Synthetic amyloid beta does not induce a robust transcriptional response in innate immune cell culture systems.

BACKGROUND: Alzheimer's disease (AD) is a progressive neurodegenerative disease that impacts nearly 400 million people worldwide. The accumulation of amyloid beta (Aß) in the brain has historically been associated with AD, and recent evidence suggests that neuroinflammation plays a central role in its origin and progression. These observations have given rise to the theory that Aß is the primary trigger of AD, and induces proinflammatory activation of immune brain cells (i.e., microglia), which culminates in neuronal damage and cognitive decline. To test this hypothesis, many in vitro systems have been established to study Aß-mediated activation of innate immune cells. Nevertheless, the transcriptional resemblance of these models to the microglia in the AD brain has never been comprehensively studied on a genome-wide scale. METHODS: We used bulk RNA-seq to assess the transcriptional differences between in vitro cell types used to model neuroinflammation in AD, including several established, primary and iPSC-derived immune cell lines (macrophages, microglia and astrocytes) and their similarities to primary cells in the AD brain. We then analyzed the transcriptional response of these innate immune cells to synthetic Aß or LPS and INFγ. RESULTS: We found that human induced pluripotent stem cell (hIPSC)-derived microglia (IMGL) are the in vitro cell model that best resembles primary microglia. Surprisingly, synthetic Aß does not trigger a robust transcriptional response in any of the cellular models analyzed, despite testing a wide variety of Aß formulations, concentrations, and treatment conditions. Finally, we found that bacterial LPS and INFγ activate microglia and induce transcriptional changes that resemble many, but not all, aspects of the transcriptomic profiles of disease associated microglia (DAM) present in the AD brain. CONCLUSIONS: These results suggest that synthetic Aß treatment of innate immune cell cultures does not recapitulate transcriptional profiles observed in microglia from AD brains. In contrast, treating IMGL with LPS and INFγ induces transcriptional changes similar to those observed in microglia detected in AD brains.

Uterine Transplantation: Scientific Impact Paper No. 65 April 2021.

A uterine transplant, or womb transplant, provides a potential treatment for women who cannot become pregnant or carry a pregnancy because they do not have a womb, or have a womb that is unable to maintain a pregnancy. This is estimated to affect one in 500 women. Options for those who wish to start a family include adoption and surrogacy, but these are associated with legal, cultural, ethical and religious implications that may not be appropriate for some women and their families. A womb transplant is undertaken when the woman is ready to start a family, and is removed following the completion of their family. Womb transplants have been performed all over the world, with more than 70 procedures carried out so far. At least 23 babies have been born as a result, demonstrating that womb transplants can work. While the procedure offers a different option to adoption and surrogacy, it is associated with significant risks, including multiple major surgeries and the need to take medications that help to dampen the immune system to prevent rejection of the womb. To date there has been a 30% risk of a transplant being unsuccessful. Although the number of transplants to date is still relatively small, the number being performed globally is growing, providing an opportunity to learn from the experience gained so far. This paper looks at the issues that have been encountered, which may arise at each step of the process, and proposes a framework for the future. However, long term follow-up of cases will be essential to draw reliable conclusions about any overall benefits of this procedure.

Functional Interplay of Type-2 Corticotrophin Releasing Factor and Dopamine Receptors in the Basolateral Amygdala-Medial Prefrontal Cortex Circuitry.

