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Abstract Case investigation and contact tracing (CICT) are public health measures that aim to break the chain of pathogen transmission. Changes in viral characteristics of COVID-19 variants have likely affected the effectiveness of CICT programs. We estimated and compared the cases averted in Vermont when the original COVID-19 strain circulated (Nov. 25, 2020–Jan. 19, 2021) with two periods when the Delta strain dominated (Aug. 1–Sept. 25, 2021, and Sept. 26–Nov. 20, 2021). When the original strain circulated, we estimated that CICT prevented 7180 cases (55% reduction in disease burden), compared to 1437 (15% reduction) and 9970 cases (40% reduction) when the Delta strain circulated. Despite the Delta variant being more infectious and having a shorter latency period, CICT remained an effective tool to slow spread of COVID-19; while these viral characteristics did diminish CICT effectiveness, non-viral characteristics had a much greater impact on CICT effectiveness.

Abstract Background Facing a surge of COVID-19 cases in late August 2021, the U.S. state of Illinois re-enacted its COVID-19 mask mandate for the general public and issued a requirement for workers in certain professions to be vaccinated against COVID-19 or undergo weekly testing. The mask mandate required any individual, regardless of their vaccination status, to wear a well-fitting mask in an indoor setting. Methods We used Illinois Department of Public Health’s COVID-19 confirmed case and vaccination data and investigated scenarios where masking and vaccination would have been reduced to mimic what would have happened had the mask mandate or vaccine requirement not been put in place. The study examined a range of potential reductions in masking and vaccination mimicking potential scenarios had the mask mandate or vaccine requirement not been enacted. We estimated COVID-19 cases and hospitalizations averted by changes in masking and vaccination during the period covering October 20 to December 20, 2021. Results We find that the announcement and implementation of a mask mandate are likely to correlate with a strong protective effect at reducing COVID-19 burden and the announcement of a vaccinate-or-test requirement among frontline professionals is likely to correlate with a more modest protective effect at reducing COVID-19 burden. In our most conservative scenario, we estimated that from the period of October 20 to December 20, 2021, the mask mandate likely prevented approximately 58,000 cases and 1,175 hospitalizations, while the vaccinate-or-test requirement may have prevented at most approximately 24,000 cases and 475 hospitalizations. Conclusion Our results indicate that mask mandates and vaccine-or-test requirements are vital in mitigating the burden of COVID-19 during surges of the virus.

Because of constrained personnel time, the Philadelphia Department of Public Health (Philadelphia, PA, USA) adjusted its COVID-19 contact tracing protocol in summer 2021 by prioritizing recent cases and limiting staff time per case. This action reduced required staff hours to prevent each case from 21–30 to 8–11 hours, while maintaining program effectiveness.

Excessive waste production has led to the concept of a circular bioeconomy to deliver valuable by-products and improve environmental sustainability. The annual worldwide rice production accounts for more than 750 million tons of grain and 150 million tons of husk. Rice husk (RH) contains valuable biomaterials with extensive applications in various fields. The proportions of each component depend primarily on rice genotype, soil chemistry, and climatic conditions. RH and its derivatives, including ash, biochar, hydrochar, and activated carbon have been placed foreground of applications in agriculture and other industries. While the investigation on RH’s compositions, microstructures, and by-products has been done copiously, owing to its unique features, it is still an open-ended area with enormous scope for innovation, research, and technology. Here, we reviewed the latest applications of RH and its derivatives, including fuel and other energy resources, construction materials, pharmacy, medicine, and nanobiotechnology to keep this versatile biomaterial in the spotlight.

Abstract Background Exercise is beneficial to bone health. However, little is known about the interaction effect of gender and sport type on bone turnover in young athletes. This study aimed to examine the influence of gender and sports categories (high, medium, and low impact) on bone turnover: reabsorption markers–osteocalcin, calcium, inorganic phosphate (IP), alkaline phosphatase (ALP), and resorption marker–cross-linked N-telopeptides of type 1 collagen (NTx) among a university’s undergraduate athletes. Methods The study was an ex-post facto design involving forty-seven purposively recruited gender- and sport-type-matched undergraduate athletes whose demographic characteristics and BMI were obtained. Participants’ 5 mL antecubital blood samples were collected and analysed for serum levels of osteocalcin, calcium, IP, ALP, and NTx using standard laboratory protocols, Bio-Tek spectrometer, and KC4 (3.3) software. Data were analysed using descriptive statistics and two-way ANOVA. Results The study involved 24 females and 23 males (n = 47) aged 22.15 ± 3.35 years with an average BMI of 23.34 ± 4.66. There was no significant gender effect on the biomarkers. However, there was a significant effect of the sports category on IP (F = 4.307, p = 0.020), calcium (F = 6.807, p = 0.003), and ALP serum levels (F = 11.511, p

Abstract Purpose To explore the lived experiences of alcohol consumption among young adults with type 1 diabetes. Methods Fourteen semi-structured interviews were conducted amongst young adults aged between 18 and 25 years, inclusive, with type 1 diabetes and experience consuming alcohol. Interviews were transcribed verbatim and analysed to identify common themes regarding their experiences. Results The interviews confirmed that young adults with type 1 diabetes engage in social, and occasionally excessive, drinking behaviour. Furthermore, the interviews revealed four key themes: (i) Several sources contribute to a widely inconsistent understanding of the impact and management of alcohol consumption; (ii) Perceived inconvenience of maintaining healthy glycaemic control whilst drinking socially; (iii) Engagement in proactive strategies for harm reduction occurred when convenient; and (iv) Impact of modern diabetes technology in overcoming previous burdens and promoting glycaemic safety. Conclusion Young adults with type 1 diabetes continue to need anticipatory education surrounding safe alcohol consumption and behaviours, as well as ongoing support and encouragement to ensure engagement with traditional self-management tasks. Significant alcohol-diabetes related safety issues, particularly hypoglycaemia do occur, and were captured within this small sample and study. Diabetes technology has an important complementary role along with education and tailored support strategies to support health and safe glucose control during alcohol consumption.

