Exploring Phenolic Compounds in Crop By-Products for Cosmetic Efficacy.

Phenolic compounds represent a group of secondary metabolites that serve essential functions in plants. Beyond their positive impact on plants, these phenolic metabolites, often referred to as polyphenols, possess a range of biological properties that can promote skin health. Scientific research indicates that topically using phenolics derived from plants can be advantageous, but their activity and stability highly depend on storage of the source material and the extraction method. These compounds have the ability to relieve symptoms and hinder the progression of different skin diseases. Because they come from natural sources and have minimal toxicity, phenolic compounds show potential in addressing the causes and effects of skin aging, skin diseases, and various types of skin damage, such as wounds and burns. Hence, this review provides extensive information on the particular crops from which by-product phenolic compounds can be sourced, also emphasizing the need to conduct research according to proper plant material storage practices and the choice of the best extracting method, along with an examination of their specific functions and the mechanisms by which they act to protect skin.

Discovery of potent small-molecule inhibitors of lipoprotein(a) formation.

Lipoprotein(a) (Lp(a)), an independent, causal cardiovascular risk factor, is a lipoprotein particle that is formed by the interaction of a low-density lipoprotein (LDL) particle and apolipoprotein(a) (apo(a))1,2. Apo(a) first binds to lysine residues of apolipoprotein B-100 (apoB-100) on LDL through the Kringle IV (KIV) 7 and 8 domains, before a disulfide bond forms between apo(a) and apoB-100 to create Lp(a) (refs. 3-7). Here we show that the first step of Lp(a) formation can be inhibited through small-molecule interactions with apo(a) KIV7-8. We identify compounds that bind to apo(a) KIV7-8, and, through chemical optimization and further application of multivalency, we create compounds with subnanomolar potency that inhibit the formation of Lp(a). Oral doses of prototype compounds and a potent, multivalent disruptor, LY3473329 (muvalaplin), reduced the levels of Lp(a) in transgenic mice and in cynomolgus monkeys. Although multivalent molecules bind to the Kringle domains of rat plasminogen and reduce plasmin activity, species-selective differences in plasminogen sequences suggest that inhibitor molecules will reduce the levels of Lp(a), but not those of plasminogen, in humans. These data support the clinical development of LY3473329-which is already in phase 2 studies-as a potent and specific orally administered agent for reducing the levels of Lp(a).

Classical BSE dismissed as the cause of CWD in Norwegian red deer despite strain similarities between both prion agents.

The first case of CWD in a Norwegian red deer was detected by a routine ELISA test and confirmed by western blotting and immunohistochemistry in the brain stem of the animal. Two different western blotting tests were conducted independently in two different laboratories, showing that the red deer glycoprofile was different from the Norwegian CWD reindeer and CWD moose and from North American CWD. The isolate showed nevertheless features similar to the classical BSE (BSE-C) strain. Furthermore, BSE-C could not be excluded based on the PrPSc immunohistochemistry staining in the brainstem and the absence of detectable PrPSc in the lymphoid tissues. Because of the known ability of BSE-C to cross species barriers as well as its zoonotic potential, the CWD red deer isolate was submitted to the EURL Strain Typing Expert Group (STEG) as a BSE-C suspect for further investigation. In addition, different strain typing in vivo and in vitro strategies aiming at identifying the BSE-C strain in the red deer isolate were performed independently in three research groups and BSE-C was not found in it. These results suggest that the Norwegian CWD red deer case was infected with a previously unknown CWD type and further investigation is needed to determine the characteristics of this potential new CWD strain.

Lower Range of Recurrent Instability Rates Following Bankart Repair and Remplissage Compared to Isolated Bankart Repair in Patients with "Non-Engaging/On-Track" Hill-Sachs Lesions and <20% Glenoid Bone Loss.

