Adherence to Antiretrovirals and HIV Viral Suppression Under COVID-19 Pandemic Interruption - Findings from a Randomized Clinical Trial Using Ingestible Sensors to Monitor Adherence.

The COVID-19 pandemic had a significant impact on vulnerable populations, including people living with HIV. California implemented a coronavirus lockdown (stay-at-home order) in March 2020, which ended in January 2021. We evaluated the pandemic's impact on both clinical outcomes of HIV RNA viral load (VL) and retention rate in a randomized clinical trial conducted from May 2018 to October 2020. The intervention group took co-encapsulated antiretrovirals (ARVs) with ingestible sensor (IS) pills from baseline through week 16. The IS system has the capacity to monitor adherence in real-time using a sensor patch, a mobile device, and supporting software. Both the IS and usual care (UC) groups were followed monthly for 28 weeks. Longitudinal mixed-effects models with random intercept and slope (RIAS) were used to fit log VL and self-reported adherence. The sample size of the study was 112 (54 in IS). Overall, the retention rate at week 28 was 86%, with 90% before the lockdown and 83% after the lockdown. The lockdown strengthened the associations between adherence and VL. Before the lockdown, a 10% increase in adherence was associated with a 0.2 unit decrease in log VL (ß = -1.88, p = 0.004), while during the lockdown, the association was a 0.41-unit decrease (ß = -2.27, p = 0.03). The pandemic did not have a significant impact on our adherence-focused intervention. Our findings regarding the intervention effect remain valid. TRIAL REGISTRATION NUMBER: NCT02797262. Date registration: September 2015.

Buildings' Biaxial Tilt Assessment Using Inertial Wireless Sensors and a Parallel Training Model.

Applications of MEMS-based sensing technology are beneficial and versatile. If these electronic sensors integrate efficient processing methods, and if supervisory control and data acquisition (SCADA) software is also required, then mass networked real-time monitoring will be limited by cost, revealing a research gap related to the specific processing of signals. Static and dynamic accelerations are very noisy, and small variations of correctly processed static accelerations can be used as measurements and patterns of the biaxial inclination of many structures. This paper presents a biaxial tilt assessment for buildings based on a parallel training model and real-time measurements using inertial sensors, Wi-Fi Xbee, and Internet connectivity. The specific structural inclinations of the four exterior walls and their severity of rectangular buildings in urban areas with differential soil settlements can be supervised simultaneously in a control center. Two algorithms, combined with a new procedure using successive numeric repetitions designed especially for this work, process the gravitational acceleration signals, improving the final result remarkably. Subsequently, the inclination patterns based on biaxial angles are generated computationally, considering differential settlements and seismic events. The two neural models recognize 18 inclination patterns and their severity using an approach in cascade with a parallel training model for the severity classification. Lastly, the algorithms are integrated into monitoring software with 0.1° resolution, and their performance is verified on a small-scale physical model for laboratory tests. The classifiers had a precision, recall, F1-score, and accuracy greater than 95%.

MITF Downregulation Induces Death in Human Mast Cell Leukemia Cells and Impairs IgE-Dependent Degranulation.

Activating mutations in KIT (CD117) have been associated with several diseases, including gastrointestinal stromal tumors and mastocytosis. Rapidly progressing pathologies or drug resistance highlight the need for alternative treatment strategies. Previously, we reported that the adaptor molecule SH3 binding protein 2 (SH3BP2 or 3BP2) regulates KIT expression at the transcriptional level and microphthalmia-associated transcription factor (MITF) expression at the post-transcriptional level in human mast cells and gastrointestinal stromal tumor (GIST) cell lines. Lately, we have found that the SH3BP2 pathway regulates MITF through miR-1246 and miR-5100 in GIST. In this study, miR-1246 and miR-5100 were validated by qPCR in the SH3BP2-silenced human mast cell leukemia cell line (HMC-1). MiRNA overexpression reduces MITF and MITF-dependent target expression in HMC-1. The same pattern was observed after MITF silencing. In addition, MITF inhibitor ML329 treatment reduces MITF expression and affects the viability and cell cycle progression in HMC-1. We also examine whether MITF downregulation affected IgE-dependent mast cell degranulation. MiRNA overexpression, MITF silencing, and ML329 treatment reduced IgE-dependent degranulation in LAD2- and CD34+-derived mast cells. These findings suggest MITF may be a potential therapeutic target for allergic reactions and deregulated KIT mast-cell-mediated disorders.

