FlowAtlas: an interactive tool for high-dimensional immunophenotyping analysis bridging FlowJo with computational tools in Julia.

As the dimensionality, throughput and complexity of cytometry data increases, so does the demand for user-friendly, interactive analysis tools that leverage high-performance machine learning frameworks. Here we introduce FlowAtlas: an interactive web application that enables dimensionality reduction of cytometry data without down-sampling and that is compatible with datasets stained with non-identical panels. FlowAtlas bridges the user-friendly environment of FlowJo and computational tools in Julia developed by the scientific machine learning community, eliminating the need for coding and bioinformatics expertise. New population discovery and detection of rare populations in FlowAtlas is intuitive and rapid. We demonstrate the capabilities of FlowAtlas using a human multi-tissue, multi-donor immune cell dataset, highlighting key immunological findings. FlowAtlas is available at https://github.com/gszep/FlowAtlas.jl.git.

Therapeutic Effects of Arctiin on Alzheimer's Disease-like Model in Rats by Reducing Oxidative Stress, Inflammasomes and Fibrosis.

BACKGROUND: Alzheimer's disease (AD) affects approximately 50 million people globally and is expected to triple by 2050. Arctiin is a lignan found in the Arctium lappa L. plant. Arctiin possesses anti-proliferative, antioxidative and anti-adipogenic. OBJECTIVES: We aimed to explore the potential therapeutic effects of Arctiin on rats with AD by evaluating the expression of TLR4, NLRP3, STAT3, TGF-ß, cyclin D1, and CDK2. METHODS: AD was induced in rats by administering 70 mg/kg of aluminum chloride through intraperitoneal injection daily for six weeks. After inducing AD, some rats were treated with 25 mg/kg of Arctiin daily for three weeks through oral gavage. Furthermore, to examine the brain tissue structure, hippocampal sections were stained with hematoxylin/eosin and anti-TLR4 antibodies. The collected samples were analyzed for gene expression and protein levels of TLR4, NLRP3, STAT3, TGF-ß, cyclin D1, and CDK2. RESULTS: In behavioral tests, rats showed a significant improvement in their behavior when treated with Arctiin. Microimages stained with hematoxylin/eosin showed that Arctiin helped to improve the structure and cohesion of the hippocampus, which was previously impaired by AD. Furthermore, Arctiin reduced the expression of TLR4, NLRP3, STAT3, TGF-ß, cyclin D1, and CDK2. CONCLUSION: Arctiin can enhance rats' behavior and structure of the hippocampus in AD rats. This is achieved through its ability to reduce the expression of both TLR4 and NLRP3, hence inhibiting the inflammasome pathway. Furthermore, Arctiin can improve tissue fibrosis by regulating STAT3 and TGF-ß. Lastly, it can block the cell cycle proteins cyclin D1 and CDK2.

Factors Affecting Patients' Atttendance for Periodontal Follow-up Visits after Crown Lengthening Surgery.

PURPOSE: To assess adherence to follow-up maintenance visits among patients who had previously undergone crown-lengthening surgery and investigate the different factors impacting their compliance. MATERIALS AND METHODS: A total of 314 patients were identified for follow-up appointments. Based on their responses, participants were categorised into four groups: attendees, non-attendees, refusals, and unreachable. Furthermore, data on sociodemographic factors (age, sex, nationality, marital status, education, occupation, and residential area), medical history, dental history (including missing teeth, implants, or orthodontic treatment history), and past appointment attendance (average yearly appointments, missed appointment percentage, and last appointment date) were collected and analysed to understand their influence on patient compliance. RESULTS: In a sample of 314 patients, 102 (32.5%) attended the appointments successfully. Improved attendance rates were significantly associated with being female, Saudi Arabian, married, and employed (p < 0.05). Moreover, patients with a high frequency of annual appointments and a recent history of appointments exhibited better compliance. None of the analysed dental factors affected the attendance rates. CONCLUSION: About one-third of patients who had undergone crown lengthening surgery were compliant with the follow-up visits. Different factors influenced this compliance pattern to varying extents, with more efforts needed to enhance patients' commitment to these visits.

eIF4F complex dynamics are important for the activation of the integrated stress response.

