Nutritional analysis and characterization of carbapenemase producing-<i>Klebsiella pneumoniae</i> resistant genes associated with bovine mastitis infected cow’s milk

by Mr. Saddam, Muddasir Khan, Muhsin Jamal, Sadeeq Ur Rahman, Abdul Qadeer, Imad Khan, Mohamed H. Mahmoud, Gaber El-Saber Batiha, Syed Hussain Shah

The current study was designed to analyze nutritional parameters and to characterize carbapenemase producing-Klebsiella pneumoniae isolates from bovine mastitic cow’s milk. Out of 700 milk samples K. pneumoniae was identified by phenotypic and molecular techniques along with their antibiogram analysis and nutritional analysis was performed using the procedure of Association of Official Analytical Chemists. Carbapenemase-producing K. pneumoniae was detected by phenotypic CarbaNP test followed by molecular characterization of their associated resistant genes bla_VIM, bla_KPC, bla_OXA-48, bla_NDM, and bla_IMP along with insertion sequence common region 1 (ISCR1) and integrons (Int1, Int2, and Int3) genes. Among nutritional parameters, fat content was observed (2.99%) followed by protein (2.78%), lactose (4.32%), and total solid (11.34%), respectively. The prevalence of K. pneumoniae among bovine mastitis was found 25.71%. Antibiogram analysis revealed that more effective antibiotics was ceftazidime (80%) followed by amikacin (72%), while highly resistant antibiotics was Fusidic acid (100%). Distribution of carbapenemase producer K. pneumoniae was found 44.4%. Among carbapenem resistant genes bla_KPC was found 11.25%, bla_VIM 2.75%, bla_NDM 17.5%, and bla_OXA-48 7.5%, while bla_IMP gene was not detected. Furthermore, distribution of ISCR1 was found 40%, while integron 1 was found 61.2% followed by integron 2 (20%), and integron 3 (5%). In conclusion, the recent scenario of carbapenemase resistant K. pneumoniae isolates responsible for mastitis may affect not only the current treatment regime but also possess a serious threat to public health due to its food borne transmission and zoonotic potential.

The BREAK study protocol: Effects of intermittent energy restriction on adaptive thermogenesis during weight loss and its maintenance

by Filipa M. Cortez, Catarina L. Nunes, Luís B. Sardinha, Analiza M. Silva, Vítor H. Teixeira

Background

Adaptive thermogenesis, defined as the decrease in the energy expenditure components beyond what can be predicted by changes in body mass stores, has been studied as a possible barrier to weight loss and weight maintenance. Intermittent energy restriction (IER), using energy balance refeeds, has been pointed out as a viable strategy to reduce adaptive thermogenesis and improve weight loss efficiency (greater weight loss per unit of energy deficit), as an alternative to a continuous energy restriction (CER). Following a randomized clinical trial design, the BREAK Study aims to compare the effects of IER versus CER on body composition and in adaptive thermogenesis, and understand whether participants will successfully maintain their weight loss after 12 months.

Methods

Seventy-four women with obesity and inactive (20–45 y) will be randomized to 16 weeks of CER or IER (8x2 weeks of energy restriction interspersed with 7x1 week in energy balance). Both groups will start with 2 weeks in energy balance before energy restriction, followed by 16 weeks in energy restriction, then 8 weeks in energy balance and finally a 12-month weight maintenance phase. Primary outcomes are changes in fat-mass and adaptive thermogenesis after weight loss and weight maintenance. Secondary outcomes include weight loss, fat-free mass preservation, alterations in energy expenditure components, and changes in hormones (thyroid function, insulin, leptin, and cortisol).

Discussion

We anticipate that The BREAK Study will allow us to better understand adaptive thermogenesis during weight loss and weight maintenance, in women with obesity. These findings will enable evidence-based decisions for obesity treatment.

Trial registration

ClinicalTrials.gov: NCT05184361.

Investigating the role of the relaxin-3/RXFP3 system in neuropsychiatric disorders and metabolic phenotypes: A candidate gene approach

by Win Lee Edwin Wong, Ryan Arathimos, Cathryn M. Lewis, Allan H. Young, Gavin S. Dawe

The relaxin-3/RXFP3 system has been implicated in the modulation of depressive- and anxiety-like behaviour in the animal literature; however, there is a lack of human studies investigating this signalling system. We seek to bridge this gap by leveraging the large UK Biobank study to retrospectively assess genetic risk variants linked with this neuropeptidergic system. Specifically, we conducted a candidate gene study in the UK Biobank to test for potential associations between a set of functional, candidate single nucleotide polymorphisms (SNPs) pertinent to relaxin-3 signalling, determined using in silico tools, and several outcomes, including depression, atypical depression, anxiety and metabolic syndrome. For each outcome, we used several rigorously defined phenotypes, culminating in subsample sizes ranging from 85,881 to 386,769 participants. Across all outcomes, there were no associations between any candidate SNP and any outcome phenotype, following corrections for multiple testing burden. Regression models comprising several SNPs per relevant candidate gene as exploratory variables further exhibited no prediction of outcome. Our findings corroborate conclusions from previous literature about the limitations of candidate gene approaches, even when based on firm biological hypotheses, in the domain of genetic research for neuropsychiatric disorders.

