Clinical outcomes and frequency of persistent infection among immunosuppressed patients treated with bebtelovimab for COVID-19 infection at an ambulatory cancer center.

BACKGROUND: There are limited data on clinical outcomes associated with the use of bebtelovimab for the treatment of coronavirus disease 2019 (COVID-19) among cancer patients. We aimed to define the clinical characteristics and outcomes among patients receiving bebtelovimab as part of the COVID-19 therapeutics program at our cancer center. METHODS: This is a retrospective cohort study of immunosuppressed adult patients who received bebtelovimab at Fred Hutchinson Cancer Center between March 2022, and November 2022. We reviewed medical records to capture the date of the first positive COVID-19 test, clinical characteristics, outcomes, and follow-up COVID-19 testing for 60 days after the first positive. Persistent infection was defined as a positive test beyond day 30; these patients were reviewed beyond day 60. RESULTS: Among 93 patients who received bebtelovimab, 64 (69%) had hematologic malignancy. Sixty-nine (74%) patients received bebtelovimab within 2 days after diagnosis. Two (2%) patients were hospitalized, none required ICU care, and one patient died on day 52; although it is unknown if death was directly related to COVID-19. Ten (11%) patients had persistent COVID-19 infection; of these, four received additional COVID-19 therapy with either nirmatrelvir/ritonavir or remdesivir, and five out of six patients with sequencing data available had spike protein mutations associated with bebtelovimab resistance. CONCLUSION: A coordinated systems-based approach led to prompt initiation of bebtelovimab within two days of testing positive in most patients. We observed few hospitalizations or deaths. Persistent infection was noted in 11% of patients with four requiring additional therapies, highlighting a need for novel strategies to manage immunosuppressed patients.

Periparturient blood T-lymphocyte PD-1 and CTLA-4 expression as potential predictors of new intramammary infections in dairy cows during early lactation (short communication).

BACKGROUND: The periparturient period in dairy cows is marked by immunosuppression which increases the likelihood of infectious disorders, particularly also mastitis. An in-depth understanding of peripartum leukocyte biology is vital for the implementation of highly successful post-partum disease prevention measures. Immune checkpoint molecules, such as programmed death 1 (PD-1) and cytotoxic T-lymphocyte antigen 4 (CTLA-4), are critical inhibitory receptors expressed on immune cells, particularly T cells, that drive immunosuppressive signaling pathways. However, the potential role of immune checkpoint molecules expression in T-cells on udder health has never been explored. Thus, the association between the occurrence of new postpartum intramammary infections (IMIs) and the expression of programmed cell death protein 1 (PD-1) and cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4) on blood T-cells during the peripartum period was investigated. RESULTS: In this study, the incidence of IMIs by any pathogen in early lactation was not associated with a higher expression of PD-1 and CTLA-4 in the periparturient period. However, the incidence of IMIs by major pathogens throughout the first month of lactation was significantly associated with higher expression of PD-1 at 14 days before calving (P = 0.03) and CTLA-4 at parturition (P = 0.03) by blood T-cells. Also, the expression of CTLA-4 at D0 (P = 0.012) by T-cells was associated with the occurrence of persistent IMIs during the first month of lactation. CONCLUSIONS: To our knowledge, this is the first report to investigate the expression of PD-1 and CTLA-4 by blood T-lymphocytes during the periparturient period in dairy cows and to explore their relationship with the incidence of new IMIs in the postpartum period. Thus, a comprehensive understanding of leukocyte biology during peripartum would appear to be a prerequisite for the identification of resilient dairy cows or targets innovative (immunological) non-antibiotic approaches in the transition period.

Lymphogranuloma venereum: an unusual cause of rectal stenosis.