BACKGROUND: Basolateral amygdala (BLA) excitatory projections to medial prefrontal cortex (PFC) play a key role controlling stress behavior, pain, and fear. Indeed, stressful events block synaptic plasticity at the BLA-PFC circuit. The stress responses involve the action of corticotrophin releasing factor (CRF) through type 1 and type 2 CRF receptors (CRF1 and CRF2). Interestingly, it has been described that dopamine receptor 1 (D1R) and CRF peptide have a modulatory role of BLA-PFC transmission. However, the participation of CRF1 and CRF2 receptors in BLA-PFC synaptic transmission still is unclear. METHODS: We used in vivo microdialysis to determine dopamine and glutamate (GLU) extracellular levels in PFC after BLA stimulation. Immunofluorescence anatomical studies in rat PFC synaptosomes devoid of postsynaptic elements were performed to determine the presence of D1R and CRF2 receptors in synaptical nerve endings. RESULTS: Here, we provide direct evidence of the opposite role that CRF receptors exert over dopamine extracellular levels in the PFC. We also show that D1R colocalizes with CRF2 receptors in PFC nerve terminals. Intra-PFC infusion of antisauvagine-30, a CRF2 receptor antagonist, increased PFC GLU extracellular levels induced by BLA activation. Interestingly, the increase in GLU release observed in the presence of antisauvagine-30 was significantly reduced by incubation with SCH23390, a D1R antagonist. CONCLUSION: PFC CRF2 receptor unmasks D1R effect over glutamatergic transmission of the BLA-PFC circuit. Overall, CRF2 receptor emerges as a new modulator of BLA to PFC glutamatergic transmission, thus playing a potential role in emotional disorders.

The vaginal microbiome in uterine transplantation.

Women with congenital absolute uterine factor infertility (AUFI) often need vaginal restoration to optimise sexual function. Given their lack of procreative ability, little consideration has previously been given to the resultant vaginal microbiome (VM). Uterine transplantation (UTx) now offers the opportunity to restore these women's reproductive potential. The structure of the VM is associated with clinical and reproductive implications that are intricately intertwined with the process of UTx. Consideration of how vaginal restoration methods impact VM is now warranted and assessment of the VM in future UTx procedures is essential to understand the interrelation of the VM and clinical and reproductive outcomes. TWEETABLE ABSTRACT: The vaginal microbiome has numerous implications for clinical and reproductive outcomes in the context of uterine transplantation.

Human uterine transplantation: a review of outcomes from the first 45 cases.

Uterine transplantation restores reproductive anatomy in women with absolute uterine factor infertility and allows the opportunity to conceive, experience gestation, and acquire motherhood. The number of cases being performed is increasing exponentially, with detailed outcomes from 45 cases, including nine live births, now available. In light of the data presented herein, including detailed surgical, immunosuppressive and obstetric outcomes, the feasibility of uterine transplantation is now difficult to refute. However, it is associated with significant risk with more than one-quarter of grafts removed because of complications, and one in ten donors suffering complications requiring surgical repair. TWEETABLE ABSTRACT: Uterine transplantation is feasible in women with uterine factor infertility, but is associated with significant risk of complication.

Efficacy of respiratory muscle training in weaning of mechanical ventilation in patients with mechanical ventilation for 48hours or more: A Randomized Controlled Clinical Trial. / Eficacia del entrenamiento muscular respiratorio en el destete de la ventilación mecánica en pacientes con ventilación mecánica por 48 o más horas: un ensayo clínico controlado.

OBJECTIVE: To evaluate the efficacy of respiratory muscular training in the weaning of mechanical ventilation and respiratory muscle strength in patients on mechanical ventilation of 48hours or more. DESIGN: Randomized controlled trial of parallel groups, double-blind. Ambit: Intensive Care Unit of a IV level clinic in the city of Cali. PATIENTS: 126 patients in mechanical ventilation for 48hours or more. INTERVENTIONS: The experimental group received daily a respiratory muscle training program with treshold, adjusted to 50% of maximal inspiratory pressure, additional to standard care, conventional received standard care of respiratory physiotherapy. MAIN INTEREST VARIABLES: weaning of mechanical ventilation. Other variables evaluated: respiratory muscle strength, requirement of non-invasive mechanical ventilation and frequency of reintubation. ANALYSIS: intention-to-treat analysis was performed with all variables evaluated and analysis stratified by sepsis condition. RESULTS: There were no statistically significant differences in the median weaning time of the MV between the groups or in the probability of extubation between groups (HR: 0.82 95% CI: 0.55-1.20 P=.29). The maximum inspiratory pressure was increased in the experimental group on average 9.43 (17.48) cmsH20 and in the conventional 5.92 (11.90) cmsH20 (P=.48). The difference between the means of change in maximal inspiratory pressure was 0.46 (P=.83 95%CI -3.85 to -4.78). CONCLUSIONS: respiratory muscle training did not demonstrate efficacy in the reduction of the weaning period of mechanical ventilation nor in the increase of respiratory muscle strength in the study population. Registered study at ClinicalTrials.gov (NCT02469064).