Mutation in KARS: A novel mechanism for severe anaphylaxis.

BACKGROUND: Anaphylaxis is a severe allergic reaction that can be lethal if not treated adequately. The underlying molecular mechanisms responsible for the severity are mostly unknown. OBJECTIVE: This study is based on a clinical case of a patient with extremely severe anaphylaxis to paper wasp venom. This patient has a mutation in the KARS gene, which encodes lysyl-tRNA synthetase (LysRS), a moonlight protein with a canonical function in protein synthesis and a noncanonical function in antigen dependent-FcεRI activation in mast cells. In this study, the objective was to characterize the mutation at the molecular level. METHODS: Analysis of the KARS mutation was carried out using biochemical and functional approaches, cell transfection, Western blot, confocal microscopy, cell degranulation, prostaglandin D2 secretion, and proteases gene transcription. Structural analysis using molecular dynamics simulations and well-tempered metadynamics was also performed. RESULTS: The mutation found, P542R (proline was replaced by arginine at aminoacid 542), affects the location of the protein as we show in biochemical and structural analyses. The mutation resembles active LysRS and causes a constitutive activation of the microphthalmia transcription factor, which is involved in critical mast cell functions such as synthesis of mediators and granule biogenesis. Moreover, the structural analysis provides insights into how LysRS works in mast cell activation. CONCLUSIONS: A link between the aberrant LysRS-P542R function and mast cell-exacerbated activation with increase in proinflammatory mediator release after antigen-IgE-dependent response could be established.

Measuring student satisfaction as the first assessment of the Program of Combined Studies in Medicine, an MD/PhD-like program of the Faculty of Medicine, National Autonomous University of Mexico.

BACKGROUND: The Program of Combined Studies in Medicine (PECEM, by its acronym in Spanish) is a program for simultaneous bachelor and doctorate studies (MD/PhD) that enrolls students who show academic excellence and interest in scientific research. The initial doctoral training comprises seven six-month research stays in different laboratories or clinical or computer areas with different high-quality scientific advisors who provide students with a unique experience for their scientific training. Therefore, satisfaction in this stage is decisive for students' performance and physical and psychological health. The aim of the present study was to administer a questionnaire to measure students' satisfaction with their research experience as a service-product bundle. METHODS: Students answered an online questionnaire that evaluated three dimensions: perceived quality of the advisor, skills development, and infrastructure and support. Several satisfiers were also evaluated: recommendation of the advisor to peers, fulfillment of student expectations and satisfaction with the program. Correlations were calculated using Fisher's exact test. The significance was set at p < 0.05. RESULTS: The high quality of the advisor, skills development and guidance during the stay were satisfiers correlated to the students' recommendation of their advisors to their peers and to the fulfillment of the students' scientific expectations. Conversely, skills development and infrastructure and support were satisfiers for a good to excellent experience as a PECEM student. A lack of direct interaction with the advisor's workgroup was related to dissatisfaction. CONCLUSIONS: The nontangible products of the service, such as a positive interaction between the student, the advisor and the advisor's workgroup as well as support obtained during the research stay, were satisfiers. These data indicate that promoting a fruitful bond between the student and advisor is a priority to ensure the quality of our innovative MD/PhD program.

Fibre-type-specific and Mitochondrial Biomarkers of Muscle Damage after Mountain Races.

