Major Risk Research Articles

Aberrant TSC-Rheb axis in Oxytocin receptor+ cells mediate stress-induced anxiety.

Stress is a major risk for the onset of several maladaptive processes including pathological anxiety, a diffuse state of heightened apprehension over anticipated threats 1 . Pathological anxiety is prevalent in up to 59% of patients with Tuberous Sclerosis complex (TSC) 2 , a neurodevelopmental disorder (NDD) caused by loss-of-function mutations in genes for Tuberin ( Tsc2 ) and/or Hamartin ( Tsc1 ) that together comprise the eponymous protein complex. Here, we generated cell type-specific heterozygous knockout of Tsc2 in cells expressing oxytocin receptor (OTRCs) to model pathological anxiety-like behaviors observed in TSC patient population. The stress of prolonged social isolation induces a sustained negative affective state that precipitates behavioral avoidance, often by aberrant oxytocin signaling in the limbic forebrain 3,4 . In response to social isolation, there were striking sex differences in stress susceptibility in conditional heterozygote mice when encountering situations of approach-avoidance conflict. Socially isolated male mutants exhibited behavioral avoidance in anxiogenic environments and sought more social interaction for buffering of stress. In contrast, female mutants developed resilience during social isolation and approached anxiogenic environments, while devaluing social interaction. Systemic and medial prefrontal cortex (mPFC)-specific inhibition of downstream effector of TSC, the integrated stress response (ISR), rescued behavioral approach toward anxiogenic environments and conspecifics in male and female mutant mice respectively. Further, we found that Tsc2 deletion in OTRCs leads to OTR-signaling elicited network suppression, i.e., hypofrontality, in male mPFC, which is relieved by inhibiting the ISR. Our findings present evidence in support of a sexually dimorphic role of prefrontal OTRCs in regulating emotional responses in anxiogenic environments, which goes awry in TSC. Our work has broader implications for developing effective treatments for subtypes of anxiety disorders that are characterized by cell-autonomous ISR and prefrontal network suppression.

Standardizing the diagnosis and treatment of ocular hypertension based on evidence-based medicine

Ocular hypertension (OHT) refers to a condition in which the intraocular pressure increases without causing glaucomatous optic nerve changes or visual field damage. The incidence rate of OHT in people over 40 years old is as high as 4% to 10%. According to the OHT Treatment Study (OHTS), the incidence of primary open angle glaucoma (POAG) among OHT patients is increasing year by year, so it is necessary to conduct long-term follow-up. This article elaborates on five major risk factors for the progression of OHT to POAG: age, intraocular pressure, vertical cup-disc ratio, pattern standard deviation of visual field, and central corneal thickness. It also summarizes other potential risk factors, such as long-term fluctuations in intraocular pressure, asymmetry of intraocular pressure and visual field between the two eyes, structural phenotypes of the optic disk, and optic disk hemorrhage. Predicting the risk of OHT progression to POAG based on risk factors, patients with different risk levels require different timing for treatment initiation and follow-up intervals. Those with higher risks should start preventive treatment earlier and have shorter follow-up intervals. Both drug therapy and selective laser trabeculoplasty can serve as initial treatment options for OHT. Combining evidence-based medicine research and individualized evaluation of treatment can enhance the clinical diagnosis and treatment level of OHT.

Differential Effect of Hyperglycemia on the Odds of Cancer Among the Adult Population of the United States.