PURPOSE: To compare recurrent instability and return to sport rates along with external rotation differences between on-track (non-engaging) Hill-Sachs lesion patients undergoing either an isolated Bankart repair (IBR) or a Bankart repair augmented with a remplissage procedure (B+R). METHODS: A search was conducted using 3 databases (PubMed, EMBASE, CINAHL) in accordance with the Preferred Reporting Items for Systematic Review and Meta-Analyses guidelines. Only clinical comparative (level of evidence I-III) studies were considered for inclusion. Quality assessment was performed using the MINORS criteria. RESULTS: Six, level of evidence III studies, totaling 537 patients (202 B+R and 335 IBR) were included for analysis. All patients had <20% glenoid bone loss and a non-engaging, on-track Hill Sachs lesion. At a median final follow-up of 34.7 months, recurrent dislocation rates ranged from 0-7.7% and 3.5-30% in the B+R and IBR groups, respectively. Moreover, subjective instability and revision surgery rates presented lower ranges in the B+R upon comparison with the IBR cohort (0-32% versus 5-71.4% and 0-5% versus 0-35%, respectively). Furthermore, return to pre-injury level of sports ranged from 64-100% in the remplissage augmented group and 50-90% in the IBR cohort. Post-operative external rotation at side varied from 50-63º in the B+R and 55º-63º in the IBR arm. Additional subgroup analysis revealed recurrent dislocation rates in athletes and patients with near-track Hill-Sachs lesions undergoing remplissage augmentation to be 0-5% and 2-47% while ranging 8.8-30% and 9-66% for IBR patients, respectively. CONCLUSION: Upon qualitative analysis, ranges of recurrent instability measures including recurrent dislocation rates, are higher in patients undergoing IBR in comparison to B+R. Activity level influences outcomes as athletes were found to have a higher range of recurrent dislocation rates in the IBR group. The addition of remplissage showed a higher range of return to sport rates with comparable post-operative external rotation between groups. LEVEL OF EVIDENCE: Systematic Review of Level III studies.

Adults Have a Higher Incidence of Discoid Lateral Meniscus Tears Than Children-Adults Tend to Present With Complex Tears, While Horizontal Tear Patterns are Frequently Encountered in Children: A Systematic Review.

PURPOSE: To systematically review the available literature in patients with discoid lateral meniscus (DLM) with the goal of elucidating the rates and types of meniscal tears, clinical symptoms, treatment strategies, and postoperative clinical, and radiographic outcomes in adult patients compared with a pediatric population. METHODS: A literature search was performed using the PubMed, Embase, and Scopus databases from database inception to October 2023 according to the 2020 Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Level of evidence I through IV human clinical studies evaluating rate and type of meniscal tears, clinical symptoms, patient-reported outcome measures, and postoperative radiographical assessments in patients with DLM were included. Comparisons were made by age below and above 16 years. Study quality was assessed using the Methodological Index for Non-Randomized Studies (MINORS) criteria. RESULTS: Thirteen studies comprising of 1772 adult patients (>16 years old) with DLM (n=1856 knees) and eight studies conducted in 304 pediatric patients (≤16 years old, n=353 knees) were include. The reported mean age ranged from 22.4 to 45 years (mean follow-up, 24 to 157.5 months) in the adult group and from 5 to 12.9 years (mean follow-up,37 to 234 months) in the pediatric DLM group. The majority of adult (n=553; 96.5%) and pediatric (n=163; 71.8%) patients had tears of the DLM. Complete DLM was the predominant type of DLM in both study groups (range in adults, 49.6 to 88%; range in pediatric, 19 to 100%) with complex (46.1%; range, 5.3-100%) and horizontal tears (18.2%; range, 20-37.5) being the most frequently described tear patterns in the adult and pediatric DLM groups, respectively. Pain was the predominant reported symptom in both study groups (range in adults, 12.1 to 99.3%; range in pediatrics, 32.4 to 100%). Partial meniscectomy was the most frequently reported treatment option conducted in 334 adult (39.5%; range, 24.2-100%) and 66 pediatric knees (63.5%; range, 15-100%).. Overall, improved postoperative clinical outcomes were reported in both study groups; however, radiographic progression of degenerative changes after subtotal meniscectomy was noted. CONCLUSIONS: More adult patients with DLM present with tears in the literature compared with the pediatric population. Complex and horizontal tear patterns are the most frequently reported tears in adult and pediatric patients, respectively. . Pain is the most relevant symptom in both study groups. There was generally significant improvement in postoperative clinical outcome scores; partial meniscectomy however remains the most frequently reported treatment option and is associated with fewer degenerative changes than in subtotal meniscectomy. . STUDY DESIGN: Level IV, Systematic review of Level I-IV studies.

