Smartphone-Related Neck Pain: A Study Among Saudi Residents in the Eastern Province.

BACKGROUND: The pervasive use of mobile phones has raised concerns about their impact on musculoskeletal health, particularly neck pain. This issue is notably relevant in the Eastern Province of Saudi Arabia, where high mobile phone usage intersects with demographic diversity. While extensive phone use has been linked to neck pain and other musculoskeletal disorders globally, specific data on this issue in the Eastern Province are limited. This study addresses this gap by examining phone use patterns, neck positions, and associated symptoms in the region. METHODS: Using an online, self-administered survey, this cross-sectional study investigated the relationship between phone use and neck pain in the Eastern Province of Saudi Arabia. Participants aged 18 years and older were recruited via social media, community groups, and university networks. The survey collected data on demographics, phone use patterns, neck positions, awareness of health risks, and pain symptoms. It was pre-tested, administered through Google Forms (Google, Mountain View, CA), and available for four weeks. Data were analyzed using descriptive statistics and cross-tabulations with SPSS 26.0 (IBM Corp., Armonk, NY). RESULTS: The study included 400 participants, with 273 females (68.3%) and 127 males (31.8%). Most participants were single (245, 61.3%) and held a university degree (301, 75.3%). Daily phone use varied: 228 participants (57.0%) used their phones for less than five hours daily, while 43 (10.8%) used them for 10-15 hours or more. Neck positions ranged from 0° to 60°, with 168 participants (42.0%) maintaining a 30° angle. Awareness of health risks associated with phone use was high, with 364 participants (91.0%) aware of these risks. Neck pain was reported by 244 participants (61.0%), with additional symptoms including headache (22 participants, 5.5%) and upper back pain (five participants, 1.3%). CONCLUSION: This study found a significant link between prolonged phone use and neck pain in the Eastern Province of Saudi Arabia. Despite high awareness of the risks, many individuals report discomfort. These findings underscore the need for public health interventions and ergonomic education to improve phone use practices and musculoskeletal health.

Artificial Intelligence-Enhanced Electrocardiography Identifies Patients With Normal Ejection Fraction at Risk of Worse Outcomes.

Background: An artificial intelligence (AI)-based electrocardiogram (ECG) model identifies patients with a higher likelihood of low ejection fraction (EF). Patients with an abnormal AI-ECG score but normal EF (false positives; FP) more often developed future low EF. Objective: The purpose of this study was to evaluate echocardiographic characteristics and all-cause mortality risk in FP patients. Methods: Patients with transthoracic echocardiography and ECG were classified retrospectively into FP, true negatives (TN) (EF ≥50%, normal AI-ECG), true positives (TP) (EF <50%, abnormal AI-ECG), or false negatives (FN) (EF <50%, normal AI-ECG). Echocardiographic abnormalities included systolic and diastolic left ventricular function, valve disease, estimated pulmonary pressures, and right heart parameters. Cox regression was used to assess factors associated with all-cause mortality. Results: Of 100,586 patients (median age 63 years; 45.5% females), 79% were TN, 7% FP, 5% FN, and 8% TP. FPs had more echocardiographic abnormalities than TN but less than FN or TP patients. An echocardiographic abnormality was present in 97% of FPs. Over median 2.7 years, FPs had increased mortality risk (age and sex-adjusted HR: 1.64 [95% CI: 1.55-1.73]) vs TN. Age and sex-adjusted mortality was higher in FP with abnormal echocardiography than FP with normal echocardiography and to TN regardless of echocardiography result; FP with normal echocardiography had comparable mortality risk to TN with abnormal echocardiography. Conclusions: FP patients were more likely than TNs to have echocardiographic abnormalities with 97% of exams showing an abnormality. FP patients had higher mortality rates, especially when their echocardiograms also had an abnormality; the concomitant use of AI ECG and echocardiography helps in stratifying risk in patients with normal LVEF.

Loss-of-function in testis-specific serine/threonine protein kinase triggers male infertility in an invasive moth.