In response to stress, eukaryotes activate the integrated stress response (ISR) via phosphorylation of eIF2α to promote the translation of pro-survival effector genes, such as GCN4 in yeast. Complementing the ISR is the target of rapamycin (TOR) pathway, which regulates eIF4E function. Here, we probe translational control in the absence of eIF4E in Saccharomyces cerevisiae. Intriguingly, we find that loss of eIF4E leads to de-repression of GCN4 translation. In addition, we find that de-repression of GCN4 translation is accompanied by neither eIF2α phosphorylation nor reduction in initiator ternary complex (TC). Our data suggest that when eIF4E levels are depleted, GCN4 translation is de-repressed via a unique mechanism that may involve faster scanning by the small ribosome subunit due to increased local concentration of eIF4A. Overall, our findings suggest that relative levels of eIF4F components are key to ribosome dynamics and may play important roles in translational control of gene expression.

The effectiveness of water jet flossing and interdental flossing for oral hygiene in orthodontic patients with fixed appliances: a randomized clinical trial.

BACKGROUND: Orthodontic treatment presents challenges with plaque accumulation around brackets, archwires, and elastics, leading to retained plaque and gingival inflammation. Conventional toothbrushing may not be enough, requiring additional oral hygiene aids like interproximal brushes, dental flosses, and water flossers. Limited research exists on comparing water flossing and interdental flossing in orthodontic patients. Therefore, this study aims to assess their effectiveness in maintaining oral hygiene during active orthodontic treatment. METHODS: A single-blind, randomized, parallel clinical study recruited orthodontic patients with full-mouth brackets and archwires. Thirty participants were randomly assigned to either water jet flossing or interdental flossing groups. All participants were instructed to brush twice daily with a provided toothbrush and toothpaste and use the assigned intervention once daily at night. Clinical measures, including the Gingival Bleeding Index (BI), Plaque Index (PI), and Gingival Index (GI), were recorded at baseline and day 14. Descriptive statistics and statistical tests were performed using SPSS software. RESULTS: The water jet flossing group demonstrated a slightly higher, albeit non-significant, benefit in plaque removal (median difference of 6.79%%, P = 0.279) and bleeding reduction (median difference of 5.21%%, P = 0.172) compared to the interdental flossing group after two weeks. Both groups showed significant reductions in gingival bleeding index and plaque index from baseline to the 2-week follow-up. The interdental flossing group had median mean percentage differences of 16.13%% (plaque index) and 23.57% (gingival bleeding index), while the water jet flossing group had median percentage differences of 21.87% (plaque index) and 32.29% (gingival bleeding index). No significant changes in gingival index grades were observed in either group. CONCLUSION: Both water jet flossing and interdental flossing were effective in reducing plaque accumulation and gingival bleeding among orthodontic patients. While no significant differences were found between the two methods, water jet flossing showed a potential advantage. Further research is needed to validate its effectiveness, assess long-term impact, and understand its benefits for orthodontic patients.

Inability to rescue stalled ribosomes results in overactivation of the integrated stress response.

Endogenous and exogenous chemical agents are known to compromise the integrity of RNA and cause ribosome stalling and collisions. Recent studies have shown that collided ribosomes serve as sensors for multiple processes, including ribosome quality control (RQC) and the integrated stress response (ISR). Since RQC and the ISR have distinct downstream consequences, it is of great importance that organisms activate the appropriate process. We previously showed that RQC is robustly activated in response to collisions and suppresses the ISR activation. However, the molecular mechanics behind this apparent competition were not immediately clear. Here we show that Hel2 does not physically compete with factors of the ISR, but instead its ribosomal-protein ubiquitination activity, and downstream resolution of collided ribosomes, is responsible for suppressing the ISR. Introducing a mutation in the RING domain of Hel2-which inhibits its ubiquitination activity and downstream RQC but imparts higher affinity of the factor for collided ribosomes-resulted in increased activation of the ISR upon MMS-induced alkylation stress. Similarly, mutating Hel2's lysine targets in uS10, which is responsible for RQC activation, resulted in increased Gcn4 target induction. Remarkably, the entire process of RQC appears to be limited by the action of Hel2, as the overexpression of this one factor dramatically suppressed the activation of the ISR. Collectively, our data suggest that cells evolved Hel2 to bind collided ribosomes with a relatively high affinity but kept its concentration relatively low, ensuring that it gets exhausted under stress conditions that cannot be resolved by quality control processes.

