Phenotypic, genotypic and proteomic variations between poor and robust colonizing Campylobacter jejuni strains.

Campylobacter jejuni is one of the major causes of bacterial gastrointestinal disease in humans worldwide. This foodborne pathogen colonizes the intestinal tracts of chickens, and consumption of chicken and poultry products is identified as a common route of transmission. We analyzed two C. jejuni strains after oral challenge with 105 CFU/ml of C. jejuni per chick; one strain was a robust colonizer (A74/C) and the other a poor colonizer (A74/O). We also found extensive phenotypic differences in growth rate, biofilm production, and in vitro adherence, invasion, intracellular survival, and transcytosis. Strains A74/C and A74/O were genotypically similar with respect to their whole genome alignment, core genome, and ribosomal MLST, MLST, flaA, porA, and PFGE typing. The global proteomes of the two congenic strains were quantitatively analyzed by ultra-high performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) and 618 and 453 proteins were identified from A74/C and A74/O isolates, respectively. Cluster of Orthologous Groups (COG) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses showed that carbon metabolism and motility proteins were distinctively overexpressed in strain A74/C. The robust colonizer also exhibited a unique proteome profile characterized by significantly increased expression of proteins linked to adhesion, invasion, chemotaxis, energy, protein synthesis, heat shock proteins, iron regulation, two-component regulatory systems, and multidrug efflux pump. Our study underlines phenotypic, genotypic, and proteomic variations of the poor and robust colonizing C. jejuni strains, suggesting that several factors may contribute to mediating the different colonization potentials of the isogenic isolates.

Electrochemical detection of nalbuphine drug using oval-like ZnO nanostructure-based sensor.

Monitoring pharmaceutical drugs in various mediums is crucial to mitigate adverse effects. This study presents a chemical sensor using an oval-like zinc oxide (ZnO) nanostructure for electrochemical detection of nalbuphine. The ZnO nanostructure, produced via an efficient sol-gel technique, was extensively characterized using field emission scanning electron microscopy (FESEM), transmission electron microscopy (TEM), X-ray diffraction (XRD), UV-visible spectrophotometry, and fourier transform infrared spectroscopy (FTIR). A slurry of the ZnO nanostructure in a binder was applied to a glassy carbon electrode (GCE). The sensor's responsiveness to nalbuphine was assessed using linear sweep voltammetry (LSV), achieving optimal performance by fine-tuning the pH. The sensor demonstrated a proportional response to nalbuphine concentrations up to 150.0 nM with a good regression coefficient (R2) and a detection limit of 6.20 nM (S/N ratio of 3). Selectivity was validated against various interfering substances, and efficacy was confirmed through real sample analysis, highlighting the sensor's successful application for nalbuphine detection.

Vagal Nerve Stimulation in the Pediatric Population and Correlation Between Family and Treatment Team Perspectives: Single-center Experience.

BACKGROUND: Vagal nerve stimulation (VNS) is an adjunctive therapy to pharmacological treatment in patients with drug-resistant epilepsy. This study aimed to assess the efficacy of VNS therapy for seizure frequency reduction and improving quality of life (QOL) measures in children with refractory epilepsy and to evaluate the correlation between the perspectives of families and those of the treating team. METHODS: This was a prospective cohort study conducted at Abha Maternity and Children's Hospital, Saudi Arabia, from 2018 to 2022. A total of 21 pediatric patients who completed one year of follow-up after VNS implantation were included. Patients were aged between 2 and 14 years, with a mean age of 8.14 ± 3.92; 11 (52.4%) patients were female. Family and physician assessments were collected blinded to each other using Clinical Global Impression of Improvement (CGI-I) scores and QOL assessments to evaluate the correlation between the families' and treating team's perspectives on VNS outcomes. RESULTS: In this study involving 21 patients with intractable epilepsy, VNS showed significant efficacy in reducing the frequency of seizures. VNS significantly reduced the number of seizures per week from a baseline median of 35 to a median of 0.25 at the end of the follow-up period, representing a dramatic reduction of 99.3% (p < 0.001). The number of emergency department visits per year decreased from a baseline median of 12 to a median of 2, a reduction of 83.3% (p < 0.001), whereas the number of hospital admissions per year decreased from a baseline median of 3 to a median of 1, a 66.7% decrease (p < 0.001). The number of antiepileptic medications taken decreased from a median of 4 to 3 (p < 0.001). Notably, 28.57% of the patients achieved complete seizure freedom, and 38% exhibited significant improvement, with at least 50% reduction in seizure frequency. Importantly, none of the patients experienced an escalation in seizure frequency following VNS treatment. The family and physician assessments showed varying degrees of alignment in perceptions, with "concentration" exhibiting a significant positive correlation (r = 0.498, p = 0.022), indicating noteworthy agreement, whereas verbal communication did not show a substantial correlation (r = -0.062, p = 0.791), indicating a divergence of views. CONCLUSION: VNS is a promising and well-tolerated therapy for individuals with intractable seizures, offering clinical benefits and potential enhancements in various aspects of QOL. The varying perceptions between family and physician assessments highlight the importance of considering multiple perspectives when evaluating treatment outcomes.

