Immune Response to the Recombinant Apa Protein from Mycobacterium tuberculosis Expressed in Streptomyces lividans After Intranasal Administration in Mice. Induction of Protective Response to Tubercle Bacillus Aerosols Exposure.

Identifying and evaluating potential vaccine candidates has become one of the main objectives to combat tuberculosis. Among them, mannosylated Apa antigen from Mycobacterium tuberculosis and the non-mannosylated protein expressed in Escherichia coli, have been studied. Although both proteins can induce a protective response in mice, it has been considered that native protein can be dispensed. In this work, we study the protective response induced by Apa expressed in E. coli and in Streptomyces lividans. The latter, like native is secreted as a double band of 45/47 kDa, however, only its 47 kDa band is mannosylated. Both antigens and BCG were intranasal administrated in mice, and animals were then challenged by aerosol with M. tuberculosis H37Rv. The results showed that both, Apa from S. lividans and E. coli conferred statistically significantly protection to animals compared to controls. The cytokine immune response was studied by an immunoassay after animals' immunization, revealing that Apa from S. lividans induced a statistically significant proliferation of T cell, as well as the expression of IFN-γ, IL-1ß, IL-17 and IL-10. In contrast, non-proliferation was obtained with non-mannosylated protein, but induction of IL-12 and IL-17 was observed. Together, these results demonstrate that both proteins were able to modulate a specific immune response against M. tuberculosis, that could be driven by different mechanisms possibly associated with the presence or not of mannosylation. Furthermore, stimulation of cells from BCG-vaccinated animals with the proteins could be an important tool, to help define the use of a given subunit-vaccine after BCG vaccination.

Optimizing Anesthetic Selection in Transcatheter Aortic Valve Replacement: Striking a Delicate Balance between Efficacy and Minimal Intervention.

Patients with severe calcific native aortic valve stenosis (AS) who require valve replacement have two options, surgical aortic valve replacement (SAVR) or transcatheter aortic valve replacement (TAVR). TAVR was approved in late 2011 for extremely high-risk patients and was subsequently approved for high-risk (2012), intermediate-risk (2016), and low-risk (2019) patients. In 2019, TAVR procedures surpassed SAVR procedures for the first time in the United States. The approach to anesthesia for this procedure has also evolved. Initially, general anesthesia (GA) was preferred, but currently, conscious sedation (CS) is favored. This review aims to clarify the indications and contraindications for both approaches, as well as the advantages of one approach over the other. Recent studies show that conscious sedation has better outcomes in terms of all-cause mortality, procedure complications such as stroke, myocardial infarction, infection requiring antibiotics, acute kidney injury, and the need for inotropes or vasopressors.

A Case of Prolonged Recovery for Post-percutaneous Coronary Intervention (PCI) Sodium-Glucose Cotransporter-2 (SGLT2) Inhibitor-Induced Euglycemic Diabetic Ketoacidosis in a 28-Year-Old.

Euglycemic diabetic ketoacidosis (DKA) is a rare, but clinically important, presentation that can lead to significant morbidity and mortality in patients with diabetes mellitus. It has been associated with multiple etiologies, including sodium-glucose cotransport-2 (SGLT2) inhibitor use. This case report details the presentation of a 28-year-old male patient who was recently diagnosed with non-ST elevated myocardial infarction (NSTEMI) status post-percutaneous coronary intervention (PCI) to left anterior descending (LAD) and type 2 diabetes mellitus (T2DM) and discharged on a new medical regiment that included an SGLT2 inhibitor. The patient presented five days later with dyspnea, nausea, and vomiting. On initial evaluation, he had tachycardia and hypertension. Lab work revealed hyperkalemia, metabolic anion gap acidosis, and the presence of ketones and glucose in the urine, which led to the diagnosis of euglycemic DKA. The patient was started on intravenous (IV) insulin, bicarbonate, and D5 ½ normal saline (NS) and required five days of continuous treatment for the anion gap to close. Considering studies have shown that SGLT2 inhibitors are associated with euglycemic DKA, it is proposed that the use of an SGLT2 inhibitor in this newly diagnosed, post-PCI patient led to the development of euglycemic DKA. DKA most commonly resolves within 24 hours of treatment; however, our patient did not recover until after 120 hours of treatment. Recent studies have suggested that SGLT2-inhibitor euglycemic DKA may be associated with longer recovery time; however, there is still a need to further research the consistency of these findings and quantify the estimated duration of treatment across populations. There is also a need for investigation into how co-morbid factors, such as a recent NSTEMI and PCI, may affect recovery times or predispose patients who are taking SGLT2-inhibitors to develop euglycemic DKA as SGLT2 inhibitors are being more widely prescribed. This case report highlights the importance of creating more detailed and evidence-based guidelines for prescribing SGLT2 inhibitors for patients with diabetes and encourages more research into the expected duration of treatment for patients with SGLT2-induced euglycemic DKA and factors that may affect it.