Abstract Phyllachora maydis is a fungal pathogen causing tar spot of corn (Zea mays L.), a new and emerging, yield-limiting disease in the United States. Since being first reported in Illinois and Indiana in 2015, P. maydis can now be found across much of the corn growing regions of the United States. Knowledge of the epidemiology of P. maydis is limited but could be useful in developing tar spot prediction tools. The research presented here aims to elucidate the environmental conditions necessary for the development of tar spot in the field and the creation of predictive models to anticipate future tar spot epidemics. Extended periods (30-day windowpanes) of moderate mean ambient temperature (18–23 °C) were most significant for explaining the development of tar spot. Shorter periods (14- to 21-day windowpanes) of moisture (relative humidity, dew point, number of hours with predicted leaf wetness) were negatively correlated with tar spot development. These weather variables were used to develop multiple logistic regression models, an ensembled model, and two machine learning models for the prediction of tar spot development. This work has improved the understanding of P. maydis epidemiology and provided the foundation for the development of a predictive tool for anticipating future tar spot epidemics.

Objectives To determine the prevalence and incidence of polypharmacy/hyperpolypharmacy and which medications are most prescribed to patients with varying burden of polypharmacy.Design Retrospective, population-based cohort study.Setting Iceland.Participants Including patients (≥18 years) admitted to internal medicine services at Landspitali – The National University Hospital of Iceland, between 1 January 2010 with a follow-up of clinical outcomes through 17 March 2022.Main outcomes measures Participants were categorised into medication use categories of non-polypharmacy (10) based on the number of medications filled in the year predischarge and postdischarge. The primary outcome was prevalence and incidence of new polypharmacy. Secondary outcomes were mortality, length of hospital stay and re-admission.Results Among 85 942 admissions (51% male), the median (IQR) age was 73 (60–83) years. The prevalence of preadmission non-polypharmacy was 15.1% (95% CI 14.9 to 15.3), polypharmacy was 22.9% (95% CI 22.6 to 23.2) and hyperpolypharmacy was 62.5% (95% CI 62.2 to 62.9). The incidence of new postdischarge polypharmacy was 33.4% (95% CI 32.9 to 33.9), and for hyperpolypharmacy was 28.9% (95% CI 28.3 to 29.5) for patients with preadmission polypharmacy. Patients with a higher level of medication use were more likely to use multidose drug dispensing and have a diagnosis of adverse drug reaction. Other comorbidities, including responsible subspeciality and estimates of comorbidity and frailty burden, were identical between groups of varying polypharmacy. There was no difference in length of stay, re-admission rate and mortality.Conclusions Preadmission polypharmacy/hyperpolypharmacy and postdischarge new polypharmacy/hyperpolypharmacy is common amongst patients admitted to internal medicine. A higher level of medication use category was not found to be associated with demographic, comorbidity and clinical outcomes. Medications that are frequently inappropriately prescribed were among the most prescribed medications in the group. An increased focus on optimising medication usage is needed after hospital admission.Trial registration number NCT05756400.

Rhizobacteria are capable of inducing defense responses via the expression of pathogenesis-related proteins (PR-proteins) such as chitinases, and many studies have validated the functions of plant chitinases in defense responses. Soybean (Glycine max) is an economically important crop worldwide, but the functional validation of soybean chitinase in defense responses remains limited. In this study, genome-wide characterization of soybean chitinases was conducted, and the defense contribution of three chitinases (GmChi01, GmChi02, or GmChi16) was validated in Arabidopsis transgenic lines against the soil-borne pathogen Fusarium oxysporum. Compared to the Arabidopsis Col-0 and empty vector controls, the transgenic lines with GmChi02 or GmChi16 exhibited fewer chlorosis symptoms and wilting. While GmChi02 and GmChi16 enhanced defense to F. oxysporum, GmChi02 was the only one significantly induced by Burkholderia ambifaria. The observation indicated that plant chitinases may be induced by different rhizobacteria for defense responses. The survey of 37 soybean chitinase gene expressions in response to six rhizobacteria observed diverse inducibility, where only 10 genes were significantly upregulated by at least one rhizobacterium and 9 genes did not respond to any of the rhizobacteria. Motif analysis on soybean promoters further identified not only consensus but also rhizobacterium-specific transcription factor-binding sites for the inducible chitinase genes. Collectively, these results confirmed the involvement of GmChi02 and GmChi16 in defense enhancement and highlighted the diverse inducibility of 37 soybean chitinases encountering F. oxysporum and six rhizobacteria.

Introduction: During the COVID-19 pandemic, the U.S. Centers for Disease Control and Prevention developed a simple spreadsheet-based tool to help state and local public health officials assess the performance and impact of COVID-19 case investigation and contact tracing in their jurisdiction. The applicability and feasibility of building such a tool for sexually transmitted diseases were assessed. Methods: The key epidemiologic differences between sexually transmitted diseases and respiratory diseases (e.g., mixing patterns, incubation period, duration of infection, and the availability of treatment) were identified, and their implications for modeling case investigation and contact tracing impact with a simple spreadsheet tool were remarked on. Existing features of the COVID-19 tool that are applicable for evaluating the impact of case investigation and contact tracing for sexually transmitted diseases were also identified. Results: Our findings offer recommendations for the future development of a spreadsheet-based modeling tool for evaluating the impact of sexually transmitted disease case investigation and contact tracing efforts. Generally, we advocate for simplifying sexually transmitted disease–specific complexities and performing sensitivity analyses to assess uncertainty. The authors also acknowledge that more complex modeling approaches might be required but note that it is possible that a sexually transmitted disease case investigation and contact tracing tool could incorporate features from more complex models while maintaining a user-friendly interface. Conclusions: A sexually transmitted disease case investigation and contact tracing tool could benefit from the incorporation of key features of the COVID-19 model, namely its user-friendly interface. The inherent differences between sexually transmitted diseases and respiratory viruses should not be seen as a limitation to the development of such tool.

Abstract Plant disease resistance genes are widely used in agriculture to reduce disease outbreaks and epidemics and ensure global food security. In soybean, Rps (Resistance to Phytophthora sojae) genes are used to manage Phytophthora sojae, a major oomycete pathogen that causes Phytophthora stem and root rot (PRR) worldwide. This study aims to identify temporal changes in P. sojae pathotype complexity, diversity, and Rps gene efficacy. Pathotype data was collected from 5121 isolates of P. sojae, derived from 29 surveys conducted between 1990 and 2019 across the United States, Argentina, Canada, and China. This systematic review shows a loss of efficacy of specific Rps genes utilized for disease management and a significant increase in the pathotype diversity of isolates over time. This study finds that the most widely deployed Rps genes used to manage PRR globally, Rps1a, Rps1c and Rps1k, are no longer effective for PRR management in the United States, Argentina, and Canada. This systematic review emphasizes the need to widely introduce new sources of resistance to P. sojae, such as Rps3a, Rps6, or Rps11, into commercial cultivars to effectively manage PRR going forward.

