Chronic Stress-Induced Neuroinflammation: Relevance of Rodent Models to Human Disease.

The brain is the central organ of adaptation to stress because it perceives and determines threats that induce behavioral, physiological, and molecular responses. In humans, chronic stress manifests as an enduring consistent feeling of pressure and being overwhelmed for an extended duration. This can result in a persistent proinflammatory response in the peripheral and central nervous system (CNS), resulting in cellular, physiological, and behavioral effects. Compounding stressors may increase the risk of chronic-stress-induced inflammation, which can yield serious health consequences, including mental health disorders. This review summarizes the current knowledge surrounding the neuroinflammatory response in rodent models of chronic stress-a relationship that is continually being defined. Many studies investigating the effects of chronic stress on neuroinflammation in rodent models have identified significant changes in inflammatory modulators, including nuclear factor-κB (NF-κB) and toll-like receptors (TLRs), and cytokines, including tumor necrosis factor-alpha (TNF-α), interleukin (IL)-1ß, and IL-6. This suggests that these are key inflammatory factors in the chronic stress response, which may contribute to the establishment of anxiety and depression-like symptoms. The behavioral and neurological effects of modulating inflammatory factors through gene knockdown (KD) and knockout (KO), and conventional and alternative medicine approaches, are discussed.

Predictive factors and quality of life assessment among patients with spinal cord injury in the Middle East: a systematic review.

PURPOSE: Spinal cord injury (SCI) is impairment of the spinal cord that adversely affects patients' health and quality of life (QoL). The aim of the study was to assess the quality of life (QoL) and related factors in patients with traumatic spinal cord injury in Middle Eastern countries. METHODS: PubMed, Ovid Medline, Cumulative Index to Nursing and Allied Health Literature (CINAHL), EBSCOhost, psycINFO, and Google Scholar were systematically searched for eligible studies published in peer-reviewed journals up till October 2023. RESULTS: Out of 1060 papers found in the literature, only 18 studies from Iran, Lebanon, and Turkey met the inclusion criteria. The majority of the studies employed the SF-36 scale to assess for QoL. In general, all SCI patients had reduced QoL scores when compared to the healthy population. Some of the factors such as age, education level, the level of injury, time since injury onset, marriage, and job opportunities were correlated with SCI subjects QoL. Our papers were assessed and found to be of both good and high quality. CONCLUSION: This review emphasizes the significant shortage of QoL studies among SCI patients in the Middle East countries and highlights the importance of improving the QoL of this marginalized population. This work should enhance the governments to establish rehabilitation centers, social and economic support systems, and mental health services to diminish complications arising from SCI.

Assessing Surgical Outcomes for Cage Plate System versus Stand-Alone Cage in Anterior Cervical Discectomy and Fusion: A Systematic Review and Meta-Analysis.

BACKGROUND: Anterior cervical discectomy and fusion (ACDF) is a common surgical procedure for addressing cervical spine conditions. It involves the utilization of either cage plate system (CPS) or stand-alone cage (SC). The objective of our study is to compare perioperative complications, patient-reported clinical outcomes measures, and radiographic outcomes of SC versus CPS in ACDF. METHODS: We carried out a literature search in PubMed, Embase, Cochrane library, Web of science, Medline, and Google Scholar. All studies comparing the outcomes between CPS versus SC in ACDF were included. RESULTS: Forty-one studies, 33 observational and 8 randomized clinical trials met the inclusion criteria. We found that both devices demonstrated comparable effectiveness in monosegmental ACDF with respect to Japanese Orthopedic Association Score, Neck Disability Index score, visual analog score, and fusion rates. CPS demonstrated superior performance in maintaining disc height, cervical lordosis, and exhibited lower incidence rates of cage subsidence. SC showed significant advantages over CPS in terms of shorter surgical duration, less intraoperative bleeding, shorter duration of hospitalization, as well as lower incidence rates of early postoperative dysphagia and adjacent segment disease. CONCLUSIONS: Most of the included studies had monosegmented fusion, and there wasn't enough data to set recommendations for the multisegmented fusions. Larger studies with longer follow-up are necessary to draw more definitive conclusions to provide evidence for clinicians to make clinical decisions.

Cervical intradural traumatic neuroma without history of trauma: illustrative case.