Superior Mesenteric Artery Syndrome in Systemic Lupus Erythematosus.

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

Laparoscopic Sleeve Gastrectomy (LSG) in a Patient With Situs Inversus Totalis (SIT): A Case Report.

Obesity is associated with several preventable health issues, such as diabetes mellitus and hypertension. Bariatric surgery has shown potential in treating obesity. Laparoscopic sleeve gastrectomy (LSG) is one of several bariatric surgical techniques gaining popularity as a primary procedure. Situs inversus totalis (SIT) is an uncommon hereditary abnormality that can present challenges in laparoscopic surgery due to the mirror-image anatomy. We present the case of a 54-year-old female with a body mass index (BMI) of 54.36 kg/m2. She was diagnosed with SIT and had no other known diseases, medication use, or allergies. We performed a conventional LSG, modifying the original trocar port positions to match the anatomy. LSG is a safe and effective procedure for patients with SIT. Preoperative diagnosis can help reduce the risk of complications by facilitating proper surgical planning.

Revisional Single-Anastomosis Gastric Bypass for a Patient With Severe Protein-Calorie Malnutrition: A Case Report.

Obesity is a chronic disorder with numerous manifestations as well as pandemic occurrence on a global scale. One-anastomosis gastric bypass (OAGB) is a safe and effective surgical procedure for the treatment of obesity and metabolic diseases. Revision surgery may be necessary due to postoperative issues, such as protein-calorie deficiency, weight increase, or inadequate weight loss. This case describes a 40-year-old female patient who came to our service due to protein-caloric malnutrition, with a history of OAGB. The patient underwent revision surgery for OAGB reversal. One year after surgery the patient had a body mass index (BMI) of 25; today she is healthy, consumes a regular diet, and has no associated complications.

One-anastomosis gastric bypass reversal due to severe malnutrition and acute hepatic failure: a case report.

The one-anastomosis gastric bypass (OAGB) is one of the most popular performed bariatric surgeries and has good long-term success for treating obesity and metabolic diseases. However, some patients can develop severe complications such as malnutrition and hepatic steatosis, which can be corrected with a reversal procedure, as seen in this case. A 20-year-old woman underwent OAGB surgery, which was converted to Roux-en-Y gastric bypass 4 months after the initial procedure due to malnutrition, both surgeries were performed at a hospital in southern Mexico. After the second surgery, she presented to our hospital with intolerance to oral feeding, vomiting and loss of 44 kg in 4 months. The patient was stabilized and scheduled for reversion surgery to normal anatomy 5 months later. She had good short-term nutritional outcomes and at the 1-year follow-up her total weight gain was 14 kg.

Unexpected finding of leiomyoma during laparoscopic gastric sleeve: a case report.

Obesity is a chronic disease with pandemic levels of prevalence worldwide. The most often performed bariatric procedure is sleeve gastrectomy. Although the patient's history may not indicate preoperative imaging studies, coincidental findings of unexpected pathology are not uncommon, such as leiomyoma. A 41-year-old female was scheduled to laparoscopic gastric sleeve with no contraindications for surgery. A tumor-like mass was identified on the left lateral face of the distal third of the esophagus. Trans-surgical endoscopy and pneumatic test were performed to rule out any type of communication. The surgeon managed to remove the tumor mass, that was sent to histopathological study, and concluded the procedure without complications. Benign tumors of the esophagus are rarely found lesions. Occasionally unexpected findings may occur during surgery, and they should be resolved intraoperatively when possible to allow the completion of the originally planned surgical procedure.

Effectiveness of adherence to a renal health program in a health network in Peru.

