Dipolar skyrmions and antiskyrmions of arbitrary topological charge at room temperature.

Magnetic skyrmions are localized, stable topological magnetic textures that can move and interact with each other like ordinary particles when an external stimulus is applied. The efficient control of the motion of spin textures using spin-polarized currents opened an opportunity for skyrmionic devices such as racetrack memory and neuromorphic or reservoir computing. The coexistence of skyrmions with high topological charge in the same system promises further possibilities for efficient technological applications. In this work, we directly observe dipolar skyrmions and antiskyrmions with arbitrary topological charge in Co/Ni multilayers at room temperature. We explore the dipolar-stabilized spin objects with topological charges of up to 10 and characterize their nucleation process, their energy dependence on the topological charge and the effect of the material parameters on their stability. Furthermore, our micromagnetic simulations demonstrate spin-transfer-induced motion of these spin objects, which is important for their potential device application.

The role of dietitian follow-ups on nutritional outcomes post-bariatric surgery.

BACKGROUND: Current evidence recommends dietary counselling with a registered dietitian (RD) for successful weight loss after metabolic bariatric surgery; however, there are limited data on the effect of RD follow-ups on micronutrient deficiencies. This study evaluated the effects of the number of postoperative RD visits on nutritional outcomes, including weight loss and micronutrient deficiencies. OBJECTIVES: The aim of this study was to evaluate the effects of the number of postoperative registered dietitian visits on nutritional outcomes, including weight loss and micronutrient deficiencies after metabolic and bariatric surgery. SETTING: Cleveland Clinic Abu Dhabi, United Arab Emirates METHODS: This retrospective study included patients who underwent bariatric surgery between September 2015 and June 2020. Demographics, weight loss, micronutrients, and the number of postoperative RD visits were evaluated. Baseline and 12-month postsurgery outcomes were compared based on the number of RD follow-ups. RESULTS: A total of 174 primary and 46 revisions were included. Patients were 73.6% female, with a mean age of 40 years. The initial mean body mass index was 42.8 kg/m2. Number of RD visits were as follows: 0-1 (39 patients), 2 (59 patients), 3 (55 patients), and 4 or more (67 patients). Baseline (pre-operative) micronutrient values were within normal range. In comparison with the reference group (REF = 0-1 post-op RD visits), patients with 3 RD visits had 7% higher total body weight loss (P < .001) and maintained micronutrients within the normal range at 12 months postoperative. Mean differences in postoperative values were statistically significant (P < .05) for weight, vitamin B12, and vitamin D but not for hemoglobin, ferritin, calcium, folate, vitamin B1, copper, and zinc. CONCLUSION: Our study suggests that three or more RD visits during the first 12 months after bariatric surgery are associated with improved outcomes, including significant percent total body weight loss and lower rates of micronutrient deficiencies.

Efficacy of Handheld Ultrasound in Medical Education: A Comprehensive Systematic Review and Narrative Analysis.

Miniaturization has made ultrasound (US) technology ultraportable and, in association with their relatively low cost, made handheld devices attractive for medical education training programs. However, performing an ultrasound requires complex skills, and it is unclear whether handheld devices are suitable for the training of novices. Our study aimed to identify to what extent handheld US devices can be employed in medical undergraduates' and residents' education. We selected studies that evaluate the results obtained by students and/or residents who have participated in ultrasound training programs using handheld devices. The studies were included if they reported post-test (pre-test optional) achievements or a comparison with a control group (a group of experts or novices who underwent a different intervention). Twenty-six studies were selected, and their characteristics were summarized. Handheld ultrasound devices were used in training programs to learn echocardiography, abdominal, and/or musculoskeletal ultrasound. Statistically significant progress was noted in the ability of naïve participants to capture and interpret ultrasound images, but training duration influenced the outcomes. While ultrasound training using handheld devices has proven to be feasible for various body regions and purposes (e.g., better understanding of anatomy, clinical applications, etc.), the long-term impacts of handheld education interventions must be considered in addition to the short-term results to outline guidelines for targeted educational needs.