Perceived Access to Healthcare of Indigenous Peoples in Canada With Rheumatoid Arthritis and Their First-Degree Relatives.

OBJECTIVE: There are complex and interrelated factors that lead to inequitable healthcare delivery in Canada. Many of the factors that underlie these inequities for Canada's geographically dispersed Indigenous peoples remain underexamined. METHODS: A cohort of 831 First Nations (FN) individuals from urban and remote communities were recruited into a longitudinal study of rheumatoid arthritis (RA) risk from 2005 to 2017. Data from each participant's initial enrollment visit were assessed using a survey that captured concerns with healthcare access. RESULTS: We found that remote participants with RA reported poor access compared to remote first-degree relatives (FDRs; P < 0.001); this difference was not observed for urban participants with RA. We observed substantial differences based on sex; female participants perceived access to care to be more difficult than male participants in both urban and remote cohorts (P < 0.001). We also observed that male participants with RA reported poor access to care compared to male FDRs. Importantly, access to care in remote communities appeared to improve over the duration of the study (P = 0.01). In a logistic regression analysis, female sex, remote location, and older age were independent predictors of poor access to care. Predictors of poor access in participants with RA also included female sex, remote location, and older age. CONCLUSION: FN peoples living in remote communities, particularly those with an established RA diagnosis, report more problems accessing health care. Sex-based inequities exist, with FN female individuals reporting greater difficulties in accessing appropriate health care, regardless of RA diagnosis. Addressing these sex-based inequities should be a high priority for improving healthcare delivery.

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.

Efficacy of Three Interdental Cleaning Methods for Peri-Implant Health Maintenance of Single Implant-Supported Crowns: A Randomised Clinical Trial.

PURPOSE: To compare the effectiveness of an interproximal brush, a water flosser, and dental floss in removing plaque and reducing inflammation around implant-supported crowns. MATERIALS AND METHODS: A randomised controlled trial was conducted involving 45 participants with implant-supported single crowns. The participants were randomly assigned to three groups: interproximal brush, water flosser, and dental floss. Plaque index scores, gingival index scores, and interleukin-6 (IL-6) levels were assessed at baseline and after a two-week period. Statistical analysis was performed to compare the outcomes among the groups. RESULTS: Following the second visit, improvements in plaque control were observed across all three interdental cleaning methods. The water flosser demonstrated a slight reduction in IL-6 levels (60.17 ± 3.07 vs 58.79 ± 4.04) compared to the initial visit, although this decrease was not statistically significant. Conversely, both the interdental brush and dental floss exhibited a slight increase in IL-6 levels at the second visit (60.73 ± 2.93 and 55.7 ± 10.64, respectively) compared to the mean at the first visit (58.38 ± 3.24 and 54.6 ± 2.22, respectively). Among the groups, only the interproximal brush demonstrated a statistically significant difference in IL-6 levels (p=0.008), while no statistically significant differences were observed in the dental floss and water flosser groups. CONCLUSION: Within the study's limitations, our findings suggest that all three methods of interdental cleaning effectively improve plaque control and reduce gingival inflammation. However, using a water flosser appears to reduce inflammation more effectively, highlighting its potential advantage over the other two methods. Further research is needed to evaluate the long-term efficacy and impact of these methods on implant survival.