Tar spot is a devasting corn disease caused by the obligate fungal pathogen Phyllachora maydis. Since its initial identification in the United States in 2015, P. maydis has become an increasing threat to corn production. Despite this, P. maydis has remained largely understudied at the molecular level, due to difficulties surrounding its obligate lifestyle. Here, we generated a significantly improved P. maydis nuclear and mitochondrial genome, using a combination of long- and short-read technologies, and also provide the first transcriptomic analysis of primary tar spot lesions. Our results show that P. maydis is deficient in inorganic nitrogen utilization, is likely heterothallic, and encodes for significantly more protein-coding genes, including secreted enzymes and effectors, than previous determined. Furthermore, our expression analysis suggests that, following primary tar spot lesion formation, P. maydis might reroute carbon flux away from DNA replication and cell division pathways and towards pathways previously implicated in having significant roles in pathogenicity, such as autophagy and secretion. Together, our results identified several highly expressed unique secreted factors that likely contribute to host recognition and subsequent infection, greatly increasing our knowledge of the biological capacity of P. maydis, which have much broader implications for mitigating tar spot of corn. [Graphic: see text] Copyright © 2023 The Author(s). This is an open access article distributed under the CC BY-NC-ND 4.0 International license.

Abstract Background Persistent symptoms are common after SARS-CoV-2 infection but correlation with objective measures is unclear. Methods We invited all 3098 adults who tested SARS-CoV-2 positive in Iceland before October 2020 to the deCODE Health Study. We compared multiple symptoms and physical measures between 1706 Icelanders with confirmed prior infection (cases) who participated, and 619 contemporary and 13,779 historical controls. Cases participated in the study 5–18 months after infection. Results Here we report that 41 of 88 symptoms are associated with prior infection, most significantly disturbed smell and taste, memory disturbance, and dyspnea. Measured objectively, cases had poorer smell and taste results, less grip strength, and poorer memory recall. Differences in grip strength and memory recall were small. No other objective measure associated with prior infection including heart rate, blood pressure, postural orthostatic tachycardia, oxygen saturation, exercise tolerance, hearing, and traditional inflammatory, cardiac, liver, and kidney blood biomarkers. There was no evidence of more anxiety or depression among cases. We estimate the prevalence of long Covid to be 7% at a median of 8 months after infection. Conclusions We confirm that diverse symptoms are common months after SARS-CoV-2 infection but find few differences between cases and controls in objective parameters measured. These discrepancies between symptoms and physical measures suggest a more complicated contribution to symptoms related to prior infection than is captured with conventional tests. Traditional clinical assessment is not expected to be particularly informative in relating symptoms to a past SARS-CoV-2 infection.

ABSTRACTTo address the ongoing global tuberculosis crisis, there is a need for shorter, more effective treatments. A major reason why tuberculosis requires prolonged treatment is that, following a short initial phase of rapid killing, the residual Mycobacterium tuberculosis withstands drug killing. Because existing methods lack sensitivity to quantify low-abundance mycobacterial RNA in drug-treated animals, cellular adaptations of drug-exposed bacterial phenotypes in vivo remain poorly understood. Here, we used a novel RNA-seq method called SEARCH-TB to elucidate the Mycobacterium tuberculosis transcriptome in mice treated for up to 28 days with standard doses of isoniazid, rifampin, pyrazinamide, and ethambutol. We compared murine results with in vitro SEARCH-TB results during exposure to the same regimen. Treatment suppressed genes associated with growth, transcription, translation, synthesis of rRNA proteins, and immunogenic secretory peptides. Bacteria that survived prolonged treatment appeared to transition from ATP-maximizing respiration toward lower-efficiency pathways and showed modification and recycling of cell wall components, large-scale regulatory reprogramming, and reconfiguration of efflux pump expression. Although the pre-treatment in vivo and in vitro transcriptomes differed profoundly, genes differentially expressed following treatment in vivo and in vitro were similar, with differences likely attributable to immunity and drug pharmacokinetics in mice. These results reveal cellular adaptations of Mycobacterium tuberculosis that withstand prolonged drug exposure in vivo, demonstrating proof of concept that SEARCH-TB is a highly granular pharmacodynamic readout. The surprising finding that differential expression is concordant in vivo and in vitro suggests that insights from transcriptional analyses in vitro may translate to the mouse.IMPORTANCEA major reason that curing tuberculosis requires prolonged treatment is that drug exposure changes bacterial phenotypes. The physiologic adaptations of Mycobacterium tuberculosis that survive drug exposure in vivo have been obscure due to low sensitivity of existing methods in drug-treated animals. Using the novel SEARCH-TB RNA-seq platform, we elucidated Mycobacterium tuberculosis phenotypes in mice treated for with the global standard 4-drug regimen and compared them with the effect of the same regimen in vitro. This first view of the transcriptome of the minority Mycobacterium tuberculosis population that withstands treatment in vivo reveals adaptation of a broad range of cellular processes, including a shift in metabolism and cell wall modification. Surprisingly, the change in gene expression induced by treatment in vivo and in vitro was largely similar. This apparent “portability” from in vitro to the mouse provides important new context for in vitro transcriptional analyses that may support early preclinical drug evaluation.

BackgroundYaws is a disease caused by the bacteria Treponema pallidum subspecies pertenue, which is most commonly seen among children below 15 years. In the twentieth century yaws was endemic in Nigeria but eradication strategies markedly reduced the disease burden. Currently there is minimal data on the ongoing transmission of yaws in Nigeria, despite reports of confirmed yaws cases in neighbouring West African countries.MethodsWe conducted both community and school-based active yaws case search among school-aged children in southeast Nigeria. Children were screened by trained community volunteers. Suspected yaws cases were clinically reviewed and tested using rapid diagnostic serological tests.ResultsBetween February and May 2021, up to 28 trained community volunteers screened a total of 105,015 school children for yaws. Overall, 7,706 children with various skin lesions were identified. Eight (8) suspected cases of yaws were reported, reviewed and screened, but none was confirmed using rapid diagnostic tests. The four most common skin conditions identified were scabies (39%), papular urticaria (29%), tinea corporis (14%) and tinea capitis (12%).ConclusionsNo case of yaws was confirmed in this large population of children in south-east Nigeria. Continuous community awareness and yaws case finding activities have been recommended across Nigeria.