BACKGROUND: Traumatic neuroma typically refers to a reactive process in the injured peripheral nerve, characterized by an excessive growth of axons, Schwann cells, and fibroblasts at the proximal end of the nerve after its interruption. The authors report a case of a traumatic neuroma in the cervical nerve root in a patient with no history of trauma. OBSERVATIONS: The patient presented with sensation loss in the right-hand ulnar distribution, right flank around the T4-11 region, and right small toe along with motor power weakness over the right upper and lower extremity. Magnetic resonance imaging revealed an intradural extramedullary mass lesion with extension along the C7 nerve root. Histological examination showed traumatic neuroma. A total resection of the lesion along with the resolution of sensory and motor deficits was achieved directly after surgery. LESSONS: Traumatic neuroma should always be kept in the armamentarium for diagnosis of an intradural nerve sheath tumor.

Racial Disparities and Surgical Outcomes After Anterior Cervical Discectomy and Fusion: National Surgical Quality Improvement Program Analysis 2015-2020.

BACKGROUND: Our objective was to assess the effect of race on outcomes in patients undergoing anterior cervical discectomy and fusion (ACDF). METHODS: We identified 57,913 adult patients who underwent elective ACDF spine surgery from 2015 to 2020. Data were extracted from the American College of Surgeons National Surgical Quality Improvement Program (ACS NSQIP) database. Demographics, comorbidities, perioperative course, and 30-day postoperative outcomes were stratified by race. RESULTS: A total of 57,913 patients, white (n = 49,016), African American (AA; n = 7200), Native American (NA; n = 565), and Asian (n = 1132) underwent ACDF fusion surgery. AA patients had higher comorbidities, including diabetes (24.7%), dyspnea (5.9%), and hypertension (61.6%) compared with the other groups (P < 0.001). NA and AA were higher tobacco users, (33.1%) and (28.7%), respectively (P < 0.001). Most of the patients reported in this dataset had single-level surgeries. AAs had a longer average hospital stay (2.51±7.31 days) and operative time (144.13±82.26 min) (P < 0.001). Lower risk of superficial surgical site infection (adjusted odds ratio [ORadj], 0.41; 95% confidence interval [CI], 0.22-0.77; P = 0.005) and greater risk of reintubation (ORadj, 1.65; 95% CI, 1.25-2.17; P < 0.001), pulmonary embolism (ORadj, 1.88; 95% CI, 1.27-2.79; P = 0.001), renal insufficiency (ORadj, 3.15; 95% CI, 1.38-7.20; P = 0.006), and return to the operating room (ORadj, 1.41; 95% CI, 1.18-1.65; P < 0.001 were reported in AAs compared with whites. NAs showed an increased risk of superficial surgical site infection compared with whites (ORadj, 2.59; 95% CI, 1.05-6.36; P = 0.037). CONCLUSIONS: Racial disparities were found to independently affect rates of complications after surgery for ACDF.

Linkage drag analysis in three Aegilops speltoides introgressions carrying Sr47 in modern durum and hard red spring wheat germplasm.

KEY MESSAGE: Yield and quality tests of wheat lines derived from RWG35 show they carry little, or no linkage drag and are the preferred source of Sr47 for stem rust resistance. Three durum wheat (Triticum turgidum L. subsp. durum) lines, RWG35, RWG36, and RWG37 carrying slightly different Aegilops speltoides introgressions, but each carrying the Sr47 stem rust resistance gene, were backcrossed to three durum and three hard red spring (HRS) wheat (Triticum aestivum L.) cultivars to produce 18 backcross populations. Each population was backcrossed to the recurrent parent six times and prepared for yield trials to test for linkage drag. Lines carrying the introgression (S-lines) were compared to euploid sibling lines (W-lines) and their parent. Yield trials were conducted from 2018 to 2021 at three locations. Three agronomic and several quality traits were studied. In durum, lines derived from RWG35 had little or no linkage drag. Lines derived from RWG36 and RWG37 still retained linkage drag, most notably involving yield and thousand kernel weight, but also test weight, falling number, kernel hardness index, semolina extract, semolina protein content, semolina brightness, and peak height. In HRS wheat, the results were more complex, though the general result of RWG35 lines having little or no linkage drag and RWG36 and RWG37 lines retaining linkage drag still applied. But there was heterogeneity in the Glenn35S lines, and Linkert lines had problems combining with the Ae. speltoides introgressions. We concluded that introgressions derived from RWG35 either had eliminated linkage drag or any negative effects were minor in nature. We recommend that breeders who wish to incorporate Sr47 into their cultivars should work exclusively with germplasm derived from RWG35.