Whole-Genome Sequence Analysis of Antibiotic Resistance, Virulence, and Plasmid Dynamics in Multidrug-Resistant E. coli Isolates from Imported Shrimp.

We analyzed antimicrobial resistance and virulence traits in multidrug-resistant (MDR) E. coli isolates obtained from imported shrimp using whole-genome sequences (WGSs). Antibiotic resistance profiles were determined phenotypically. WGSs identified key characteristics, including their multilocus sequence type (MLST), serotype, virulence factors, antibiotic resistance genes, and mobile elements. Most of the isolates exhibited resistance to gentamicin, streptomycin, ampicillin, chloramphenicol, nalidixic acid, ciprofloxacin, tetracycline, and trimethoprim/sulfamethoxazole. Multilocus sequence type (MLST), serotype, average nucleotide identity (ANI), and pangenome analysis showed high genomic similarity among isolates, except for EC15 and ECV01. The EC119 plasmid contained a variety of efflux pump genes, including those encoding the acid resistance transcriptional activators (gadE, gadW, and gadX), resistance-nodulation-division-type efflux pumps (mdtE and mdtF), and a metabolite, H1 symporter (MHS) family major facilitator superfamily transporter (MNZ41_23075). Virulence genes displayed diversity, particularly EC15, whose plasmids carried genes for adherence (faeA and faeC-I), invasion (ipaH and virB), and capsule (caf1A and caf1M). This comprehensive analysis illuminates antimicrobial resistance, virulence, and plasmid dynamics in E. coli from imported shrimp and has profound implications for public health, emphasizing the need for continued surveillance and research into the evolution of these important bacterial pathogens.

The Depression Anxiety Stress Scale 8: investigating its cutoff scores in relevance to loneliness and burnout among dementia family caregivers.

The global trend of advanced aging comes at the cost of amplified onset of age-related diseases. Dementia is a common multifactorial age-related neurodegenerative disorder, which manifests with progressive declines in cognitive functioning and ability to perform activities of daily living. As polices discourage institutionalized care, family members act as primary caregivers and endure increased vulnerability to physical and mental health problems secondary to care-related changes in life routine and relationships. Targeting clinically significant distress at earlier stages through valid brief measures may promote caregivers' wellbeing and dementia care continuity/quality. This study aimed to determine the optimal cutoff score of the Depression Anxiety Stress Scale 8-items (DASS-8) in a convenience sample of 571 European caregivers (Mean age = 53 ± 12 years, Italian = 74.4%, Swiss = 25.6%) through three methods. K-means clustering classified the sample into high- and low-distress clusters based on DASS-8 score of 19. Receiver operator curve (ROC) analysis using 48 and 7 cutoffs of the Zarit Burden Interview (ZBI) and the Three-Item University of California, Los Angeles, Loneliness Scale-version 3 (UCLALS3), revealed two DASS-8 cutoffs (12.5 and 14.5, area under the curve (AUC) = 0.85 and 0.92, p values < .001, 95% CI 0.82-0.88 and 0.89 to 0.94, sensitivity = 0.81 and 0.78, specificity = 0.76 and 0.89, Youden index = 0.57 and 0.67, respectively). Decision modeling produced two DASS-8 cutoffs (9.5 and 14.5) for predicting low and high caregiving burden and loneliness, respectively. According to the median of all DASS-8 cutoffs (14.5) the prevalence of mental distress was 50.8%. Distress correlated with key mental problems such as burnout and loneliness-in path analysis, DASS-8 scores were predicted by the ZBI, UCLALS3, care dependency, and receiving help with care, especially among older, female, and spouse caregivers. Further diagnostic workup should follow to confirm psycho-pathogenicity among caregivers with DASS-8 scores above 14.5. Investigations of the DASS-8 in other countries/populations may confirm the validity of this cutoff score.