Incremental mortality associated with nontuberculous mycobacterial lung disease among US Medicare beneficiaries with chronic obstructive pulmonary disease.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is a common comorbidity in patients with nontuberculous mycobacterial lung disease (NTMLD). Both conditions are associated with increased morbidity and mortality, but data are lacking on the additional burden associated with NTMLD among patients with COPD. Thus, the goal of this study was to assess the incremental mortality risk associated with NTMLD among older adults with COPD. METHODS: A retrospective cohort study was conducted using the US Medicare claims database (2010-2017). Patients with preexisting COPD and NTMLD (cases) were matched 1:3 by age and sex with patients with COPD without NTMLD (control patients). Patients were followed up until death or data cutoff (December 31, 2017). Incremental risk of mortality was evaluated by comparing the proportions of death, annualized mortality rate, and mortality hazard rate between cases and control patients using both univariate and multivariate analyses adjusting for age, sex, comorbidities, and COPD severity. RESULTS: A total of 4,926 cases were matched with 14,778 control patients. In univariate analyses, a higher proportion of cases (vs. control patients) died (41.5% vs. 26.7%; P < 0.0001), unadjusted annual mortality rates were higher among cases (158.5 vs. 86.0 deaths/1000 person-years; P < 0.0001), and time to death was shorter for cases. This increased mortality risk was also reflected in subsequent multivariate analyses. Patients with COPD and NTMLD were more likely to die (odds ratio [95% CI], 1.39 [1.27-1.51]), had higher mortality rates (rate ratio [95% CI], 1.36 [1.28-1.45]), and had higher hazard of death (hazard ratio [95% CI], 1.37 [1.28-1.46]) than control patients. CONCLUSIONS: The substantial incremental mortality burden associated with NTMLD in patients with COPD highlights the importance of developing interventions targeting this high-risk group and may indicate an unmet need for timely and appropriate management of NTMLD.

Ocular Mucoadhesive and Biodegradable Sponge-Like Inserts for the Sustained and Controlled Delivery of Voriconazole; Preparation, D-optimal Factorial Optimization and in-vivo Evaluation.

The aim of this study was to formulate and optimize by statistical means mucoadhesive and biodegradable sponge-like inserts loaded with voriconazole (VCZ) which increases the contact time of the drug with the eye and sustain its release from the formula in a controlled manner. This avoids the pulsed effect reported for the drug suspension and results in reducing the number of drug instillations in the eye with the result of enhancing the patient compliance. Also, the sponge like nature of the insert reduces the foreign body sensation caused by other ocular solid dosage forms. They were prepared using casting/freeze-drying technique using five polymers namely high molecular weight chitosan (CH), sodium alginate (AL), sodium carboxy methyl cellulose (CMC), gellan gum (GG) and xanthan gum (XG). The prepared inserts were subjected to evaluations of their visual appearance, weight variation, drug content, surface pH, in-vitro release (percent drug released after 1h (Q1 (%)), mean dissolution time (MDT) and dissolution efficiency (DE)) in addition to kinetic analysis of the release data, water uptake, mucoadhesion and rheology of the forming plain polymer solution at the maximum rate of shear. The independent variables of the D-optimal factorial design were the polymer type and concentration while Q1 (%), MDT, DE, % water uptake after 15 minutes and rheology at the maximum rate of shear were chosen as dependant variables. The performed optimization process using design expert software showed an optimum formula consisting of 2 % GG. It showed slow release behavior compared to the drug suspension. FTIR and DSC studies showed that there is no interaction between VCZ and GG. The optimum formula has good in-vitro mucoadhesive properties and pH in the safe ocular range. Moreover, it showed promising in-vivo results of rapid hydration and gelling in addition to good mucoadhesive behavior when instilled in the eye, high ocular safety and biocompatibility, sustained antifungal activity in comparison to the drug suspension and finally biodegradation. So, it may be taken into consideration as an outstanding carrier for the ocular delivery of VCZ.

Safety assessment of Enterococcus lactis strains complemented with comparative genomics analysis reveals probiotic and safety characteristics of the entire species.