Aging is associated with a progressive decline of innate and adaptive immune responses, called immunosenescence. This phenomenon links to different multiple sclerosis (MS) disease courses among different age groups. While clinical relapse and active demyelination are mainly related to the altered adaptive immunity, including invasion of T- and B-lymphocytes, impairment of innate immune cell (e.g., microglia, astrocyte) function is the main contributor to disability progression and neurodegeneration. Most patients with MS manifest the relapsing-remitting phenotype at a younger age, while progressive phenotypes are mainly seen in older patients. Current disease-modifying therapies (DMTs) primarily targeting adaptive immunity are less efficacious in older patients, suggesting that immunosenescence plays a role in treatment response. This review summarizes the recent immune mechanistic studies regarding immunosenescence in patients with MS and discusses the clinical implications of these findings.

We combined field-based data with mathematical modeling to estimate the effectiveness of smartphone-enabled COVID-19 exposure notification in Pennsylvania, USA. We estimated that digital notifications potentially averted 7–69 cases/1,000 notifications during November 8, 2020–January 2, 2021. Greater use and increased compliance could increase the effectiveness of digital notifications.

BackgroundTechnology use, including continuous glucose monitoring (CGM) and insulin pump therapy, is associated with improved outcomes in youth with type 1 diabetes (T1D). In 2017 CGM was universally funded for youth with T1D in Australia. In contrast, pump access is primarily accessed through private health insurance, self-funding or philanthropy. The study aim was to investigate the use of diabetes technology across different socioeconomic groups in Australian youth with T1D, in the setting of two contrasting funding models.MethodsA cross-sectional evaluation of 4957 youth with T1D aged

Abstract Background It has been hypothesised that the gut microbiota causally affects obesity via its capacity to extract energy from the diet. Yet, evidence elucidating the role of particular human microbial community structures and determinants of microbiota-dependent energy harvest is lacking. Results Here, we investigated whether energy extraction from the diet in 85 overweight adults, estimated by dry stool energy density, was associated with intestinal transit time and variations in microbial community diversity and overall structure stratified as enterotypes. We hypothesised that a slower intestinal transit would allow for more energy extraction. However, opposite of what we expected, the stool energy density was positively associated with intestinal transit time. Stratifications into enterotypes showed that individuals with a Bacteroides enterotype (B-type) had significantly lower stool energy density, shorter intestinal transit times, and lower alpha-diversity compared to individuals with a Ruminococcaceae enterotype (R-type). The Prevotella (P-type) individuals appeared in between the B- and R-type. The differences in stool energy density between enterotypes were not explained by differences in habitual diet, intake of dietary fibre or faecal bacterial cell counts. However, the R-type individuals showed higher urinary and faecal levels of microbial-derived proteolytic metabolites compared to the B-type, suggesting increased colonic proteolysis in the R-type individuals. This could imply a less effective colonic energy extraction in the R-type individuals compared to the B-type individuals. Notably, the R-type had significantly lower body weight compared to the B-type. Conclusions Our findings suggest that gut microbial energy harvest is diversified among individuals by intestinal transit time and associated gut microbiome ecosystem variations. A better understanding of these associations could support the development of personalised nutrition and improved weight-loss strategies. Video Abstract

A study of 768 convalescent SARS CoV-2-infected and 500 uninfected Icelanders reveals broad and stable T-cell responses 3-8 months from infection. HLA alleles, disease severity, and age contribute to the heterogeneity of cellular immunity.

Abstract Background The severity of SARS-CoV-2 infection varies from asymptomatic state to severe respiratory failure and the clinical course is difficult to predict. The aim of the study was to develop a prognostic model to predict the severity of COVID-19 in unvaccinated adults at the time of diagnosis. Methods All SARS-CoV-2-positive adults in Iceland were prospectively enrolled into a telehealth service at diagnosis. A multivariable proportional-odds logistic regression model was derived from information obtained during the enrollment interview of those diagnosed between February 27 and December 31, 2020 who met the inclusion criteria. Outcomes were defined on an ordinal scale: (1) no need for escalation of care during follow-up; (2) need for urgent care visit; (3) hospitalization; and (4) admission to intensive care unit (ICU) or death. Missing data were multiply imputed using chained equations and the model was internally validated using bootstrapping techniques. Decision curve analysis was performed. Results The prognostic model was derived from 4756 SARS-CoV-2-positive persons. In total, 375 (7.9%) only required urgent care visits, 188 (4.0%) were hospitalized and 50 (1.1%) were either admitted to ICU or died due to complications of COVID-19. The model included age, sex, body mass index (BMI), current smoking, underlying conditions, and symptoms and clinical severity score at enrollment. On internal validation, the optimism-corrected Nagelkerke’s R 2 was 23.4% (95%CI, 22.7–24.2), the C-statistic was 0.793 (95%CI, 0.789-0.797) and the calibration slope was 0.97 (95%CI, 0.96–0.98). Outcome-specific indices were for urgent care visit or worse (calibration intercept -0.04 [95%CI, -0.06 to -0.02], E max 0.014 [95%CI, 0.008–0.020]), hospitalization or worse (calibration intercept -0.06 [95%CI, -0.12 to -0.03], E max 0.018 [95%CI, 0.010–0.027]), and ICU admission or death (calibration intercept -0.10 [95%CI, -0.15 to -0.04] and E max 0.027 [95%CI, 0.013–0.041]). Conclusion Our prognostic model can accurately predict the later need for urgent outpatient evaluation, hospitalization, and ICU admission and death among unvaccinated SARS-CoV-2-positive adults in the general population at the time of diagnosis, using information obtained by telephone interview.