Unrevealing the multitargeted potency of 3-1-BCMIYPPA against lung cancer structural maintenance and suppression proteins through pharmacokinetics, QM-DFT, and multiscale MD simulation studies.

Lung cancer, a relentless and challenging disease, demands unwavering attention in drug design research. Single-target drugs have yielded limited success, unable to effectively address this malignancy's profound heterogeneity and often developed resistance. Consequently, the clarion call for lung cancer drug design echoes louder than ever, and multitargeted drug design emerges as an imperative approach in this landscape, which is done by concurrently targeting multiple proteins and pathways and offering a beacon of hope. This study is focused on the multitargeted drug designing approach by identifying drug candidates against human cyclin-dependent kinase-2, SRC-2 domains of C-ABL, epidermal growth factor and receptor extracellular domains, and insulin-like growth factor-1 receptor kinase. We performed the multitargeted molecular docking studies of Drug Bank compounds using HTVS, SP and XP algorithms and poses filter with MM\GBSA against all proteins and identified DB02504, namely [3-(1-Benzyl-3-Carbamoylmethyl-2-Methyl-1h-Indol-5-Yloxy)-Propyl-]-Phosphonic Acid (3-1-BCMIYPPA) as multitargeted lead with docking and MM\GBSA score range from -8.242 to -6.274 and -28.2 and -44.29 Kcal/mol, respectively. Further, the QikProp-based pharmacokinetic computations and QM-based DFT showed acceptance results against standard values, and interaction fingerprinting reveals that THR, MET, GLY, VAL, LEU, GLU and ASP were among the most interacting residues. The NPT ensemble-based 100ns MD simulation in a neutralised state with an SPC water model has also shown a stable performance and produced deviation and fluctuations <2Å with huge interactions, making it a promising multitargeted drug candidate-however, experimental studies are suggested.

Chicken Juice Enhances C. jejuni NCTC 11168 Biofilm Formation with Distinct Morphological Features and Altered Protein Expression.

Campylobacter jejuni is the foodborne pathogen causing most gastrointestinal infections. Understanding its ability to form biofilms is crucial for devising effective control strategies in food processing environments. In this study, we investigated the growth dynamics and biofilm formation of C. jejuni NCTC 11168 in various culture media, including chicken juice (CJ), brain heart infusion (BHI), and Mueller Hinton (MH) broth. Our results demonstrated that C. jejuni exhibited a higher growth rate and enhanced biofilm formation in CJ and in 1:1 mixtures of CJ with BHI or MH broth compared to these measures in BHI or MH broth alone. Electron microscopy unveiled distinct morphological attributes of late-stage biofilm cells in CJ, including the presence of elongated spiral-shaped cells, thinner stretched structures compared to regular cells, and extended thread-like structures within the biofilms. Proteomic analysis identified significant alterations in protein expression profiles in C. jejuni biofilms, with a predominance of downregulated proteins associated with vital functions like metabolism, energy production, and amino acid and protein biosynthesis. Additionally, a significant proportion of proteins linked to biofilm formation, virulence, and iron uptake were suppressed. This shift toward a predominantly coccoid morphology echoed the reduced energy demands of these biofilm communities. Our study unlocks valuable insights into C. jejuni's biofilm in CJ, demonstrating its adaptation and survival.