BACKGROUND: The gut microbiota is considered a rich source for potential novel probiotics. Enterococcus genus is a normal component of a healthy gut microbiota, suggesting its vital role. Nosocomial infections caused mainly by E. facalis and E. faecium have been attributed to the plasticity of the Enterococcus genomes. In this study, we assessed the probiotic and safety characteristics of two E. lactis strains isolated from the human gut microbiota using in-vitro and in silico approaches. Additionally, the safety of the E. lactis species was evaluated using comparative genomics analysis. RESULTS: The two E. lactis strains 10NA and 50NA showed resistance to bile salts and acid tolerance with antibacterial activity against Escherichia coli, Salmonella typhi, and Clostridioides difficile. For safety assays, the two strains did not display any type of hemolysis on blood agar, and the survival of Caco-2 cells was not significantly different (P-value > 0.05) compared to the control using cell free supernatants at 100% (v/v), 50% (v/v), 10% (v/v), and 5% (v/v) concentrations. Regarding antibiotic susceptibility, both strains were sensitive to vancomycin, tetracycline, and chloramphenicol. Comprehensive whole-genome analysis revealed no concerning associations between virulence or antibiotic resistance genes and any of the identified mobile genetic elements. Comparative genome analysis with closely related E. faecium species genomes revealed the distinctive genomic safety of the E. lactis species. CONCLUSIONS: Our two E. lactis strains showed promising probiotic properties in-vitro. Their genomes were devoid of any transferable antibiotic resistance genes. In silico comparative analysis confirmed the safety of the E. lactis species. These results suggest that E. lactis species could be a potential source for safer Enterococcus probiotic supplements.

The HACE1 E3 ligase mediates RAC1-dependent control of mTOR signaling complexes.

HACE1 is a HECT family E3 ubiquitin-protein ligase with broad but incompletely understood tumor suppressor activity. Here, we report a previously unrecognized link between HACE1 and signaling complexes containing mammalian target of rapamycin (mTOR). HACE1 blocks mTORC1 and mTORC2 activities by reducing mTOR stability in an E3 ligase-dependent manner. Mechanistically, HACE1 binds to and ubiquitylates Ras-related C3 botulinum toxin substrate 1 (RAC1) when RAC1 is associated with mTOR complexes, including at focal adhesions, leading to proteasomal degradation of RAC1. This in turn decreases the stability of mTOR to reduce mTORC1 and mTORC2 activity. HACE1 deficient cells show enhanced mTORC1/2 activity, which is reversed by chemical or genetic RAC1 inactivation but not in cells expressing the HACE1-insensitive mutant, RAC1K147R . In vivo, Rac1 deletion reverses enhanced mTOR expression in KRasG12D -driven lung tumors of Hace1-/- mice. HACE1 co-localizes with mTOR and RAC1, resulting in RAC1-dependent loss of mTOR protein stability. Together, our data demonstrate that HACE1 destabilizes mTOR by targeting RAC1 within mTOR-associated complexes, revealing a unique ubiquitin-dependent process to control the activity of mTOR signaling complexes.

Tejocote Root's Role in Symptomatic Mobitz Type 1 Heart Block: A Compelling Case Report.

The clinical presentation and diagnosis of Tejocote root toxicity causing Mobitz Type 1 remains a scarcely clinical phenomenon, often resulting in delayed diagnosis and treatment. This case report highlights a 30-year-old female presenting with a constellation of symptoms, including fatigue, dizziness, chest pressure, myalgias, nausea, vomiting, and peripheral tingling. Significantly, the patient had been using Tejocote root as an over-the-counter laxative acquired from Mexico. Laboratory findings revealed detectable Digoxin levels in her bloodstream, while an electrocardiogram (EKG) indicated sinus bradycardia with Mobitz Type 1 heart block. The patient was treated with a single dose of atropine 0.5 mg IV push. A repeat EKG before discharge showed resolution of the Mobitz type 1. This case underscores the potential cardiovascular repercussions of Tejocote root consumption and emphasizes the importance of heightened clinical awareness, especially in regions where such herbal supplement usage is prevalent.

Persistent Headaches in an Avid Hiker: A Case of Chronic Coccidioidal Meningitis.