Lymphogranuloma Venereum (LGV) is a notifiable disease linked to high-risk sexual practices such as cruising, chemsex, or orgies. The anorectal manifestation is associated with receptive anal sex and presents with characteristic symptoms such as proctitis, tenesmus, suppuration, and in advanced cases, anorectal fistulas or stenosis. The case of a 57-year-old man engaging in high-risk sexual practices is presented, showing symptoms such as discharge, fistulizations, rectal stenosis, and a weight loss of 15 kg. Following diagnostic studies, a neoplastic and inflammatory origin was ruled out, confirming the LGV diagnosis. Although the patient responded positively to a three-week course of doxycycline, the stenosis persisted, ultimately necessitating a terminal colostomy. The patient was scheduled to undergo a protectomy to control the inflammatory and infectious process, a procedure that took place months later without significant incidents. The primary treatment for LGV continues to be doxycycline. In cases of complications, such as fistulas, abscesses, or stenosis, surgical interventions, drainage, or pneumatic dilations may be necessary.

Production of high molecular-ordered stilbene oligomers for the study of their biological activity: total synthesis, bio-catalyzed synthesis and production by plant systems.

Though the iconic stilbene resveratrol and its related dimers constitute a top storyline in the field of natural product research, resveratrol oligomers (condensation >2) have been left aside despite their higher biological activity compared to that of the monomers. This situation largely results from the difficulty of getting them in sufficient quantities to enable evaluation of their biological properties in vivo. We present here a synthetic and critical analysis of the methods used for the production of high molecular-ordered stilbene oligomers of potential biomedical interest, gathering the most salient data regarding the approaches employed to prepare them by total synthesis, use of biomimetic approaches or through plant systems.

Hypofractionated Stereotactic Re-irradiation and Anti-PDL1 Durvalumab Combination in Recurrent Glioblastoma: STERIMGLI Phase I Results.

BACKGROUND: Hypofractionated stereotactic radiotherapy (hFSRT) is a salvage option for recurrent glioblastoma (GB) which may synergize anti-PDL1 treatment. This phase I study evaluated the safety and the recommended phase II dose of anti-PDL1 durvalumab combined with hFSRT in patients with recurrent GB. METHODS: Patients were treated with 24 Gy, 8 Gy per fraction on days 1, 3, and 5 combined with the first 1500 mg Durvalumab dose on day 5, followed by infusions q4weeks until progression or for a maximum of 12 months. A standard 3 + 3 Durvalumab dose de-escalation design was used. Longitudinal lymphocytes count, cytokines analyses on plasma samples, and magnetic resonance imaging (MRI) were collected. RESULTS: Six patients were included. One dose limiting toxicity, an immune-related grade 3 vestibular neuritis related to Durvalumab, was reported. Median progression-free interval (PFI) and overall survival (OS) were 2.3 and 16.7 months, respectively. Multi-modal deep learning-based analysis including MRI, cytokines, and lymphocytes/neutrophil ratio isolated the patients presenting pseudoprogression, the longest PFI and those with the longest OS, but statistical significance cannot be established considering phase I data only. CONCLUSION: Combination of hFSRT and Durvalumab in recurrent GB was well tolerated in this phase I study. These encouraging results led to an ongoing randomized phase II. (ClinicalTrials.gov Identifier: NCT02866747).

SARSCoV-2 antibody prevalence and titers in persons living with HIV cared for at a large tertiary reference center in Mexico City.

OBJECTIVE: To assess SARS-CoV-2 antibody prevalence and titers in people living with HIV (PLWHIV) on antiretroviral treatment (ART) enrolled at a tertiary reference hospital in Mexico. METHODS: Two plasma aliquots per person, used for HIV viral load follow-up between 01/2020 and 09/2021, were used to assess total anti-N and neutralizing SARS-CoV-2 antibodies. Sociodemographic, clinical, and SARS-CoV-2 exposure risk information were collected. The risk associated with SARS-CoV-2 exposure and associations with antibody titers were analyzed with logistic, Cox, and linear multivariable models. RESULTS: 803 PLWHIV participated; 233 had detectable SARS-CoV-2 antibodies (prevalent cases), and 132 seroconverted (incident cases). Overall, the adjusted prevalence was 46.45%, with an incidence rate of 3.78 cases/100 person-months. Factors associated with prevalent cases included lower age, location (western zone of Mexico City and the neighboring Mexico State), use of public transport, attendance at meetings without social distancing, and higher CD4 + T cell counts (p < 0.05; multivariable logistic model). BNT162b2 vaccination reduced incident cases (Cox adjusted HR = 0.4; p = 0.013). Notably, previously infected and vaccinated individuals showed maximization of neutralizing activity (p < 0.001). No associations between SARS-CoV-2 neutralization and HIV-related variables (CD4 + T cell counts, viral load, number of years in viral suppression, ART regimen) were found in multivariable analysis. CONCLUSIONS: SARS-CoV-2 infection was associated with community risk rather than HIV-associated variables in PLWH on ART and clinical follow-up. Antibody neutralization activity in vaccinated participants was maximized with previous SARS-CoV-2 infection.