Macrophomina phaseolina causes charcoal rot, which can significantly reduce yield and seed quality of soybean and dry bean resulting from primarily environmental stressors. Although charcoal rot has been recognized as a warm climate-driven disease of increasing concern under global climate change, knowledge regarding population genetics and climatic variables contributing to the genetic diversity of M. phaseolina is limited. This study conducted genome sequencing for 95 M. phaseolina isolates from soybean and dry bean across the continental United States, Puerto Rico, and Colombia. Inference on the population structure using 76,981 single nucleotide polymorphisms (SNPs) revealed that the isolates exhibited a discrete genetic clustering at the continental level and a continuous genetic differentiation regionally. A majority of isolates from the United States (96%) grouped in a clade with a predominantly clonal genetic structure, while 88% of Puerto Rican and Colombian isolates from dry bean were assigned to a separate clade with higher genetic diversity. A redundancy analysis (RDA) was used to estimate the contributions of climate and spatial structure to genomic variation (11,421 unlinked SNPs). Climate significantly contributed to genomic variation at a continental level with temperature seasonality explaining the most variation while precipitation of warmest quarter explaining the most when spatial structure was accounted for. The loci significantly associated with multivariate climate were found closely to the genes related to fungal stress responses, including transmembrane transport, glycoside hydrolase activity and a heat-shock protein, which may mediate climatic adaptation for M. phaseolina. On the contrary, limited genome-wide differentiation among populations by hosts was observed. These findings highlight the importance of population genetics and identify candidate genes of M. phaseolina that can be used to elucidate the molecular mechanisms that underly climatic adaptation to the changing climate.

BackgroundDiets rich in whole grains are associated with health benefits. Yet, it remains unclear whether the benefits are mediated by changes in gut function and fermentation.ObjectiveWe explored the effects of whole-grain vs. refined-grain diets on markers of colonic fermentation and bowel function, as well as their associations with the gut microbiome.MethodsFifty overweight individuals with increased metabolic risk and a high habitual intake of whole grains (~69 g/day) completed a randomised cross-over trial with two 8-week dietary intervention periods comprising a whole-grain diet (≥75 g/day) and a refined-grain diet (

Approximately 476,000 cases of Lyme disease are diagnosed in the United States annually, yet comprehensive economic evaluations are lacking. In a prospective study among reported cases in Lyme disease–endemic states, we estimated the total patient cost and total societal cost of the disease. In addition, we evaluated disease and demographic factors associated with total societal cost. Participants had a mean patient cost of ≈$1,200 (median $240) and a mean societal cost of ≈$2,000 (median $700). Patients with confirmed disseminated disease or probable disease had approximately double the societal cost of those with confirmed localized disease. The annual, aggregate cost of diagnosed Lyme disease could be $345–968 million (2016 US dollars) to US society. Our findings emphasize the importance of effective prevention and early diagnosis to reduce illness and associated costs. These results can be used in cost-effectiveness analyses of current and future prevention methods, such as a vaccine.

The characterization of cortical myelination is essential for the study of structure-function relationships in the human brain. However, knowledge about cortical myelination is largely based on post-mortem histology, which generally renders direct comparison to function impossible. The repeating pattern of pale-thin-pale-thick stripes of cytochrome oxidase (CO) activity in the primate secondary visual cortex (V2) is a prominent columnar system, in which histology also indicates different myelination of thin/thick versus pale stripes. We used quantitative magnetic resonance imaging (qMRI) in conjunction with functional magnetic resonance imaging (fMRI) at ultra-high field strength (7 T) to localize and study myelination of stripes in four human participants at sub-millimeter resolution in vivo. Thin and thick stripes were functionally localized by exploiting their sensitivity to color and binocular disparity, respectively. Resulting functional activation maps showed robust stripe patterns in V2 which enabled further comparison of quantitative relaxation parameters between stripe types. Thereby, we found lower longitudinal relaxation rates (R1) of thin and thick stripes compared to surrounding gray matter in the order of 1–2%, indicating higher myelination of pale stripes. No consistent differences were found for effective transverse relaxation rates (R2*). The study demonstrates the feasibility to investigate structure-function relationships in living humans within one cortical area at the level of columnar systems using qMRI.

Summary: Background: Continuous glucose monitoring (CGM) improves glycaemia for people affected by type 1 diabetes (T1D), but is not funded in Aotearoa/New Zealand. This study explores the impact of non-funded CGM on equity of access and associated glycaemic outcomes. Methods: Cross-sectional population-based study collected socio-demographic (age, gender, prioritised ethnicity, socioeconomic status) and clinical data from all regional diabetes centres in New Zealand with children

Oscillatory synchronization in the theta-frequency band was found to play a causal role in binding information of different modalities in declarative memory. Moreover, there is first evidence from a laboratory study that theta-synchronized (vs. asynchronized) multimodal input in a classical fear conditioning paradigm resulted in better discrimination of a threat-associated stimulus when compared to perceptually similar stimuli never associated with the aversive unconditioned stimulus (US). Effects manifested in affective ratings and ratings of contingency knowledge. However, theta-specificity was not addressed so far. Thus, in the present pre-registered web-based fear conditioning study, we compared synchronized (vs. asynchronized) input in a theta-frequency band vs. the same synchronization manipulation in a delta frequency. Based on our previous laboratory design, five visual gratings of different orientations (25°, 35°, 45°, 55°, 65°) served as conditioned stimuli (CS) with only one (CS+) paired with the auditory aversive US. Both CS and US were luminance or amplitude modulated, respectively, in a theta (4 Hz) or delta (1.7 Hz) frequency. In both frequencies, CS-US pairings were presented either in-phase (0° phase lag) or out-of-phase (90°, 180°, 270°), resulting in four independent groups (each group N = 40). Phase synchronization augmented the discrimination of CSs in CS-US contingency knowledge but did not affect valence and arousal ratings. Interestingly, this effect occurred independent of frequency. In sum, the current study proves the ability to successfully conduct complex generalization fear conditioning in an online setting. Based on this prerequisite, our data supports a causal role of phase synchronization in the declarative CS-US associations for low frequencies rather than in the specific theta-frequency band.