The clinical presentation, diagnosis, treatment, and complications of coccidioidal meningitis caused by the dimorphic pathogenic fungus Coccidioides (Coccidioides immitis and Coccidioides posadasii) have been well documented in the literature. Despite the abundance of literature concerning this disease manifestation, it is not very commonly seen in clinical practice, delaying its diagnosis and treatment and leading to devastating neurological sequelae. Therefore, considering this disease process as a potential diagnosis in endemic areas is important for appropriate and timely treatment. We present the case of a 26-year-old male who was found to have chronic coccidioidal meningitis on further investigation. The patient presented as a transfer for an abnormal head MRI with a three-month history of progressive occipital headaches and shortness of breath. Associated symptoms included transit vision loss, upper extremity numbness, night sweats, decreased appetite, and weight loss. Relevant risk factors were being a hiker and living in the southwest of Texas. The patient was started on empiric ceftriaxone and vancomycin. A repeat MRI showed leptomeningeal enhancement and acute infarcts in the left temporal lobe and lentiform nucleus. Cerebrospinal fluid (CSF) analysis showed pleocytosis with lymphocytic predominance, the presence of eosinophils, elevated protein level, and an extremely low glucose level. Further workup ruled out syphilis and tuberculosis. Therefore, considering his clinical presentation, risk factors, and workup results, ceftriaxone and vancomycin were discontinued, and high-dose oral fluconazole was started, which produced a marked clinical response within the next 48 hours. A CT thorax showed findings suggestive of pulmonary coccidioidomycosis, and Coccidioides serology in both serum and CSF specimens returned positive.

Prevalence of Depressive Symptoms Among an Undergraduate Health Sciences Student Population: A Cross-Sectional Study.

PURPOSE: Undergraduate health sciences students are irrefutably liable to intrapersonal tension that may provoke the almost imperceptible onset and incremental expansion of depressive symptoms. Mental health is often a deplorably neglected topic despite posing as a catalyst in many students' academic demise. Thus, the primary objective of this paper is to provide an insight into a multitude of variables that foster depressive symptoms. In doing so, the scope of subclinical depression that could be hindering a student's academic performance shall be illuminated. METHODOLOGY: A cross-sectional study was conducted among health sciences students comprising both genders, any nationality, students 18 years of age or older, and students within their first three years of undergraduate study. The well-established Patient Health Questionnaire-9 was distributed along with a non-standardized questionnaire that inquires about additional risk factors. The chi-square test method was used to associate the dependent and independent variables, and statistical significance was done at p-value ≤ 0.05. FINDINGS: It was observed that 34.8% of participants suffer depressive symptoms. Participants' sex and marital status, among many other factors, like age, program and year of study, are found to be statistically insignificant. Conversely, nationality, university-related workload, smoking, alcohol intake and more are noted to be significantly associated with the development of depressive symptoms. ORIGINALITY: This study is an original work done by the authors to investigate the prevalence of depressive symptoms among undergraduate health sciences students. The non-standardized questionnaire employed has been reviewed to ensure that it is without discrimination of any gender or biased towards any stakeholders.

Chronic Recurrent Multifocal Osteomyelitis: A Comprehensive Literature Review.

Chronic recurrent multifocal osteomyelitis (CRMO) is a non-infectious, inflammatory disorder of the bones. CRMO typically affects children, with a predisposition to females. Bone-related pain is often felt in the metaphysis of long bones, particularly of the lower extremities, but it can also target other sites at varied time intervals. Patients are likely to complain of tenderness and swelling that may cause considerable disability and adversely impact quality of life. There are three main pathophysiological mechanisms that have been hypothesized to drive CRMO including imbalanced cytokine expression, increased inflammasome activation, and enhanced osteoclast differentiation. Therapies have been based on targeting and suppressing these key players in CRMO patients. The first step in management involves pain control. Non-steroidal anti-inflammatory drugs should provide initial relief, albeit temporarily. It is imperative to initiate immunosuppressive medication that will help limit bone involvement and thereby prevent the development of fractures or leg-length discrepancies, for example. The purpose of this literature review is to study the pathophysiology of CRMO and carefully dissect the agents that have been previously employed in the management of CRMO patients. This could allow for the purposeful formulation of individualized care plans and improving the overall well-being of patients. The authors included a multitude of PubMed-indexed articles published from 2000 onwards in this review.