Voluntary wheel running promotes resilience to the behavioral effects of unpredictable chronic mild stress in male and female mice.

Besides significant benefits to physical health, exercise promotes mental health, reduces symptoms of mental illness, and enhances psychological development. Exercise can offset the impact of chronic stress, which is a major precursor to the development of mental disorders. The effects of exercise on chronic stress-induced behaviors are contradictory in preclinical studies, primarily due to the lack of data and sex-specific investigations. We sought to evaluate the effects of exercise on chronic stress-induced behavioral changes in both male and female mice. Mice were subjected to an Unpredictable Chronic Mild Stress (UCMS) paradigm with accessibility to running wheels for 2 h daily. Physiological and behavioral evaluations were conducted throughout the stress paradigm to determine if exercise blunts the effects of UCMS. Chronic stress induced voluntary wheel running (VWR) and weight loss in male and female mice. Compared to males, increased VWR was reported in females who also regained their weight lost by the end of the UCMS protocol. Exercise promoted resilience to stress-induced hyponeophagia in the novelty-suppressed feeding test and increased sucrose consumption. Exercise induced a sex-specific reduction in immobility and avoidance behavior in the tail suspension and open field tests and increased exploratory behavior in the light-dark test. These results indicate that exercise can promote resilience to the behavioral effects of chronic stress in males and females, and can affect behavior independent of chronic stress.

How Good Are Surgeons at Achieving Their Preoperative Goal Sagittal Alignment Following Adult Deformity Surgery?

STUDY DESIGN: Multicenter, prospective cohort. OBJECTIVES: Malalignment following adult spine deformity (ASD) surgery can impact outcomes and increase mechanical complications. We assess whether preoperative goals for sagittal alignment following ASD surgery are achieved. METHODS: ASD patients were prospectively enrolled based on 3 criteria: deformity severity (PI-LL ≥25°, TPA ≥30°, SVA ≥15 cm, TCobb≥70° or TLCobb≥50°), procedure complexity (≥12 levels fused, 3-CO or ACR) and/or age (>65 and ≥7 levels fused). The surgeon documented sagittal alignment goals prior to surgery. Goals were compared with achieved alignment on first follow-up standing radiographs. RESULTS: The 266 enrolled patients had a mean age of 61.0 years (SD = 14.6) and 68% were women. Mean instrumented levels was 13.6 (SD = 3.8), and 23.2% had a 3-CO. Mean (SD) offsets (achieved-goal) were: SVA = -8.5 mm (45.6 mm), PI-LL = -4.6° (14.6°), TK = 7.2° (14.7°), reflecting tendencies to undercorrect SVA and PI-LL and increase TK. Goals were achieved for SVA, PI-LL, and TK in 74.4%, 71.4%, and 68.8% of patients, respectively, and was achieved for all 3 parameters in 37.2% of patients. Three factors were independently associated with achievement of all 3 alignment goals: use of PACs/equivalent for surgical planning (P < .001), lower baseline GCA (P = .009), and surgery not including a 3-CO (P = .037). CONCLUSIONS: Surgeons failed to achieve goal alignment of each sagittal parameter in ∼25-30% of ASD patients. Goal alignment for all 3 parameters was only achieved in 37.2% of patients. Those at greatest risk were patients with more severe deformity. Advancements are needed to enable more consistent translation of preoperative alignment goals to the operating room.

Computed tomography findings as early predictors of long-term language impairment in patients with traumatic brain injury.

This study aims to assess the relationship between computed tomography (CT) findings, during the acute phase of hospitalization, and long-term language impairment in people with traumatic brain injury (TBI). Another aim was to assess the receptive and expressive abilities of subjects with TBI based on the location of the injury. This is a retrospective observational study including 49 participants with TBI due to war injuries. The Arabic Diagnostic Aphasia Battery (A-DAB-1) was administered to the participants and the Helsinki CT score was computed to quantify brain damage. The results showed that the Helsinki CT score was negatively correlated with the total score of the A-DAB-1 (r = -0.544, p-value < 0.0001). Simple linear regression supported such findings and reflected an inversely proportional relationship between both variables (p-value < 0.0001). When compared with subjects having right hemisphere damage, subjects with left hemisphere and bilateral brain damage performed more poorly on language tasks respectively as follows: A-DAB-1 overall score (92.08-66.08-70.28, p-value = 0.021), Content of descriptive speech (9.57-6.69-7.22, p-value = 0.034), Verbal fluency (6.57-3.54-3.89, p-value = 0.002), Auditory comprehension (9.71-7.54-7.78, p-value = 0.039), Complex auditory commands (9.71-7.65-7.56, p-value = 0.043), Repetition (9.75-7.08-7.61, p-value = 0.036), Naming (9.93-7.15-8.11, p-value = 0.046). Following TBI, CT findings on admission can significantly predict long-term language abilities, with left side lesions inducing poorer outcomes.