Genetic biocontrol technologies present promising and eco-friendly strategies for the management of pest and insect-transmitted diseases. Although considerable advancements achieve in gene drive applications targeting mosquitoes, endeavors to combat agricultural pests have been somewhat restricted. Here, we identify that the testis-specific serine/threonine kinases (TSSKs) family is uniquely expressed in the testes of Cydia pomonella, a prominent global invasive species. We further generated male moths with disrupted the expression of TSSKs and those with TSSKs disrupted using RNA interference and CRISPR/Cas9 genetic editing techniques, resulting in significant disruptions in spermiogenesis, decreased sperm motility, and hindered development of eggs. Further explorations into the underlying post-transcriptional regulatory mechanisms reveales the involvement of lnc117962 as a competing endogenous RNA (ceRNA) for miR-3960, thereby regulating TSSKs. Notably, orchard trials demonstrates that the release of male strains can effectively suppress population growth. Our findings indicate that targeting TSSKs could serve as a feasible avenue for managing C. pomonella populations, offering significant insights and potential strategies for controlling invasive pests through genetic sterile insect technique (gSIT) technology.

Prediction of homologous recombination deficiency from routine histology with attention-based multiple instance learning in nine different tumor types.

BACKGROUND: Homologous recombination deficiency (HRD) is recognized as a pan-cancer predictive biomarker that potentially indicates who could benefit from treatment with PARP inhibitors (PARPi). Despite its clinical significance, HRD testing is highly complex. Here, we investigated in a proof-of-concept study whether Deep Learning (DL) can predict HRD status solely based on routine hematoxylin & eosin (H&E) histology images across nine different cancer types. METHODS: We developed a deep learning pipeline with attention-weighted multiple instance learning (attMIL) to predict HRD status from histology images. As part of our approach, we calculated a genomic scar HRD score by combining loss of heterozygosity (LOH), telomeric allelic imbalance (TAI), and large-scale state transitions (LST) from whole genome sequencing (WGS) data of n = 5209 patients across two independent cohorts. The model's effectiveness was evaluated using the area under the receiver operating characteristic curve (AUROC), focusing on its accuracy in predicting genomic HRD against a clinically recognized cutoff value. RESULTS: Our study demonstrated the predictability of genomic HRD status in endometrial, pancreatic, and lung cancers reaching cross-validated AUROCs of 0.79, 0.58, and 0.66, respectively. These predictions generalized well to an external cohort, with AUROCs of 0.93, 0.81, and 0.73. Moreover, a breast cancer-trained image-based HRD classifier yielded an AUROC of 0.78 in the internal validation cohort and was able to predict HRD in endometrial, prostate, and pancreatic cancer with AUROCs of 0.87, 0.84, and 0.67, indicating that a shared HRD-like phenotype occurs across these tumor entities. CONCLUSIONS: This study establishes that HRD can be directly predicted from H&E slides using attMIL, demonstrating its applicability across nine different tumor types.

Evaluating the persistence of large choroidal hypertransmission defects using SS-OCT imaging.

In age-related macular degeneration (AMD), large choroidal hypertransmission defects (hyperTDs) are identified on en face optical coherence tomography (OCT) images as bright lesions measuring at least 250 µm in greatest linear dimension (GLD). These choroidal hyperTDs arise from focal attenuation or loss of the retinal pigment epithelium (RPE). We previously reported that once large hyperTDs formed, they were likely to persist compared with smaller lesions that were more likely to be transient. Due to their relative persistence, these large persistent choroidal hyperTDs are a point-of-no-return in the progression of intermediate AMD to the late stage of atrophic AMD. Moreover, the onset of these large choroidal hyperTDs can serve as a clinical trial endpoint when studying therapies that might slow disease progression from intermediate AMD to late atrophic AMD. To confirm the persistence of these large choroidal hyperTDs, we studied an independent dataset of AMD eyes enrolled in an ongoing prospective swept-source OCT (SS-OCT) natural history study to determine their overall persistence. We identified a total of 202 eyes with large choroidal hyperTDs containing 1725 hyperTDs followed for an average of 46.6 months. Of the 1725 large hyperTDs, we found that 1718 (99.6%) persisted while only 7 hyperTDs (0.4%) were non-persistent. Of the 7 non-persistent large hyperTDs in 6 eyes, their average GLD at baseline was 385 µm. Of the large hyperTDs ranging in size between 250 and 300 µm when first detected, only one was not persistent with a baseline GLD of 283 µm. In 6 of the non-persistent hyperTDs, the loss of a detectable large hyperTD was due to the accumulation of hyperreflective material along the retinal pigment epithelium (RPE) and in the retina over the area where the hyperTD was located. This hyperreflective material is thought to represent the migration and aggregation of RPE cells into this focal region where the choroidal hyperTD arose due to attenuated or lost RPE.