The rise and potential fall of pancreas transplantation.

BACKGROUND: The aim of this review is to bring pancreatic transplantation out of the specialist realm, informing practitioners about this important procedure, so that they feel better equipped to refer suitable patients for transplantation and manage, counsel and support when encountering them within their own speciality. SOURCES OF DATA: Narrative review conducted in May 2017. OVID interface searching EMBASE and MEDLINE databases, using Timeframe: Inception to June 1, 2017. Articles were assessed for clinical relevance and most up to date content with articles written in english as the only inclusion criteria. Other sources, used included conference proceedings/presentations, unpublished data from our institution (Oxford Transplant Centre). AREAS OF AGREEMENT: Pancreas transplantation has evolved from an experimental procedure to the gold standard of care for patients with type 1 diabetes and uraemia. Currently, it remains the most effective method of establishing and maintaining euglycemia over the longer term, halting and potentially reversing many of the secondary complications associated with diabetes. Significant improvements to quality of life and better life expectancy make it in the longer term, a lifesaving procedure compared to waiting candidates. AREAS OF CONTROVERSY: The future of solid organ pancreas transplantation remains uncertain, with extensive comorbidity and advances in alternative therapies makes the long-term growth of the procedure questionable. GROWING POINTS AND AREAS TIMELY FOR DEVELOPING RESEARCH: Therapies to alleviate problems associated with ischaemia reperfusion injury, graft pancreatitis and more effective monitoring methods for detecting and treating organ rejection are the key areas of growth.

Dolor abdominal y hematoquecia / Abdominal pain and hematochezia

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Herida por proyectil de alta velocidad en ambiente naval. Cirugía de control del daño abdominal / Gun shot wound in naval environment. Damage control abdominal surgery

Estudio de un caso de herida abdominal por arma de fuego tratada mediante premisas de cirugía de control del daño, atendido en primera instancia por personal del Cuerpo Militar de Sanidad destinado en el buque petrolero de la Armada ‘Marqués de la Ensenada’. Evacuación sobre un segundo escalón quirúrgico francés y aplicación de procedimientos quirúrgicos de control del daño. El interés de esta comunicación breve radica en que se analiza el manejo de una lesión traumática por arma de fuego de gran interés militar, desarrollado en un ambiente naval, con un tiempo de evacuación prolongado y efectuado en dos escalones médicos pertenecientes a diferentes países

Case study of abdominal gunshot wound treated through damage control surgery by the Military Health Corps posted in the Army oil tanker ‘Marqués de la Ensenada’. Evacuated later by a second French chirurgical echelon with application of surgical procedure of damage control. The interest of this brief paper focuses on the analysis of a traumatic gunshot wound management which is considered to be of interest as it deals with issues such as long evacuation time, the involvement of two medical echelons from different countries and the involvement of the Navy

Traumatismo de alta velocidad por arma de fuego en zona de conflicto / High velocity trauma by gunshot in conflict área

Presentamos el caso de una baja por arma de fuego ingresada en el Role 2E español de Herat (Afganistán) analizando el diagnóstico, tratamiento y evacuación en el teatro de operaciones

We present a case of a casualty by gunshot who was admitted in Spanish Role 2E (Herat –Afghanistan-) showing the diagnosis, treatment and evacuation in the theatre