The effectiveness of dental water jet in reducing dental plaque and gingival bleeding in orthodontic patients: A systematic review and meta-analysis of randomized clinical trials.

INTRODUCTION: This systematic review and meta-analysis tests the effectiveness of dental water jet (DWJ) with manual toothbrushes (MTB) compared to MTB alone in oral health maintenance in orthodontic patients. METHODS: Four databases were systematically searched: PubMed, Scopus, Web of Science (WoS) and Cochrane Library until 6 January 2022 using a combination of medical subject heading (MeSH) terms and keywords. Randomized clinical trials (RCTs) were only included and critically appraised using the Cochrane Risk of Bias (ROB) tool. The mean difference (MD) effect measure was calculated using the Mantel-Haenszel statistical test (95% confidence interval [CI]) to compare both study groups (p-value < 0.05). RESULTS: After reviewing 5881 studies from a systematic search, six were selected for inclusion, with four involved in the quantitative analysis. The risk of bias was low in two studies, moderate in two studies and high in the remaining two studies. The meta-analysis showed a significant improvement in plaque index and bleeding scores in DWJ + MTB group compared MTB alone group in orthodontic patients with generalized gingivitis (MD = -0.75, 95% CI [-1.29, -0.22], p = 0.006) and (MD = -0.17, 95% CI [-0.27, -0.08], p = 0.0003), respectively. However, no significant improvement was detected between both groups in the gingival index. CONCLUSIONS: The use of DWJ as an adjunctive device in addition to MTB can be an effective strategy for maintaining oral hygiene in orthodontic patients with gingivitis. However, more high-quality RCTs are needed to confirm the findings.

Addressing Occupational Back Pain: A Systematic Review of Preventive and Therapeutic Strategies.

Occupational back pain has emerged as a significant public health concern. Despite several efforts to mitigate the adverse effects of occupational back pain, this issue still persists across the globe. This systematic review summarizes the preventive and therapeutic options available for managing occupational back pain. A systemic search was carried out in various databases including PubMed, Web of Science, CINAHL Ultimate, and Scopus to identify relevant literature. The search was also extended to Google Scholar to identify more relevant studies. A combination of keywords was used during the search. Studies were included if they focused on occupational back pain, investigated preventive and treatment options, and were published in English. A total of 20 relevant studies, including 62,176 participants, were included in this systemic review. Out of these 20 studies, 10 were randomized control trials, four were cross-sectional studies, two were longitudinal studies, one was a single-blinded clinical study, two were prospective studies, and the remaining one was a pilot study. This systemic review identified various interventions to improve occupational back pain. The common therapeutic strategies included educational programs, physio and rehab interventions, acupuncture, mixed treatment strategies, reflexology, massage, yoga, active physical therapy, and real-time occupational internet-based interventions. Some studies also reported the effectiveness of opioid therapy and non-steroidal anti-inflammatory drugs for managing back pain. Findings indicated that these therapies effectively reduced occupational back pain and improved quality of life. However, opioid therapy uses also raised safety concerns. The findings of this systemic review highlight the importance of adopting evidence-based strategies to address occupational back pain effectively.

Chemotherapeutic Activity of Imidazolium-Supported Pd(II) o-Vanillylidene Diaminocyclohexane Complexes Immobilized in Nanolipid as Inhibitors for HER2/neu and FGFR2/FGF2 Axis Overexpression in Breast Cancer Cells.