BackgroundProgress toward measles and rubella (MR) elimination has stagnated as countries are unable to reach the required 95% vaccine coverage. Microarray patches (MAPs) are anticipated to offer significant programmatic advantages to needle and syringe (N/S) presentation and increase MR vaccination coverage. A demand forecast analysis of the programmatic doses required (PDR) could accelerate MR-MAP development by informing the size and return of the investment required to manufacture MAPs.MethodsUnconstrained global MR-MAP demand for 2030–2040 was estimated for three scenarios, for groups of countries with similar characteristics (archetypes), and four types of uses of MR-MAPs (use cases). The base scenario 1 assumed that MR-MAPs would replace a share of MR doses delivered by N/S, and that MAPs can reach a proportion of previously unimmunised populations. Scenario 2 assumed that MR-MAPs would be piloted in selected countries in each region of the World Health Organization (WHO); and scenario 3 explored introduction of MR-MAPs earlier in countries with the lowest measles vaccine coverage and highest MR disease burden. We conducted sensitivity analyses to measure the impact of data uncertainty.ResultsFor the base scenario (1), the estimated global PDR for MR-MAPs was forecasted at 30 million doses in 2030 and increased to 220 million doses by 2040. Compared to scenario 1, scenario 2 resulted in an overall decrease in PDR of 18%, and scenario 3 resulted in a 21% increase in PDR between 2030 and 2040. Sensitivity analyses revealed that assumptions around the anticipated reach or coverage of MR-MAPs, particularly in the hard-to-reach and MOV populations, and the market penetration of MR-MAPs significantly impacted the estimated PDR.ConclusionsSignificant demand is expected for MR-MAPs between 2030 and 2040, however, efforts are required to address remaining data quality, uncertainties and gaps that underpin the assumptions in this analysis.

Abstract Whether females should prefer to mate with old males is controversial. Old males may sire offspring of low quality because of an aging germline, but their proven ability to reach an old age can also be an excellent indicator of superior genetic quality, especially in natural populations. These genetic effects are, however, hard to study in nature, because they are often confounded with direct benefits offered by old males to the female, such as experience and high territory quality. We, therefore, used naturally occurring extra‐pair young to disentangle different aspects of male age on female fitness in a natural population of collared flycatchers because any difference between within‐ and extra‐pair young within a nest should be caused by paternal genetic effects only. Based on 18 years of long‐term data, we found that females paired with older males as social partners experienced an overall reproductive advantage. However, offspring sired by old males were of lower quality as compared to their extra‐pair half‐siblings, whereas the opposite was found in nests attended by young males. These results imply a negative genetic effect of old paternal age, given that extra‐pair males are competitive middle‐age males. Thus, offspring may benefit from being sired by young males but raised by old males, to maximize both genetic and direct effects. Our results show that direct and genetic benefits from pairing with old males may act in opposing directions and that the quality of the germline may deteriorate before other signs of senescence become obvious.

IntroductionFluid overload in patients in the intensive care unit (ICU) is associated with higher mortality. There are few randomized controlled trials to guide physicians in treating patients with fluid overload in the ICU, and no guidelines exist. We aimed to elucidate how ICU physicians from Nordic countries define, assess, and treat fluid overload in the ICU.Materials and methodsWe developed an online questionnaire with 18 questions. The questions were pre-tested and revised by specialists in intensive care medicine. Through a network of national coordinators. The survey was distributed to a wide range of Nordic ICU physicians. The distribution started on January 5th, 2022 and ended on May 6th, 2022.ResultsWe received a total of 1,066 responses from Denmark, Norway, Finland, Sweden, and Iceland. When assessing fluid status, respondents applied clinical parameters such as clinical examination findings, cumulative fluid balance, body weight, and urine output more frequently than cardiac/lung ultrasound, radiological appearances, and cardiac output monitoring. A large proportion of the respondents agreed that a 5% increase or more in body weight from baseline supported the diagnosis of fluid overload. The preferred de-resuscitation strategy was diuretics (91%), followed by minimization of maintenance (76%) and resuscitation fluids (71%). The majority declared that despite mild hypotension, mild hypernatremia, and ongoing vasopressor, they would not withhold treatment of fluid overload and would continue diuretics. The respondents were divided when it came to treating fluid overload with loop diuretics in patients receiving noradrenaline. Around 1% would not administer noradrenaline and diuretics simultaneously and 35% did not have a fixed upper limit for the dosage. The remaining respondents 63% reported different upper limits of noradrenaline infusion (0.05–0.50 mcg/kg/min) when administering loop diuretics.ConclusionSelf-reported practices among Nordic ICU physicians when assessing, diagnosing, and treating fluid overload reveals variability in the practice. A 5% increase in body weight was considered a minimum to support the diagnosis of fluid overload. Clinical examination findings were preferred for assessing, diagnosing and treating fluid overload, and diuretics were the preferred treatment modality.

Quantifying the effect of public health actions on population health is essential when justifying sustained public health investment. Using modeling, we conservatively estimated that rapid response to a multistate foodborne outbreak of Salmonella Typhimurium in the United States in 2018 potentially averted 106 cases and $715,458 in medical costs and productivity losses.

Abstract Crustaceans are notoriously difficult to age because of their indeterminate growth and the moulting of their exoskeleton throughout life. The poor knowledge of population age structure in crustaceans therefore hampers accurate assessment of population dynamics and consequently sustainable fisheries management. Quantification of DNA methylation of the evolutionarily conserved ribosomal DNA (rDNA) may allow for age prediction across diverse species. However, the rDNA epigenetic clock remains to be tested in crustaceans, despite its potential to inform both ecological and evolutionary understanding, as well as conservation and management practices. Here, patterns of rDNA methylation with age were measured across 5154 bp of rDNA corresponding to 355 quality‐filtered loci in the economically important European lobster (Homarus gammarus). Across 0‐ to 51‐month‐old lobsters (n = 155), there was a significant linear relationship between age and percentage rDNA methylation in claw tissue at 60% of quality‐filtered loci (n = 214). An Elastic Net regression model using 46 loci allowed for the accurate and precise age estimation of individuals (R2 = 0.98; standard deviation = 1.6 months). Applying this ageing model to antennal DNA from wild lobsters of unknown age (n = 38) resulted in predicted ages that are concordant with estimates of minimum size at age in the wild (mean estimated age = 40.1 months; range 32.8–55.7 months). Overall, the rDNA epigenetic clock shows potential as a novel, nonlethal ageing technique for European lobsters. However, further validation is required across a wider range of known‐age individuals and tissue types before the model can be used in fisheries management.

For many polymers, recycling via mechanical processes is not feasible and these materials are destined for landfills or incineration. Here the authors show an open-loop recycling method for superabsorbent polymers that involves decrosslinking via hydrolysis, an optional chain-shortening step via sonication, and functionalizing via Fischer esterification.