The Risk of Adverse Events in Smokers Undergoing Spinal Fusion: A Systematic Review and Meta-Analysis.

STUDY DESIGN: Systematic review and meta-analysis. OBJECTIVES: Determine if tobacco use is associated with increased risk of postoperative adverse events within 90 days in patients undergoing spinal fusion surgery. METHODS: Databases were queried to identify cohort studies that directly compared smokers with non-smokers and provided the absolute number of adverse events and the population at risk. Data quality was evaluated using the Quality in Prognosis Studies tool. Risk ratios (RR) and 95% confidence intervals were calculated and compared between studies. The grading of recommendation, assessment, development and evaluation (GRADE) criteria were used to assess the strength of the evidence. RESULTS: Seventeen studies assessing 37 897 participants met the inclusion criteria. Of these, 10 031 (26.5%) were smokers and 27 866 (73.5%) were nonsmokers. The mean age for the study population was 58 years, and 45% were males. Smoking was not associated with increased risk of one or more major adverse events within 90 days following spine surgery (seven studies, pooled RR 1.13, 95% CI [.75-1.71], I2 = 41%). However, smoking was significantly associated with one or more major adverse events in ≤2 level fusion (three studies, pooled RR 2.46, 95% CI [1.18-5.12], I2 = 0%), but not in fusions of ≥3 levels (four studies, pooled RR .87, 95% CI [.70-1.08], I2 = 0%). Additionally, there was no statistically significant association between smoking and any adverse event, nor increased reoperation risk due to adverse events. CONCLUSIONS: In this meta-analysis, tobacco use was not associated with a statistically significant increased risk of adverse events within 90 days in patients undergoing spinal fusion surgery. Our results are limited by the variable reporting methodology for both complication rates as well as smoking incidence between the included individual studies.

Novel Platinum(II) and Platinum(IV) Antitumor Agents that Exhibit Potent Cytotoxicity and Selectivity.

A novel platinum(II) complex 47OMESS(II) and its platinum(IV) derivative 47OMESS(IV) were synthesized and characterized. Cytotoxicity studies against mesenchymal cells (MCs) and lung (A549), breast (MDA-MB-231), and melanoma (A375) cancer cells demonstrated 7-20-fold superior activity for both complexes relative to cisplatin. Remarkably, 47OMESS(IV) demonstrated 17-22-fold greater selectivity toward the cancerous cells compared to the non-cancerous MCs. Western blot analysis on A549 cells showed the involvement of the intrinsic apoptotic pathway. Cellular fractionation and uptake experiments in A549 cells using ICP-mass spectrometry (MS) indicated that 47OMESS(II) and 47OMESS(IV) cross the cellular membrane predominantly via active transport mechanisms. The significant improvement in selectivity that is exhibited by 47OMESS(IV) is reported for the first time for this class of complexes.

Operative treatment outcomes for adult cervical deformity: a prospective multicenter assessment with mean 3-year follow-up.