Consecutive treatments of methamphetamine promote the development of cardiac pathological symptoms in zebrafish

by Jimmy Zhang, Anh H. Nguyen, Daniel Jilani, Ramses Seferino Trigo Torres, Lauren Schmiess-Heine, Tai Le, Xing Xia, Hung Cao

Chronic methamphetamine use, a widespread drug epidemic, has been associated with cardiac morphological and electrical remodeling, leading to the development of numerous cardiovascular diseases. While methamphetamine has been documented to induce arrhythmia, most results originate from clinical trials from users who experienced different durations of methamphetamine abuse, providing no documentation on the use of methamphetamine in standardized settings. Additionally, the underlying molecular mechanism on how methamphetamine affects the cardiovascular system remains elusive. A relationship was sought between cardiotoxicity and arrhythmia with associated methamphetamine abuse in zebrafish to identify and to understand the adverse cardiac symptoms associated with methamphetamine. Zebrafish were first treated with methamphetamine 3 times a week over a 2-week duration. Immediately after treatment, zebrafish underwent electrocardiogram (ECG) measurement using an in-house developed acquisition system for electrophysiological analysis. Subsequent analyses of cAMP expression and Ca²⁺ regulation in zebrafish cardiomyocytes were conducted. cAMP is vital to development of myocardial fibrosis and arrhythmia, prominent symptoms in the development of cardiovascular diseases. Ca²⁺ dysregulation is also a factor in inducing arrhythmias. During the first week of treatment, zebrafish that were administered with methamphetamine displayed a decrease in heart rate, which persisted throughout the second week and remained significantly lower than the heart rate of untreated fish. Results also indicate an increased heart rate variability during the early stage of treatment followed by a decrease in the late stage for methamphetamine-treated fish over the duration of the experiment, suggesting a biphasic response to methamphetamine exposure. Methamphetamine-treated fish also exhibited reduced QTc intervals throughout the experiment. Results from the cAMP and Ca²⁺ assays demonstrate that cAMP was upregulated and Ca²⁺ was dysregulated in response to methamphetamine treatment. Collagenic assays indicated significant fibrotic response to methamphetamine treatment. These results provide potential insight into the role of methamphetamine in the development of fibrosis and arrhythmia due to downstream effectors of cAMP.

Access to therapy for child sexual abuse survivors: Preliminary dialogue of barriers and facilitators between caregivers

by Jonathan Jin, Huda Al-Shamali, Lorraine Smith-MacDonald, Matthew Reeson, Wanda Polzin, Yifeng Wei, Hannah Pazderka, Peter H. Silverstone, Andrew J. Greenshaw

Background

Difficulties in access to therapy were highlighted by COVID-19 measures restricting in-person gatherings. Additional challenges arise when focusing on caregivers of child sexual abuse (CSA) survivors in particular, which are a population that has been historically difficult to engage with due to issues of stigma and confidentiality.

Objectives

To present preliminary qualitative results from caregivers of CSA survivors.

Methods

This study was conducted with caregivers of CSA survivors. Two hybrid webinar/focus groups were conducted using a video conferencing platform in fall of 2021 with two groups of stakeholders (11 caregivers and 5 moderators/clinical staff at Little Warriors, an intensive episodic treatment facility). Sessions were recorded, transcribed, and thematically-analyzed using standard qualitative methodology.

Results

A total of 11 caregivers contributed to the data. Themes include: (1) Challenges of starting and maintaining treatment (i.e., emotional impact of intake day, challenges of enrolling), (2) Therapeutic benefits of specialized treatment (i.e., feeling safe and supported and the importance of trauma-informed care), and (3) Barriers and facilitators of treatment (i.e., avenues to scale-up and self-care).

Conclusion

The importance of a strong therapeutic alliance was highlighted by both caregivers/clinical staff and further support is needed for families post-treatment. The present hybrid webinar/focus group also achieved engagement goals in a population that is typically difficult to reach. Overall, the response rate (12%) was equivalent to reported registrant attendance rates for general business to consumer webinars and the recommended focus group size. This preliminary approach warrants replication in other populations outside our clinical context.