Expanding the Phenotypic Spectrum of TRAF7-Related Cardiac, Facial, and Digital Anomalies With Developmental Delay: Report of 11 New Cases and Literature Review.

BACKGROUND: TRAF7-related cardiac, facial, and digital anomalies with developmental delay (CAFDADD), a multisystemic neurodevelopmental disorder caused by germline missense variants in the TRAF7 gene, exhibits heterogeneous clinical presentations. METHODS: We present a detailed description of 11 new TRAF7-related CAFDADD cases, featuring eight distinct variants, including a novel one. RESULTS: Phenotypic analysis and a comprehensive review of the 58 previously reported cases outline consistent clinical presentations, emphasizing dysmorphic features, developmental delay, endocrine manifestations, and cardiac defects. In this enlarged collection, novelties include a wider range of cognitive dysfunction, with some individuals exhibiting normal development despite early psychomotor delay. Communication challenges, particularly in expressive language, are prevalent, necessitating alternative communication methods. Autistic traits, notably rigidity, are observed in the cohort. Also, worth highlighting are hearing loss, sleep disturbances, and endocrine anomalies, including growth deficiency. Cardiac defects, frequently severe, pose early-life complications. Facial features, including arched eyebrows, contribute to the distinct gestalt. A novel missense variant, p.(Arg653Leu), further underscores the complex relationship between germline TRAF7 variants and somatic changes linked to meningiomas. CONCLUSIONS: Our comprehensive analysis expands the phenotypic spectrum, emphasizing the need for oncological evaluations and proposing an evidence-based schedule for clinical management. This study contributes to a better understanding of TRAF7-related CAFDADD, offering insights for improved diagnosis, intervention, and patient care.

Person-centered care assessment tool with a focus on quality healthcare: a systematic review of psychometric properties.

BACKGROUND: The person-centered care (PCC) approach plays a fundamental role in ensuring quality healthcare. The Person-Centered Care Assessment Tool (P-CAT) is one of the shortest and simplest tools currently available for measuring PCC. The objective of this study was to conduct a systematic review of the evidence in validation studies of the P-CAT, taking the "Standards" as a frame of reference. METHODS: First, a systematic literature review was conducted following the PRISMA method. Second, a systematic descriptive literature review of validity tests was conducted following the "Standards" framework. The search strategy and information sources were obtained from the Cochrane, Web of Science (WoS), Scopus and PubMed databases. With regard to the eligibility criteria and selection process, a protocol was registered in PROSPERO (CRD42022335866), and articles had to meet criteria for inclusion in the systematic review. RESULTS: A total of seven articles were included. Empirical evidence indicates that these validations offer a high number of sources related to test content, internal structure for dimensionality and internal consistency. A moderate number of sources pertain to internal structure in terms of test-retest reliability and the relationship with other variables. There is little evidence of response processes, internal structure in measurement invariance terms, and test consequences. DISCUSSION: The various validations of the P-CAT are not framed in a structured, valid, theory-based procedural framework like the "Standards" are. This can affect clinical practice because people's health may depend on it. The findings of this study show that validation studies continue to focus on the types of validity traditionally studied and overlook interpretation of the scores in terms of their intended use.

Two siblings with uncombable hair syndrome: A new pathogenic variant.

Two siblings presented with straw-colored, frizzy, and wiry hair. They had no associated abnormalities and no family history of abnormal hair. Trichoscopy showed the longitudinal groove in the hair shafts, characteristic of uncombable hair syndrome. Molecular genetic analysis revealed a new pathogenic variant (c.1374dup; p. Val459ArgfsTer15) in PADI3, not previously described.

Epidemiology of childhood acute leukemias in marginalized populations of the central-south region of Mexico: results from a population-based registry.