Mechanistic insight into immunomodulatory effects of food-functioned plant secondary metabolites.

Medicinally important plant-foods offer a balanced immune function, which is essential for protecting the body against antigenic invasion, mainly by microorganisms. Immunomodulators play pivotal roles in supporting immune function either suppressing or stimulating the immune system's response to invading pathogens. Among different immunomodulators, plant-based secondary metabolites have emerged as high potential not only for immune defense but also for cellular immunoresponsiveness. These natural immunomodulators can be developed into safer alternatives to the clinically used immunosuppressants and immunostimulant cytotoxic drugs which possess serious side effects. Many plants of different species have been reported to possess strong immunomodulating properties. The immunomodulatory effects of plant extracts and their bioactive metabolites have been suggested due to their diverse mechanisms of modulation of the complex immune system and their multifarious molecular targets. Phytochemicals such as alkaloids, flavonoids, terpenoids, carbohydrates and polyphenols have been reported as responsible for the immunomodulatory effects of several medicinal plants. This review illustrates the potent immunomodulatory effects of 65 plant secondary metabolites, including dietary compounds and their underlying mechanisms of action on cellular and humoral immune functions in in vitro and in vivo studies. The clinical potential of some of the compounds to be used for various immune-related disorders is highlighted.

Bovine-associated staphylococci and mammaliicocci trigger T-lymphocyte proliferative response and cytokine production differently.

We examined whether distinct staphylococcal and mammaliicoccal species and strains trigger B- and T-lymphocyte proliferation and interleukin (IL)-17A and interferon (IFN)-γ production by peripheral blood mononuclear cells in nulliparous, primiparous, and multiparous dairy cows. Flow cytometry was used to measure lymphocyte proliferation with the Ki67 antibody, and specific monoclonal antibodies were used to identify CD3, CD4, and CD8 T lymphocyte and CD21 B lymphocyte populations. The supernatant of the peripheral blood mononuclear cell culture was used to measure IL-17A and IFN-γ production. Two distinct, inactivated strains of bovine-associated Staphylococcus aureus [one causing a persistent intramammary infection (IMI) and the other from the nose], 2 inactivated Staphylococcus chromogenes strains [one causing an IMI and the other from a teat apex), as well as an inactivated Mammaliicoccus fleurettii strain originating from sawdust from a dairy farm, and the mitogens concanavalin A and phytohemagglutinin M-form (both specifically to measure lymphocyte proliferation) were studied. In contrast to the "commensal" Staph. aureus strain originating from the nose, the Staph. aureus strain causing a persistent IMI triggered proliferation of CD4+ and CD8+ subpopulations of T lymphocytes. The M. fleurettii strain and the 2 Staph. chromogenes strains had no effect on T- or B-cell proliferation. Furthermore, both Staph. aureus and Staph. chromogenes strains causing persistent IMI significantly increased IL-17A and IFN-γ production by peripheral blood mononuclear cells. Overall, multiparous cows tended to have a higher B-lymphocyte and a lower T-lymphocyte proliferative response than primiparous and nulliparous cows. Peripheral blood mononuclear cells of multiparous cows also produced significantly more IL-17A and IFN-γ. In contrast to concanavalin A, phytohemagglutinin M-form selectively stimulated T-cell proliferation.

Prostate gland metastasis as a late relapse of rectal adenocarcinoma.