Intravenous acetaminophen for postoperative pain in the neonatal intensive care unit: A protocol for a pilot randomized controlled trial (IVA POP)

by Victoria Anne Archer, Samira Samiee-Zafarghandy, Forough Farrokyhar, Daniel Briatico, Luis H. Braga, J. Mark Walton

Background

In neonates, uncontrolled pain and opioid exposure are both correlated with short- and long-term adverse events. Therefore, managing pain using opioid-sparing approaches is critical in neonatal populations. Multimodal pain control offers the opportunity to manage pain while reducing short- and long-term opioid-related adverse events. Intravenous (IV) acetaminophen may represent an appropriate adjunct to opioid-based postoperative pain control regimes. However, no trials assess this drug in patients less than 36 weeks post-conceptual age or weighing less than 1500 g.

Objective

The proposed study aims to determine the feasibility of conducting a randomized control trial to compare IV acetaminophen and fentanyl to a saline placebo and fentanyl for patients admitted to the neonatal intensive care unit (NICU) undergoing major abdominal or thoracic surgery.

Methods and design

This protocol is for a single-centre, external pilot randomized controlled trial (RCT). Infants in the NICU who have undergone major thoracic or abdominal surgery will be enrolled. Sixty participants will undergo 1:1 randomization to receive intravenous acetaminophen and fentanyl or saline placebo and fentanyl. After surgery, IV acetaminophen or placebo will be given routinely for eight days (192 hours). Appropriate dosing will be determined based on the participant’s gestational age. Patients will be followed for eight days after surgery and will undergo a chart review at 90 days. Primarily feasibility outcomes include recruitment rate, follow-up rate, compliance, and blinding index. Secondary clinical outcomes will be collected as well.

Conclusion

This external pilot RCT will assess the feasibility of performing a multicenter RCT comparing IV acetaminophen and fentanyl to a saline placebo and fentanyl in NICU patients following major abdominal and thoracic surgery. The results will inform the design of a multicenter RCT, which will have the appropriate power to determine the efficacy of this treatment.

Trial registration

ClinicalTrials.gov NCT05678244, Registered December 6, 2022.

Assessing the impact of a comprehensive mental health program on frontline health service workers

by Emily J. Ward, Maren S. Fragala, Charles E. Birse, Matt Hawrilenko, Casey Smolka, Geetu Ambwani, Millard Brown, John H. Krystal, Philip R. Corlett, Adam Chekroud

Mental health issues are a growing concern in the workplace, linked to negative outcomes including reduced productivity, increased absenteeism, and increased turnover. Employer-sponsored mental health benefits that are accessible and proactive may help address these concerns. The aim of this retrospective cohort study was to evaluate the impact of a digital mental health benefit (Spring Health) on frontline healthcare service workers’ clinical and workplace outcomes. The benefit was sponsored by a national health services company from 2021–2022 and included mental health screening, care navigation, psychotherapy and/or medication management. We hypothesized program use would be associated with improvements in depression and anxiety symptoms, and increased productivity and retention. Participants were employees enrolled in the benefit program, had at least moderate anxiety or depression, at least 1 treatment appointment, and at least 2 outcome assessments. Clinical improvement measures were PHQ-9 scale (range, 0–27) for depression and GAD-7 scale (range, 0–21) for anxiety; workplace measures were employee retention and the Sheehan Disability Scale (SDS) for functional impairment. A total of 686 participants were included. Participants using the mental health benefit had a 5.60 point (95% CI, 4.40–6.79, d = 1.28) reduction in depression and a 5.48 point (95% CI, 3.88–7.08, d = 1.64) reduction in anxiety across 6 months. 69.9% (95% CI, 61.8%–78.1%) of participants reliably improved (≥5 point change) and 84.1% (95% CI, 78.2%–90.1%) achieved reliable improvement or recovery (

Cumulative violence exposures among men who have sex with men living with HIV in India: Psychosocial correlates of HIV care continuum outcomes

by Bushra Sabri, Chakra Budhathoki, Allison M. McFall, Shruti H. Mehta, David D. Celentano, Sunil S. Solomon, Aylur K. Srikrishnan, Santhanam Anand, Canjeevaram K. Vasudevan, Gregory M. Lucas