Consequences of running mountain races on muscle damage were investigated by analysing serum muscle enzymes and fibre-type-specific sarcomere proteins. We studied 10 trained amateur and 6 highly trained runners who ran a 35 km and 55 km mountain trail race (MTR), respectively. Levels of creatine kinase (CK), CK-MB isoform (CK-MB), sarcomeric mitochondrial CK (sMtCK), transaminases (AST and ALT), cardiac troponin I (cTnI) and fast (FM) and slow myosin (SM) isoforms, were assessed before, 1 h, 24 h and 48 h after the beginning of MTR. Significant SM increases were found at 24 h in the 55 km group. Levels of CK, CK-MB, AST and cTnI were significantly elevated in both groups following MTR, but in the 55 km group they tended to stabilize in at 48 h. Using pooled data, time-independent serum peaks of SM and CK-MB were significantly correlated. Moreover, concentration of sMtCK was significantly elevated at 1 and 24 h after the race in the 35 km group. Although training volume could confer protection on the mitochondria, the increase in serum CK-MB and SM in the 55 km group might be related to damage to the contractile apparatus type I fibres. Competing in long-distance MTRs might be related to deeper type I muscle fibre damage, even in highly trained individuals.

A Remotely-Delivered CBT and Contingency Management Therapy for Substance Using People with HIV.

Substance using HIV patients are at risk for non-adherence, and most prior interventions in this population have had only modest effects on adherence. Contingency management (CM) is a promising intervention. The Centralized Off-site Adherence Enhancement (CARE) program involved 12 telephone-delivered substance and adherence-targeted cognitive behavior therapy sessions coupled with CM for adherence to antiretroviral therapy (ART) and counseling participation. CM involved 6 weeks of escalating reinforcement for taking prescribed doses followed by 6 weeks of tapering variable rate reinforcement, and separate reinforcement for counseling ($806 possible). Participants' adherence was measured by devices which wirelessly provided real-time notification of device-opening. HIV infected patients on ART (N = 10) with recent stimulant or alcohol use completed 10.2 of 12 possible telephone sessions, spent 42.8 min/call, and rated the counseling 6.2 on a 1-7 scale. Medication adherence improved from 81 to 93 % (p = 0.04). CARE appears to be acceptable and engaging.

Blood ammonia and lactate as markers of muscle metabolites during leg press exercise.

To examine whether blood lactate and ammonia concentrations can be used to estimate the functional state of the muscle contractile machinery with regard to muscle lactate and adenosine triphosphate (ATP) levels during leg press exercise. Thirteen men (age, 34 ± 5 years; 1 repetition maximum leg press strength 199 ± 33 kg) performed either 5 sets of 10 repetitions to failure (5×10RF), or 10 sets of 5 repetitions not to failure (10×5RNF) with the same initial load (10RM) and interset rests (2 minutes) on 2 separate sessions in random order. Capillary blood samples were obtained before and during exercise and recovery. Six subjects underwent vastus lateralis muscle biopsies at rest, before the first set and after the final exercise set. The 5×10RF resulted in a significant and marked decrease in power output (37%), muscle ATP content (24%), and high levels of muscle lactate (25.0 ± 8.1 mmol·kg wet weight), blood lactate (10.3 ± 2.6 mmol·L), and blood ammonia (91.6 ± 40.5 µmol·L). During 10×5RNF no or minimal changes were observed. Significant correlations were found between: (a) blood ammonia and muscle ATP (r = -0.75), (b) changes in peak power output and blood ammonia (r = -0.87) and blood lactate (r = -0.84), and (c) blood and muscle lactate (r = 0.90). Blood lactate and ammonia concentrations can be used as extracellular markers for muscle lactate and ATP contents, respectively. The decline in mechanical power output can be used to indirectly estimate blood ammonia and lactate during leg press exercise.

Proprotein convertase subtisilin/kexin 9 levels decline with hepatitis C virus therapy in people with HIV/hepatitis C virus and correlate with inflammation.