We present a case report of a 49 year old patient with a known history of rectal adenocarcinoma treated with extended abdominal perineal resection. After five the patient was diagnosed with metastases to the prostate gland. This case stands out not only due to the infrequency of an onset of a colorectal tumor in the prostatic gland but also the late onset of the tumor. In these cases the differential diagnosis between a metastatic tumor and a primary urologic tumor is difficult due to similar morphology and histology, making the CDX-2 immunohistochemical maker expression an important tool to define the histopathology of the tumor.

Clinical and Biochemical Profile Associated with Renal Recovery after Acute Kidney Injury in A Mexican Population: Retrospective Cohort Study.

Background and Objectives: Our primary objective was to study the clinical and biochemical characteristics associated with acute kidney injury (AKI) remission in a group of Mexican patients. Materials and methods: We retrospectively enrolled 75 patients who were diagnosed with AKI and separated the sample into two groups: nonremitting patients (n = 27, 36%) vs. remitting patients (n = 48, 64%). Results: We found significant relationships between nonremitting AKI and previous diagnosis of chronic kidney disease (p = 0.009), higher serum creatinine (Cr) at admission (p < 0.0001), lower estimated glomerular filtration rate (eGFR) (p < 0.0001), maximum serum creatinine during hospitalization (p < 0.0001), higher fractional excretion of sodium (FENa) (p < 0.0003) and 24-h urine protein (p = 0.005), higher serum potassium on admission (p = 0.025), abnormal levels of procalcitonin (p = 0.006), and increased risk of death (p = 0.015). Conclusion: Chronic kidney disease (CKD), lower eGFR, higher levels of serum creatinine during hospitalization, higher FENa and 24-h urine protein, abnormal levels of procalcitonin, and higher serum potassium on admission were associated with nonremitting AKI. These findings may facilitate the rapid identification of patients at risk for nonremitting AKI based on clinical and biochemical characteristics. Furthermore, these findings may inform the design of timely strategies for the vigilance, prevention, and treatment of AKI.

Evaluating the Use of Parenteral Naloxone in the Emergency Department of a Community Hospital.

Background:Thousands of patients die every year from opioid overdose. Naloxone is a lifesaving medication FDA approved for opioid overdose reversal. Many patients may present to the emergency department (ED) and require naloxone administration. The purpose of this study was to evaluate parenteral naloxone usage in the ED. It assessed parenteral naloxone indication of use and the patient population requiring its administration in order to support the need of a take home naloxone distribution program. Methods: This study was a retrospective, randomized, single center, chart review that took place at a community hospital ED. A computerized report was generated to identify all patients 18 years of age or older who were administered naloxone in the ED from June 2020 to June 2021. The charts of 100 patients randomly selected from the generated report were reviewed to collect the following information: gender, age, indication for use, dosing, drug being reversed, risk factors for overdose, ED revisits within 1 year. Results: Out of the 100 patients randomly reviewed, 55 (55%) patients were administered parenteral naloxone for overdose indication. Eighteen (32%) of overdose patients revisited the hospital within 1 year for overdose. Thirty-six (65%) of patients administered naloxone for overdose had history of substance abuse with 45 (82%) being under the age of 65 years. Conclusion: These results support the need for a take home naloxone distribution program to be implemented for patients at risk for opioid overdose or individuals at risk of witnessing a drug overdose.

Alternative technologies for the production of popped sorghum: a comparative study.

Sorghum is the fifth most harvested crop worldwide, being the popped sorghum as one of the most common snacks in India and some Asian regions. Therefore, this study evaluated how the processing method influences the microstructure, volumetric and textural properties of popped sorghum microstructure, volumetric and textural properties. White sorghum "Paloma" variety (11% moisture) was assessed, which was popped using three processing methods: microwave, pan-frying, and hot salt-frying using three temperature levels. Volumetric and yield characteristics were evaluated for the popped kernels, as their microstructure and texture profile. The popped sorghum obtained through the hot salt-frying method had a microstructure composed of polygonal cells. Also, it showed the best volumetric characteristics (volume), good expansion index, and high process yield. Finally, the hot salt-frying method showed better textural features associated with the attributes of a satisfactory product for consumers.