The Role of Epithelial Cell Adhesion Molecule Cancer Stem Cell Marker in Evaluation of Hepatocellular Carcinoma.

Background and Objectives: Hepatocellular carcinoma (HCC) is a prevalent form of malignancy that is characterized by high mortality rates and prognosis that remain suboptimal, largely due to treatment resistance mechanisms. Recent studies have implicated cancer stem cells (CSCs), particularly those expressing epithelial cell adhesion molecule (EpCAM), in HCC progression and resistance. In the present study, we sought to assess EpCAM expression in HCC patients and its correlation with various clinicopathological parameters. Materials and Methods: Tissue samples from 42 HCC patients were subjected to immunohistochemical staining to evaluate EpCAM expression. Clinicopathological data were obtained including the size, grade and stage of tumors, vascular invasion status, alpha-fetoprotein levels, and cirrhosis status. The Chi square and Fisher's exact tests were employed to assess the association between categorical groups. Independent Student-t test or Mann-Whitney U test was used to investigate the association between continuous patient characteristics and survival. Results: Immunohistochemical analysis revealed EpCAM expression in 52.5% of HCC cases. EpCAM-positive tumors exhibited characteristics indicative of aggressive disease, including larger tumor sizes (p = 0.006), greater tumor multiplicity (p = 0.004), higher grades (p = 0.002), more advanced stages (p = 0.003), vascular invasion (p = 0.023), elevated alpha-fetoprotein levels (p = 0.013), and cirrhosis (p = 0.052). Survival analysis demonstrated that EpCAM expression was significantly associated with lower overall rates of survival and higher rates of recurrence in HCC patients. Conclusions: Our findings suggest that EpCAM expression may serve as a prognostic biomarker for HCC with a potential role in patient management. Targeting EpCAM-positive CSCs may represent a promising approach to overcome treatment resistance and improve clinical outcomes in HCC. However, further investigation into the molecular mechanisms underlying EpCAM's role in HCC progression is warranted to facilitate the development of personalized therapeutic interventions.

Selecting EEG channels and features using multi-objective optimization for accurate MCI detection: validation using leave-one-subject-out strategy.

Effective management of dementia requires the timely detection of mild cognitive impairment (MCI). This paper introduces a multi-objective optimization approach for selecting EEG channels (and features) for the purpose of detecting MCI. Firstly, each EEG signal from each channel is decomposed into subbands using either variational mode decomposition (VMD) or discrete wavelet transform (DWT). A feature is then extracted from each subband using one of the following measures: standard deviation, interquartile range, band power, Teager energy, Katz's and Higuchi's fractal dimensions, Shannon entropy, sure entropy, or threshold entropy. Different machine learning techniques are used to classify the features of MCI cases from those of healthy controls. The classifier's performance is validated using leave-one-subject-out (LOSO) cross-validation (CV). The non-dominated sorting genetic algorithm (NSGA)-II is designed with the aim of minimizing the number of EEG channels (or features) and maximizing classification accuracy. The performance is evaluated using a publicly available online dataset containing EEGs from 19 channels recorded from 24 participants. The results demonstrate a significant improvement in performance when utilizing the NSGA-II algorithm. By selecting only a few appropriate EEG channels, the LOSO CV-based results show a significant improvement compared to using all 19 channels. Additionally, the outcomes indicate that accuracy can be further improved by selecting suitable features from different channels. For instance, by combining VMD and Teager energy, the SVM accuracy obtained using all channels is 74.24%. Interestingly, when only five channels are selected using NSGA-II, the accuracy increases to 91.56%. The accuracy is further improved to 95.28% when using only 8 features selected from 7 channels. This demonstrates that by choosing informative features or channels while excluding noisy or irrelevant information, the impact of noise is reduced, resulting in improved accuracy. These promising findings indicate that, with a limited number of channels and features, accurate diagnosis of MCI is achievable, which opens the door for its application in clinical practice.

Exploring the association between microscopic colitis and celiac disease: A comprehensive analysis using the national in-patient data (2016-2019).