Prophylactic influences of prebiotics on gut microbiome and immune response of heat-stressed broiler chickens.

Climatic changes and elevated ambient temperature are significant environmental stressors with a negative impact on birds' physiological, immunological, and behavioral status, increasing their susceptibility to stressors and immunosuppression and consequently increasing intestinal permeability (leaky gut). Prebiotics have been utilized to stop or diminish the harmful effects of stress in chickens. We aimed to evaluate the role of mannan-oligosaccharides, and beta-D-glucan prebiotics supplements in drinking water against experimentally induced heat stress (HS) on broiler chickens and study their impact on birds' performance, gut microbiome, and immune response. A total of 120 1-day-old Ross broiler chicks were allocated into four groups (30 birds/group), and each group was subdivided into triplicates (10 birds each). The experimental groups were classified as follows; the 1st (G1) control birds, the 2nd (G2) birds exposed experimentally to HS, the 3rd (G3) birds administered prebiotics in drinking water without exposure to HS, and the 4th (G4) birds exposed to HS and administered prebiotics in drinking water. After each vaccination, blood samples and serum samples were collected to evaluate the birds' immune status. Fecal samples were also collected for the molecular evaluation of the gut microbiome based on the genetic analyses and sequencing of 16S rRNA gene. The results showed that HS has reduced the birds' performance and badly affected the birds' immune response and gut microbiome. However, the addition of prebiotics to drinking water, with or without stress, enhanced the growth rate, maintained a normal gut microbiome, and improved immune parameters. Moreover, the usage of prebiotics improved the chicken gut microbiome and alleviated the negative effect of heat stress. Administering prebiotics significantly (p < 0.05) increased the relative abundance of beneficial bacteria and eradicated pathogenic ones in the birds' gut microbiome. Prebiotics showed a positive effect on the gut microbiome and the immune status of chickens under HS in addition to their efficacy as a growth promoter.

Superior Mesenteric Artery Syndrome in Systemic Lupus Erythematosus.

Although the gastrointestinal (GI) manifestations of systemic lupus erythematosus (SLE) are relatively less reported, they are common and occur in approximately half of individuals with SLE. These symptoms vary and include, but are not limited to, oral ulceration, dysphagia, nausea, vomiting, diarrhea, abdominal pain, and intestinal perforation. Gastrointestinal manifestations are often triggered by an inciting event, such as an infection or the side effects of medication. This case report presents a rare GI-related SLE complication, namely superior mesenteric artery syndrome.

Investigation of the phytochemical composition, antioxidant, antibacterial, anti-osteoarthritis, and wound healing activities of selected vegetable waste.

Agri-food wastes, produced following industrial food processing, are mostly discarded, leading to environmental hazards and losing the nutritional and medicinal values associated with their bioactive constituents. In this study, we performed a comprehensive analytical and biological evaluation of selected vegetable by-products (potato, onion, and garlic peels). The phytochemical analysis included UHPLC-ESI-qTOF-MS/MS in combination with molecular networking and determination of the total flavonoid and phenolic contents. Further, the antimicrobial, anti-osteoarthritis and wound healing potentials were also evaluated. In total, 47 compounds were identified, belonging to phenolic acids, flavonoids, saponins, and alkaloids as representative chemical classes. Onion peel extract (OPE) showed the higher polyphenolic contents, the promising antioxidant activity, the potential anti-osteoarthritis activity, and promising antimicrobial activity, especially against methicillin-resistant Staphylococcus aureus (MRSA). Furthermore, OPE revealed to have promising in vivo wound healing activity, restoring tissue physiology and integrity, mainly through the activation of AP-1 signaling pathway. Lastly, when OPE was loaded with nanocapsule based hydrogel, the nano-formulation revealed enhanced cellular viability. The affinities of the OPE major metabolites were evaluated against both p65 and ATF-2 targets using two different molecular docking processes revealing quercetin-3,4'-O-diglucoside, alliospiroside C, and alliospiroside D as the most promising entities with superior binding scores. These results demonstrate that vegetable by-products, particularly, those derived from onion peels can be incorporated as natural by-product for future evaluation against wounds and osteoarthritis.