OBJECTIVE To evaluate the effectiveness of adherence to a multidisciplinary renal health program in reducing mortality and progression to hemodialysis. METHODS We used a database that included patient monitoring (2013-2017), dialysis admissions and all cause of mortality in Peru. Adherence to the program was established by meeting minimum visits during the first year of monitoring. The outcome of interest was hemodialysis admissions or all cause-mortality. Kaplan-Meier curves, Log-Rank test and competing survival analysis methods were used to estimate the differential risk between adherent and non-adherent patients. RESULTS A total of 20,354 participants was evaluated; 54.1% were male, 72.1 years old in average, 2.2 years average follow-up, and 15,279 (75.1%) belonged to the early stages (1 to 3a) of Chronic Kidney Disease. Adherence decreased the risk of renal replacement therapy in 41.0% (HR = 0.59, 95%CI 0.41-0.85) in the low-risk group and mortality in the high-risk group was 31.0% (HR = 0.69, 95%CI 0.57-0.83). CONCLUSIONS The multidisciplinary care strategy with standardized assessments by stage is effective in reducing admission to .0when the patient is identified in early stages and in reducing mortality in advanced stages.

Association of microtubules and axonal RNA transferred from myelinating Schwann cells in rat sciatic nerve.

Transference of RNAs and ribosomes from Schwann cell-to-axon was demonstrated in normal and regenerating peripheral nerves. Previously, we have shown that RNAs transfer is dependent on F-actin cytoskeleton and Myosin Va. Here, we explored the contribution of microtubules to newly synthesized RNAs transport from Schwann cell nuclei up to nodal microvilli in sciatic nerves. Results using immunohistochemistry and quantitative confocal FRET analysis indicate that Schwann cell-derived RNAs co-localize with microtubules in Schwann cell cytoplasm. Additionally, transport of Schwann cell-derived RNAs is nocodazole and colchicine sensitive demonstrating its dependence on microtubule network integrity. Moreover, mRNAs codifying neuron-specific proteins are among Schwann cell newly synthesized RNAs population, and some of them are associated with KIF1B and KIF5B microtubules-based motors.

ENANO: Encoder for NANOpore FASTQ files.

MOTIVATION: The amount of genomic data generated globally is seeing explosive growth, leading to increasing needs for processing, storage and transmission resources, which motivates the development of efficient compression tools for these data. Work so far has focused mainly on the compression of data generated by short-read technologies. However, nanopore sequencing technologies are rapidly gaining popularity due to the advantages offered by the large increase in the average size of the produced reads, the reduction in their cost and the portability of the sequencing technology. We present ENANO (Encoder for NANOpore), a novel lossless compression algorithm especially designed for nanopore sequencing FASTQ files. RESULTS: The main focus of ENANO is on the compression of the quality scores, as they dominate the size of the compressed file. ENANO offers two modes, Maximum Compression and Fast (default), which trade-off compression efficiency and speed. We tested ENANO, the current state-of-the-art compressor SPRING and the general compressor pigz on several publicly available nanopore datasets. The results show that the proposed algorithm consistently achieves the best compression performance (in both modes) on every considered nanopore dataset, with an average improvement over pigz and SPRING of >24.7% and 6.3%, respectively. In addition, in terms of encoding and decoding speeds, ENANO is 2.9× and 1.7× times faster than SPRING, respectively, with memory consumption up to 0.2 GB. AVAILABILITY AND IMPLEMENTATION: ENANO is freely available for download at: https://github.com/guilledufort/EnanoFASTQ. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

Axon microdissection and transcriptome profiling reveals the in vivo RNA content of fully differentiated myelinated motor axons.

Axonal protein synthesis has been shown to play a role in developmental and regenerative growth, as well as in the maintenance of the axoplasm in a steady state. Recent studies have begun to identify the mRNAs localized in axons, which could be translated locally under different conditions. Despite that by now hundreds or thousands of mRNAs have been shown to be localized into the axonal compartment of cultured neurons in vitro, knowledge of which mRNAs are localized in mature myelinated axons is quite limited. With the purpose of characterizing the transcriptome of mature myelinated motor axons of peripheral nervous systems, we modified the axon microdissection method devised by Koenig, enabling the isolation of the axoplasm RNA to perform RNA-seq analysis. The transcriptome analysis indicates that the number of RNAs detected in mature axons is lower in comparison with in vitro data, depleted of glial markers, and enriched in neuronal markers. The mature myelinated axons are enriched for mRNAs related to cytoskeleton, translation, and oxidative phosphorylation. Moreover, it was possible to define core genes present in axons when comparing our data with transcriptomic data of axons grown in different conditions. This work provides evidence that axon microdissection is a valuable method to obtain genome-wide data from mature and myelinated axons of the peripheral nervous system, and could be especially useful for the study of axonal involvement in neurodegenerative pathologies of motor neurons such as amyotrophic lateral sclerosis (ALS) and spinal muscular atrophies (SMA).