BACKGROUND: Several investigations suggested correlation between microscopic colitis (MC) and celiac disease (CD). This study aimed to examine this relationship using large-sized, population-based data with adequate control for confounding factors. METHODS: This study employed the National Inpatient Sample (NIS) database over 4 years (2016-2019). Patients with/without MC in the presence/absence of CD were identified through ICD-10 codes. Univariate and multi-variate analyses involving odds ratios (OR) and 95% confidence intervals (CI) were performed. RESULTS: Overall, 26,836,118 patients were analyzed. Of whom, 6,836 patients had MC (n = 179 with CD and n = 6,657 without CD). The mean hospital stay was not significantly different between both groups (5.42 ± 5.44 days vs. 4.95 ± 4.66 days, P = 0.202). The univariate analysis revealed a significant association between MC and CD (OR = 22.69, 95% [19.55, 26.33], P < 0.0001). In the multi-variate analysis, which adjusted for potential confounders including age, race, hospital region, hospital teaching status, ZIP income, smoking status, alcohol overuse, hypertension, diabetes mellitus, lipidemia-related disorders, non-steroidal anti-inflammatory drug use, and selected auto-immune diseases, the association remained significant (OR = 15.71, 95% CI [13.52, 18.25], P < 0.0001). Moreover, in patients with MC, the presence of CD emerged as a significant, independent variable of in-hospital mortality in univariate (OR = 2.87, 95% [1.14, 7.21], P = 0.025) and multi-variate (OR = 3.37, 95% CI [1.32, 8.60], P = 0.011) analyses. CONCLUSION: This study establishes a probable link between MC and CD, backed by both univariate and multi-variate analyses, while also identifying CD as an independent risk factor for increased mortality among MC patients. These findings need to be validated in real-world clinical studies.

CYP2D6 inhibition by diphenhydramine leading to fatal hydrocodone overdose.

OBJECTIVES: Fatal drug overdoses often involve multiple co-intoxicants, including opioids. Hydrocodone, the most prescribed opioid for pain management, is metabolized to the active metabolite hydromorphone by hepatic CYP2D6. Inhibition of CYP2D6 by other compounds can disrupt the analgesic properties of hydrocodone and extend its half-life. Diphenhydramine is an over-the-counter cold medication and is known to inhibit CYP2D6 activity. CASE PRESENTATION: A woman in her late 50s was prescribed hydrocodone/acetaminophen (Norco® 10/325). Days before her death, she began taking diphenhydramine for cold symptoms. A post-mortem toxicology report detected the following compounds by High Performance Liquid Chromatography/Time of Flight-Mass Spectrometry (LC/TOF-MS) analysis: acetaminophen (14 µg/mL), hydrocodone (410 ng/mL), dihydrocodeine (24 ng/mL), and diphenhydramine (150 ng/mL). Hydromorphone was not detected (<2 ng/mL). All compounds were detected in therapeutic concentrations, except for hydrocodone, which was present at lethal concentrations. CONCLUSIONS: This case highlights a fatal drug-drug interaction between hydrocodone and diphenhydramine. The estimated total body burden of hydrocodone was 6- to 12-fold higher than acetaminophen, which is unexpected, as these two drugs were administered as a single formulation and have similar half-lives. Furthermore, hydromorphone was undetectable. Taken together, these findings are highly suggestive of a fatal opioid overdose precipitated by diphenhydramine.

Anthropometry of the nose pre- and post-photogrammetric adjustments in a sample of Syrian medical students. A cross-sectional study.