Introduction: Acute leukemias (AL) are the main types of cancer in children worldwide. In Mexico, they represent one of the main causes of death in children under 20 years of age. Most of the studies on the incidence of AL in Mexico have been developed in the urban context of Greater Mexico City and no previous studies have been conducted in the central-south of the country through a population-based study. The aim of the present work was to identify the general and specific incidence rates of pediatric AL in three states of the south-central region of Mexico considered as some of the marginalized populations of Mexico (Puebla, Tlaxcala, and Oaxaca). Methods: A population-based study was conducted. Children aged less than 20 years, resident in these states, and newly diagnosed with AL in public/private hospitals during the period 2021-2022 were identified. Crude incidence rates (cIR), standardized incidence rates (ASIRw), and incidence rates by state subregions (ASIRsr) were calculated. Rates were calculated using the direct and indirect method and reported per million children under 20 years of age. In addition, specific rates were calculated by age group, sex, leukemia subtype, and immunophenotype. Results: A total of 388 cases with AL were registered. In the three states, the ASIRw for AL was 51.5 cases per million (0-14 years); in Puebla, it was 53.2, Tlaxcala 54.7, and Oaxaca de 47.7. In the age group between 0-19 years, the ASIRw were 44.3, 46.4, 48.2, and 49.6, in Puebla, Tlaxcala, and Oaxaca, respectively. B-cell acute lymphoblastic leukemia was the most common subtype across the three states. Conclusion: The incidence of childhood AL in the central-south region of Mexico is within the range of rates reported in other populations of Latin American origin. Two incidence peaks were identified for lymphoblastic and myeloid leukemias. In addition, differences in the incidence of the disease were observed among state subregions which could be attributed to social factors linked to the ethnic origin of the inhabitants. Nonetheless, this hypothesis requires further investigation.

Clinical and Genetic Analysis of Patients With TK2 Deficiency.

Objectives: Thymidine kinase 2 deficiency (TK2d) is a rare autosomal recessive disorder that stems from a perturbation of the mitochondrial DNA maintenance. Nucleoside treatment has recently shown promise as a disease-modifying therapy. TK2d was initially associated with rapidly progressive fatal myopathy in children featuring mitochondrial DNA depletion. Subsequently, less severe variants of the disease were described, with onset of symptoms during adolescence or adulthood and associated with the presence of multiple mtDNA deletions. These less severe phenotypes have been reported in only 15% of the approximately 120 patients described worldwide. However, some reports suggest that these juvenile and adult-onset presentations may be more common. The objective of this study was to describe the clinical phenotype in a sample of patients from Spain. Methods: This study includes 53 patients harboring biallelic TK2 pathogenic variants, compiling data retrospectively from 7 Spanish centers. We analyzed allele frequency, investigated the most recent common ancestor of core haplotypes, and used the Runs of Homozygosity approach to investigate variant coalescence. Results: Symptom onset distribution revealed that 32 patients (60%) experienced symptoms beyond 12 years of age. Approximately 30% of patients died of respiratory insufficiency, while 56% of surviving patients needed mechanical ventilation. Genetic analysis identified 16 distinct variants in TK2. Two variants, p.Lys202del and p.Thr108Met, exhibited significantly higher prevalence in the Spanish population than that reported in gnomAD database (86-fold and 13-fold, respectively). These variants are estimated to have originated approximately 16.8 generations ago for p.Thr108Met and 95.2 generations ago for p.Lys202del within the Spanish population, with the increase in frequency attributed to various forms of inbreeding. In late-onset cases, 46.9% carried the p.Lys202del variant. Discussion: The higher frequency of TK2d in Spain can be partially attributed to the increased prevalence of 2 variants and consanguinity. Notably, in 60% of the cohort, the disease was late-onset, emphasizing the potential underdiagnosis of this subgroup of patients in other regions. Raising awareness of this potentially treatable disorder is of utmost importance because early interventions can significantly affect the quality of life and survival of affected individuals.

Diagnostic yield of genetic testing in adults with sensorineural hearing loss.

INTRODUCTION: The contribution of genetic causes to sensorineural hearing loss (SNHL) in adults is less clear than in children, and genetic diagnosis is still not standardized in adults. In this study we present the genetic results obtained in a cohort of adult patients with SNHL. MATERIALS AND METHODS: We included 63 adults with SNHL that received genetic testing between 2019 and 2022. Whole exome sequencing was performed and variants in genes related to hearing loss (virtual panel with 244 genes) were prioritised and analysed. RESULTS: 24% (15/63) of patients were genetically diagnosed: 87% (13/15) of patients had non-syndromic hearing loss and 13% (2/15) had syndromic hearing loss. We identified pathogenic and likely pathogenic variants in 11 different genes. CONCLUSIONS: Our results show that a significant proportion of adults with SNHL have a genetic origin, and that implementation of genetic testing improves diagnostic accuracy and allows personalized management of these patients.