OBJECTIVE: Adult cervical deformity (ACD) has high complication rates due to surgical complexity and patient frailty. Very few studies have focused on longer-term outcomes of operative ACD treatment. The objective of this study was to assess minimum 2-year outcomes and complications of ACD surgery. METHODS: A multicenter, prospective observational study was performed at 13 centers across the United States to evaluate surgical outcomes for ACD. Demographics, complications, radiographic parameters, and patient-reported outcome measures (PROMs; Neck Disability Index, modified Japanese Orthopaedic Association, EuroQol-5D [EQ-5D], and numeric rating scale [NRS] for neck and back pain) were evaluated, and analyses focused on patients with ≥ 2-year follow-up. RESULTS: Of 169 patients with ACD who were eligible for the study, 102 (60.4%) had a minimum 2-year follow-up (mean 3.4 years, range 2-8.1 years). The mean age at surgery was 62 years (SD 11 years). Surgical approaches included anterior-only (22.8%), posterior-only (39.6%), and combined (37.6%). PROMs significantly improved from baseline to last follow-up, including Neck Disability Index (from 47.3 to 33.0) and modified Japanese Orthopaedic Association score (from 12.0 to 12.8; for patients with baseline score ≤ 14), neck pain NRS (from 6.8 to 3.8), back pain NRS (from 5.5 to 4.8), EQ-5D score (from 0.74 to 0.78), and EQ-5D visual analog scale score (from 59.5 to 66.6) (all p ≤ 0.04). More than half of the patients (n = 58, 56.9%) had at least one complication, with the most common complications including dysphagia, distal junctional kyphosis, instrumentation failure, and cardiopulmonary events. The patients who did not achieve 2-year follow-up (n = 67) were similar to study patients based on baseline demographics, comorbidities, and PROMs. Over the course of follow-up, 23 of the total 169 enrolled patients were reported to have died. Notably, these represent all-cause mortalities during the course of follow-up. CONCLUSIONS: This multicenter, prospective analysis demonstrates that operative treatment for ACD provides significant improvement of health-related quality of life at a mean 3.4-year follow-up, despite high complication rates and a high rate of all-cause mortality that is reflective of the overall frailty of this patient population. To the authors' knowledge, this study represents the largest and most comprehensive prospective effort to date designed to assess the intermediate-term outcomes and complications of operative treatment for ACD.

Outcomes of operative treatment for adult spinal deformity: a prospective multicenter assessment with mean 4-year follow-up.

OBJECTIVE: The current literature has primarily focused on the 2-year outcomes of operative adult spinal deformity (ASD) treatment. Longer term durability is important given the invasiveness, complications, and costs of these procedures. The aim of this study was to assess minimum 3-year outcomes and complications of ASD surgery. METHODS: Operatively treated ASD patients were assessed at baseline, follow-up, and through mailings. Patient-reported outcome measures (PROMs) included scores on the Oswestry Disability Index (ODI), Scoliosis Research Society-22r (SRS-22r) questionnaire, mental component summary (MCS) and physical component summary (PCS) of the SF-36, and numeric rating scale (NRS) for back and leg pain. Complications were classified as perioperative (≤ 90 days), delayed (90 days to 2 years), and long term (≥ 2 years). Analyses focused on patients with minimum 3-year follow-up. RESULTS: Of 569 patients, 427 (75%) with minimum 3-year follow-up (mean ± SD [range] 4.1 ± 1.1 [3.0-9.6] years) had a mean age of 60.8 years and 75% were women. Operative treatment included a posterior approach for 426 patients (99%), with a mean ± SD 12 ± 4 fusion levels. Anterior lumbar interbody fusion was performed in 35 (8%) patients, and 89 (21%) underwent 3-column osteotomy. All PROMs improved significantly from baseline to last follow-up, including scores on ODI (45.4 to 30.5), PCS (31.0 to 38.5), MCS (45.3 to 50.6), SRS-22r total (2.7 to 3.6), SRS-22r activity (2.8 to 3.5), SRS-22r pain (2.3 to 3.4), SRS-22r appearance (2.4 to 3.5), SRS-22r mental (3.4 to 3.7), SRS-22r satisfaction (2.7 to 4.1), NRS for back pain (7.1 to 3.8), and NRS for leg pain (4.8 to 3.0) (all p < 0.001). Degradations in some outcome measures were observed between the 2-year and last follow-up evaluations, but the magnitudes of these degradations were modest and arguably not clinically significant. Overall, 277 (65%) patients had at least 1 complication, including 185 (43%) perioperative, 118 (27%) delayed, and 56 (13%) long term. Notably, the 142 patients who did not achieve 3-year follow-up were similar to the study patients in terms of demographic characteristics, deformities, and baseline PROMs and had similar rates and types of complications. CONCLUSIONS: This prospective multicenter analysis demonstrated that operative ASD treatment provided significant improvement of health-related quality of life at minimum 3-year follow-up (mean 4.1 years), suggesting that the benefits of surgery for ASD remain durable at longer follow-up. These findings should prove useful for counseling, cost-effectiveness assessments, and efforts to improve the safety of care.