A comparative study of machine learning and deep learning algorithms to classify cancer types based on microarray gene expression data.

Cancer classification is a topic of major interest in medicine since it allows accurate and efficient diagnosis and facilitates a successful outcome in medical treatments. Previous studies have classified human tumors using a large-scale RNA profiling and supervised Machine Learning (ML) algorithms to construct a molecular-based classification of carcinoma cells from breast, bladder, adenocarcinoma, colorectal, gastro esophagus, kidney, liver, lung, ovarian, pancreas, and prostate tumors. These datasets are collectively known as the 11_tumor database, although this database has been used in several works in the ML field, no comparative studies of different algorithms can be found in the literature. On the other hand, advances in both hardware and software technologies have fostered considerable improvements in the precision of solutions that use ML, such as Deep Learning (DL). In this study, we compare the most widely used algorithms in classical ML and DL to classify the tumors described in the 11_tumor database. We obtained tumor identification accuracies between 90.6% (Logistic Regression) and 94.43% (Convolutional Neural Networks) using k-fold cross-validation. Also, we show how a tuning process may or may not significantly improve algorithms' accuracies. Our results demonstrate an efficient and accurate classification method based on gene expression (microarray data) and ML/DL algorithms, which facilitates tumor type prediction in a multi-cancer-type scenario.

Effectiveness of adherence to a renal health program in a health network in Peru / Efectividad de la adherencia a un programa de salud renal en una red sanitaria de Perú

ABSTRACT OBJECTIVE To evaluate the effectiveness of adherence to a multidisciplinary renal health program in reducing mortality and progression to hemodialysis. METHODS We used a database that included patient monitoring (2013-2017), dialysis admissions and all cause of mortality in Peru. Adherence to the program was established by meeting minimum visits during the first year of monitoring. The outcome of interest was hemodialysis admissions or all cause-mortality. Kaplan-Meier curves, Log-Rank test and competing survival analysis methods were used to estimate the differential risk between adherent and non-adherent patients. RESULTS A total of 20,354 participants was evaluated; 54.1% were male, 72.1 years old in average, 2.2 years average follow-up, and 15,279 (75.1%) belonged to the early stages (1 to 3a) of Chronic Kidney Disease. Adherence decreased the risk of renal replacement therapy in 41.0% (HR = 0.59, 95%CI 0.41-0.85) in the low-risk group and mortality in the high-risk group was 31.0% (HR = 0.69, 95%CI 0.57-0.83). CONCLUSIONS The multidisciplinary care strategy with standardized assessments by stage is effective in reducing admission to .0when the patient is identified in early stages and in reducing mortality in advanced stages.

RESUMEN OBJETIVO Evaluar la efectividad de la adherencia a un programa de salud renal en la reducción de mortalidad y progresión a hemodiálisis. MÉTODOS Utilizamos una base de datos que condensaba el seguimiento de los pacientes (2013-2017), los ingresos a diálisis de los mismos y la mortalidad por todas las causas en Perú. La adherencia al programa se estableció con el cumplimiento de visitas mínimas durante su primer año de seguimiento. La efectividad de la adherencia al programa se midió en términos de debut a hemodiálisis o muerte por todas las causas. Se utilizaron curvas de Kaplan-Meier, test de diferencias en la distribución (Log-Rank test) y métodos de análisis de supervivencia. Los análisis se realizaron utilizando R estudio 3.5.0 RESULTADOS Fueron evaluados 20.354 participantes, 54,1% varones, edad media de 72,1 años, con un seguimiento medio de 2,2 años; 15.279 (75.1%) tuvieron ERC en estadios tempranos (estadio 1 al 3a). La adherencia disminuyó en un 41,0% el riesgo de terapia de reemplazo renal (HR = 0,59; IC95% 0,41-0,85) en el grupo de bajo riesgo y en un 31,0% (HR = 0,69; IC95% 0,57-0,83) la mortalidad en el grupo de alto riesgo. CONCLUSIONES La estrategia de cuidado multidisciplinario con evaluaciones estandarizadas según estadio es efectiva en reducir el ingreso a terapia de reemplazo renal cuando se identifica al paciente en estadios tempranos y en reducir la mortalidad en estadios avanzados.

Pneumatosis intestinalis: cost paid for rheumatoid arthritis treatment.