Objective Accumulating evidence indicates a relationship between diabetes and cancer risk, with obesity, insulin resistance, and hyperglycemia being implicated as the major underlying pathogenetic mechanisms of increased cancer risk among people with diabetes. We aim to assess the differential effect of dysglycemia (prediabetes and diabetes) on the strength of association (odds) of cancer amongst the adult US diabetic population. Material and methods We analyzed data from the 1997-2013 National Health Interview Survey (NHIS) dataset, which applies a multistage area probability sampling design. We used descriptive statistics and logistic regression analyses to test the strengths of the association between diabetes, prediabetes, and cancer before and after adjusting for major risk factors for cancer, including age and body mass index (BMI). Results A total of 722,532 individuals were surveyed, with a mean age of 47.18 ±0.3 years (±SEM) and a BMI of 26.9 ±0.01 kg/m2. Between 1997 and 2013, BMI increased from 26.0 to 27.4 kg/m2, the diabetes rate increased from 4.1% to 7.6%, and associated cancer rates increased from 6.6% to 9.0%. Body mass index was 27.1 vs. 26.8 kg/m2, P < 0.01, for those with and without cancer, respectively. The unadjusted odds ratio for cancer was 1.92 (1.78-2.08) (95% CI) and 2.20 (2.13-2.27) for prediabetes and diabetes, respectively. After adjusting for age, BMI, race, and cigarette smoking, the odds ratio for cancer was 1.12 (1.03-1.22), P < 0.01, and 1.15 (1.11-1.18), P <0.01, for prediabetes and diabetes, respectively. Conclusion Among US adults, the increasing rate of diabetes over the years was associated with an increased rate of cancer. Diabetes and prediabetes have a graduated effect on cancer risk. While obesity is generally implicated as an underlying pathophysiologic link between diabetes and cancer, our study showed a modest difference in BMI between those with and without cancer. In addition, the effect of diabetes and prediabetes on the odds of cancer persisted after adjusting for BMI. These data collectively suggest that hyperglycemia is an attractive pathophysiologic mechanism that may play a role in increasing the odds of cancer among diabetic and prediabetic populations. Our study is consistent with the accumulating evidence implicating hyperglycemia in the pathogenesis of cancer, where glucose is used in PET scanning to detect cancer (the Warburg effect), and the ketogenic diet appears to be useful in cancer management, enhancing the effect of chemotherapeutic agents.

Prevalence of Gastroesophageal Reflux Disease and Its Impact on the Quality of Life Among Obese Individuals in Al-Baha Region, Saudi Arabia.

Background Gastroesophageal reflux disease (GERD) is a global gastrointestinal disorder, and obesity is a particular risk factor. Symptoms of GERD, such as heartburn and acid reflux, are caused by abnormal relaxation in the lower esophagus, causing gastric acid reflux. Persistent symptoms can affect the patient's quality of life (QOL) and can cause complications, such as esophageal adenocarcinoma. Management of GERD includes lifestyle changes, antacids, and anti-reflux surgery. Even though GERD is a common disease, few research has been carried out on it in Saudi Arabia. Aim This study aimed to estimate the prevalence of GERD and its associated risk factors among obese individuals in the Al-Baha region population and the effect of GERD on their QOL. Methods A cross-sectional study included 314 obese participants from the Al-Baha region. A questionnaire was filled out to measure the prevalence of GERD, risk factors, and effects on the QOL of the participants. Data were analyzed by the IBM SPSS Statistics for Windows, version 26.0 (released 2019, IBM Corp., Armonk, NY). Descriptive statistics and the chi-squared test were applied. Logistic regression analysis was used to determine the factors associated with the incidence of GERD. A p-value of <0.05 was considered statistically significant. Results A total of 314 patients who met our inclusion criteria completed the survey; 42% of them were women, the mean age of all patients was 35.3 ± 12.9 years, and 38.2% of the patients were diagnosed with GERD. Epigastric pain and burning sensation were the most common symptoms (44.9%). Five out of six domains in the QOL questionnaire showed more effects among GERD participants than non-GERD participants, and the results were statistically significant (p = 0.001). Logistic regression analysis showed that men are 1.8 times more likely than women to be diagnosed with GERD, and smokers have 2.6 times the risk of being diagnosed with GERD than non-smokers. Conclusion The present study showed a high prevalence of GERD among obese patients in the Al-Baha region, negatively affecting their QOL. Major risk factors included gender, smoking, dyslipidemia, and hypertension. Public health programs to raise awareness of these risk factors and lifestyle habits are necessary to improve QOL and prevent complications.