Aspects of trauma related to violence, accidents and falls before and during the COVID-19 pandemic / Aspectos del trauma relacionados con la violencia, accidentes y caídas antes y durante la pandemia COVID-19

Abstract Introduction: Trauma is the second leading cause of mortality and the sixth leading cause of hospitalization in the country, with violence, accidents, and falls being the most prevalent. However, the country is experiencing reflexes of the COVID-19 pandemic, together with a lack of studies on trauma, as well as on clinical care. Objective: To analyze the clinical and epidemiological characteristics of trauma related to violence, accidents, and falls among the years 2019, 2020, and 2021, considered as before and during the COVID-19 pandemic. Material and Methods: Retrospective cohort study, with adults aged 25-55 years, who suffered trauma related to violence, falls, and other accidents, in the period between March and June of 2019, 2020, and 2021, in the city of São Paulo. Data surveys were carried out using the TABNET system, of the Municipal Health Department. Within this system, the search was carried out through the Information System for the Surveillance of Accidents, of the Coordination of Health Surveillance, in which situations of violence were notified and recorded by the National Information System for Notifiable Diseases. Subsequently, the Information System for Surveillance of Violence and Accidents was accessed, focusing on notifications and records of falls and other accidents. Results: Trauma remained more prevalent for males, with complete primary education, and ethnicity predominantly between white or brown. When analyzing the different types of violence: physical, torture, and sexual, there was a prevalence of higher percentages during the year 2019, the pre-pandemic period of COVID-19, except for psychological/moral violence, which was higher in 2021. It should also be noted that the different mechanisms of violence were significantly more prevalent in 2019, as well as the different causes of violence, falls, and car trauma involving pedestrians, occupants, drivers, and passengers. Outpatient care confirmed the higher trend in the pre-pandemic period; however, emergency hospital care showed a greater number of requests in 2020 and 2021. Conclusión: Trauma from violence, accidents, and falls was higher pre-pandemic compared to the period during the COVID-19 pandemic; as well as the search for health care in hospitals and outpatient clinics. These findings show a possible reduction in trauma reports and lower demand for assistance during the pandemic.

Resumen Introducción: El trauma es la segunda causa de mortalidad y la sexta de hospitalización en el país, siendo la violencia, los accidentes y las caídas las más prevalentes. Sin embargo, el país está experimentando reflejos de una pandemia de COVID-19, junto a una falta de estudios sobre el trauma, así como sobre la atención clínica. Objetivo: Analizar las características clínicas y epidemiológicas del trauma junto a la violencia, accidentes y caídas entre los años 2019, 2020 y 2021, considerados antes y durante la pandemia COVID-19. Materiales y métodos: Estudio de cohorte retrospectivo, con adultos de 25 a 55 años, que sufrieron trauma relacionado con violencia, caídas y otros accidentes, en el período comprendido entre marzo y junio de 2019, 2020 y 2021, en la ciudad de São Paulo. Las encuestas de datos fueron realizadas por el sistema TABNET, por el Departamento Municipal de Salud. Dentro de este sistema, la búsqueda se realizó a través del Sistema de Información para la Vigilancia de Accidentes, de la Coordinación de Vigilancia en Salud, en el cual las situaciones de violencia fueron notificadas y registradas por el Sistema Nacional de Información de Enfermedades Notificables. Posteriormente, se accedió al Sistema de Información de Vigilancia de Violencia y Accidentes, con enfoque en notificaciones y registro de caídas y otros accidentes. Resultados: El trauma siguió siendo más prevalente para los hombres, con educación primaria completa y raza predominantemente entre blancos y morenos. Al analizar los diferentes tipos de violencia: física, tortura y sexual, hubo mayores porcentajes de prevalencia durante el año 2019, período prepandémico de COVID-19, a excepción de la violencia psicológica / moral, que fue mayor en 2021. Nótese que los diferentes mecanismos de violencia fueron significativamente más prevalentes en 2019, así como las diferentes causas de violencia, caídas y traumatismos automovilísticos que involucran a peatones, ocupantes, conductores y pasajeros. La atención ambulatoria confirmó la tendencia de superioridad en el período prepandémico, sin embargo, la atención hospitalaria de emergencia mostró un mayor número de solicitudes en 2020 y 2021. Conclusión: Los traumas de violencia, accidentes y caídas son más prepandémico en comparación con el período durante la pandemia COVID-19; así como la búsqueda de asistencia sanitaria en hospitales y clínicas. Estos hallazgos muestran una posible reducción en los informes de trauma y una menor demanda de asistencia durante la pandemia.

Novel Pharmacological Approaches to the Treatment of Depression.