Safety and Efficacy of Metformin for Idiopathic Intracranial Hypertension. A U.S-Based Real-World Data Retrospective Multicenter Cohort Study.

Introduction: Idiopathic intracranial hypertension (IIH) remains a challenging condition to manage, with limited therapeutic options. This study investigated the potential of metformin as a novel treatment for IIH, exploring its effects on disease outcomes and safety profile. Methods: We conducted a retrospective cohort study using the TriNetX database, analyzing data from 2009 to August 2024. Patients diagnosed with IIH were included, with exclusions for other causes of elevated intracranial pressure and pre-existing diabetes. Propensity score matching was employed to balance cohorts according to age, sex, race, ethnicity, Hemoglobin A1C, and baseline body mass index (BMI) at the time of metformin initiation. Outcomes were assessed at various follow-up points up to 24 months. Results: Our study initially comprised 1,268 patients in the metformin group and 49,262 in the control group, with notable disparities in several parameters. Post-matching, both cohorts were refined to 1,267 patients each after matching with metformin group. Metformin-treated patients showed significantly lower risks of papilledema, headache, and refractory IIH status at all follow-up points (p<0.0001). The metformin group also had reduced rates of therapeutic spinal punctures and acetazolamide continuation. BMI reductions were more pronounced in the metformin group, with significant differences observed from 6 months onward (p<0.0001). Notably, metformin's beneficial effects persisted independently of BMI changes. The safety profile of metformin was favorable, with no significant differences in adverse events compared to the control group which did not receive metformin during the study timeframe. Conclusions: Our study provides evidence for metformin's potential as a disease-modifying therapeutic approach in IIH, demonstrating improvements across multiple outcomes. The benefits appear to extend beyond weight loss, suggesting complex mechanisms of action. These findings warrant further investigation through prospective clinical trials to establish metformin's role in IIH management and explore its underlying therapeutic mechanisms.

Optimizing Western blotting immunodetection: Streamlining antibody cocktails for reduced protocol time and enhanced multiplexing applications.

Adaptive, rather than innate, immunity relies mainly on antigen-antibody recognition. This recognition is driven by the binding of specific antibody paratopes to distinct epitopes found on antigens. This interaction is pivotal for immune responses that have been re-purposed for diagnostic and therapeutic purposes. This article focuses on Western blotting, an in vitro technique performed for protein immunodetection. Traditionally, this technique requires separate incubations of both primary and secondary antibodies, for which these antibodies recognize different antigen epitopes (conventional method). We propose a modified protocol combining both antibodies, involving a single incubation step that reduces time and conserves reagents (non-conventional/improved method). This improved protocol will enhance efficiency without compromising detection accuracy. It will support multiplexing, enabling the simultaneous detection of multiple proteins. Despite the positive results found by applying available antibodies, further optimization is required for a more thorough evaluation, to ensure that all antibodies consistently yield successful results in every detection attempt for broader use. Our findings indicate that the tested antibody cocktails remained stable over time, which suggests potential for commercialization of this modified Western blot protocol with a wide scope towards multiplex diagnostic application.

Safety and Effectiveness of Mavacamten Use in Hypertrophic Obstructive Cardiomyopathy: A Systematic Review and Meta-Analysis.