Lifetime exposures to violence among men who have sex with men (MSM) are associated with multiple psychosocial health risks and can affect engagement and outcomes of HIV treatment. This study a) explored relationships between levels of exposures to violence and HIV care continuum outcomes among MSM living with HIV in India, and b) identified psychosocial correlates of HIV care continuum outcomes among MSM living with HIV and those with lifetime cumulative exposures to violence (CVE). CVE referred to exposures to violence in both childhood and adulthood. This cross-sectional analysis used survey data collected between August 2016 and May 2017 from 1763 men who have sex with men living with HIV across 10 cities in India, using respondent-driven sampling. We found that higher levels of violence exposure were significantly associated with lower awareness of HIV positive status, and lower likelihood of initiating antiretroviral therapy. Compared with MSM living with HIV that had no CVE, those with CVE were more likely to report perpetration of interpersonal violence, alcohol misuse, depressive symptoms, and HIV transmission risk behaviors and to have two to four co-occurring psychosocial problems. In multivariable analysis with the subset of MSM with CVE, psychosocial correlates significantly associated with at least one HIV care continuum outcome were HIV transmission risk behaviors, perpetration of interpersonal violence, depression, and alcohol misuse. The findings highlight the need for integrating care for lifetime violence exposures and associated behavioral problems in HIV care settings for men who have sex with men living with HIV in India.

A medium-chain fatty acid analogue prevents hepatosteatosis and decreases inflammatory lipid metabolites in a murine model of parenteral nutrition-induced hepatosteatosis

by Bennet S. Cho, Scott C. Fligor, Gillian L. Fell, Jordan D. Secor, Savas T. Tsikis, Amy Pan, Lumeng J. Yu, Victoria H. Ko, Duy T. Dao, Lorenzo Anez-Bustillos, Thomas I. Hirsch, Jenny Lund, Arild C. Rustan, David A. Fraser, Kathleen M. Gura, Mark Puder

Background

Parenteral (intravenous) nutrition is lifesaving for patients with intestinal failure, but long-term use of parenteral nutrition often leads to liver disease. SEFA-6179 is a synthetic medium-chain fatty acid analogue designed to target multiple fatty acid receptors regulating metabolic and inflammatory pathways. We hypothesized that SEFA-6179 would prevent hepatosteatosis and lipotoxicity in a murine model of parenteral nutrition-induced hepatosteatosis.

Methods

Two in vivo experiments were conducted. In the first experiment, six-week-old male mice were provided an ad lib fat-free high carbohydrate diet (HCD) for 19 days with orogastric gavage of either fish oil, medium-chain triglycerides, or SEFA-6179 at a low (0.3mmol/kg) or high dose (0.6mmol/kg). In the second experiment, six-week-old mice were provided an ad lib fat-free high carbohydrate diet for 19 days with every other day tail vein injection of saline, soybean oil lipid emulsion, or fish oil lipid emulsion. Mice then received every other day orogastric gavage of medium-chain triglyceride vehicle or SEFA-6179 (0.6mmol/kg). Hepatosteatosis was assessed by a blinded pathologist using an established rodent steatosis score. Hepatic lipid metabolites were assessed using ultra-high-performance liquid chromatography-mass spectrometry. Effects of SEFA-6179 on fatty acid oxidation, lipogenesis, and fatty acid uptake in human liver cells were assessed in vitro.

Results

In the first experiment, mice receiving the HCD with either saline or medium-chain triglyceride treatment developed macrovesicular steatosis, while mice receiving fish oil or SEFA-6179 retained normal liver histology. In the second experiment, mice receiving a high carbohydrate diet with intravenous saline or soybean oil lipid emulsion, along with medium chain triglyceride vehicle treatment, developed macrovescular steatosis. Treatment with SEFA-6179 prevented steatosis. In each experiment, SEFA-6179 treatment decreased arachidonic acid metabolites as well as key molecules (diacylglycerol, ceramides) involved in lipotoxicity. SEFA-6179 increased both β- and complete fatty oxidation in human liver cells, while having no impact on lipogenesis or fatty acid uptake.

Conclusions

SEFA-6179 treatment prevented hepatosteatosis and decreased toxic lipid metabolites in a murine model of parenteral nutrition-induced hepatosteatosis. An increase in both β- and complete hepatic fatty acid oxidation may underlie the reduction in steatosis.

Association between lignan polyphenol bioavailability and enterotypes of isoflavone metabolism: A cross-sectional analysis

by Tomoko Fujitani, Mariko Harada Sassa, Zhaoqing Lyu, Yukiko Fujii, Kouji H. Harada