IMPACT OF DIFFERENT ORGANIC AND INORGANIC AMENDMENTS ON GROWTH AND YIELD OF MUNG BEAN IRRIGATED WITH TEXTILE EFFLUENTS

Water is an important substance for all life on earth, and it is essential for human beings, financial improvement, and the existence of ecological units. The quality and quantity of the water supply is very important, especially during irrigation. Due to the extensive measurement of water and colour associated with the manufacturing process, textile printing, and dyeing production lines around the world pose a major environmental risk. Textile wastewater contains a lot of pollutants including pH, temperature, shade, COD, BOD, TSS, TDS, EC, and heavy metals. This textile runoff continues to irrigate agricultural land, causing contamination of soils and plant systems with heavy metals. Therefore, adding organic and inorganic modifiers to soil is an effective technique for fixing heavy metals. Irrigate pots with textile wastewater of selected concentrations (10%, 25%, 50%, and 100%) collected in specific industrial sectors. The parameters of vegetative growth are reduced by increasing the concentration of textile effluent. Note the substantial reduction in the growth of plants applying wastewater at 100% concentration. In the case of T5, a significant increase in growth parameters was observed, where only tap water was used to pressurize the sludge, while dilute wastewater also enhanced growth at concentrations of 10% and 25%. For the chlorophyll content of mung bean plants, when the wastewater concentration is 100%, the recorded decrease is greater, followed by 10% and 25% respectively. The presence of heavy metals in wastewater reduces plant growth. In the experiment, all four treatments contained organic amendments (pressed sludge, poultry manure, biogas slurry, and farmyard manure). The other four treatment methods are pressure treatment of textile wastewater and the amount of organic modifier is 2%. By adding a correcting agent, the utilization rate of Cr is reduced, as the correcting agent will increase the pH of the soil, thus reducing the solubility of the metal. In addition, Cr can form insoluble complexes with organic materials, thus reducing its solubility.

Mitigating Social Isolation Following the COVID-19 Pandemic: Remedy Messages Shared by Older People

At the beginning of July 2022, when public health restrictions were lifted, we deployed a country-wide e-survey about how older people were managing now after COVID-19 pandemic-related anxiety. Our responder sample was stratified by age, sex, and education to approximate the Canadian population. E-survey responders were asked to share open-text messages about what contemporaries could do to live less socially isolated lives at this tenuous turning point following the pandemic as the COVID-19 virus still lingered. Contracting COVID-19 enhanced older Canadians’ risk for being hospitalized and/or mortality risk. Messages were shared by 1189 of our 1327 e-survey responders. Content analysis revealed the following four calls to action: (1) cultivating community; (2) making room for what is good; (3) not letting your guard down; and (4) voicing out challenges. Responders with no chronic illnesses were more likely to endorse making room for what is good. Those with no diploma, degree, or certificate least frequently instructed others to not let their guard down. While COVID-19 is no longer a major public health risk, a worrisome proportion of older people across the globe are still living socially isolated. We encourage health and social care practitioners and older people to share messages identified in this study with more isolated persons.

Knowledge of cardiovascular diseases and associated risk factors in the general adult population of Jeddah, Saudi Arabia: A cross-sectional study examining gender disparities.

To assess knowledge about cardiovascular diseases (CVD) among the general population, we emphasized gender-related disparities and other lifestyle and health-related factors. This cross-sectional study was conducted among 395 individuals from the general population of Jeddah, Saudi Arabia. An online questionnaire was administered to assess knowledge of CVD types, symptoms, and risk factors. The majority of participants identified coronary heart disease (73.7%) as having CVD, with no sex effect. Males had higher knowledge regarding cerebrovascular disease (44% vs 31.5%) and congenital heart diseases (60% vs 51.9%) as being part of CVD, while they had lower knowledge of peripheral arterial disease (44% vs 50.7%) than females, respectively (P < .05). Males exhibited better knowledge of heart attack and stroke symptoms than females. Knowledge was optimal for major CVD risk factors, such as smoking (90.6%) and high low-density lipoprotein cholesterol levels (85.1%); however, gaps were observed in recognizing diabetes (56.2%) and stress (69.4%) as factors for CVD. The mean overall knowledge score was 16.33 ± 5.72 25, with no difference between sexes (P = .239). Predictors of good CVD knowledge included university-level education, daily healthy food consumption, and perceived life as highly stressful; nonetheless, sex showed no significant effect. While the general population displayed a suboptimal understanding of CVD, notable sex disparities were observed, highlighting the need for tailored public health interventions. Emphasizing cognitive and behavioral aspects can foster better prevention and management strategies, given the evident gender disparities.