BACKGROUND: Proprotein convertase subtisilin/kexin 9 (PCSK9) raises low-density lipoprotein cholesterol (LDL-C) levels and is associated with inflammation, which is elevated in HIV and hepatitis C virus (HCV) infection. We compared PCSK9 levels in people with co-occurring HIV and HCV (HIV/HCV) vs. HIV alone, and evaluated the impact of HCV direct-acting antiviral (DAA) therapy on PCSK9. DESIGN: A prospective, observational cohort study. METHODS: Thirty-five adults with HIV/HCV and 37 with HIV alone were evaluated, all with HIV virologic suppression and without documented cardiovascular disease. Circulating PCSK9 and inflammatory biomarkers were measured at baseline and following HCV treatment or at week 52 (for HIV alone) and compared using Wilcoxon tests and Spearman correlations. RESULTS: At baseline, PCSK9 trended higher in HIV/HCV vs. HIV alone (307 vs. 284 ng/ml, P  = 0.06). Twenty-nine participants with HIV/HCV completed DAA therapy with sustained virologic response. PCSK9 declined from baseline to posttreatment 1 (median 7.3 weeks after end of therapy [EOT]) and posttreatment 2 (median 43.5 weeks after EOT), reaching levels similar to HIV alone; median within-person reduction was -60.5 ng/ml ( P  = 0.003) and -55.6 ng/ml ( P  = 0.02), respectively. Decline in PCSK9 correlated with decline in soluble (s)E-selectin and sCD163 ( r  = 0.64, P  = 0.002; r  = 0.58, P  = 0.008, respectively), but not with changes in LDL-C or other biomarkers. No significant change in PCSK9 occurred in the HIV alone group over 52 weeks. CONCLUSION: PCSK9 declined with DAA therapy in participants with HIV/HCV, correlating with declines in several inflammatory biomarkers but not LDL-C. Elevated PCSK9 with HCV may be linked to particular HCV-associated inflammatory pathways more so than cholesterol homeostasis.

MRGPRX2 signaling involves the Lysyl-tRNA synthetase and MITF pathway.

MRGPRX2, a G-protein-coupled-seven transmembrane domain receptor, is mainly expressed in mast cells and neurons and is involved in skin immunity and pain. It is implicated in the pathophysiology of non-IgE-mediated immediate hypersensitivity and has been related to adverse drug reactions. Moreover, a role has been proposed in asthma, atopic dermatitis, contact dermatitis, and chronic spontaneous urticaria. Although it has a prominent role in disease, its signaling transduction is poorly understood. This study shows that MRGPRX2 activation with substance P increased Lysyl t-RNA synthetase (LysRS) translocation to the nucleus. LysRS is a moonlighting protein with a dual role in protein translation and IgE signaling in mast cells. Upon allergen- IgE-FcεRI crosslinking, LysRS is translocated to the nucleus and activates microphthalmia-associated transcription factor (MITF) activity. In this study, we found that MRGPRX2 triggering led to MITF phosphorylation and increased MITF activity. Therefore, overexpression of LysRS increased MITF activity after MRGPRX2 activation. MITF silencing reduced MRGPRX2-dependent calcium influx and mast cell degranulation. Furthermore, a MITF pathway inhibitor, ML329, impaired MITF expression, calcium influx, and mast cell degranulation. Moreover, drugs such as atracurium, vancomycin, and morphine, reported to induce MRGPRX2-dependent degranulation, increased MITF activity. Altogether, our data show that MRGPRX2 signaling enhances MITF activity, and its abrogation by silencing or inhibition resulted in defective MRGPRX2 degranulation. We conclude that MRGPRX2 signaling involves the LysRS and MITF pathway. Thus, MITF and MITF-dependent targets may be considered therapeutic approaches to treat pathologies where MRGPRX2 is implicated.

Alterations of gray and white matter volumes and cortical thickness in treated HIV-positive patients.

Brain structural changes in HIV identified by voxel-based morphometry (VBM) alone could arise from a variety of causes that are difficult to distinguish without further information, such as cortical thickness (CT), gyrification index (GI) or sulcal depth (SD). Hence, our goal was to assess these additional metrics in HIV using high-resolution 3D T1-weighted images and investigate if surface-based morphometric (SBM) analysis would reveal significant changes in the gray matter (GM) and white matter (WM) volumes combined with alterations in cortical thickness (CT), gyrification index (GI), sulcal depth (SD). T1-w magnetization-prepared-rapid-acquisition gradient-echo (MP-RAGE) scans were acquired in 27 HIV-infected individuals on antiretroviral therapy (ART) and 15 HIV-uninfected healthy controls using a 3T MRI scanner equipped with a 16-channel head "receive" and a quadrature body "transmit" coil. Voxel-based and surface-based morphometric analyses were performed using the MATLAB based SPM Computational Anatomy Toolbox (CAT12.7(1700)). HIV-infected patients showed significantly altered GM and WM volumes, CT, GI, and SD, in multiple brain regions. This study showed the association of altered GM and WM volumes in local brain regions with the changes in region-wise CT, GI and SD measures of HIV-infected patients, especially in the parahippocampal and middle frontal regions as compared to uninfected healthy controls. The outcome of this study suggests that the findings of VBM may not necessarily indicate the volumetric shrinkage or increase alone, but might also be due to altered CT, GI, or SD. Correlation analysis showed a significantly accelerated gray matter loss with age in HIV-infected individuals compared to uninfected healthy controls.