Lignan polyphenols derived from plants are metabolized by bacteria in the gut to mammalian lignans, such as enterolactone (ENL) and enterodiol (END). Mammalian lignan intake has been reported to be associated with obesity and low blood glucose levels. However, the factors that are responsible for individual differences in the metabolic capacity for ENL and END are not well understood. In the present study, the effects of enterotypes of isoflavone metabolism, equol producers (EQP) and O-desmethylangolensin producers (O-DMAP), on lignan metabolism were examined. EQP was defined by urinary daidzein (DAI) and equol concentrations as log(equol/DAI) ≥ –1.42. O-DMAP was defined by urinary DAI and O-DMA concentrations as O-DMA/DAI > 0.018. Isoflavone and lignan concentrations in urine samples from 440 Japanese women were measured by gas chromatography-mass spectrometry. Metabolic enterotypes were determined from the urinary equol and O-DMA concentrations. Urinary END and ENL concentrations were compared in four groups, combinations of EQP (+/–) and O-DMAP (+/–). The urinary lignan concentration was significantly higher in the O-DMAP/EQP group (ENL: P

Characterising the gut microbiome of stranded harbour seals (<i>Phoca vitulina</i>) in rehabilitation

by Ana Rubio-Garcia, Aldert L. Zomer, Ruoshui Guo, John W. A. Rossen, Jan H. van Zeijl, Jaap A. Wagenaar, Roosmarijn E. C. Luiken

Animal rehabilitation centres provide a unique opportunity to study the microbiome of wild animals because subjects will be handled for their treatment and can therefore be sampled longitudinally. However, rehabilitation may have unintended consequences on the animals’ microbiome because of a less varied and suboptimal diet, possible medical treatment and exposure to a different environment and human handlers. Our study describes the gut microbiome of two large seal cohorts, 50 pups (0–30 days old at arrival) and 23 weaners (more than 60 days old at arrival) of stranded harbour seals admitted for rehabilitation at the Sealcentre Pieterburen in the Netherlands, and the effect of rehabilitation on it. Faecal samples were collected from all seals at arrival, two times during rehabilitation and before release. Only seals that did not receive antimicrobial treatment were included in the study. The average time in rehabilitation was 95 days for the pups and 63 days for the weaners. We observed that during rehabilitation, there was an increase in the relative abundance of some of the Campylobacterota spp and Actinobacteriota spp. The alpha diversity of the pups’ microbiome increased significantly during their rehabilitation (p-value

Temporal trends of hemoglobin among pregnant women: The Mutaba’ah study

by Aminu S. Abdullahi, Abubaker Suliman, Moien AB Khan, Howaida Khair, Saad Ghazal-Aswad, Iffat Elbarazi, Fatima Al-Maskari, Tom Loney, Rami H. Al-Rifai, Luai A. Ahmed

Background

Low hemoglobin (Hb) level is a leading cause of many adverse pregnancy outcomes. Patterns of changes in Hb levels during pregnancy are not well understood.

Aim

This study estimated Hb levels, described its changing patterns across gestational trimesters, and identified factors associated with these changes among pregnant women.

Materials and methods

Data from the ongoing maternal and child health cohort study–The Mutaba’ah Study, was used (N = 1,120). KML machine learning algorithm was applied to identify three distinct cluster trajectories of Hb levels between the first and the third trimesters. Descriptive statistics were used to profile the study participants. Multinomial multivariable logistic regression was employed to identify factors associated with change patterns in Hb levels.

Results

The three identified clusters–A, B and C–had, respectively, median Hb levels (g/L) of 123, 118, and 104 in the first trimester and 119, 100, and 108 in the third trimester. Cluster ’A’ maintained average normal Hb levels in both trimesters. Cluster ’B’, on average, experienced a decrease in Hb levels below the normal range during the third trimester. Cluster ’C’ showed increased Hb levels in the third trimester but remained, on average, below the normal range in both trimesters. Pregnant women with higher gravida, diabetes mellitus (type 1 or 2), nulliparity or lower level of education were more likely to be in cluster ’B’ than the normal cluster ’A’. Pregnant women who reported using iron supplements before pregnancy or those with low levels of education. were more likely to be in cluster ’C’ than the normal cluster ’A’.

Conclusion

The majority of pregnant women experienced low Hb levels during pregnancy. Changes in Hb levels during pregnancy were associated with parity, gravida, use of iron before pregnancy, and the presence of diabetes mellitus (type 1 or 2).

Rapid detection of <i>Mycobacterium tuberculosis</i> using recombinase polymerase amplification: A pilot study

by Michael Sciaudone, Renzo Carpena, Maritza Calderón, Patricia Sheen, Mirko Zimic, Jorge Coronel, Robert H. Gilman, Natalie M. Bowman