Opioid Use and Its Relationship to Cardiovascular Disease and Brain Health: A Presidential Advisory From the American Heart Association.

The misuse of opioids continues to be epidemic, resulting in dependency and a recent upsurge in drug overdoses that have contributed to a significant decrease in life expectancy in the United States. Moreover, recent data suggest that commonly used opioids for the management of pain may produce undesirable pharmacological actions and interfere with critical medications commonly used in cardiovascular disease and stroke; however, the impact on outcomes remains controversial. The American Heart Association developed an advisory statement for health care professionals and researchers in the setting of cardiovascular and brain health to synthesize the current literature, to provide approaches for identifying patients with opioid use disorder, and to address pain management and overdose. A literature and internet search spanning from January 1, 2012, to February 15, 2021, and limited to epidemiology studies, reviews, consensus statements, and guidelines in human subjects was conducted. Suggestions and considerations listed in this document are based primarily on published evidence from this review whenever possible, as well as expert opinion. Several federal and institutional consensus documents and clinical resources are currently available to both patients and clinicians; however, none have specifically addressed cardiovascular disease and brain health. Although strategic tools and therapeutic approaches for recognition of opioid use disorder and safe opioid use are available for health care professionals who manage patients with cardiovascular disease and stroke, high-quality evidence does not currently exist. Therefore, there is an urgent need for more research to identify the most effective approaches to improve care for these patients.

Regulation of DAPK1 by Natural Products: An Important Target in Treatment of Stroke.

Stroke is a sudden neurological disorder that occurs due to impaired blood flow to an area of the brain. Stroke can be caused by the blockage or rupture of a blood vessel in the brain, called ischemic stroke and hemorrhagic stroke, respectively. Stroke is more common in men than women. Atrial fibrillation, hypertension, kidney disease, high cholesterol and lipids, genetic predisposition, inactivity, poor nutrition, diabetes mellitus, family history and smoking are factors that increase the risk of stroke. Restoring blood flow by repositioning blocked arteries using thrombolytic agents or endovascular therapy are the most effective treatments for stroke. However, restoring circulation after thrombolysis can cause fatal edema or intracranial hemorrhage, and worsen brain damage in a process known as ischemia-reperfusion injury. Therefore, there is a pressing need to find and develop more effective treatments for stroke. In the past, the first choice of treatment was based on natural compounds. Natural compounds are able to reduce the symptoms and reduce various diseases including stroke that attract the attention of the pharmaceutical industry. Nowadays, as a result of the numerous studies carried out in the field of herbal medicine, many useful and valuable effects of plants have been identified. The death-associated protein kinase (DAPK) family is one of the vital families of serine/threonine kinases involved in the regulation of some biological functions in human cells. DAPK1 is the most studied kinase within the DAPKs family as it is involved in neuronal and recovery processes. Dysregulation of DAPK1 in the brain is involved in the developing neurological diseases such as stroke. Natural products can function in a variety of ways, including reducing cerebral edema, reducing brain endothelial cell death, and inhibiting TNFα and interleukin-1ß (IL-1ß) through regulating the DAPK1 signal against stroke. Due to the role of DAPK1 in neurological disorders, the aim of this article was to investigate the role of DAPK1 in stroke and its modulation by natural compounds.

Ontogeny and anatomy of Bouteloua (Poaceae: Chloridoideae) species display a basipetal branch formation and a novel modified leaf structure in grasses.