Major depressive disorder is one of the most prevalent mental health disorders. Monoamine-based antidepressants were the first drugs developed to treat major depressive disorder. More recently, ketamine and other analogues were introduced as fast-acting antidepressants. Unfortunately, currently available therapeutics are inadequate; lack of efficacy, adverse effects, and risks leave patients with limited treatment options. Efforts are now focused on understanding the etiology of depression and identifying novel targets for pharmacological treatment. In this review, we discuss promising novel pharmacological targets for the treatment of major depressive disorder. Targeting receptors including N-methyl-D-aspartate receptors, peroxisome proliferator-activated receptors, G-protein-coupled receptor 39, metabotropic glutamate receptors, galanin and opioid receptors has potential antidepressant effects. Compounds targeting biological processes: inflammation, the hypothalamic-pituitary-adrenal axis, the cholesterol biosynthesis pathway, and gut microbiota have also shown therapeutic potential. Additionally, natural products including plants, herbs, and fatty acids improved depressive symptoms and behaviors. In this review, a brief history of clinically available antidepressants will be provided, with a primary focus on novel pharmaceutical approaches with promising antidepressant effects in preclinical and clinical studies.

The Risk of Nonunion in Smokers Revisited: A Systematic Review and Meta-Analysis.

STUDY DESIGN: Systemic review and meta-analysis. OBJECTIVE: To review and establish the effect of tobacco smoking on risk of nonunion following spinal fusion. METHODS: A systematic search of Medline, Embase, Cochrane Central Register of Controlled Trials, and the Cochrane Database of Systematic Reviews from inception to December 31, 2020, was conducted. Cohort studies directly comparing smokers with nonsmokers that provided the number of nonunions and fused segments were included. Following data extraction, the risk of bias was assessed using the Quality in Prognosis Studies Tool, and the strength of evidence for nonunion was evaluated using the GRADE working group criteria. All data analysis was performed in Review Manager 5, and a random effects model was used. RESULTS: Twenty studies assessing 3009 participants, which included 1117 (37%) smokers, met inclusion criteria. Pooled analysis found that smoking was associated with increased risk of nonunion compared to not smoking ≥1 year following spine surgery (RR 1.91, 95% CI 1.56 to 2.35). Smoking was significantly associated with increased nonunion in those receiving either allograft (RR 1.39, 95% CI 1.12 to 1.73) or autograft (RR 2.04, 95% CI 1.54 to 2.72). Both multilevel and single level fusions carried increased risk of nonunion in smokers (RR 2.30, 95% CI 1.64 to 3.23; RR 1.79, 95% CI 1.12 to 2.86, respectively). CONCLUSION: Smoking status carried a global risk of nonunion for spinal fusion procedures regardless of follow-up time, location, number of segments fused, or grafting material. Further comparative studies with robust methodology are necessary to establish treatment guidelines tailored to smokers.

Erector Spinae Blocks for Spine Surgery: Fact or Fad? Systematic Review of Randomized Controlled Trials.

BACKGROUND: Patients undergoing spine surgery may experience substantial postoperative pain. The aim of this systematic review is to examine the clinical efficacy of a newly introduced regional anesthetic block, the erector spinae plane block (ESPB), for adults undergoing posterior spine surgeries. METHODS: A formal systematic database search was conducted in PubMed, Ovid Medline, Embase, Cochrane library, and Google Scholar for randomized controlled trials comparing ESPB with control or placebo. RESULTS: Our systematic review demonstrates a reduction of postoperative pain and opioid consumption in patients who had ESPB compared with control groups for lumbar spine surgery. However, the effect obtained revealed only a short-term benefit. CONCLUSIONS: Current evidence is insufficient to support the widespread use of ESPB for spine surgery. More studies are warranted to confirm or refute its role in clinical practice.

Novel stripe rust all-stage resistance loci identified in a worldwide collection of durum wheat using genome-wide association mapping.

Durumwheat [Triticum turgidum L. ssp. durum (Desf.)] production is constrained by fungal diseases including stripe rust caused by Puccinia striiformis Westend. f. sp. tritici Erikss. (Pst). Continuous mining of germplasm for the discovery and deployment of stripe rust resistance (Yr) genes is needed to counter the impact of this disease. In this study, we evaluated a worldwide collection of 432 durum wheat accessions to seven U.S. Pst races that carry diverse virulence and avirulence combinations on wheat Yr genes. We found that 47-82% of the durum wheat accessions were susceptible to each of the tested Pst races. A total of 32 accessions were resistant to all seven races. Genome-wide association studies (GWAS) using over 97,000 single-nucleotide polymorphism markers generated from genotyping-by-sequencing of 364 accessions identified 56 quantitative trait loci (QTL) associated with all-stage stripe rust resistance located on all 14 durum wheat chromosomes. Six of these QTL were associated with resistance to 2-4 Pst races, and none were associated with resistance to all seven races. The remaining 50 QTL were race specific. Eighteen of the 56 identified QTL had relatively large effects against at least one of the races. A map-based comparison of the discovered QTL in this study with previously published Yr genes and QTL showed that 29 were previously identified, whereas the remaining 27 QTL appeared to be novel. This study reports effective sources of stripe rust resistance to contemporary races in the United States and shows that this durum wheat collection is abundant in novel resistance loci that can be transferred into adapted durum cultivars.