Pulmonary exacerbations in insured patients with bronchiectasis over 2†years.

Background: Patients with bronchiectasis experience persistent symptoms and frequent pulmonary exacerbations; this study investigated the frequency of exacerbations and all-cause hospitalisation. Methods: This longitudinal, retrospective, claims database study (IBM® MarketScan®) identified patients aged ≥18 years from 1 July 2015 through 30 September 2018. Exacerbations were identified by bronchiectasis inpatient claim or a healthcare interaction, followed by antibiotic prescription within 7 days. Patients with ≥36 months of continuous health plan enrolment (12 months preceding the first bronchiectasis claim, i.e., baseline period and ≥24 months of follow-up) were included. Patients with cystic fibrosis at baseline were excluded. A multivariable logistic regression model identified baseline factors associated with having ≥2 exacerbations over the 2-year follow-up period. Results: In total, 14 798 patients with bronchiectasis were identified; 64.5% were female, 82.7% were aged ≥55 years and 42.7% had ≥2 exacerbations at baseline. Having ≥2 exacerbations after 2 years was positively associated with chronic macrolide use, long-acting ß2 agonist use, gastro-oesophageal reflux disease, heart failure and Pseudomonas aeruginosa. Frequent exacerbations (≥2) at baseline were significantly associated with greater likelihood of experiencing ≥2 exacerbations during the first and second year's follow-up (unadjusted odds ratios 3.35 (95% CI 3.1-3.6) and 2.96 (95% CI 2.8-3.2), respectively). The proportion of patients experiencing ≥1 all-cause hospitalisation cumulatively increased from 41.0% in the first year of follow-up to 51.1% over 2 years' follow-up. Conclusion: Frequent exacerbations in patients with bronchiectasis may increase the likelihood of future exacerbations over 2 years of follow-up, with increased hospitalisation rates over time.

Salt-inducible kinases regulate androgen synthesis in theca cells by enhancing CREB signaling.

Ovulation is the pinnacle of folliculogenesis, a process that requires an interplay between the oocyte, the granulosa cells, and the theca cells (TCs). TCs are the only source of ovarian androgens, which play a vital role in female fertility. However, abnormally elevated androgen levels reduce fertility. Therefore, uncovering novel mechanisms regulating androgen synthesis in TCs is of great significance. We have shown that salt-inducible kinases (SIKs) regulate granulosa cell steroidogenesis. Here, we investigated whether SIKs regulate androgen production in TCs. SIK2 and SIK3 were detected in the TCs of mouse ovaries and isolated TCs. Next, TCs in culture were treated with luteinizing hormone (LH) in the presence or absence of a highly specific SIK inhibitor. SIK inhibition enhanced the stimulatory effect of LH on steroidogenic gene expression and androgen production in a concentration-dependent manner. SIK inhibition alone stimulated the expression of steroidogenic genes and increased androgen production. Activation of adenylyl cyclase with forskolin or emulation of increased intracellular cyclic AMP levels stimulated steroidogenesis, an effect that was enhanced by the inhibition of SIK activity. The stimulatory effect of downstream targets of cyclic AMP was also significantly augmented by SIK inhibition, suggesting that SIKs control targets downstream cyclic AMP. Finally, it is shown that SIK2 knockout mice have higher circulating testosterone than controls. This evidence shows that TCs express SIKs and reveal novel roles for SIKs in the regulation of TC function and androgen production. This information could contribute to uncovering therapeutic targets to treat hyperandrogenic diseases.

Controlling the Evolution of Selective Vancomycin Resistance through Successful Ophthalmic Eye-Drop Preparation of Vancomycin-Loaded Nanoliposomes Using the Active-Loading Method.