Background: Enterobacter cloacae causes nosocomial infections in 15% of patients in low- and middle-income countries with emergence of carbapenem resistance. The utilisation of bacteriophages for therapeutic purposes is crucial for eradicating these resistant bacterial strains. Objective: This study evaluated the efficacy of lytic phages on bacterial isolates of E. cloacae and determined their stability in various physicochemical conditions. Methods: Twenty-nine lytic phages were isolated from the waste water of six informal settlements in Nairobi County, Kenya, from July 2019 to December 2020 and cross-reacted with 30 anonymised clinical isolates of E. cloacae. Six phages were then selected for physicochemical property studies. Phages were described as potent upon lysing any bacterial strain in the panel. Results: Selected phages were stable at 4 °C – 50 °C with a 5.1% decrease in titre in four of six phages and a 1.8% increase in titre in two of six phages at 50 °C. The phages were efficient following two weeks incubation at 4 °C with optimal activity at human body temperature (37 °C) and an optimal pH of 7.5. Phages were active at 0.002 M and 0.015 M concentrations of Ca2+ ions. The efficiency of all phages decreased with increased exposure to ultraviolet light. All phages (n = 29) showed cross-reactivity against anonymised clinical isolates of E. cloacae strains (n = 30). The most potent phage lysed 67.0% of bacterial strains; the least potent phage lysed 27.0%. Conclusion: This study reveals the existence of therapeutic phages in Kenya that are potent enough for treatment of multi-drug resistant E. cloacae.

The phylogenetic relationships among Tirmania were investigated using the internal transcribed spacer (ITS) and large subunit (LSU) regions of the nuclear-encoded ribosomal DNA (rDNA) and compared with morphological and bioclimatic data. The combined analyses of forty-one Tirmania samples from Algeria and Spain supported four lineages corresponding to four morphological species. Besides the two previously described taxa, Tirmania pinoyi and Tirmania nivea, here we describe and illustrate a new species, Tirmania sahariensis sp. nov., which differs from all other Tirmania by its distinct phylogenetic position and its specific combination of morphological features. We also present a first record of Tirmania honrubiae from North Africa (Algeria). Our findings suggest that restrictions imposed by the bioclimatic niche have played a key role in driving the speciation process of Tirmania along the Mediterranean and Middle East.

Abstract Dog vaccination is a cost-effective approach to preventing human rabies deaths. In Haiti, the last nation-wide dog vaccination campaign occurred in 2018. We estimated the number of human lives that could be saved by resuming dog vaccination in 2021 compared to 2022 and compared the cost-effectiveness of these two scenarios. We modified a previously published rabies transmission and economic model to estimate trends in dog and human rabies cases in Haiti from 2005 to 2025, with varying assumptions about when dog vaccinations resume. We compared model outputs to surveillance data on human rabies deaths from 2005 to 2020 and animal rabies cases from 2018 to 2020. Model predictions and surveillance data both suggest a 5- to 8-fold increase in animal rabies cases occurred in Haiti’s capital city between Fall 2019 and Fall 2020. Restarting dog vaccination in Haiti in 2021 compared to 2022 could save 285 human lives and prevent 6541 human rabies exposures over a five-year period. It may also decrease program costs due to reduced need for human post-exposure prophylaxis. These results show that interruptions in dog vaccination campaigns before elimination is achieved can lead to significant human rabies epidemics if not promptly resumed.

It is unclear why different antibiotics vary in their ability to shorten treatment of tuberculosis. Here, the authors show that a measure based on ribosomal RNA synthesis in Mycobacterium tuberculosis correlates with treatment shortening in culture, in mice and in human studies.

Abstract Background Transposable elements are significant components of most organism’s genomes, yet the reasons why their abundances vary significantly among species is poorly understood. A recent study has suggested that even in the absence of traditional molecular evolutionary explanations, transposon proliferation may occur through a process known as ‘transposon engineering’. However, their model used a fixed beneficial transposon insertion frequency of 20%, which we believe to be unrealistically high. Results Reducing this beneficial insertion frequency, while keeping all other parameters identical, prevented transposon proliferation. Conclusions We conclude that the author’s original findings are better explained through the action of positive selection rather than ‘transposon engineering’, with beneficial insertion effects remaining important during transposon proliferation events.

We first briefly summarize data from microelectrode studies on visual maps in non-human primates and other mammals, and characterize differences among the features of the approximately topological maps in the three main sensory modalities. We then explore the almost 50% of human neocortex that contains straightforward topological visual, auditory, and somatomotor maps by presenting a new parcellation as well as a movie atlas of cortical area maps on the FreeSurfer average surface, fsaverage. Third, we review data on moveable map phenomena as well as a recent study showing that cortical activity during sensorimotor actions may involve spatially locally coherent traveling wave and bump activity. Finally, by analogy with remapping phenomena and sensorimotor activity, we speculate briefly on the testable possibility that coherent localized spatial activity patterns might be able to ‘escape’ from topologically mapped cortex during ‘serial assembly of content’ operations such as scene and language comprehension, to form composite ‘molecular’ patterns that can move across some cortical areas and possibly return to topologically mapped cortex to generate motor output there.

The experiences of youth with high-risk glycaemic control using intermittently scanned continuous glucose monitoring (isCGM) systems are not well known. In the context of a randomised controlled trial investigating a 6-month isCGM intervention, this sub-study aimed to explore the experiences of youth using isCGM for 6 months. Semi-structured interviews were conducted with 14 youth aged 14–20 years who had Type 1 diabetes for ≥12 months and a glycated haemoglobin (HbA1c) of ≥75 mmol/mol (≥9%) pre-isCGM intervention. Interviews were recorded, transcribed and coded using Nvivo. A thematic analytic approach was used to identify key themes overall and by comparing participants who at 6 months had: (1) experienced a ≥10 mmol/L (0.9%) reduction in HbA1c and (2) sustained scanning frequency ≥3/day to those who did not. All participants expressed a strong preference for isCGM over self-monitoring blood glucose. Overall, isCGM contributed to perceived reduced diabetes burden without a requirement for more support in diabetes management. Increased engagement with self-management, including successful changes in dosage of basal or bolus insulin and increased frequency of administration of insulin, were behaviours reported by those experiencing the greatest improvement in HbA1c (>10 mmol/L [>0.9%], n = 6). They noted feeling more energetic, thus, making it easier to maintain self-management behaviours. Most youths reported best practices, such as following prompts to rescan in 10 min and timely sensor replacement; however, most did not check capillary blood glucose levels in recommended situations. Over 6 months, youth with high-risk diabetes experienced isCGM as a useful short-term tool for overcoming diabetes burden and facilitating self-management.