Tratamiento del dolor perioperatorio en la baja de combate. Experiencia desde el Hospital Militar Español de Herat (Afganistán) / Perioperative pain treatment in combat casualty. Experience from the Spanish Military Hospital in Herat (Afghanistan)

La analgesia siempre se ha considerado uno de los pilares fundamentales de la asistencia médica a la baja de combate. Esta opinión sigue vigente en los actuales conflictos de Irak y Afganistán. La sanidad militar española lleva desplegada en el Hospital Militar de Herat (Afganistán) desde 2005. En este centro se han atendido a casi 30.000 pacientes (algunos de ellos bajas en combate), obteniéndose una importante experiencia en el tratamiento de este tipo de politraumatismo. Se expone el caso de un militar, que tras sufrir un atentado con herida de arma de fuego y explosivos, sufre traumatismo craneoencefálico, lesión ocular, traumatismo abdominal y en una extremidad. Se exponen las medidas de control del dolor perioperatorias prestadas a este herido (AU)

Analgesia has been considered always a vital role in the casualty medical assistant. This opinion is present in Irak and Afghanistan conflicts, too. Since 2005, Spanish military corps has been deployed in the Spanish Military Hospital in Herat (Afghanistan). In this medical facility 30.000 patients (some of them casualties) have been treated, kept an important experience in the treatment of this kind of politrauma. e show a medical report about a military, who is injured by an gunshot and explosive attack suffering traumatic brain injury, ocular lesion, abdominal and leg trauma. Perioperative painkiller treatment is described in this casualty (AU)

Ortopedia de control del daño infantil en zona de combate / Pediatrics Damage Control Ortopaedic Surgery in Area of Operations

El objeto de esta comunicación breve es presentar un caso de fractura pediátrica tratada mediante premisas de Ortopedia de Control del Daño en el segundo escalón quirúrgico español de Camp Arena, Herat, Afganistán

This is case report about a femoral shaft pediatric fracture treated with Orthopaedic Damage Control Means completed at the Second Surgical Echelon in Herat, Afghanistan. We show the benefits of this kind of procedures

Ogilvie Syndrome and Chilaiditi Syndrome: a Strange Association.

Chilaiditi syndrome is a strange disease which includes the existence of Chilaiditi sign and other abdominal symptoms. Chilaiditi sign refers the interposition of the colon between the liver and diaphragm that could be misinterpreted to be a pneumoperitoneum. We present a 46-year-old male patient who was admitted in the hospital with constipation and abdominal oppressive pain located in the epigastric area. He showed signs of peritoneal irritation, no bowel sounds, hernias, or organ enlargements. Laboratory analysis only revealed CPK elevation (462 U/L). Abdominal and chest radiographs showed an image which suggested a pneumoperitoneum. The patient underwent emergency surgical treatment, under diagnosis of viscera perforation. At laparotomy, an interposition of the transverse colon between the liver and diaphragm were visualized, although no perforations were present. Psychiatric treatment was held until this moment due to the high risk of schizophrenia outbreak. During the next 48 h, intestinal transit was restored and he was discharged on postoperative day 40, diagnosed with Ogilvie syndrome secondary to psychotropics. The relationship between Ogilvie syndrome and psychiatric treatments is known, but the association between Ogilvie and Chilaiditi syndrome is very strange. Nevertheless, it could be misinterpreted like a pneumoperitoneum and led to the performance of emergency surgery.

Evaluation of recombinant antigens of Trypanosoma cruzi to diagnose infection in naturally infected dogs from Chaco region, Argentina.