Hypertrophic obstructive cardiomyopathy (HOCM) is a complex genetic cardiac disease that causes left ventricular hypertrophy and obstruction of the outflow tract. Mavacamten, a novel cardiac myosin inhibitor, has emerged as a potentially beneficial therapeutic option. This meta-analysis aimed to determine whether mavacamten is effective and safe for use in patients with HOCM. A systematic literature search was performed in PubMed and the Cochrane Central Register of Controlled Trials to identify randomized controlled trials (RCTs) that compared mavacamten to placebo in patients with HOCM. The primary objectives were changes in the gradients associated with the Valsalva maneuver and resting left ventricular outflow tract (LVOT). Alterations in the left atrial volume index (LAVI), left ventricular mass index (LVMI), and NT-proBNP level were secondary outcomes. Safety outcomes were also evaluated. Random effects models were used in the meta-analysis. Two RCTs comprising 332 patients were included. Mavacamten significantly reduced the Valsalva LVOT gradient (mean difference (MD) = -54.94 mmHg; 95% CI: -70.32, -39.56; P = 0.13) and resting LVOT gradient (MD = -42.44 mmHg; 95% CI: -67.52, -17.36; P<0.001) compared to placebo. Significant improvements were also observed in LAVI (MD = -7.18 mL/m²; 95% CI: -11.00, -3.37; P = 0.24) and NT-proBNP levels (RR = 0.58; 95% CI: 0.39, 0.84; P<0.001). LVMI showed a trend toward reduction (MD = -19.15 g/m²; 95% CI: -41.98, 3.69; P<0.001). Mavacamten demonstrated a favorable safety profile with few reported adverse events. This meta-analysis aimed to demonstrate the efficacy and short-term safety of mavacamten in patients with HOCM. Considerable improvement was observed in the LVOT gradients, cardiac remodeling measures, and indicators of cardiac stress when mavacamten was administered. Based on this data, mavacamten appears to offer the potential for a paradigm shift in the management of HOCM. However, studies conducted over an extended period are required to validate its long-term effectiveness and safety profile.

KS18, a Mcl-1 inhibitor, improves the effectiveness of bortezomib and overcomes resistance in refractory multiple myeloma by triggering intrinsic apoptosis.

Despite a record number of clinical studies investigating various anti-myeloma treatments, the 5-year survival rate for multiple myeloma (MM) patients in the US is only 55%, and almost all patients relapse. Poor patient outcomes demonstrate that myeloma cells are "born to survive" which means they can adapt and evolve following treatment. Thus, new therapeutic approaches to combat survival mechanisms and target treatment resistance are required. Importantly, Mcl-1, anti-apoptotic protein, is required for the development of MM and treatment resistance. This study looks at the possibility of KS18, a selective Mcl-1 inhibitor, to treat MM and overcome resistance. Our investigation demonstrates that KS18 effectively induces cell death in MM by dual regulatory mechanisms targeting the Mcl-1 protein at both transcriptional and post-translational levels. Specifically, KS18 suppresses Mcl-1 activation via STAT-3 pathway and promotes Mcl-1 phosphorylation/ubiquitination/proteasome-dependent protein degradation (UPS). Significantly, KS18 triggered caspase-dependent apoptosis in MM patient samples and bortezomib-resistant cells, synergizing with venetoclax to boost apoptosis. KS18 promises to overcome bortezomib and venetoclax resistance and re-sensitize myeloma cells to chemotherapy. Furthermore, the study shows the tremendous impact of KS18 in inhibiting colony formation in bortezomib-resistant cells and demonstrates significant tumor shrinkage in KS18-treated NSG mice without notable toxicity signs after 4 weeks of therapy with a single acceptable dose each week, indicating its powerful anti-neoplastic and anti-resistance characteristics. This study strongly implies that KS18 may treat MM and provide new hope to patients who are experiencing recurrence or resistance.

Dual Coronary Artery Thrombosis: An Unforeseen Angiographic Encounter.