Two bis-(imidazolium-vanillylidene)-(R,R)-diaminocyclohexane ligands (H2(VAN)2dach, H2L1,2) and their Pd(II) complexes (PdL1 and PdL2) were successfully synthesized and structurally characterized using microanalytical and spectral methods. Subsequently, to target the development of new effective and safe anti-breast cancer chemotherapeutic agents, these complexes were encapsulated by lipid nanoparticles (LNPs) to formulate (PdL1LNP and PdL2LNP), which are physicochemically and morphologically characterized. PdL1LNP and PdL2LNP significantly cause DNA fragmentation in MCF-7 cells, while trastuzumab has a 10% damaging activity. Additionally, the encapsulated Pd1,2LNPs complexes activated the apoptotic mechanisms through the upregulated P53 with p < 0.001 and p < 0.05, respectively. The apoptotic activity may be triggered through the activity mechanism of the Pd1,2LNPs in the inhibitory actions against the FGFR2/FGF2 axis on the gene level with p < 0.001 and the Her2/neu with p < 0.05 and p < 0.01. All these aspects have triggered the activity of the PdL1LNP and PdL2LNP to downregulate TGFß1 by p < 0.01 for both complexes. In conclusion, LNP-encapsulated Pd(II) complexes can be employed as anti-cancer drugs with additional benefits in regulating the signal mechanisms of the apoptotic mechanisms among breast cancer cells with chemotherapeutic-safe actions.

3-Substituted Coumarins Inhibit NorA and MepA Efflux Pumps of Staphylococcus aureus.

Coumarins are compounds with scientifically proven antibacterial properties, and modifications to the chemical structure are known to improve their effects. This information is even more relevant with the unbridled advances of antibiotic resistance, where Staphylococcus aureus and its efflux pumps play a prominent role. The study's objective was to evaluate the potential of synthetic coumarins with different substitutions in the C-3 position as possible inhibitors of the NorA and MepA efflux pumps of S. aureus. For this evaluation, the following steps took place: (i) the determination of the minimum inhibitory concentration (MIC); (ii) the association of coumarins with fluoroquinolones and ethidium bromide (EtBr); (iii) the assessment of the effect on EtBr fluorescence emission; (iv) molecular docking; and (v) an analysis of the effect on membrane permeability. Coumarins reduced the MICs of fluoroquinolones and EtBr between 50% and 87.5%. Coumarin C1 increased EtBr fluorescence emission between 20 and 40% by reinforcing the evidence of efflux inhibition. The molecular docking results demonstrated that coumarins have an affinity with efflux pumps and establish mainly hydrogen bonds and hydrophobic interactions. Furthermore, C1 did not change the permeability of the membrane. Therefore, we conclude that these 3-substituted coumarins act as inhibitors of the NorA and MepA efflux pumps of S. aureus.

The anticancer and anti-inflammatory activity screening of pyridazinone-based analogs against human epidermoid skin cancer with detailed mechanistic analyses.

3(2H)-Pyridazinone derivatives based on 4-biphenyl, naphtha-2-yl, pyridine, or piperidine moiety were synthesized and characterized using I-R and 1HNMR spectra. The activity and cytotoxicity of some synthesized compounds on the skin epidermoid cancer cell proliferation and progression were investigated. The pyridazine isomer with pyridine revealed a significant decrease in the level of nitric oxide p < 0.01 than the activity of caffeine phenecyl ester. The activity of the three active isomers recorded significant activity for their total antioxidant content that triggers their ability for the scavenging the oxygen free radicals significantly p < 0.01. Moreover, revealing the pharmaceutical activity of the isomers as anti-inflammatory agents, IL-6, IL10, and IL12 have been decreased by variable significant values. Additionally, the active isomers revealed variable actions on the skin cancer cell to induce apoptosis using annexin V-FITC/PI. Pyridine was the highest isomer to induce late apoptosis and necrosis for the skin cancer cells against the use of cisplatin. Importantly, Molecular modeling experiments including docking and dynamic simulations were done for the most active 3 analogs to explore the ligand binding and stability leading to exploring the structure-activity relationship with biological target PARP1 which showed a good binding propensity to pyridazine binding site which supports the in vitro data. In conclusion, the pyridazine moieties with piperdine, naphthayl, and pyridine have pharmacological activities against skin cancer epidermoid by triggering action in inhibition of the proliferation and progression with an up-regulated apoptotic mechanism that evades the emergence of cisplatin resistance among different cancer cells.Communicated by Ramaswamy H. Sarma.