Mucormycosis in Diabetes

Abstract Fungal infections are a major health challenge especially in immunocompromised patients. Mucormycosis, a severe, frequently fatal fungal infection, has a unique predisposition to infect patients with diabetes. The infection is caused by organisms belonging to the order Mucorales, among which Rhizopus species are the most common. Uncontrolled diabetes complicated by diabetic ketoacidosis is one of the major risk factors for upsurge in mucormycosis cases. The defense mechanisms, involving macrophages and neutrophils for phagocytosis, are compromised in diabetes. In 2 cases of rhino-orbital-cerebral mucormycosis with underlying diabetes, we observed a marked immune imbalance, with elevated Th17 and diminished T regulatory cells. Recovery of CD4+CD25+ T cells after treatment indicated a favorable phenotype outcome; though high circulating CD4+CD161+ can be detrimental to the patient predisposing to future relapse(s). Mucorale specific T cells contributing to human immune responses against the fungi can be investigated to identify a surrogate diagnostic marker of invasive mucormycosis.

Mass spectrometry-based proteomic profiling of extracellular vesicle proteins in diabetic and non-diabetic ischemic stroke patients: a case-control study

Mass spectrometry-based proteomic profiling of extracellular vesicle proteins in diabetic and non-diabetic ischemic stroke patients: a case-control study

Modern Management of Pregnancy in Systemic Lupus Erythematosus: From Prenatal Counseling to Postpartum Support.

Systemic lupus erythematosus (SLE) is a chronic autoimmune disease that predominantly affects women of childbearing age. Pregnancy in SLE patients poses unique challenges due to the potential impact on maternal and fetal outcomes. We provide an overview of the management of SLE during pregnancy, including preconception risk stratification and counseling, treatment, and disease activity monitoring. These assessments are critical to minimize maternal and fetal adverse events in pregnant patients with SLE. Disease flares, preeclampsia, antiphospholipid syndrome complications, and maternal mortality are the major risks for a woman with SLE during gestation. Timely treatment of SLE relapse, differentiation of preeclampsia from lupus nephritis, and tailored management for antiphospholipid syndrome are essential for a successful pregnancy. Fetal outcomes include neonatal lupus (NL), preterm birth, cesarean delivery, fetal growth restriction (FGR), and small-for-gestational-age (SGA) infants. We focused on NL, linked to maternal anti-Ro/SS-A and anti-La/SS-B antibodies, which can lead to various manifestations, particularly cardiac abnormalities, in newborns. While there is a common consensus regarding the preventive effect of hydroxychloroquine, the role of echocardiographic monitoring and fluorinated steroid treatment is still debated. Finally, close postpartum monitoring and counseling for subsequent pregnancies are crucial aspects of care.

Major Failures and Key Risks Linked to Dental Fixed Prostheses: An in vivo Clinical Study

This clinical investigation aimed to identify factors leading to fixed partial denture failures and their implications, crucial for enhancing clinical outcomes. Conducted in Tripoli, Libya, with 75 patients contributing 235 units, the study utilized John F. Johnston's and John J. Manappallil’s classifications to categorize failure causes. Mechanical issues, predominantly in female patients, were identified as the primary cause of dental bridge failure, particularly in porcelain fused to metal (PFM) bridges with a "Fixed-Fixed" design, mostly in the upper jaw. The study underscores the importance of a multifactorial approach in preventing and managing fixed partial denture failures, emphasizing meticulous prosthesis design, manufacturing, and placement, alongside patient selection, diagnosis, treatment planning, and oral hygiene education.