A photoactivatable chemotherapeutic Ru(II) complex bearing bathocuproine ligand efficiently induces cell death in human malignant melanoma cells through a multi-mechanistic pathway.

Photoactivated chemotherapy (PACT) is an emerging strategy for targeted cancer therapy. Strained Ru complexes with pseudo-octahedral geometry may undergo photo-induced ligand dissociation, forming aquated photoproducts that are significantly more cytotoxic compared to the precursor complex. The complexes investigated were the strained complex [Ru(bpy)2BC]Cl2 (where bpy = 2,2'-bipyridine and BC = bathocuproine) and its unstrained control [Ru(bpy)2phen]Cl2 (where phen = 1,10-phenanthroline). The uptake of [Ru(bpy)2BC]Cl2, assessed by ICP/MS, started immediately post-incubation and plateaued after 24 h. Active transport was found as the main mode of intracellular transport. Cell viability assays on A375 cells indicated a mean phototoxicity index of 340-fold, and the effect was shown to be primarily mediated by the aquated photoproducts rather than the dissociating ligands. A significant increase in ROS production and DNA damage was also observed. Flow cytometry confirmed the induction of early apoptosis at 48 h that proceeds to late apoptosis/necrosis by 72 h post-treatment. Western blot analysis of pro- and anti-apoptotic proteins revealed that apoptosis was mediated through an interplay between the intrinsic and extrinsic pathways, as well as autophagy and via inhibition of the MAPK and PI3K pathways. In conclusion, this study demonstrates that [Ru(bpy)2BC]Cl2 is a multi-mechanistic PACT drug which exhibits promising anticancer potential.

Identification of Main-Effect and Environmental Interaction QTL and Their Candidate Genes for Drought Tolerance in a Wheat RIL Population Between Two Elite Spring Cultivars.

Understanding the genetics of drought tolerance can expedite the development of drought-tolerant cultivars in wheat. In this study, we dissected the genetics of drought tolerance in spring wheat using a recombinant inbred line (RIL) population derived from a cross between a drought-tolerant cultivar, 'Reeder' (PI613586), and a high-yielding but drought-susceptible cultivar, 'Albany.' The RIL population was evaluated for grain yield (YLD), grain volume weight (GVW), thousand kernel weight (TKW), plant height (PH), and days to heading (DH) at nine different environments. The Infinium 90 k-based high-density genetic map was generated using 10,657 polymorphic SNP markers representing 2,057 unique loci. Quantitative trait loci (QTL) analysis detected a total of 11 consistent QTL for drought tolerance-related traits. Of these, six QTL were exclusively identified in drought-prone environments, and five were constitutive QTL (identified under both drought and normal conditions). One major QTL on chromosome 7B was identified exclusively under drought environments and explained 13.6% of the phenotypic variation (PV) for YLD. Two other major QTL were detected, one each on chromosomes 7B and 2B under drought-prone environments, and explained 14.86 and 13.94% of phenotypic variation for GVW and YLD, respectively. One novel QTL for drought tolerance was identified on chromosome 2D. In silico expression analysis of candidate genes underlaying the exclusive QTLs associated with drought stress identified the enrichment of ribosomal and chloroplast photosynthesis-associated proteins showing the most expression variability, thus possibly contributing to stress response by modulating the glycosyltransferase (TraesCS6A01G116400) and hexosyltransferase (TraesCS7B01G013300) unique genes present in QTL 21 and 24, respectively. While both parents contributed favorable alleles to these QTL, unexpectedly, the high-yielding and less drought-tolerant parent contributed desirable alleles for drought tolerance at four out of six loci. Regardless of the origin, all QTL with significant drought tolerance could assist significantly in the development of drought-tolerant wheat cultivars, using genomics-assisted breeding approaches.