Saudi Health System and Health Security Structure: A Scope Review Study Addressing the National Need for Governing the Health Security.

Health security has gained significant attention at the national and global levels, "security" is not a simple term; instead, it is "essentially contested" - that is, it induces debates about what it means and how to use it. This study aimed to define three terms frequently used in health security discussions. These terms are national health security, Global Health Security, and public health. The research method was a scoping review performed in three stages. The first stage was electronic searching based on selection criteria among multiple sources at various time points during the year 2023. These sources included online literature searches, websites of non-governmental organizations (NGOs), and other governmental health agencies. The second stage involved determining the relevance of the selected papers to the study's objectives; the selected papers had moderate to high relevance to the study's objectives. The third stage was to evaluate the methodological quality of a study; we selected peer-reviewed published papers and websites recognized as trustworthy sources of information. The search yielded 143 articles; five met the inclusion criteria and were subjected to the definition of health security. Despite proposed definitions, agreement has yet to be reached on the content and scope of health security. Another main finding is that health security requires more state and international collaboration efforts to reach Global Health Security. To the best of our knowledge, no known government body or organization is responsible for governing health security in Saudi Arabia. However, the current study presents a definition of health security and differentiates it from the public health approach, in addition to emphasizing the importance of governing the related health sectors within each country in order to improve health security and have a positive impact on overall Global Health Security.

Prevalence of Radiographic Alveolar Bone Loss as a Function of Age in the Periodontics Clinic Population at the College of Dentistry, King Saud University, Riyadh, Saudi Arabia.

PURPOSE: The purpose of the present observational study was to assess the prevalence of radiographic alveolar bone loss (ABL) as a function of age at the Periodontics Clinics at the College of Dentistry, King Saud University, Riyadh, Saudi Arabia. MATERIALS AND METHODS: Medical and dental healthcare records of individuals visiting the Periodontics Clinics at College of Dentistry, King Saud University, Riyadh Saudi Arabia were assessed. The following information was retrieved: age, gender, educational status, and systemic diseases (diabetes mellitus [DM], hypertension, osteoporosis and obesity). Digital full-mouth radiographs were retrieved from patients' dental records, and marginal bone loss (MBL) was assessed on the mesial and distal surfaces of all teeth. Logistic regression analyses (LRA) were done to assess the correlation between ABL and gender, age, educational status and duration since diagnosis of the aforementioned systemic conditions. p < 0.05 was considered statistically significant. RESULTS: In total, medical and periodontal healthcare records of 495 individuals were retrieved and assessed. All individuals were citizens of the KSA. Among these, 107 were healthy controls and 98, 95, 96 and 99 individuals had a medical diagnosis of type-2 DM, hypertension, obesity and osteoporosis, respectively. There was no statistically significant difference in the mean age and gender of all medically compromised participants. The prevalence of mild, moderate, and severe periodontitis in the total patient population was 51.4%, 37.5% and 36.5%, respectively. Among all healthy controls, the prevalence of mild, moderate, and severe periodontitis was 16.3%, 25.5% and 33.4%, respectively. There was no difference in the prevalence of mild, moderate, and severe periodontitis in relation to advancing age in the entire patient population. CONCLUSION: Advancing age did not seem to affect ABL in the present patient population. Patient education, oral hygiene maintenance and SES seem to be more predictable indicators of ABL than increasing age.

Modifiable risk factors linked to the development of rheumatoid arthritis: evidence, immunological mechanisms and prevention.