Illuminating health aspects for immigrant Thai women in Swedish transnational marriages

BackgroundWomen who are migrants experience discrimination and face major risks, including sexual exploitation, trafficking, and violence, which affect their health and well-being.This study explored critical health incidents experienced by immigrant Thai women in marriage migration.MethodsA qualitative explorative approach with in-depth interviews was used. Forty immigrant Thai women who currently or previously had a Swedish spouse were recruited for the study. An inductive critical incident technique was used to collect and analyze the data as the first step. In a second deductive step, the Newman system model was used to categorize health dilemmas.ResultsThe women reported 438 critical health incidents in five main areas. Psychological health dilemmas included emotional abuse, feeling overwhelmed due to family responsibilities and the stress of leaving family behind. Sociocultural health dilemmas included transnational family duties or not performing family duties. Physiological health dilemmas included experiencing physical violence and environmental, domestic or work accidents. Developmental health dilemmas included failing health, difficulties upholding the duties expected of a spouse in the target culture and caring for an elderly husband. Spiritual health dilemmas included critical incidents in which the women perceived themselves to have failed in their hopes and duties as a wife, which intensified their dependence on faith, particularly the Buddhist concept of karma.ConclusionProfessionals in health and welfare practices in Thailand together with professionals in Western countries who work with women in marriage migration situations need to recognize the psychological, sociocultural, physiological, developmental, and spiritual health dilemmas experienced by these women. Furthermore, civil organizations that meet Thai women in foreign countries, such as Buddhist cultural associations, would benefit from the multicultural knowledge revealed by the present study. This knowledge can facilitate healthcare and welfare support for women in marriage migration situations.

Hypertension in Patients With Peripheral Artery Disease: An Updated Literature Review.

Peripheral artery disease (PAD), a condition where there is reduced blood flowdue to narrowing or blockage of the arteries of the peripheral vasculature, is an epidemic that currently affects eight million people in the United States alone and is a major risk equivalent to having active coronary artery disease (CAD). However, it is commonly underdiagnosed in the general population. Hypertension is a common cardiovascular condition characterized by elevated blood pressure levels. There are several mitigating risk factors that can reduce the risk of complications of PAD, with hypertension playing a major role. This literature review aims to explore the relationship between hypertension and PAD, including their shared risk factors, pathophysiological mechanisms, and management strategies. In addition, we will analyze how this impacts major cardiovascular outcomes, such as critical limb ischemia, vascular amputation, myocardial infarction (MI), ischemic stroke, and cardiovascular-related death by examining relevant studies, current guidelines, and evidence. This literature review is intended to guide practitioners on ideal blood pressure parameters and evidence-based anti-hypertensives that provide overall cardiovascular benefit in both the primary care and hospital-based setting. By understanding the association between hypertension and PAD and the underlying pathophysiological mechanisms, healthcare professionals can improve diagnosis, treatment, and management strategies for affected individuals.

Left ventricular structure and function following renal sympathetic denervation in patients with HFpEF: an echocardiographic 9-year long-term follow-up.

High blood pressure is a major risk factor for cardiac remodeling and left ventricular hypertrophy, increasing cardiovascular risk and leading to heart failure with preserved ejection fraction (HFpEF). Since renal sympathetic denervation (RDN) reduces blood pressure in the long term, we aimed to investigate the long-term effect of RDN in patients with HFpEF in the present analysis. Patients previously enrolled in a local RDN registry who underwent high-frequency RDN with the use of the Symplicity Flex® renal denervation system between 2011 and 2014 were followed up. The patients were assessed by 24-h ambulatory blood pressure measurement, transthoracic echocardiography, and laboratory tests. We used the echocardiographic and biomarker criteria of the Heart Failure Association (HFA)-PEFF (Pre-test assessment, Echocardiography and Natriuretic Peptide Score, Funkctional testing, and Final aetiology) score to identify patients with HFpEF. Echocardiographic assessment was available for 70 patients at a 9-year long-term follow-up. Of these patients, 21 had HFpEF according to the HFA-PEFF score. We found a significant reduction of the HFA-PEFF score from 5.48 ± 0.51 points at baseline to 4.33 ± 1.53 points at the 9-year follow-up (P < 0.01). This decrease was due to a greater reduction in morphological and biomarker subcategories [from 1.95 ± 0.22 to 1.43 ± 0.51 points (P < 0.01) and from 1.52 ± 0.52 to 0.90 ± 0.63 points (P < 0.01), respectively] than in the functional one. Morphologically, there was a reduction in left ventricular hypertrophy and left atrial dilation. The present analysis suggests that RDN may lead to a regression of the extent of HFpEF beyond a reduction in blood pressure and thus possibly contribute to an improvement in prognosis. More detailed information will be provided by ongoing randomized sham-controlled trials.