BACKGROUND AND AIMS: Shoot ontogenesis in grasses follows a transition from a vegetative phase into a reproductive phase. Current studies provide insight into how branch and spikelet formation occur during the reproductive phase. However, these studies do not explain all the complex diversity of grass inflorescence forms and are mostly focused on model grasses. Moreover, truncated inflorescences of the non-model grass genus Urochloa (Panicoideae) with formation of primary branches have basipetal initiation of branches. Bouteloua species (Chloridoideae) are non-model grasses that form truncated inflorescences of primary branches with apical vestiges of uncertain homology at the tips of branching events and sterile florets above the lowermost fertile floret. Sterile florets are reduced to rudimentary lemmas composed of three large awns diverging from an awn column. Conflict about the awn column identity of this rudimentary lemma is often addressed in species descriptions of this genus. We test if Bouteloua species can display basipetal initiation of branches and explore the identity of vestiges and the awn column of rudimentary lemmas. METHODS: We surveyed the inflorescence ontogeny and branch/awn anatomy of Bouteloua species and compared results with recent ontogenetic studies of chloridoids. KEY RESULTS: Bouteloua arizonica has florets with basipetal maturation. Branches display basipetal branch initiation and maturation. Branch vestiges are formed laterally by meristems during early branching events. The spikelet meristem forms the awn column of rudimentary lemmas. Vestiges and sterile floret awns have anatomical similarities to C4 leaves. CONCLUSIONS: Basipetal initiation of branches is a novel feature for Chloridoideae grasses. Branch vestiges are novel vegetative grass structures. Sterile floret awn columns are likely to be extensions of the rachilla.

Community-based accompaniment for adolescents transitioning to adult HIV care in urban Peru: a pilot study.

We piloted a community-based intervention to improve outcomes among adolescents living with HIV who were transitioning to adult-oriented care in Lima, Peru. We assessed feasibility and potential effectiveness, including within-person changes in self-reported adherence, psychosocial metrics (NIH Toolbox), and transition readiness ("Am I on TRAC" questionnaire, "Got Transition" checklist). From October 2019 to January 2020, we enrolled 30 adolescents (15-21 years). The nine-month intervention consisted of logistical, adherence and social support delivered by entry-level health workers and group sessions to improve health-related knowledge and skills and social support. In transition readiness, we observed within-person improvements relative to baseline. We also observed strong evidence of improvements in adherence, social support, self-efficacy, and stress, which were generally sustained three months post-intervention. All participants remained in treatment after 12 months. The intervention was feasible and potentially effective for bridging the transition to adult HIV care. A large-scale evaluation, including biological endpoints, is warranted.

RESUMEN: Piloteamos una intervención comunitaria para mejorar los resultados de adolescentes viviendo con el VIH que se encontraban en transición a la atención de VIH orientada a adultos en Lima, Perú. Evaluamos la viabilidad y la eficacia potencial, incluidos los cambios personales en la adherencia auto-reportada, criterios psicosociales (NIH Toolbox), y preparación para la transición (cuestionario "Estoy en el TRAC", lista de verificación "Got Transition"). Desde octubre de 2019 hasta enero de 2020, enrolamos a 30 adolescentes (15 a 21 años). La intervención de nueve meses consistió en apoyo logístico, de adherencia y social brindado por técnicos de enfermería y sesiones grupales para mejorar tanto el conocimiento y las habilidades relacionados con la salud, como el apoyo social. En cuanto a la preparación para la transición, observamos mejoras comparada con el basal. También observamos una fuerte evidencia de mejoras en la adherencia, apoyo social, autoeficacia y estrés, que se mantuvieron, generalmente, tres meses después del fin de la intervención. Todos los participantes seguían en tratamiento después de 12 meses. La intervención fue factible y potencialmente efectiva para tender un puente en la transición a la atención del VIH para adultos. Esto amerita una evaluación a mayor escala y que incluya criterios clínicos.

Female sexuality before and after sacrocolpopexy or vaginal mesh: is vaginal length one of the key factors?