Rheumatoid Arthritis (RA) is a common autoimmune disease that targets the synovial joints leading to arthritis. Although the etiology of RA remains largely unknown, it is clear that numerous modifiable risk factors confer increased risk to developing RA. Of these risk factors, cigarette smoking, nutrition, obesity, occupational exposures and periodontal disease all incrementally increase RA risk. However, the precise immunological mechanisms by which these risk factors lead to RA are not well understood. Basic and translational studies have provided key insights into the relationship between inflammation, antibody production and the influence in other key cellular events such as T cell polarization in RA risk. Improving our general understanding of the mechanisms which lead to RA will help identify targets for prevention trials, which are underway in at-risk populations. Herein, we review the modifiable risk factors that are linked to RA development and describe immune mechanisms that may be involved. We highlight the few studies that have sought to understand if modification of these risk factors reduces RA risk. Finally, we speculate that modification of risk factors may be an appealing avenue for prevention for some at-risk individuals, specifically those who prefer lifestyle interventions due to safety and economic reasons.

Outcome of a conservatively treated large Pipkin I fracture dislocation: a case report.

Pipkin I fracture dislocation is a rare injury. They commonly present following high mechanism trauma with possible devastating complications regardless of the treatment option. Treatment consensus depends on fracture reduction, size, site, and displacement. Surgical management is reserved for large fragments. We present a 42-year-old female presented with multiple chest injuries and left sided Pipkin I fracture dislocation Two days following the trauma. The fracture was found to be vertical in nature and was managed by closed reduction and a period of bed rest and skeletal traction. She was followed over a 3-year period and showed satisfactory results. We believe that the vertical nature of the fracture and maintenance of the anatomic reduction led to her successful outcome.

The tRNA methyltransferase TrmB is critical for Acinetobacter baumannii stress responses and pulmonary infection.

IMPORTANCE: As deficiencies in tRNA modifications have been linked to human diseases such as cancer and diabetes, much research has focused on the modifications' impacts on translational regulation in eukaryotes. However, the significance of tRNA modifications in bacterial physiology remains largely unexplored. In this paper, we demonstrate that the m7G tRNA methyltransferase TrmB is crucial for a top-priority pathogen, Acinetobacter baumannii, to respond to stressors encountered during infection, including oxidative stress, low pH, and iron deprivation. We show that loss of TrmB dramatically attenuates a murine pulmonary infection. Given the current efforts to use another tRNA methyltransferase, TrmD, as an antimicrobial therapeutic target, we propose that TrmB, and other tRNA methyltransferases, may also be viable options for drug development to combat multidrug-resistant A. baumannii.

Isolation and Detection of Drug-Resistant Bacterial Pathogens in Postoperative Wound Infections at a Tertiary Care Hospital in Saudi Arabia.

Background: Surgical site infections (SSIs), especially when caused by multidrug-resistant (MDR) bacteria, are a major healthcare concern worldwide. For optimal treatment and prevention of antimicrobial resistance, it is important for clinicians to be aware of local drug-resistant bacterial pathogens that cause SSIs. Objective: To determine the frequency patterns of drug-resistant bacterial strains causing SSIs at a tertiary care hospital in Saudi Arabia. Methods: This retrospective study was conducted at the Microbiology laboratory of Al-Noor Specialist Hospital, Makkah, Saudi Arabia, and included wound swab samples from all cases of SSI between January 01, 2017, and December 31, 2021. The swabs were processed for the identification of bacterial strains and their resistance pattern to antibiotics according to the Clinical and Laboratory Standards Institute. Results: A total of 5409 wound swabs were analyzed, of which 3604 samples (66.6%) were from male. Most samples were from the Department of Surgery (43.3%). A total of 14 bacterial strains were isolated, of which 9 were Gram-negative bacteria. The most common isolates were Klebsiella pneumoniae, followed by Pseudomonas aeruginosa, Escherichia coli, Acinetobacter baumannii, methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-resistant Enterococci (VRE), and vancomycin-resistant S. aureus (VRSA). In terms of MDR in 2021, the highest rate of carbapenem-resistance was in A. baumannii (97%). MDR was as follows: A. baumannii, 97%; K. pneumoniae, 81%; E. coli, 71%; MRSA, 60%; P. aeruginosa, 33%; VRE, 22%; and VRSA, 2%. Conclusion: This study showed that in the city of Makkah, Saudi Arabia, the rates of MDR bacteria are high, with the majority being Gram-negative.