A 75-year-old woman with rheumatoid arthritis on rituximab presented with a 1-week history of constipation and abdominal distension. Subsequent workup showed presence of air in the bowel wall without perforation initially. Due to positive blood cultures, worsening leucocytosis and high suspicion for perforation, an exploratory laparotomy was performed revealing necrotic bowel, walled off perforation and abscess. Patient underwent right hemicolectomy with diversion loop ileostomy. Clinicians must recognise that monoclonal antibodies like rituximab can mask signs of inflammation and therefore should maintain a high index of suspicion for intestinal perforation when evaluating patients with minimal symptoms and pneumatosis intestinalis.

Hepatic artery pseudoaneurysm following percutaneous transhepatic cholangiogram: an extremely rare complication.

A 72-year-old female patient who was admitted for ischaemic stroke had developed ascending cholangitis. Percutaneous transhepatic cholangiogram was performed to drain the infected bile, but this was complicated by haemorrhagic shock and hepatic haematoma. Mesenteric angiogram showed right hepatic artery (RHA) pseudoaneurysm which was embolised, there by stopping her bleeding. RHA is normally located posterior to common bile duct (CBD). An uncommon location of RHA is anterior to CBD, which can lead to haemorrhagic complications during percutaneous cholangiogram.

Toward Axonal System Biology: Genome Wide Views of Local mRNA Translation.

Neurons present a highly polarized morphology, often displaying a significantly imbalanced distribution of the cytoplasm between the somatic and axonal domains. This imbalance requires cell-specific mechanisms for the maintenance of the axoplasmic mass during development, neuronal homeostasis, and recovery after injury. Although it has been clearly demonstrated that axoplasmic transport contributes a large amount of proteins to the axons, local protein synthesis has been fully accepted as an important complementary source of proteins, which aids in the maintenance of the axoplasmic mass in both normal and regenerating conditions. This review analyzes and highlights the most important advances in the knowledge of the axonal transcriptome, translatome, and proteome at a genome-wide scale. It is discussed how this knowledge has provided researchers with new insights regarding the involvement of local protein synthesis in many key neuronal functions. In addition, challenges, open questions, and methods currently available to study axonal mRNA localization and protein synthesis are addressed.

New two-step wedge liver resection technique: "zoom resection": A case report.

Different surgical procedures have been described for the treatment of colorectal liver metastases. The appropriate surgical approach depends, among many other factors, on the relationship between liver metastases and suprahepatic veins. If possible, the detachment of colorectal liver metastasis from suprahepatic veins is a good alternative liver parenchyma sparing technique. In this study, we describe a new two-step wedge liver resection technique for colorectal liver metastases located between suprahepatic veins. Prior to resection, intraoperative ultrasound is employed in order to plan and guide both steps. Initially, we place stitches and resect a cylindrical piece of normal liver parenchyma above the tumor and suprahepatic veins. Next, we place stitches on the future specimen located between suprahepatic veins, then resect it. The main advantages of this procedure are the good visualization and vascular control that may be achieved during the detachment of the tumor from suprahepatic veins. We call this procedure "zoom resection" because its dynamics are similar to the workings of a photograph camera's telescopic system. We present the case of a 55-year-old patient diagnosed with multiple colorectal liver metastases, one of which was resected through this technique.

Gallbladder to the left side of the falciform ligament in absence of Situs Inversus "Sinistroposition" - Case series of 2 patients with this anomaly who underwent mini-laparoscopic cholecystectomy.

INTRODUCTION: Gallbladders located to the left of falciform ligament, without situs inversus, are denominated sinistroposition or true left-sided gallbladders; it is considered a rare anatomic anomaly with a prevalence in between 0.1% and 0.7%. Left-sided gallbladder usually occur as a component of situs inversus. PRESENTATION OF CASES: We report a case series of two patients of true left-sided gallbladder that were found at our institution from 2015 to 2017; the anatomic anomalies were discovered during the performance of mini-laparoscopic cholecystectomy due to acute cholecystitis with cholelithiasis in both cases. Both patients underwent a successful surgery and there were no postsurgical complications. DISCUSSION: The reported prevalence of left-sided gallbladder is between 0.1% and 0.7%, thus considered a rare anatomic finding. Currently, with advances in diagnostic imaging modalities, the report of left-sided gallbladder has increased nowadays. It may be a more common anomaly than previously thought. CONCLUSION: True left-sided gallbladder can be an incidental finding; it is in part due to the fact that radiographic images do not typically detect this anomaly, therefore surgeons must be aware of this condition because it is associated with anomalies in the intrahepatic portal vein and biliary tree.