Tuberculosis remains one of the leading causes of death worldwide, especially in low- and middle-income countries. Tuberculosis treatment and control efforts are hindered by the difficulty in making the diagnosis, as currently available diagnostic tests are too slow, too expensive, or not sufficiently sensitive. Recombinase polymerase amplification (RPA) is a novel technique that allows for the amplification of DNA rapidly, at constant temperature, and with minimal expense. We calculated and compared the limit of detection, sensitivity, and specificity of two RPA-based assays for the diagnosis of pulmonary tuberculosis, using two sets of published primers. We also calculated and compared the assays’ limits of detection and compared their performance using two different DNA extraction methods prior to amplification (a commercially available DNA extraction kit vs. the chelex method). The RPA-lateral flow assay had a limit of detection of 5 fg/μL of DNA, a sensitivity of 53.2%, and a specificity of 93.3%, while the real time-RPA assay had a limit of detection of 25 fg/μL of DNA, a sensitivity of 85.1%, and a specificity of 93.3%. There was no difference in assay performance when DNA extraction was carried out using the commercial kit vs. the chelex method. The real-time RPA assay has adequate sensitivity and specificity for the diagnosis of pulmonary tuberculosis and could be a viable diagnostic tool in resource-limited settings, but the lateral flow assay did not perform as well, perhaps due to the fact we used stored sputum specimens from a biorepository. More work is needed to optimize the RPA-lateral flow assay, to get a more accurate estimate of its specificity and sensitivity using prospectively collected specimens, and to develop both assays into point-of-care tests that can be easily deployed in the field.

Investigating automated regression models for estimating left ventricular ejection fraction levels in heart failure patients using circadian ECG features

by Sona M. Al Younis, Leontios J. Hadjileontiadis, Aamna M. Al Shehhi, Cesare Stefanini, Mohanad Alkhodari, Stergios Soulaidopoulos, Petros Arsenos, Ioannis Doundoulakis, Konstantinos A. Gatzoulis, Konstantinos Tsioufis, Ahsan H. Khandoker

Heart Failure (HF) significantly impacts approximately 26 million people worldwide, causing disruptions in the normal functioning of their hearts. The estimation of left ventricular ejection fraction (LVEF) plays a crucial role in the diagnosis, risk stratification, treatment selection, and monitoring of heart failure. However, achieving a definitive assessment is challenging, necessitating the use of echocardiography. Electrocardiogram (ECG) is a relatively simple, quick to obtain, provides continuous monitoring of patient’s cardiac rhythm, and cost-effective procedure compared to echocardiography. In this study, we compare several regression models (support vector machine (SVM), extreme gradient boosting (XGBOOST), gaussian process regression (GPR) and decision tree) for the estimation of LVEF for three groups of HF patients at hourly intervals using 24-hour ECG recordings. Data from 303 HF patients with preserved, mid-range, or reduced LVEF were obtained from a multicentre cohort (American and Greek). ECG extracted features were used to train the different regression models in one-hour intervals. To enhance the best possible LVEF level estimations, hyperparameters tuning in nested loop approach was implemented (the outer loop divides the data into training and testing sets, while the inner loop further divides the training set into smaller sets for cross-validation). LVEF levels were best estimated using rational quadratic GPR and fine decision tree regression models with an average root mean square error (RMSE) of 3.83% and 3.42%, and correlation coefficients of 0.92 (p

Epidemiology and clinical manifestations of reported Lyme disease cases: Data from the Canadian Lyme disease enhanced surveillance system

by Kiera Murison, Christy H. Wilson, Katie M. Clow, Salima Gasmi, Todd F. Hatchette, Annie-Claude Bourgeois, Gerald A. Evans, Jules K. Koffi

Lyme disease cases reported in seven Canadian provinces from 2009 to 2019 through the Lyme Disease Enhanced Surveillance System are described herein by demographic, geography, time and season. The proportion of males was greater than females. Bimodal peaks in incidence were observed in children and older adults (≥60 years of age) for all clinical signs except cardiac manifestations, which were more evenly distributed across age groups. Proportions of disease stages varied between provinces: Atlantic provinces reported mainly early Lyme disease, while Ontario reported equal proportions of early and late-stage Lyme disease. Early Lyme disease cases were mainly reported between May through November, whereas late Lyme disease were reported in December through April. Increased awareness over time may have contributed to a decrease in the proportion of cases reporting late disseminated Lyme disease. These analyses help better describe clinical features of reported Lyme disease cases in Canada.

Normalization in mouse primary visual cortex

by Zaina A. Zayyad, John H. R. Maunsell, Jason N. MacLean

When multiple stimuli appear together in the receptive field of a visual cortical neuron, the response is typically close to the average of that neuron’s response to each individual stimulus. The departure from a linear sum of each individual response is referred to as normalization. In mammals, normalization has been best characterized in the visual cortex of macaques and cats. Here we study visually evoked normalization in the visual cortex of awake mice using imaging of calcium indicators in large populations of layer 2/3 (L2/3) V1 excitatory neurons and electrophysiological recordings across layers in V1. Regardless of recording method, mouse visual cortical neurons exhibit normalization to varying degrees. The distributions of normalization strength are similar to those described in cats and macaques, albeit slightly weaker on average.