Background and Aims: The individual's perceived beauty, sense of identity, and general well-being are all influenced by the social implications of the esthetics of their facial appearance. One of the major indicators of one's facial beauty is anthropometric proportions. This study was conducted to measure and evaluate the anthropometric proportions in a Syrian population, and to determine their desired nasal shape. Methods: A cross-sectional study was conducted on Syrian university students. Lateral and frontal pictures of the participants were taken using Canon EOS 250D from a standard distance of 100 cm. These pictures were analyzed, then nasal measurements were adjusted according to the participants' desire using Adobe Photoshop 2020. All anthropometric measurements were conducted on AutoCAD® 2019 software before and after the adjustments. Data was analyzed using the SPSS-25 using paired samples T test to compare the means. Results: The study included 53 females and 47 males. The mean age was 22.25. The mean unadjusted nasofrontal angle, nasolabial angle, nasomental angle, nasofacial angle, nasal index, Byrd and Hobar ratio, and Powell-modified Baum ratio were 141.80, 102.18, 129.21, 34.60, 71.71, 0.62, and 3.08 in the rhinoplasty-negative participants, and 145.89, 102.03, 130.20, 32.44, 67.96, 0.64, and 3.06 in the rhinoplasty-positive participants, respectively. While the mean of the adjusted previously mentioned angles were 144.59, 106.32, 131.19, 31.15, 62.91, 0.60, and 3.19 in the rhinoplasty-negative participants, and 146.31, 102, 130.20, 31, 62.55, 0.62, and 3.08 in the rhinoplasty-positive participants, respectively. Conclusion: In contrast to other populations, our study concluded that Syrians had unique anthropometric measurements and facial esthetics preferences. Moreover, the local plastic surgeons were able to identify most of the preferred nasal measurements for rhinoplasty in this ethnic group. It is advisable to use photogrammetry before rhinoplasty to identify the preferred nasal measurements of each individual to ensure the patient's satisfaction with the outcome of the surgery. Level of Evidence: Level IV, cross-sectional study.

Epidemiology and phylogeny of Haemonchus contortus through internal transcribed spacer 2 gene in small ruminants.

Introduction: Haemonchus contortus (H. contortus) is a blood-feeding nematode causing infectious disease haemonchosis in small ruminants of tropical and subtropical regions around the world. This study aimed to explore the prevalence and phylogeny of H. contortus in small ruminants using the internal transcribed spacer-2 (ITS-2) gene. In addition, a comprehensive review of the available literature on the status of H. contortus in Pakistan was conducted. Methods: Fecal samples were collected from sheep and goats (n = 180). Microscopically positive samples were subjected to DNA extraction followed by PCR using species-specific primers. Results: The overall prevalence of H. contortus was 25.55% in small ruminants. The prevalence of H. contortus was significantly associated with months and area. The highest occurrence of haemonchosis was documented in July (38.70%), whereas the lowest occurred in December (11.11%), with significant difference. The prevalence was highest in the Ghamkol camp (29.4%) and lowest in the arid zone of the Small Ruminant Research Institute (17.5%) (p = 0.01). The results of the systematic review revealed the highest prevalence of haemonchosis (34.4%) in Khyber Pakhtunkhwa (p = 0.001). Discussion: Phylogenetic analysis revealed a close relationship between H. contortus and isolates from Asia (China, India, Iran, Bangladesh, Malaysia, and Mongolia) and European countries (Italy and the United Kingdom). It has been concluded that H. contortus is prevalent in small ruminants of Kohat district and all over Pakistan, which could be a potential threat to food-producing animals, farmers, dairy, and the meat industry. Phylogenetic analysis indicates that H. contortus isolates share close phylogenetic relationships with species from Asia and Europe.

Pulmonary Manifestations of Systemic Lupus Erythematosus Among Adults in Aseer Region, Saudi Arabia.