Acute myocardial infarction (AMI) frequently involves single-vessel coronary artery disease, but simultaneous thrombosis in multiple coronary arteries is a rare and challenging clinical scenario. We report the case of a 42-year-old Southeast Asian male with a six-month history of hypertension controlled by a single antihypertensive agent, presenting to the emergency department with central chest pain radiating to the back. The initial electrocardiography (ECG) showed ST elevation in the inferior leads. Primary percutaneous coronary intervention (PCI) via the right femoral approach revealed complete thrombotic occlusions in the left anterior descending (LAD) and right coronary artery (RCA). Drug-eluting stents (DES) were deployed, restoring thrombolysis in myocardial infarction (TIMI) III flow. Despite initial hemodynamic stability, the patient experienced cardiogenic shock (CS), necessitating a relook angiogram that confirmed patent stents and identified an additional stenosis in the first diagonal branch (D1). An intra-aortic balloon pump (IABP) was inserted. The patient's course was complicated by recurrent CS, septic shock secondary to Fusobacterium periodonticum bacteremia, acute kidney injury, multiple supraventricular arrhythmias (SVTs), and partial thrombosis of the right radial artery leading to dry gangrene of the right index and thumb fingers. He was eventually discharged on oral warfarin for radial artery thrombosis and paroxysmal atrial fibrillation with follow-up care with vascular surgery.

Absolute and Functional Iron Deficiency in the US, 2017-2020.

Importance: The prevalence of absolute and functional iron deficiency among adults in the US is unknown. Objective: To estimate the prevalence of absolute and iron deficiency and iron supplement use in the US across age, sex, and comorbidity categories. Design, Setting, and Participants: This cross-sectional study analyzed data from the National Health and Nutritional Examination Survey (NHANES) 2017 to 2020 prepandemic cycle. Participants included noninstitutionalized, civilian women and men aged 18 years or older who had available serum ferritin, iron, and unsaturated iron binding capacity measurements. Data analysis was performed from March 21, 2023, to July 5, 2024. Exposure: Absolute iron deficiency and functional iron deficiency. Main Outcomes and Measures: Absolute iron deficiency was defined as serum ferritin less than 30 ng/mL regardless of transferrin saturation. Functional iron deficiency was defined as serum ferritin greater than or equal to 30 ng/mL with transferrin saturation less than 20%. The prevalence of absolute and functional iron deficiency was estimated among all adults in the US and separately among women and men according to age category (>18 years to <50 years, 50-65 years, and ≥65 years) using recommended sample weights and sampling design factors to provide estimates representative of the national, noninstitutionalized civilian population. The 95% CIs were calculated using the Korn-Graubard method. Results: A total of 8021 US adults (mean age, 48 years; 95% CI, 47-49 years; 52% [95% CI, 50%-53%] female) were included in this analysis. An estimated 14% (95% CI, 13%-15%) of adults in the US met the criteria for absolute iron deficiency, and an estimated 15% (95% CI, 14%-17%) met the criteria for functional iron deficiency. Among US adults without anemia, heart failure, chronic kidney disease, or current pregnancy, the estimated prevalence of absolute iron deficiency was 11% (95% CI, 10%-11%), and that of functional iron deficiency was 15% (95% CI, 14%-17%). The prevalence of functional iron deficiency exceeded that of absolute iron deficiency in all US adults except women younger than 50 years. Iron supplement use ranged from 22% (95% CI, 12%-37%) to 35% (95% CI, 29%-42%) of women with iron deficiency and 12% (95% CI, 5%-21%) to 18% (95% CI, 8%-32%) of men with iron deficiency depending on age. Conclusions and Relevance: These findings suggest that absolute and functional iron deficiency affect a large proportion of American adults even in the absence of anemia, heart failure, or chronic kidney disease. Further research on the role of functional iron deficiency in adverse health outcomes and on iron deficiency screening strategies is needed.

From whole-slide image to biomarker prediction: end-to-end weakly supervised deep learning in computational pathology.

Hematoxylin- and eosin-stained whole-slide images (WSIs) are the foundation of diagnosis of cancer. In recent years, development of deep learning-based methods in computational pathology has enabled the prediction of biomarkers directly from WSIs. However, accurately linking tissue phenotype to biomarkers at scale remains a crucial challenge for democratizing complex biomarkers in precision oncology. This protocol describes a practical workflow for solid tumor associative modeling in pathology (STAMP), enabling prediction of biomarkers directly from WSIs by using deep learning. The STAMP workflow is biomarker agnostic and allows for genetic and clinicopathologic tabular data to be included as an additional input, together with histopathology images. The protocol consists of five main stages that have been successfully applied to various research problems: formal problem definition, data preprocessing, modeling, evaluation and clinical translation. The STAMP workflow differentiates itself through its focus on serving as a collaborative framework that can be used by clinicians and engineers alike for setting up research projects in the field of computational pathology. As an example task, we applied STAMP to the prediction of microsatellite instability (MSI) status in colorectal cancer, showing accurate performance for the identification of tumors high in MSI. Moreover, we provide an open-source code base, which has been deployed at several hospitals across the globe to set up computational pathology workflows. The STAMP workflow requires one workday of hands-on computational execution and basic command line knowledge.