Dogs are considered the main mammal reservoir of Trypanosoma cruzi in domiciliary environments. Consequently, accurate detection of T. cruzi infection in canine populations is epidemiologically relevant. Here, we analysed the utility of the T. cruzi recombinant antigens FRA, SAPA, CP1, Ag1 and a SAPA/TSSA VI mixture, in an ELISA format. We used a positive control group of sera obtained from 38 dogs from the Chaco region in Argentina with positive homogenate-ELISA reaction, all of them also positive by xenodiagnosis and/or PCR. The negative group included 19 dogs from a nonendemic area. Sensitivity, specificity, area under the curve (AUC) of the receiver operating charactheristic (ROC) curve and Kappa index were obtained to compare the diagnostic efficiency of the tests. The SAPA/TSSA VI had the highest performance, with a sensitivity of 94.7% and an AUC ROC of 0.99 that indicates high accuracy. Among individual antigens, SAPA-ELISA yielded the highest sensitivity (86.8%) and AUC ROC (0.96), whereas FRA-ELISA was the least efficient test (sensitivity = 36.8%; AUC ROC = 0.53). Our results showed that the use of SAPA/TSSA VI in ELISAs could be a useful tool to study dogs naturally infected with T. cruzi in endemic areas.

Masa abdominal en neonato atendido en zona de operaciones (Afganistán) / Abdominal mass in neonate attended in operations area (Afghanistan)

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Tumores del estroma gastrointestinal (GIST): serie del Hospital Central de la Defensa Gómez Ulla / Gastrointestinal stromal tumors (GIST): series of the Defense Central Hospital «Gómez Ulla»

Objetivo: Los tumores del estroma gastrointestinal (GIST) se han diferenciado hace poco más de una década de los tumores de músculo liso y de origen neural gracias a métodos de identificación inmunohistoquímica (CD117). Al mismo tiempo, la introducción del Mesylato de Imatinib, fármaco empleado en el tratamiento de la leucemia mieloide crónica (LMC), ha mejorado la expectativa de vida, no sólo en GIST irresecables o metastáticos, sino también para aquéllos de intermedio o alto grado de malignidad como terapia adyuvante e incluso se plantea como tratamiento neoadyuvante. El objetivo de esta comunicación es estudiar los GIST diagnosticados e intervenidos quirúrgicamente en el Servicio de Cirugía General y del Aparato Digestivo del Hospital Central de la Defensa «Gómez Ulla» (Madrid) en un periodo de 9 años y realizar una revisión de la literatura enfocada fundamentalmente a los avances en el tratamiento. Material y métodos: Estudio retrospectivo observacional de los pacientes diagnosticados de GIST e intervenidos quirúrgicamente en nuestro Servicio de 2003 a 2012. Se estudia el motivo de consulta inicial, la localización, el grado histológico y el tipo de intervención quirúrgica realizado. Resultados: Se encontraron 11 pacientes entre Noviembre de 2003 y Abril de 2012, todos hombres. La edad media fue de 65’17 años (rango, 53-84). Hay que destacar que en 8 casos (72’7 %) el hallazgo fue incidental, sin ninguna sintomatología previa. La localización más frecuente fue el estómago en 6 casos (54’5%), y en el intestino delgado en 5 (45’5%). En cuanto al riesgo de malignidad, 5 casos (45’5%) fueron de bajo grado, 4 (36’4%) de grado intermedio, 1 (9%) de muy bajo grado y 1 (9’1%) de alto grado de malignidad. La técnica quirúrgica empleada fue la gastrectomía parcial en 6 casos (54’5%) seguida de la resección intestinal segmentaria en 5 casos (45’5%). Conclusiones: La incidencia anual de tumores GIST intervenidos en nuestro servicio es de 1 nuevo caso/año. Las localizaciones han sido el estómago y el intestino delgado. Todos los tumores de grado bajo se han beneficiado de cirugía, con tasas de supervivencia excelentes sin tratamiento adicional. Hasta conocer los resultados de los estudios en curso sobre la terapia neoadyuvante con Imatinib, parece que en tumores GIST operables se debería realizar primero cirugía y valorar, según los hallazgos intraoperatorios, la adyuvancia y, en casos de tumores solo parcialmente resecables o metastásicos, la neoadyuvancia (AU)