The microphthalmia-associated transcription factor is involved in gastrointestinal stromal tumor growth.

Gastrointestinal stromal tumors (GISTs) are the most common neoplasms of mesenchymal origin, and most of them emerge due to the oncogenic activation of KIT or PDGFRA receptors. Despite their relevance in GIST oncogenesis, critical intermediates mediating the KIT/PDGFRA transforming program remain mostly unknown. Previously, we found that the adaptor molecule SH3BP2 was involved in GIST cell survival, likely due to the co-regulation of the expression of KIT and Microphthalmia-associated transcription factor (MITF). Remarkably, MITF reconstitution restored KIT expression levels in SH3BP2 silenced cells and restored cell viability. This study aimed to analyze MITF as a novel driver of KIT transforming program in GIST. Firstly, MITF isoforms were characterized in GIST cell lines and GIST patients' samples. MITF silencing decreases cell viability and increases apoptosis in GIST cell lines irrespective of the type of KIT primary or secondary mutation. Additionally, MITF silencing leads to cell cycle arrest and impaired tumor growth in vivo. Interestingly, MITF silencing also affects ETV1 expression, a linage survival factor in GIST that promotes tumorigenesis and is directly regulated by KIT signaling. Altogether, these results point to MITF as a key target of KIT/PDGFRA oncogenic signaling for GIST survival and tumor growth.

G4-QuadScreen: A Computational Tool for Identifying Multi-Target-Directed Anticancer Leads against G-Quadruplex DNA.

The study presents 'G4-QuadScreen', a user-friendly computational tool for identifying MTDLs against G4s. Also, it offers a few hit MTDLs based on in silico and in vitro approaches. Multi-tasking QSAR models were developed using linear discriminant analysis and random forest machine learning techniques for predicting the responses of interest (G4 interaction, G4 stabilization, G4 selectivity, and cytotoxicity) considering the variations in the experimental conditions (e.g., G4 sequences, endpoints, cell lines, buffers, and assays). A virtual screening with G4-QuadScreen and molecular docking using YASARA (AutoDock-Vina) was performed. G4 activities were confirmed via FRET melting, FID, and cell viability assays. Validation metrics demonstrated the high discriminatory power and robustness of the models (the accuracy of all models is ~>90% for the training sets and ~>80% for the external sets). The experimental evaluations showed that ten screened MTDLs have the capacity to selectively stabilize multiple G4s. Three screened MTDLs induced a strong inhibitory effect on various human cancer cell lines. This pioneering computational study serves a tool to accelerate the search for new leads against G4s, reducing false positive outcomes in the early stages of drug discovery. The G4-QuadScreen tool is accessible on the ChemoPredictionSuite website.

Upregulation of heart PFK-2/FBPase-2 isozyme in skeletal muscle after persistent contraction.

Fructose-2,6-bisphosphate (Fru-2,6-P(2)) is the most potent allosteric activator of liver 6-phosphofructo-1-kinase enzyme, which is crucial for glycolysis. It is present in skeletal muscle but its importance is controversial as a regulator of muscle glycolysis. This study aims to determine the role of Fru-2,6-P(2) in the control of muscle glycolysis during contraction. Muscle contraction was produced by chronic low-frequency stimulation of rabbit tibialis anterior for 24 h, followed by a rest period of 48 h. To determine muscle glycolysis adaptation, we applied a short functional electrostimulation test using the same system of low-frequency stimulation for 1, 3, and 10 s. The variation in concentration of lactate and pyruvate was used to calculate the flux along the glycolysis pathway and the Fru-1,6-P(2)/Fru-6-P ratio permitted to analyze the 6-phosphofructo-1-kinase activation. Fru-2,6-P(2) levels increased over the 24 h of stimulation and remained elevated after the rest period, this being the only metabolite that kept the changes produced by chronic low-frequency stimulation during the rest. During the short functional electrostimulation test, the glycolytic pathway in stimulated and rested muscle was more active than in control muscle, which coincided with higher kinase activity of the 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase (PFK-2/FBPase-2) enzyme. Furthermore, we found a decrease in muscle, liver, and ubiquitous PFK-2/FBPase-2 isoform expression and an increase in heart isoform expression. For the first time, we demonstrate that a persistent increase in Fru-2,6-P(2) produced by a change in PFK-2/FBPase-2 isoform expression may play an important role in the regulation of muscle glycolysis during the first moments of exercise.