Circulating miRNA-373 and Vascular Endothelial Growth Factor as Potential Biomarkers for Early Detection of Breast Cancer.

Breast cancer is the leading cause of cancer-related mortality among women worldwide. MicroRNAs (miRNAs), short non-coding RNAs, have been implicated in cancer-related processes such as tumor development, metastasis, angiogenesis, and drug resistance. Circulating miRNA-373 demonstrates higher relative exosomal serum levels in breast cancer patients compared to healthy women, making it a potential non-invasive biomarker. Separately, vascular endothelial growth factor (VEGF) is crucial for angiogenesis, and is elevated in breast cancer. In this case-control study, we aimed to investigate the diagnostic accuracy of miRNA-373 and VEGF as biomarkers for early-stage breast cancer detection. Serum samples were collected from 120 participants, comprising 30 breast cancer patients, 30 benign breast tumor patients, and 60 healthy controls, over the period of April 2022 to January 2023. MiRNA-373 expression was analyzed by reverse transcription-quantitative PCR with GAPDH normalisation, while VEGF levels in serum samples were measured by ELISA. Receiver operating characteristic (ROC) curve analysis was performed to evaluate the diagnostic performance of both biomarkers. MiRNA-373 expression (∆Ct) differed significantly between the three groups (breast cancer: - 12.20 ± 1.11; benign tumors: - 12.79 ± 1.09; controls: - 13.64 ± 0.93). ROC analysis revealed moderate discriminative power for miRNA-373 (specificity = 76.7%; sensitivity = 70.0%; AUC = 0.839) and excellent discriminative power for VEGF (specificity = 85.0%; sensitivity = 90.0%; AUC = 0.944) in distinguishing early-stage breast cancer patients from healthy controls. In summary, this study demonstrates the promising potential of miRNA-373 as an early diagnostic biomarker for breast cancer detection, requiring further validation in larger cohorts. Our findings also reinforce the diagnostic value of circulating VEGF levels for breast cancer screening. Supplementary Information: The online version contains supplementary material available at 10.1007/s12291-023-01174-9.

Factors Influencing Medical Students' Choice of Anesthesiology as a Future Specialty in Saudi Arabia.

Background According to the American Society of Anesthesiologists (ASA), anesthesiologists are experts in administering anesthesia, pain management, and critical care medicine. In addition, they provide general perioperative care. Personal interests, career stability, reputation, income, and clinical rotation experience influence medical students' career choices. Studies show that anesthesiology remains one of the least popular specialties among Saudi medical students. Our study aims to determine the preference for anesthesiology among Saudi medical students and the factors influencing their career choice options. Methodology This cross-sectional study was implemented by distributing a self-administered verified survey. Results Our study included 532 medical students, predominantly female (n=344, 64.7%), aged 18-24 years (n=424, 79.7%), and Saudi nationals (n=508, 95.5%). Most were single (n=500, 94%) without children (n=522, 98.1%). A majority were not interested in anesthesiology as a future specialty (n=297, 55.8%), with some uncertainty (n=148, 27.8%) and a smaller interested group (n=87, 16.4%). Controllable lifestyle (n=294, 55.3%) and financial income (n=213, 40%) were critical factors for choosing anesthesiology as a specialty. Interest in another specialty (n=342, 64.3%) and stress (n=286, 53.8%) were significant opposing factors. Academic year significantly affected consideration (p<0.001), with second-year students showing the highest interest (61.8%) and sixth-year the lowest (24.8%). Other factors showed no significant association. Conclusion Our study reveals low interest in anesthesiology among Saudi medical students. A controllable lifestyle and financial income are key attractions. Interest declines significantly by the sixth year due to their interest in other specialties, lifestyle concerns, and stress.