Introduction: Since a little more than a decade the gastrointestinal stromal tumors (GIST) have been differentiated from the tumors of smooth muscle and of neural origin by immunohistochemical methods (CD117). Simultaneously the introduction of imatinib mesylate, utilized in the treatment of chronic myeloid leukemia (CML), has improved the life expectancy, not only in unresectable or metastatic GIST, but also in those of high or intermediate degree of malignancy as adjuvant therapy or even as neoadjuvant therapy. Objective: To study the GIST diagnosed and operated in the Department of General and Digestive Surgery of the Defense Central Hospital in 9 years and to review the literature mainly focused on therapeutic advances. Material and Methods: Retrospective observational study of the GIST patients diagnosed and operated in our Department from 2003 to 2012. The reason for the initial consultation, localization, histologic grade and type of surgery performed are analyzed. Results: Eleven patients, all male, were diagnosed between November 2003 and April 2012. Average age was 65.17 (range 53-84). It must be emphasized that in 8 cases (72.7 %) the finding was incidental, without any previous symptoms. The most frequent localization was the stomach in 6 cases (54.5%) and the small intestine in 5 (45.5%). As far as the malignancy risk is concerned 5 cases (45.5%) were low grade, 4 cases (36.4%) intermediate grade, 1 case (9%) very low grade and 1 case (9.1%) high malignancy grade. The surgical technique utilized was partial gastrectomy in 6 cases (54.5%) followed by segmental intestinal resection in 5 cases (45.5%). Conclusions: The annual incidence of GIST tumors operated in our Department is 1 new case / year. The localizations were in the stomach and small intestine. All low grade tumors have benefited from surgery with excellent survival rates without additional treatment. Until the results of the ongoing studies about neoadjuvant therapy with imatinib are known, it seems that operable GIST tumors should first undergo surgery and assess, in accordance with intraoperative findings, the adjuvancy and for only partially resectable o metastatic tumors, the neoadjuvancy (AU)

Lesiones nodulares y placas no pruriginosas / No disponible

No disponible

Hernia interna de Quain como causa de abdomen agudo / Internal hernia of Quain as a cause of acute abdomen

Presentamos el caso de una paciente de 47 años de edad que consulta en urgencias por un cuadro de 8 horas de evolución, de dolor abdominal continuo y difuso, acompañado de vómitos alimentarios al inicio y biliosos después. La paciente presenta estabilidad hemodinámica permaneciendo afebril. El hemiabdomen inferior presenta signos de irritación peritoneal. En los análisis destaca la presencia de neutrofilia y leucocitosis, la radiología simple de abdomen es compatible con suboclusión de intestino delgado, y la TAC de urgencia sugiere la posibilidad de torsión intestinal. La cirugía urgente realizada aprecia una hernia interna de un segmento de ileon de unos 25cm, a través de un orificio patológico en el lado derecho del ligamento ancho del útero. Se realiza resección del asa herniada que sufre necrosis isquémica y se cierra el orificio herniario para evitar la recidiva. El día 11 tras el ingreso, es dada de alta sin complicaciones (AU)

We present the case of a 47-year-old gravida 2, para 2, with previous 2 caesarean sections. The patient presented to our hospital with a chief complaint of diffuse continuous abdominal pain and vomiting. Her lower abdomen had tenderness and was slightly distended. The patient had no fever and was hemodynamically stable. The laboratory test showed an elevated white blood cell count with a left shift. Plain abdominal X-rays showed a lightly prominent small bowel loops in the left upper quadrant. CT scan suggests the possibility of intestinal torsion. At this stage, we elected to perform an urgent laparoscopic exploration. We discovered 25 cm of ileum strangulated through a defect in the right broad ligament of the uterus. Resection of the necrotic small bowel loop, and closure of the broad ligament were performed. The patient was discharged from the hospital on day 11, with no postoperative complications (AU)