The differential expressions of aquaporins underline the diverse strategies of cucumber and tomato against salinity and zinc stress.

Salinity and excess zinc are two main problems that have limited agriculture in recent years. Aquaporins are crucial in regulating the passage of water and solutes through cells and may be essential for mitigating abiotic stresses. In the present study, the adaptive response to moderate salinity (60 mM NaCl) and excess Zn (1 mM ZnSO4 ) were compared alone and in combination in Cucumis sativus L. and Solanum lycopersicum L. Water relations, gas exchange and the differential expression of all aquaporins were analysed. The results showed that cucumber plants under salinity maintained the internal movement of water through osmotic adjustment and the overexpression of specific PIPs aquaporins, following a "conservation strategy". As tomato has a high tolerance to salinity, the physiological parameters and the expression of most aquaporins remained unchanged. ZnSO4 was shown to be stressful for both plant species. While cucumber upregulated 7 aquaporin isoforms, the expression of aquaporins increased in a generalized manner in tomato. Despite the differences, water relations and transpiration were adjusted in both plants, allowing the RWC in the shoot to be maintained. The aquaporin regulation in cucumber plants facing NaCl+ZnSO4 stress was similar in the two treatments containing NaCl, evidencing the predominance of salt in stress. However, in tomato, the induced expression of specific isoforms to deal with the combined stress differed from independent stresses. The results clarify the key role of aquaporin regulation in facing abiotic stresses and their possible use as markers of tolerance to salinity and heavy metals in plants.

Enrichment of Immune Dysregulation Disorders in Adult Patients with Human Inborn Errors of Immunity.

Human inborn errors of immunity (IEI) comprise a group of diseases resulting from molecular variants that compromise innate and adaptive immunity. Clinical features of IEI patients are dominated by susceptibility to a spectrum of infectious diseases, as well as autoimmune, autoinflammatory, allergic, and malignant phenotypes that usually appear in childhood, which is when the diagnosis is typically made. However, some IEI patients are identified in adulthood due to symptomatic delay of the disease or other reasons that prevent the request for a molecular study. The application of next-generation sequencing (NGS) as a diagnostic technique has given rise to an ever-increasing identification of IEI-monogenic causes, thus improving the diagnostic yield and facilitating the possibility of personalized treatment. This work was a retrospective study of 173 adults with IEI suspicion that were sequenced between 2005 and 2023. Sanger, targeted gene-panel, and whole exome sequencing were used for molecular diagnosis. Disease-causing variants were identified in 44 of 173 (25.43%) patients. The clinical phenotype of these 44 patients was mostly related to infection susceptibility (63.64%). An enrichment of immune dysregulation diseases was found when cohorts with molecular diagnosis were compared to those without. Immune dysregulation disorders, group 4 from the International Union of Immunological Societies Expert Committee (IUIS), were the most prevalent among these adult patients. Immune dysregulation as a new item in the Jeffrey Model Foundation warning signs for adults significantly increases the sensitivity for the identification of patients with an IEI-producing molecular defect.

Cystic phenotype and chronic kidney disease in autosomal dominant Alport syndrome.

BACKGROUND AND HYPOTHESIS: Autosomal Dominant Alport Syndrome (ADAS), also known as Thin Basement Membrane Disease (TBMD), is caused by pathogenic variants in COL4A3 and COL4A4 genes. A cystic phenotype has been described in some patients with TBMD, but no genetic studies were performed. We conducted a genetic and radiologic investigation in a cohort of ADAS patients to analyze the prevalence of multicystic kidney disease (MKD) and its association with Chronic Kidney Disease (CKD). METHODS: Retrospective single-center cohort study. Thirty-one patients showing pathogenic or likely pathogenic variants in COL4A3 or COL4A4 from a cohort of 79 patients with persistent microscopic hematuria were included. Mean follow-up was 9.4±9.6 years. The primary objective of the study was to determine the prevalence of MKD in the cohort of ADAS patients. Secondary objectives were to determine risk factors associated with an eGFR<45 ml/min/1.73m2 at the time of genetic and radiologic evaluation and to investigate the coexistence of other genetic abnormalities associated with familial hematuria and cystic kidney disease. RESULTS: MKD was found in 16 patients (52%). Mean number of cysts per kidney was 12.7±5.5. No genetic abnormalities were found in a panel of 101 other genes related to familial hematuria, focal segmental glomerulosclerosis and cystic kidney disease. A greater number of patients with MKD had an eGFR<45 ml/min/1.73m2 (63% vs 7%, p=0.006) and more advanced CKD than patients without MKD. The annual rate of eGFR decline was greater in patients with MKD: -1.8 vs 0.06 ml/min/1.73m2/year (p=0.009). By multivariable linear regression analysis, the main determinants of eGFR change per year were time-averaged proteinuria (p=0.002) and MKD (p=0.02). CONCLUSION: MKD is commonly found in ADAS and is associated with a worse kidney outcome. No pathogenic variants were found in genes other than COL4A3/COL4A4.