Biological studies of the activity of Manuka honey against Carbapenem-resistant Enterobacterales (CRE) bacteria.

OBJECTIVES: To evaluate the potency of Manuka honey UMF +15 against Carbapenem-resistant Enterobacterales (CRE). Bacterial resistance is a worldwide problem that is increasing year by year, especially Carbapenem resistance. Alternatives to antibiotics are needed to both reduce costs, and to reduce the spread of antibiotic resistance, with the ultimate goal of saving lives. METHODS: The efficacy of Manuka honey UMF +15 was tested by 2 methods; Well diffusion assay and minimum bactericidal concentration (MBC) against twenty Carbapenem-resistant isolates which collected from Makkah city hospitals during three months of study from 1st of September 2023 up to 1st of December 2023. RESULTS: The growth of all isolates of Carbapenem-resistant Enterobacterales (CRE) was severely inhibited by low concentrations of Manuka honey, affecting 25% of isolates at 15% and 75% of isolates at 18% of Manuka honey. In addition, using the honey at different concentrations in a well diffusion assay resulted, as expected, in a variable zone diameter, ranging from large zones(14mm) to small zones (2 mm) according to the concentration of the honey. CONCLUSION: This study shows the remarkable antibacterial activity of Manuka honey and suggests that this natural remedy might be used in the future as an alternative treatment option against Carbapenem-resistant Enterobacterales (CRE); however, further clinical trials should be performed to corroborate our initial findings.

The effects of airway disease on the deposition of inhaled drugs.

INTRODUCTION: The deposition of inhaled medications is the first step in the pulmonary pharmacokinetic process to produce a therapeutic response. Not only lung dose but more importantly the distribution of deposited drug in the different regions of the lung determines local bioavailability, efficacy, and clinical safety. Assessing aerosol deposition patterns has been the focus of intense research that combines the fields of physics, radiology, physiology, and biology. AREAS COVERED: The review covers the physics of aerosol transport in the lung, experimental, and in-silico modeling approaches to determine lung dose and aerosol deposition patterns, the effect of asthma, chronic obstructive pulmonary disease, and cystic fibrosis on aerosol deposition, and the clinical translation potential of determining aerosol deposition dose. EXPERT OPINION: Recent advances in in-silico modeling and lung imaging have enabled the development of realistic subject-specific aerosol deposition models, albeit mainly in health. Accurate modeling of lung disease still requires additional refinements in existing imaging and modeling approaches to better characterize disease heterogeneity in peripheral airways. Nevertheless, recent patient-centric innovation in inhaler device engineering and the incorporation of digital technology have led to more consistent lung deposition and improved targeting of the distal airways, which better serve the clinical needs of patients.

CRISPR RNA binding drives structural ordering that primes Cas7-11 for target cleavage.

Type III-E CRISPR-Cas effectors, of which Cas7-11 is the first, are single proteins that cleave target RNAs without nonspecific collateral cleavage, opening new possibilities for RNA editing. Biochemical experiments combined with amide hydrogen-deuterium exchange (HDX-MS) experiments provide a first glimpse of the conformational dynamics of apo Cas7-11. HDX-MS revealed the backbone comprised of the four Cas7 zinc-binding RRM folds are well-folded but insertion sequences are highly dynamic and fold upon binding crRNA. The crRNA causes folding of disordered catalytic loops and ß-hairpins, stronger interactions at domain-domain interfaces, and folding of the Cas7.1 processing site. Target RNA binding causes only minor ordering around the catalytic loops of Cas7.2 and Cas7.3. We show that Cas7-11 cannot fully process the CRISPR array and that binding of partially processed crRNA induces multiple states in Cas7-11 and reduces target RNA cleavage. The insertion domain shows the most ordering upon binding of mature crRNA. Finally, we show a crRNA-induced conformational change in one of the TPR-CHAT binding sites providing an explanation for why crRNA binding facilitates TPR-CHAT binding. The results provide the first glimpse of the apo state of Cas7-11 and reveal how its structure and function are regulated by crRNA binding.