Background: Nearly half of the Systemic lupus erythematosus (SLE) patients develop lung involvement. The study assessed the extent of pulmonary involvement among SLE patients and to identify the associated factors in the population. Methodology: This retrospective cohort study was conducted at Aseer Hospital and Khamis Myshat Hospital in the Southern region of Saudi Arabia. The study spanned from January 1, 2016, to June 3, 2023. Patient inclusion criteria encompassed individuals who received a definitive diagnosis and classification as per American College of Rheumatology criteria, while patients under 18 years of age and those with mixed connective tissue diseases were exclude. Results: A total of 247 participants were included. 41.7% (n=103) aged 41 years and older, 95.1% (n = 235) were females. Around 10.10% had diabetes mellitus and 17.00% had hypertension and hypothyroidism. Lupus Nephritis was in 15.40%. Chest involvement was reported in 21.9%, in the form of pleuritis (6.10%), pleural effusion (4.00%), and lupus pneumonitis (4.00%), interstitial lung disease (4.00%), pulmonary embolism (3.60%) of individuals, and pulmonary hemorrhage (2.80%). The respiratory symptoms reported by SLE were; dyspnea, cough, and chest pain each having a prevalence of around 18.0%. Palpitations have a relatively high occurrence at 13.80%. Meanwhile, hemoptysis (blood coughing) has a lower prevalence of 1.20%, and fever is reported at 2.80%. Having chronic kidney disease and hypertension were significantly associated with having pulmonary involvement; (χ2=3.308, p=0.027) and (χ2=7.782, Fisher's p=0.002) respectively. The seropositivity for antiphospholipid Abs, anti-CCP, and antids-DNA were significantly associated with pulmonary involvement (χ2=3.239, =p=0.049), (χ2=4.621, Fisher's p=0.023), and (χ2=8.248, p=0.010) respectively. Conclusion: The study found that 21.9% of SLE patients experience chest involvement, with varying degrees of pulmonary symptoms. Factors such as chronic kidney disease, hypertension, antiphospholipid antibodies, Anti-CCP positivity, and seropositivity for Anti-dsDNA were found to be significant associations with lung involvement, contributing to our understanding of SLE.

Evaluation of Clinical Preventive Management Provided by Primary Healthcare Physicians Against Brucellosis in Saudi Arabia.

BACKGROUND:  Brucellosis is among the most common zoonotic bacterial infections, leading to major public health consequences in endemic areas such as Saudi Arabia. Primary healthcare is crucial in controlling brucellosis, as it serves as the frontline for disease prevention, early detection, and appropriate management. However, enhancing the contribution of primary healthcare to the entire brucellosis notification process is necessary to minimize the underreporting and inadequate data collection, which hinders the implementation of effective control measures. OBJECTIVE: The objective of the study is to assess primary care physicians' knowledge and practice of clinical preventive management in Saudi Arabia regarding brucellosis using an adapted assessment tool featuring a semi-structured questionnaire. SUBJECTS AND METHODS: The current study's design is a cross-sectional study based on a questionnaire. Three hundred and seventy-three primary healthcare physicians in Saudi Arabia were chosen for self-administered online standardized questionnaires. RESULTS:  One-third of the participants answered all the knowledge assessment questions correctly. Most participants had more than 10 years of professional experience and were 40 or older. In response to the practice assessment questions, 210 physicians stated that they had encountered at least one case of brucellosis, and two-thirds had no compliance with the notification process of their cases. CONCLUSION: The limited knowledge and improper practice of primary care physicians regarding human brucellosis are possible underlying reasons for the underdiagnosis and underreporting of brucellosis patients at primary health care clinics in Saudi Arabia. Most research indicates that implementing specific educational programs to improve knowledge is necessary for primary healthcare workers. Furthermore, enhancing the community interaction between healthcare centers and the community facilitates effective control measures against brucellosis.

The Effect of Death Anxiety on Work Passion: Moderating Roles of Work Centrality and Work Connection.

Fear of death is an emotional manifestation of the instinct for self-preservation. Any threat to our existence induces an anxiety response. Death anxiety can trigger obsessive-compulsive behaviours, such as an obsessive passion for work. Using a sample of 314 participants (68.2% female), with a mean age of 38.97 years (SD = 10.36), this study sought to observe the predictive effect of death anxiety on work passion, as well as the moderating effect of work-family centrality and connection on the relationship between anxiety and passion. The results revealed that death anxiety negatively affects harmonious passion, and positively affects obsessive passion. Work centrality did not moderate the influence of death anxiety on harmonious and obsessive passion. Nonetheless, work connection moderated the influence of death anxiety on harmonious passion. The negative influence of death anxiety on harmonious passion was greater in a group with high work connection than a group with low connection.

Revolutionizing Psoriasis Topical Treatment: Enhanced Efficacy Through Ceramide/Phospholipid Composite Cerosomes Co-Delivery of Cyclosporine and Dithranol: In-Vitro, Ex-Vivo, and in-Vivo Studies.