A Systematic Review and Meta-Analysis on the Prevalence of Mild Cognitive Impairment and Dementia in Mexico.

Age remains one of the major risk factors for the onset of mild cognitive impairment (MCI) and dementia. Studies on the prevalence of these conditions in Mexico used different methods, tools, and populations with different health statuses. All these heterogeneous results may be a problem in identifying the true prevalence of MCI and dementia in Mexico. To our knowledge, there is not a systematic review available that presents essential figures on the prevalence of these conditions in Mexico. Therefore, we intend to access the maximum number of reports published on the topic and determine the prevalence of MCI and dementia in older Mexican adults. A systematic review using PubMed, Cochrane, Research Gate, Lilacs, and Scielo databases was performed. Meta-analysis of the prevalence of MCI and dementia was performed using a random-effects model and presented in a forest plot among cross-sectional, epidemiological, and pooled studies. Sixteen articles were included. The overall prevalence of MCI of 18% (95% CI 0.10-0.27) was estimated from pooled information from 12 selected studies, in women 21% (95% CI 0.08-0.38) and in men 18% (95% CI 0.06-0.33). The overall prevalence of dementia of 10% (95% CI 0.06-0.14) was estimated from pooled information from 9 selected studies, in women 14% (95% CI 0.05-0.25) and in men 10% (95% CI 0.04-0.17). Mexican older individuals have a similar prevalence of dementia and MCI as reported by international data; nevertheless, the prevalence is higher than in some Latin American countries. Mexico has particular issues that must be resolved, such as a lack of research in the southern regions of the country and the high incidence of comorbidities.

Descriptive Epidemiology of Female Suicides by Race and Ethnicity

AbstractEach year millions of females develop serious mental illnesses (SMI), which are major risk factors for suicides. Using the Web-Based Injury Statistics Query and Reporting System (WISQARS) for the years 2000, 2010 and 2020, we found in 2020 9,428 females (almost 190/week) committed suicide, losing 328,653 years off potential life before age 80 years. There were pronounced increases in female suicides from 2000 to 2020 across all racial and ethnic groups. The greatest number of suicides were in non-Hispanic white females, but the highest rate of suicides was in non-Hispanic American Indians /Alaska Natives, and in females 15–24 years of age. The West had the highest female suicide rates, with methods used to commit suicides varying by census regions and race and ethnicity. Suffocation to commit suicide increased for most racial and ethnic groups and poisonings decreased for most groups between 2000 and 2020, These underscore the need for targeted primary prevention of suicides for females based on age, geographic location and method of suicide, to mitigate female suicides improved access (e.g. geographically and financially) to mental health care services is essential.

Early detection of dementia with default-mode network effective connectivity

Altered functional connectivity precedes structural brain changes and symptoms in dementia. Alzheimer’s disease is the largest contributor to dementia at the population level, and disrupts functional connectivity in the brain’s default-mode network (DMN). We investigated whether a neurobiological model of DMN effective connectivity could predict a future dementia diagnosis at the single-participant level. We applied spectral dynamic causal modeling to resting-state functional magnetic resonance imaging data in a nested case–control group from the UK Biobank, including 81 undiagnosed individuals who developed dementia up to nine years after imaging, and 1,030 matched controls. Dysconnectivity predicted both future dementia incidence (AUC = 0.82) and time to diagnosis (R = 0.53), outperforming models based on brain structure and functional connectivity. We also evaluated associations between DMN dysconnectivity and major risk factors for dementia, revealing strong relationships with polygenic risk for Alzheimer’s disease and social isolation. Neurobiological models of effective connectivity may facilitate early detection of dementia at population level, supporting rational deployment of targeted dementia-prevention strategies.