Abstract Whole‐genome duplication (WGD) events occur in all kingdoms and have been hypothesized to promote adaptability. WGDs identified in the early history of vertebrates, teleosts, and angiosperms have been linked to the large‐scale diversification of these lineages. However, the mechanics and full outcomes of WGD regarding potential evolutionary impacts remain a topic of debate. The Corydoradinae are a diverse subfamily of Neotropical catfishes with over 170 species described and a history of WGDs. They are divided into nine mtDNA lineages, with species coexisting in sympatric—and often mimetic—communities containing representatives of two or more of the nine lineages. Given their similar life histories, coexisting species of Corydoras might be exposed to similar parasite loads and because of their different histories of WGD and genome size they provide a powerful system for investigating the impacts of WGD on immune diversity and function in an animal system. Here, we compared parasite counts and the diversity of the immune‐related toll‐like receptors (TLR) in two coexisting species of Corydoras catfish (C. maculifer and C. araguaiaensis), one diploid and one putative tetraploid. In the putative tetraploid C. araguaiaensis, we found significantly lower numbers of parasites and significantly higher diversity (measured by both synonymous and nonsynonymous SNP counts) in two TLR genes than in the diploid C. maculifer. These results provide insight into how WGD may impact evolution, in this case by providing greater immunogenetic diversity.

Background. Liver transplantation (LT) has been employed for hepatic adenoma (HA) on a case-oriented basis. We aimed to describe the characteristics, waitlist, and post-LT outcomes of patients requiring LT for HA. Methods. All patients listed or transplanted for HA in the United States were identified in the United Network for Organ Sharing (UNOS) database (1987–2020). A systematic literature review was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-analysis statement. Results. A total of 199 HA patients were listed for LT in UNOS and the crude waitlist mortality was 9.0%. A total of 142 HA patients underwent LT; 118 of these were among those listed with an indication of HA who underwent LT, and 24 were diagnosed incidentally. Most did not experience hepatocellular carcinoma transformation (89.4%). Over a median follow-up of 62.9 mo, death was reported in 18.3%. The 1-, 3-, and 5-y patient survival rates were 94.2%, 89.7%, and 86.3% in the UNOS cohort. The systematic review yielded 61 articles reporting on 99 nonoverlapping patients undergoing LT for HA and 2 articles reporting on multicenter studies. The most common LT indications were suspected malignancy (39.7%), unresectable HA (31.7%), and increasing size (27.0%), whereas 53.1% had glycogen storage disease. Over a median follow-up of 36.5 mo, death was reported in 6.0% (n=5/84). The 1-, 3-, and 5-y patient survival rates were all 95.0% in the systematic review. Conclusions. LT for HA can lead to excellent long-term outcomes in well-selected patients. Prospective granular data are needed to develop more optimal selection criteria and further improve outcomes.

Binge drinking refers to a pattern of alcohol intake that raises blood alcohol concentration to or above legal intoxication levels. It is common among young adults and is associated with health risks that scale up with alcohol intake. Acute intoxication depresses neural activity via complex signaling mechanisms by enhancing inhibition mediated by gamma-amino butyric acid (GABA), and by decreasing excitatory glutamatergic effects. Evidence primarily rooted in animal research indicates that the brain compensates for the acute depressant effects under the conditions of habitual heavy use. These neuroadaptive changes are reflected in neural hyperexcitability via downregulated inhibitory signaling, which becomes apparent as withdrawal symptoms. However, human evidence on the compensatory reduction in GABA signaling is scant. The neurochemical aspect of this mechanistic model was evaluated in the present study with proton magnetic resonance spectroscopy (1H-MRS) which is sensitive to GABA plus macromolecule signal (GABA + ). Furthermore, we examined sex differences in GABA + levels as a function of a recent history of binge drinking, given interactions between endogenous neurosteroids, GABA signaling, and alcohol.The study recruited young adult women and men (22.2 ± 2.8 years of age) who were classified as binge drinkers (BDs, N = 52) if they reported ≥ 5 binge episodes in the previous six months. Light drinkers (LDs, N = 49) reported drinking regularly, but not exceeding ≤ 2 binge episodes in the past six months. GABA-edited 1H-MR spectra were acquired from the occipital cortex at 3 T with the MEGA-PRESS sequence. GABA + signal was analyzed relative to water and total creatine (Cr) levels as a function of binge drinking history and sex. Controlling for within-voxel tissue composition, both GABA + indices showed decreased GABA + levels in BDs relative to LDs. The reduced GABA + concentration was associated with occasional high-intensity drinking in the BD group.This evidence is consistent with compensatory GABA downregulation that accompanies alcohol misuse, tipping the excitation/inhibition balance towards hyperexcitability. Analysis of the time course of GABA + neuroplasticity indicated that GABA + was lowest when measured one day after the last drinking occasion in BDs. While the BD vs LD differences were primarily driven by LD women, there was no interaction between Sex and a history of binge drinking. GABA + was higher in LD women compared to LD men.Aligned with the allostasis model, the mechanistic compensatory GABA downregulation observed in young emerging adults engaging in occasional binge drinking complements direct neural measures of hyperexcitability in BDs. Notably, these results suggest that neuroadaptation to alcohol is detectable at the levels of consumption that are within a normative range, and may contribute to adverse health outcomes.

Targeted muscle reinnervation after upper-extremity amputation has demonstrated improved outcomes with myoelectric prosthesis function and postoperative neuropathic pain. This technique has been established in the setting of shoulder disarticulation as well as transhumeral and transradial amputations, but a detailed technique of targeted muscle reinnervation with free tissue transfer from the volar forearm after forequarter amputation has not yet been described. Here, we describe a technique using a volar forearm filet flap to achieve simultaneously satisfactory soft tissue coverage after resection of a tumor from the chest wall and targeted muscle reinnervation of the brachial plexus.