INTRODUCTION AND HYPOTHESIS: We aimed to demonstrate that laparoscopic sacrocolpopexy/cervicopexy (LSC-Cx) versus anterior vaginal mesh (AVM) results in a longer vaginal length without impacting sexual activity or function. METHODS: We performed a secondary analysis of sexual outcomes of a previous randomized control trial comparing LSC-Cx and AVM in 120 women (60/group) with symptomatic POP stage ≥ 3. We evaluated sexually active (SA) and non-sexually active women (NSA) using the Pelvic Organ Prolapse/Incontinence Sexual Questionnaire-IUGA-Revised (PISQ-IR) preoperatively and 1 year postoperatively. Multivariate logistic and linear regression models were built to assess the impact of different variables on sexual activity and function, respectively. RESULTS: Among 120 women included, no statistically significant differences were found between vaginal length and preoperative dyspareunia (20.7% AVM vs. 22,8% LSC-Cx) comparing SA to NSA women and LSC-Cx to AVM. Vaginal length was significantly longer after LSC-Cx versus AVM (p < 0.001). The postoperative dyspareunia rate was 17.2% AVM versus 10.5% LSC-Cx. Partnered women were significantly more likely to be SA than unpartnered women before (OR = 19.04; p = 0.006) and after surgery (OR = 36.28; p = 0.002). Only dyspareunia was independently associated with sexual function pre- (B = -0.431; p = 0.017) and postoperatively (B = -0.3 96; p = 0.007). CONCLUSIONS: Vaginal length was greater following LSC-Cx compared to AVM. While vaginal length has no impact on female sexuality pre- and postoperatively, the most important factors were "having a partner" for sexual activity and dyspareunia for sexual function. Persistence of dyspareunia was higher after AVM. LSC-Cx should be considered in women with POP undergoing mesh surgery with future sexual expectations.

The Phytochemical Profile and Biological Activity of Malva neglecta Wallr. in Surgically Induced Endometriosis Model in Rats.

Leaves and aerial parts of Malva neglecta Wallr. have been traditionally used in Anatolia for the treatment of pain, inflammation, hemorrhoids, renal stones, constipation, and infertility. This study investigated the effects of M. neglecta leaves in a rat endometriosis model. The dried plant material was extracted with n-hexane, ethyl acetate, and methanol, successively. Experimental endometriosis was surgically induced in six-week-old female, non-pregnant, Wistar albino rats by autotransplant of endometrial tissue to the abdominal wall. After twenty-eight days, rats were evaluated for a second laparotomy. Endometrial foci areas were assessed, and intraabdominal adhesions were scored. Rats were divided into five groups as control, n-hexane, ethyl acetate, methanol, and aqueous extracts, as well as reference. At the end of the treatment, all rats were sacrificed and endometriotic foci areas and intraabdominal adhesions were re-evaluated and compared with the previous findings. Moreover, peritoneal fluid was collected to detect tumor necrosis factor- α (TNF-α), vascular endothelial growth factor (VEGF), and interleukin-6 (IL-6) levels, and cDNA synthesis, and a quantitative real-time polymerase chain reaction (PCR) test was done. The phytochemical content of the most active extract was determined using High-Performance Liquid Chromatography (HPLC). Both endometrial volume and adhesion score decreased significantly in the group treated with methanol extract. In addition, significant decreases were observed in TNF-α, VEGF, and IL-6 levels in animals administered methanol extract. HPLC results showed that the activity caused by the methanol extract of M. neglecta was due to the polyphenols. Taken together, these novel findings indicate that M. neglecta may be a promising alternative for the treatment of endometriosis.

Obstructive jaundice secondary to a pseudoaneurysm of the superior mesenteric artery.

Superior mesenteric arteries pseudoaneurysms are rare entity, usually asymptomatic but they can appear as an abdominal pain, throbbing mass or shock, being jaundice an exceptional type of presentation. Diagnosis is made by imaging tests (CT) and currently the endovascular approach is the most widespread, reserving open surgery in selected cases. We describe the case of a patient with an 86mm SMA pseudoaneurysm with compression of the extrahepatic bile duct.

Call to Action: Rural Health: A Presidential Advisory From the American Heart Association and American Stroke Association.

Understanding and addressing the unique health needs of people residing in rural America is critical to the American Heart Association's pursuit of a world with longer, healthier lives. Improving the health of rural populations is consistent with the American Heart Association's commitment to health equity and its focus on social determinants of health to reduce and ideally to eliminate health disparities. This presidential advisory serves as a call to action for the American Heart Association and other stakeholders to make rural populations a priority in programming, research, and policy. This advisory first summarizes existing data on rural populations, communities, and health outcomes; explores 3 major groups of factors underlying urban-rural disparities in health outcomes, including individual factors, social determinants of health, and health delivery system factors; and then proposes a set of solutions spanning health system innovation, policy, and research aimed at improving rural health.