Incidence and outcomes of cytomegalovirus reactivation after chimeric antigen receptor T-cell therapy

AbstractCytomegalovirus (CMV) reactivation is a major complication among seropositive allogeneic hematopoietic cell transplantation recipients; however, data on CMV reactivation after chimeric antigen receptor (CAR) T-cell therapy are limited. We report the incidence and outcomes of 95 adult CMV-seropositive patients who received CAR T-cell therapy between February 2018 and February 2023. CMV outcomes were CMV reactivation (any viremia) and clinically significant CMV infection (cs-CMV). Thirty-one patients (33%) had evidence of CMV reactivation (any viremia) and 10 patients (11%) had cs-CMV. The median time from CAR T-cell infusion to CMV reactivation was 19 days (interquartile range [IQR], 9-31). The cumulative incidence of CMV (any viremia) was significantly higher among patients with grade 3 to 4 cytokine release syndrome (67 vs 28%; P = .01), and those who received corticosteroids (39 vs 21%; P = .03), anakinra (56 vs 28%; P = .02), or ≥2 immunosuppressants (41 vs 21%; P = .02). Receipt of corticosteroids (18 vs 0%; P = .004), tocilizumab (14 vs 0%; P = .04), anakinra (33 vs 7%; P = .008), and ≥2 immunosuppressants (20 vs 0%; P = .001) were all associated with cs-CMV. Receiving ≥2 immunosuppressants was associated with a twofold increase in CMV reactivation in multivariate analyses (adjusted odds ratio [aOR], 2.27; 95% confidence interval, 1.1-4.8; P = .03). Overall, the 1-year mortality was significantly higher in those with CMV reactivation (57% vs 23%; P = .001). Immunosuppression, particularly with corticosteroids, for the management of CAR T-cell toxicities, is a major risk factor for CMV reactivation.

Validation and screening of patulin in apple beverages marketed in Morocco

Patulin is one of the mycotoxins frequently detected in apples and derivatives, representing a major food safety risk. This study aimed to validate a high-performance liquid chromatography (HPLC) method with an ultraviolet (UV) detector for patulin quantification and assess its occurrence in apple beverages marketed in Morocco. The validation parameters showed satisfactory results with adequate linearity (R > 0.997), a relative standard deviation below 2.5%, repeatability between 3.6 and 7.1%, reproducibility between 3.9 and 11.5%, a limit of quantification (LOQ) of 4 μg/L, and recoveries close to 100% for three levels. Analysis of 30 samples revealed patulin levels ranging from 0 to 16.36 μg/L, with 50% of samples showing negative levels. All positive results remained below the regulatory maximum limit of 50 μg/L. These findings affirm the efficacy of the HPLC proposed method in ensuring compliance with patulin regulations in apple beverages, underlining its importance in safeguarding food safety.

Navigating the Maze of Kinases: CaMK-like Family Protein Kinases and Their Role in Atherosclerosis.

Circulating low-density lipoprotein (LDL) levels are a major risk factor for cardiovascular diseases (CVD), and even though current treatment strategies focusing on lowering lipid levels are effective, CVD remains the primary cause of death worldwide. Atherosclerosis is the major cause of CVD and is a chronic inflammatory condition in which various cell types and protein kinases play a crucial role. However, the underlying mechanisms of atherosclerosis are not entirely understood yet. Notably, protein kinases are highly druggable targets and represent, therefore, a novel way to target atherosclerosis. In this review, the potential role of the calcium/calmodulin-dependent protein kinase-like (CaMKL) family and its role in atherosclerosis will be discussed. This family consists of 12 subfamilies, among which are the well-described and conserved liver kinase B1 (LKB1) and 5' adenosine monophosphate-activated protein kinase (AMPK) subfamilies. Interestingly, LKB1 plays a key role and is considered a master kinase within the CaMKL family. It has been shown that LKB1 signaling leads to atheroprotective effects, while, for example, members of the microtubule affinity-regulating kinase (MARK) subfamily have been described to aggravate atherosclerosis development. These observations highlight the importance of studying kinases and their signaling pathways in atherosclerosis, bringing us a step closer to unraveling the underlying mechanisms of atherosclerosis.