Vancomycin is the front-line defense and drug of choice for the most serious and life-threatening methicillin-resistant Staphylococcus aureus (MRSA) infections. However, poor vancomycin therapeutic practice limits its use, and there is a consequent rise of the threat of vancomycin resistance by complete loss of its antibacterial activity. Nanovesicles as a drug-delivery platform, with their featured capabilities of targeted delivery and cell penetration, are a promising strategy to resolve the shortcomings of vancomycin therapy. However, vancomycin's physicochemical properties challenge its effective loading. In this study, we used the ammonium sulfate gradient method to enhance vancomycin loading into liposomes. Depending on the pH difference between the extraliposomal vancomycin-Tris buffer solution (pH 9) and the intraliposomal ammonium sulfate solution (pH 5-6), vancomycin was actively and successfully loaded into liposomes (up to 65% entrapment efficiency), while the liposomal size was maintained at 155 nm. Vancomycin-loaded nanoliposomes effectively enhanced the bactericidal effect of vancomycin; the minimum inhibitory concentration (MIC) value for MRSA decreased 4.6-fold. Furthermore, they effectively inhibited and killed heteroresistant vancomycin-intermediate S.aureous (h-VISA) with an MIC of 0.338 µg mL-1. Moreover, MRSA could not develop resistance against vancomycin that was loaded into and delivered by liposomes. Vancomycin-loaded nanoliposomes could be a feasible solution for enhancing vancomycin's therapeutic use and controlling the emerging vancomycin resistance.

Monoacylglycerol Lipase and Cyclooxygenase-2 Expression in Osteoarthritic Human Knees.

Background: Osteoarthritis (OA) is a progressive degenerative joint disease that presents with significant pain and functional disability. The endocannabinoid 2-arachidonoylglycerol activates cannabinoid receptors to reduce pain while its hydrolysis by the enzyme monoacylglycerol lipase (MAGL) generates arachidonic acid, the direct precursor to proalgesic eicosanoids synthesized by cyclooxygenase-2 (COX-2), highlighting the potential for crosstalk between MAGL and COX-2. While COX-2 expression in human OA cartilage has been described, the distribution of MAGL in knee osteochondral tissue has not been reported and was the goal of the current study. Methods: MAGL and COX-2 expression in International Cartilage Repair Society grade II and grade IV knee osteochondral tissue obtained from male and female subjects with OA was investigated through immunohistochemistry. Immunolocalization of both proteins was investigated within articular cartilage and subchondral bone. Results: MAGL is expressed throughout the cartilage of grade II arthritic tissue, with prominent distribution in the superficial and deep zones. Elevated expression of MAGL was evident in grade IV samples, with additional distribution observed in subchondral bone. COX-2 expression followed a similar pattern, with uniform distribution in cartilage and increased expression in grade IV tissue. Conclusions: This study establishes MAGL expression in arthritic cartilage and subchondral bone of subjects with OA. The proximity between MAGL and COX-2 suggests the potential for crosstalk between endocannabinoid hydrolysis and eicosanoid signaling in the maintenance of OA pain.

Benefit-risk assessment of brensocatib for treatment of non-cystic fibrosis bronchiectasis.

Brensocatib is a novel anti-inflammatory therapy in development for bronchiectasis treatment. Phase 2 WILLOW trial data demonstrate a low number needed to treat and negative number needed to harm, suggesting a favourable benefit-risk profile. https://bit.ly/3SbisW3.

Applying the syndemic framework to cancer research for effective cancer control in low- and middle-income countries.

Cancer burden is increasing rapidly globally, especially in low- and middle-income countries (LMICs), which already face a double burden of infectious diseases and other non-communicable diseases (NCDs). LMICs also struggle with poor social determinants of health, leading to cancer health disparities, such as delayed diagnoses and increased death rates due to cancer. Contextually, relevant research needs to be prioritised in these regions to ensure feasible, evidence-based healthcare planning and delivery for cancer prevention and control. A syndemic framework has been used to study the disease clustering of infectious diseases and NCDs across varied social contexts to understand how diseases interact adversely and how the wider environmental context and other socioeconomic factors contribute to poor health outcomes within specific populations. We propose using this model to study the 'syndemic of cancers' in the disadvantaged population of LMICs and suggest ways for the clear operationalisation of the syndemic framework through multidisciplinary evidence-generation models for the delivery of integrated, socially conscious interventions for effective cancer control.