Genetic diagnosis of childhood sensorineural hearing loss.

INTRODUCTION: Congenital/early-onset sensorineural hearing loss (SNHL) is one of the most common hereditary disorders in our environment. There is increasing awareness of the importance of an etiologic diagnosis, and genetic testing with next-generation sequencing (NGS) has the highest diagnostic yield. Our study shows the genetic results obtained in a cohort of patients with bilateral congenital/early-onset SNHL. MATERIALS AND METHODS: We included 105 children with bilateral SNHL that received genetic testing between 2019 and 2022. Genetic tests were performed with whole exome sequencing, analyzing genes related to hearing loss (virtual panel with 244 genes). RESULTS: 48% (50/105) of patients were genetically diagnosed. We identified pathogenic and likely pathogenic variants in 26 different genes, and the most frequently mutated genes were GJB2, USH2A and STRC. 52% (26/50) of variants identified produced non-syndromic hearing loss, 40% (20/50) produced syndromic hearing loss, and the resting 8% (4/50) could produce both non-syndromic and syndromic hearing loss. CONCLUSIONS: Genetic testing plays a vital role in the etiologic diagnosis of bilateral SNHL. Our cohort shows that genetic testing with NGS has a high diagnostic yield and can provide useful information for the clinical workup of patients.

Arthroscopic Bankart with remplissage results in lower rates of recurrent instability with similar range of motion compared to isolated arthroscopic Bankart for anterior glenohumeral instability: A systematic review and meta-analysis.

PURPOSE: The addition of the remplissage procedure to an arthroscopic Bankart procedure has been shown to improve clinical outcomes, yet at the expense of potentially decreasing shoulder range of motion. The purpose of this study was to assess recurrent instability, range of motion, functional outcomes and rates of return to sport outcomes in patients undergoing an isolated arthroscopic Bankart repair compared to those undergoing arthroscopic Bankart repair in addition to the remplissage procedure. METHODS: According to the Preferred Reporting Items for Systematic Review and Meta-Analyses (PRISMA) guidelines, a search was conducted using three databases (MEDLINE/OVID, EMBASE and PubMed). Retrieved studies were screened based on predefined inclusion and exclusion criteria for comparative studies. Data were extracted and meta-analysis performed using a random-effects model. RESULTS: A total of 16 studies (13 level III studies, 2 level II studies and 1 level I) were included with a total of 507 and 704 patients in the Bankart plus remplissage and isolated Bankart repair groups, respectively. No studies reported glenoid bone loss of >20% with the least percentage of glenoid bone loss reported among studies being <1%. There was a significantly increased rate of recurrent dislocations (odds ratio [OR] = 4.22, 95% confidence interval [CI]: 2.380-7.48, p < 0.00001) and revision procedures (OR = 3.36, 95% CI: 1.52-7.41, p = 0.003) in the isolated Bankart repair group compared to the Bankart plus remplissage group. Additionally, there were no significant differences between groups in terms of external rotation at side (n.s.), in abduction (n.s.) or at forward flexion (n.s.) at final follow-up. Furthermore, return to preinjury level of sport favoured the Bankart plus remplissage group (OR = 0.54, 95% CI: 0.35-0.85, p = 0.007). CONCLUSION: Patients undergoing arthroscopic Bankart plus remplissage for anterior shoulder instability have lower rates of recurrent instability, higher rates of return to sport, and no significant difference in range of motion at final follow-up when compared to an isolated arthroscopic Bankart repair. Further large, prospective studies are needed to further determine which patients and degree of bone loss would benefit most from augmentation with the remplissage procedure. LEVEL OF EVIDENCE: Level III.