Purpose: Improving the treatment of psoriasis is a serious challenge today. Psoriasis is an immune-mediated skin condition affecting 125 million people worldwide. It is commonly treated with cyclosporine-A (CsA) and dithranol (DTH). CsA suppresses the activation of T-cells, immune cells involved in forming psoriatic lesions. Meanwhile, DTH is a potent anti-inflammatory and anti-proliferative drug that effectively reduces the severity of psoriasis symptoms such as redness, scaling, and skin thickness. CsA and DTH belong to BCS class II with limited oral bioavailability. We aim to develop a drug delivery system for topical co-delivery of CsA and DTH, exploring its therapeutic potential. Methods: Firstly, we developed a niosomal drug delivery system based on ceramide IIIB to form Cerosomes. Cerosomes were prepared from a mixture of Ceramide, hyaluronic acid, and edge activator using a thin-film hydration technique. To co-deliver CsA and DTH topically for the treatment of psoriasis. These two hydrophobic drugs encapsulated into our synthesized positively charged particle cerosomes. Results:  Cerosomes had an average particle size of (222.36 nm± 0.36), polydispersity index of (0.415±0.04), Entrapment Efficiency of (96.91%± 0.56), and zeta potential of (29.36±0.38mV) for selected formula. In vitro, In silico, in vivo, permeation, and histopathology experiments have shown that cerosomes enhanced the skin penetration of both hydrophobic drugs by 66.7% compared to the CsA/DTH solution. Imiquimod (IMQ) induced psoriatic mice model was topically treated with our CsA/DTH cerosomes. We found that our formulation enhances the skin penetration of both drugs and reduces psoriasis area and severity index (PASI score) by 2.73 times and 42.85%, respectively, compared to the CsA/DTH solution. Moreover, it reduces the levels of proinflammatory cytokines, TNF-α, IL-10, and IL-6 compared to CsA/DTH solution administration. Conclusion: The Cerosomes nano-vesicle-containing CsA/DTH represents a more promising topical treatment for psoriasis, giving new hope to individuals with psoriasis, compared to commercial and other conventional alternatives.

Trastuzumab deruxtecan in human epidermal growth factor receptor 2-positive breast cancer brain metastases: a systematic review and meta-analysis.

BACKGROUND: Trastuzumab deruxtecan (T-DXd) has shown promising results in patients with breast cancer brain metastases (BCBMs). We conducted a systematic review and meta-analysis to evaluate the effectiveness and safety of T-DXd in the human epidermal growth factor receptor 2 (HER2)-positive BCBM population. PATIENTS AND METHODS: We searched PubMed, Embase, and Cochrane Library databases as well as American Society of Clinical Oncology (ASCO), European Society for Medical Oncology (ESMO), and San Antonio Breast Cancer Symposium (SABCS) websites for clinical trials (CTs) and observational studies evaluating T-DXd in patients with HER2-positive BCBM. Heterogeneity was assessed with I2 statistics. Random effects models were used for all statistical analyses, which were carried out using R software (version 4.2.2). RESULTS: Ten studies were included, six CTs (n = 189) and four observational studies (n = 130), with a total of 319 patients. The median progression-free survival was 15 months [95% confidence interval (CI) 13.9-16.1 months]. The objective response rate (ORR) was 61% (95% CI 52% to 70%), and the intracranial (IC)-ORR was 61% (95% CI 54% to 69%). No significant differences in ORR and IC-ORR were observed between CTs and observational studies (P = 0.31 and 0.58, respectively). The clinical benefit rate (CBR) was 80% (95% CI 52% to 94%), and the IC-CBR was 70% (95% CI 54% to 82%). The ORR was 68% (95% CI 57% to 77%) in the subgroup of patients with stable BMs and 60% (95% CI 48%-72%) in patients with active BM, with no significant difference between groups (P = 0.35). CONCLUSIONS: Our systematic review and meta-analysis supports the IC activity of T-DXd in patients with stable BM and active BM. TRIAL REGISTRATION: International Prospective Register of Systematic Reviews (PROSPERO) under the protocol number CRD42023422589.