How predictive of SARS-CoV-2 infection are clinical characteristics at presentation among individuals with COVID-like symptoms treated at the Mexican Institute of Social Security

by Juan Pablo Gutierrez, Gustavo Olaiz, Arturo Juárez-Flores, Víctor H. Borja-Aburto, Iván J. Ascencio-Montiel, Stefano M. Bertozzi

Background

The COVID-19 pandemic has progressed rapidly, with the emergence of new virus variants that pose challenges in treating infected individuals. In Mexico, four epidemic waves have been recorded with varying disease severity. To understand the heterogeneity in clinical presentation over time and the sensitivity and specificity of signs and symptoms in identifying COVID-19 cases, an analysis of the changes in the clinical presentation of the disease was conducted.

Aim

To analyze the changes in the clinical presentation of COVID-19 among 3.38 million individuals tested for SARS-CoV-2 at the Mexican Social Security Institute (IMSS) from March 2020 to October 2021 and evaluate the predictivity of signs and symptoms in identifying COVID-19 cases.

Methods

A retrospective analysis of clinical presentation patterns of COVID-19 among individuals treated at IMSS was performed, contrasting the signs and symptoms among SARS-CoV-2-positive individuals with those who tested negative for the virus but had respiratory infection symptoms. The sensitivity and specificity of each sign and symptom in identifying SARS-CoV-2 infection were estimated.

Results

The set of signs and symptoms reported for COVID-19-suspected patients treated at IMSS were not highly specific for SARS-CoV-2 positivity. The signs and symptoms exhibited variability based on age and epidemic wave. The area under the receiver operating characteristic (ROC) curve was 0.62 when grouping the five main symptoms (headache, dyspnea, fever, arthralgia, and cough). Most of the individual symptoms had ROC values close to 0.5 (16 out of 22 between 0.48 and 0.52), indicating non-specificity.

Conclusions

The results highlight the difficulty in making a clinical diagnosis of COVID-19 due to the lack of specificity of signs and symptoms. The variability of clinical presentation over time and among age groups highlights the need for further research to differentiate whether the changes are due to changes in the virus, who is becoming infected, or the population, particularly with respect to prior infection and vaccination status.

Detection of CTLA-4 level and humeral immune response after the second dose of COVID-19 vaccine in certain Iraqi provinces participants

by Laith A. I. K. Al-Kaif, Hussain Al-Ameri, Wael Rasheed Obaead Alfatlawi, Ammar Eesa Mahdi, Younis A. K. Al-Khafaji, Mohammad Abd-Kadhum Al-Saadi, Alaa H. Al-Charrakh, Raheem T. Al-Mammori, Mohammed Ahmed Akkaif

Background

Evaluating immune responses following COVID-19 vaccination is paramount to understanding vaccine effectiveness and optimizing public health interventions. This study seeks to elucidate individuals’ immune status after administering a second dose of diverse COVID-19 vaccines. By analyzing immune responses through serological markers, we aim to contribute valuable insights into the uniformity of vaccine performance.

Methods

A total of 80 participants were enrolled in this study, with demographic and COVID-19 infection-related data collected for categorization. Serum samples were acquired within a specified timeframe, and SARS-CoV-2 IgM/IgG rapid tests were conducted. Moreover, CTLA-4 levels were measured through ELISA assays, allowing us to assess the immune responses comprehensively. The participants were divided into eight groups based on various factors, facilitating a multifaceted analysis.

Results

The outcomes of our investigation demonstrated consistent immune responses across the diverse types of COVID-19 vaccines administered in Iraq. Statistical analysis revealed no significant distinctions among the vaccine categories. In contrast, significant differences were observed in CTLA-4 among the control group (non-infected/non-vaccinated, infected/non-vaccinated) and infected/Pfizer, non-infected/Pfizer, and infected/Sinopharm, non-infected/sinopharm (P = 0.001, Conclusions

In conclusion, our study’s results underscore the lack of discriminatory variations between different COVID-19 vaccine types utilized in Iraq. The uniform immune responses observed signify the equitable efficacy and performance of these vaccines. Despite minor quantitative discrepancies, these variations do not hold statistical significance, reaffirming the notion that the various vaccines serve a similar purpose in conferring protection against COVID-19.