Mortality and sequelae of tuberculous meningitis in a high-resource setting: A cohort study, 1990-2017.

INTRODUCTION: Tuberculous meningitis (TBM), the most serious form of tuberculosis, results in high mortality and long-term disability in low-resource countries. We investigated temporal trends in mortality and sequelae in a high-resource low-incidence country. METHODS: We performed a retrospective cohort study of all adult patients with TBM at two third-level teaching hospitals in Barcelona (Spain), between January 1990 and December 2017, assessing temporal trends in mortality and sequelae after 12 months over four consecutive 7-year time windows. Rates observed across the four periods were adjusted for covariates. RESULTS: Of the 135 cases included, all but one started tuberculosis (TB) treatment and 120 (89.6%) received rifampicin, isoniazid, and pyrazinamide, with or without ethambutol. The probability of being alive at month 12 was 81.8%, with no differences among the four periods: in comparison with the 1990-1996 period, the adjusted hazard ratios and 95% confidence intervals (CI) were 2.55 (0.71-9.25), 0.70 (0.13-3.85), and 1.29 (0.28-5.91) for the 1997-2003, 2004-2010, and 2011-2017 periods respectively. Sequelae were present in 28.3% at month 12, with no differences across the four periods in the adjusted analysis: in comparison with the 1990-1996 period, the odds ratios and 95% CIs were 0.80 (0.09-7.22); 1.94 (0.21-17.96), and 2.42 (0.25-23.07) for the 1997-2003, 2004-2010, and 2011-2017 periods respectively. CONCLUSION: This study shows that TBM still causes high mortality and disability even in a high-resource low-incidence TB setting and without improvement over time.

Antibiotic prophylaxis following low-velocity gunshot fractures: an updated review.

PURPOSE: Low-velocity gunshot fractures (LVGFs) are a common type of gunshot-induced trauma with the potential for complications such as infection and osteomyelitis. The effectiveness of antibiotic therapy in LVGFs remains uncertain, leading to ongoing debate about the appropriate treatment. In this review, we evaluate recent updates on the current understanding of antibiotic therapy in LVGFs, how previous studies have investigated the use of antibiotics in LVGFs, and the current state of institutional policies and protocols for treating LVGFs with antibiotics. METHODS: We conducted a review of PubMed, Embase, and Web of Science databases to identify studies that investigated the use of antibiotics in LVGFs after the last review in 2013. Due to the lack of quantitative clinical trial studies, we employed a narrative synthesis approach to analyze and present the findings from the included primary studies. We categorized the outcomes based on the anatomical location of the LVGFs. RESULTS: After evaluating 67 publications with the necessary qualifications out of 578 abstracts, 17 articles were included. The sample size of the studies ranged from 22 to 252 patients. The antibiotics used in the studies varied, and the follow-up period ranged from three months to ten years. The included studies investigated the use of antibiotics in treating LVGFs at various anatomic locations, including the humerus, forearm, hand and wrist, hip, femur, tibia, and foot and ankle. CONCLUSION: Our study provides updated evidence for the use of antibiotics in LVGFs and highlights the need for further research to establish evidence-based guidelines. We also highlight the lack of institutional policies for treating LVGFs and the heterogeneity in treatments among institutions with established protocols. A single-dose antibiotic approach could be cost-effective for patients with non-operatively treated LVGFs. We suggest that a national or international registry for gunshot injuries, antibiotics, and infections could serve as a valuable resource for collecting and analyzing data related to these important healthcare issues.

Similarity searching for anticandidal agents employing a repurposing approach.

Fungal infections caused by Candida are still a public health concern. Particularly, the resistance to traditional chemotherapeutic agents is a major issue that requires efforts to develop new therapies. One of the most interesting approaches to finding new active compounds is drug repurposing aided by computational methods. In this work, two databases containing anticandidal agents and drugs were studied employing cheminformatics and compared by similarity methods. The results showed 36 drugs with high similarities to some candicidals. From these drugs, trimetozin, osalmid and metochalcone were evaluated against C. albicans (18804), C. glabrata (90030), and miconazole-resistant strain C. glabrata (32554). Osalmid and metochalcone were the best, with activity in the micromolar range. These findings represent an opportunity to continue with the research on the potential antifungal application of osalmid and metochalcone as well as the design of structurally related derivatives.