0 to 8.5) and 10.5 (8.6 to 12.4) for the total concentration model, and -10.3 (-16.8 to -3.7) and 22.4 (18.2 to 26.7) for the unbound concentration model, respectively. All unbound concentrations were above 10 μg mL^-1 .

CONCLUSION: Administration of cefazolin by the TCI method showed a clinically acceptable performance. Applying the TCI method by setting the total concentration as the target concentration rather than the unbound concentration is effective in maintaining a constant target concentration of cefazolin.

PMID:37897050 | DOI:10.1111/bcp.15943