Morphological and ultrastructural investigation of the posterior atlanto-occipital membrane: Comparing children with Chiari malformation type I and controls

by Vijay M. Ravindra, Lorraina Robinson, Hailey Jensen, Elena Kurudza, Evan Joyce, Allison Ludwick, Russell Telford, Osama Youssef, Justin Ryan, Robert J. Bollo, Rajiv R. Iyer, John R. W. Kestle, Samuel H. Cheshier, Daniel S. Ikeda, Qinwen Mao, Douglas L. Brockmeyer

Introduction

The fibrous posterior atlanto-occipital membrane (PAOM) at the craniocervical junction is typically removed during decompression surgery for Chiari malformation type I (CM-I); however, its importance and ultrastructural architecture have not been investigated in children. We hypothesized that there are structural differences in the PAOM of patients with CM-I and those without.

Methods

In this prospective study, blinded pathological analysis was performed on PAOM specimens from children who had surgery for CM-I and children who had surgery for posterior fossa tumors (controls). Clinical and radiographic data were collected. Statistical analysis included comparisons between the CM-I and control cohorts and correlations with imaging measures.

Results

A total of 35 children (mean age at surgery 10.7 years; 94.3% white) with viable specimens for evaluation were enrolled: 24 with CM-I and 11 controls. There were no statistical demographic differences between the two cohorts. Four children had a family history of CM-I and five had a syndromic condition. The cohorts had similar measurements of tonsillar descent, syringomyelia, basion to C2, and condylar-to-C2 vertical axis (all p>0.05). The clival-axial angle was lower in patients with CM-I (138.1 vs. 149.3 degrees, p = 0.016). Morphologically, the PAOM demonstrated statistically higher proportions of disorganized architecture in patients with CM-I (75.0% vs. 36.4%, p = 0.012). There were no differences in PAOM fat, elastin, or collagen percentages overall and no differences in imaging or ultrastructural findings between male and female patients. Posterior fossa volume was lower in children with CM-I (163,234 mm³ vs. 218,305 mm³, p Conclusions

In patients with CM-I, the PAOM demonstrates disorganized architecture compared with that of control patients. This likely represents an anatomic adaptation in the presence of CM-I rather than a pathologic contribution.

Application of in-silico drug discovery techniques to discover a novel hit for target-specific inhibition of SARS-CoV-2 Mpro’s revealed allosteric binding with MAO-B receptor: A theoretical study to find a cure for post-covid neurological disorder

by Magdi E. A. Zaki, Sami A. AL-Hussain, Aamal A. Al-Mutairi, Abdul Samad, Vijay H. Masand, Rahul G. Ingle, Vivek Digamber Rathod, Nikita Maruti Gaikwad, Summya Rashid, Pravin N. Khatale, Pramod V. Burakale, Rahul D. Jawarkar

Several studies have revealed that SARS-CoV-2 damages brain function and produces significant neurological disability. The SARS-CoV-2 coronavirus, which causes COVID-19, may infect the heart, kidneys, and brain. Recent research suggests that monoamine oxidase B (MAO-B) may be involved in metabolomics variations in delirium-prone individuals and severe SARS-CoV-2 infection. In light of this situation, we have employed a variety of computational to develop suitable QSAR model using PyDescriptor and genetic algorithm-multilinear regression (GA-MLR) models (R² = 0.800–793, Q²_LOO = 0.734–0.727, and so on) on the data set of 106 molecules whose anti-SARS-CoV-2 activity was empirically determined. QSAR models generated follow OECD standards and are predictive. QSAR model descriptors were also observed in x-ray-resolved structures. After developing a QSAR model, we did a QSAR-based virtual screening on an in-house database of 200 compounds and found a potential hit molecule. The new hit’s docking score (-8.208 kcal/mol) and _PIC₅₀ (7.85 M) demonstrated a significant affinity for SARS-CoV-2’s main protease. Based on post-covid neurodegenerative episodes in Alzheimer’s and Parkinson’s-like disorders and MAO-B’s role in neurodegeneration, the initially disclosed hit for the SARS-CoV-2 main protease was repurposed against the MAO-B receptor using receptor-based molecular docking, which yielded a docking score of -12.0 kcal/mol. This shows that the compound that inhibits SARS-CoV-2’s primary protease may bind allosterically to the MAO-B receptor. We then did molecular dynamic simulations and MMGBSA tests to confirm molecular docking analyses and quantify binding free energy. The drug-receptor complex was stable during the 150-ns MD simulation. The first computational effort to show in-silico inhibition of SARS-CoV-2 Mpro and allosteric interaction of novel inhibitors with MAO-B in post-covid neurodegenerative symptoms and other disorders. The current study seeks a novel compound that inhibits SAR’s COV-2 Mpro and perhaps binds MAO-B allosterically. Thus, this study will enable scientists design a new SARS-CoV-2 Mpro that inhibits the MAO-B receptor to treat post-covid neurological illness.