Species distribution modeling for disease ecology: A multi-scale case study for schistosomiasis host snails in Brazil.

Species distribution models (SDMs) are increasingly popular tools for profiling disease risk in ecology, particularly for infectious diseases of public health importance that include an obligate non-human host in their transmission cycle. SDMs can create high-resolution maps of host distribution across geographical scales, reflecting baseline risk of disease. However, as SDM computational methods have rapidly expanded, there are many outstanding methodological questions. Here we address key questions about SDM application, using schistosomiasis risk in Brazil as a case study. Schistosomiasis is transmitted to humans through contact with the free-living infectious stage of Schistosoma spp. parasites released from freshwater snails, the parasite's obligate intermediate hosts. In this study, we compared snail SDM performance across machine learning (ML) approaches (MaxEnt, Random Forest, and Boosted Regression Trees), geographic extents (national, regional, and state), types of presence data (expert-collected and publicly-available), and snail species (Biomphalaria glabrata, B. straminea, and B. tenagophila). We used high-resolution (1km) climate, hydrology, land-use/land-cover (LULC), and soil property data to describe the snails' ecological niche and evaluated models on multiple criteria. Although all ML approaches produced comparable spatially cross-validated performance metrics, their suitability maps showed major qualitative differences that required validation based on local expert knowledge. Additionally, our findings revealed varying importance of LULC and bioclimatic variables for different snail species at different spatial scales. Finally, we found that models using publicly-available data predicted snail distribution with comparable AUC values to models using expert-collected data. This work serves as an instructional guide to SDM methods that can be applied to a range of vector-borne and zoonotic diseases. In addition, it advances our understanding of the relevant environment and bioclimatic determinants of schistosomiasis risk in Brazil.

The rate of blood culture contamination and common organisms isolated in Malaysian public hospitals.

INTRODUCTION: Blood culture contamination remains a dilemma issue in the diagnosis of bloodstream infection. However, to date, there is no national data on blood culture contamination and the common organism isolated in Malaysia. This is a pioneer multi-centre study involving public hospitals with medical microbiologists in Malaysia to determine the blood culture contamination rate and the common organism isolated. MATERIALS AND METHODS: This retrospective cross-sectional study involved record review of all blood culture results over 9 months period from 1st January 2018 until 30th September 2018 in 27 government hospitals in Malaysia. For each positive culture result, the type of isolated organism was classified to represent true bacteraemia or contamination. RESULTS: We analysed 448,109 blood culture records from the participating hospitals. The blood culture positivity rate was 12.5% (57395 of 448109) and 25.0% (14367 of 57395) of the positive blood culture represents contamination. The national blood culture contamination rate in Malaysia was 3.2%. The contamination rate in the adult population was significantly higher than the paediatric population (3.6% vs. 2.6%; p<0.001). The blood contamination rate by institution ranged from 1.5% to 6.8%. The most frequently isolated microorganisms in the contaminated cultures were coagulase-negative staphylococci (71.0%). CONCLUSION: Blood culture contamination is a major issue that warrants priority in recognition, and interventions should be implemented to reduce the blood contamination rate in Malaysia.

The quantum Gaussian-Schell model: a link between classical and quantum optics.

The quantum theory of the electromagnetic field uncovered that classical forms of light were indeed produced by distinct superpositions of nonclassical multiphoton wave packets. This situation prevails for partially coherent light, the most common kind of classical light. Here, for the first time, to our knowledge, we demonstrate the extraction of the constituent multiphoton quantum systems of a partially coherent light field. We shift from the realm of classical optics to the domain of quantum optics via a quantum representation of partially coherent light using its complex-Gaussian statistical properties. Our formulation of the quantum Gaussian-Schell model (GSM) unveils the possibility of performing photon-number-resolving (PNR) detection to isolate the constituent quantum multiphoton wave packets of a classical light field. We experimentally verified the coherence properties of isolated vacuum systems and wave packets with up to 16 photons. Our findings not only demonstrate the possibility of observing quantum properties of classical macroscopic objects but also establish a fundamental bridge between the classical and quantum worlds.