SH3BP2 Silencing Increases miRNAs Targeting ETV1 and Microphthalmia-Associated Transcription Factor, Decreasing the Proliferation of Gastrointestinal Stromal Tumors.

Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal tumors of the gastrointestinal tract. Gain of function in receptor tyrosine kinases type III, KIT, or PDGFRA drives the majority of GIST. Previously, our group reported that silencing of the adaptor molecule SH3 Binding Protein 2 (SH3BP2) downregulated KIT and PDGFRA and microphthalmia-associated transcription factor (MITF) levels and reduced tumor growth. This study shows that SH3BP2 silencing also decreases levels of ETV1, a required factor for GIST growth. To dissect the SH3BP2 pathway in GIST cells, we performed a miRNA array in SH3BP2-silenced GIST cell lines. Among the most up-regulated miRNAs, we found miR-1246 and miR-5100 to be predicted to target MITF and ETV1. Overexpression of these miRNAs led to a decrease in MITF and ETV1 levels. In this context, cell viability and cell cycle progression were affected, and a reduction in BCL2 and CDK2 was observed. Interestingly, overexpression of MITF enhanced cell proliferation and significantly rescued the viability of miRNA-transduced cells. Altogether, the KIT-SH3BP2-MITF/ETV1 pathway deserves to be considered in GIST cell survival and proliferation.

Ingestible sensor system for measuring, monitoring and enhancing adherence to antiretroviral therapy: An open-label, usual care-controlled, randomised trial.

BACKGROUND: Co-encapsulated antiretrovirals (ARVs) with ingestible sensor (IS) has the capacity to monitor adherence in real-time using a sensor patch, a mobile device, and supporting software. We evaluated the acceptability, effectiveness, and sustainability of the IS system with real-time text reminders. METHODS: Participants were recruited from HIV clinics in Los Angeles and were randomised 1:1 to IS or usual care (UC) group. Adherence to ARVs (primary outcome) was measured by IS system (IS group only), plasma ARV concentration, and self-report. IS-measured adherence was clustered by group-based trajectory model and was validated by ARV concentration summarized by integrated pharmacokinetic adherence measure (IPAM) score. HIV RNA viral load (VL) was compared between IS and UC group. FINDINGS: A total of 112 (IS = 54, UC = 58) participants who completed baseline with at least one follow-up data collection were included in analyses. Overall satisfaction rate for the IS system was >90%. The IPAM score was higher (0.018, 95% CI: -0.098-0.134, p = 0.75) and VL decayed faster (-0.020, 95% CI: -0.042-0.002, p = 0.08) in the IS group compared with the UC group. The ingestible sensor system was well tolerated by study participants. INTERPRETATION: The IS system was well accepted by participants and its use was associated with improved adherence and lower HIV RNA VL. The findings provide a potentially effective strategy for improving adherence. FUNDING: This work was supported by grant R01-MH110056 from the National Institute of Mental Health (NIMH)/National Institutes of Health (NIH). Y. Wang was in part supported by the NIMH/NIH award T32MH080634. E. Daar was in part supported by the National Center for Advancing Translational Sciences through UCLACTSI Grant UL1TR001881. The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH.

Concordance and diagnostic yield of stereotactic biopsies for posterior fossa: Technique and experience in a reference hospital.

AIM: Describe our stereotactic brain biopsy (SBB) technique for intra-axial lesions of the posterior fossa, evaluate its effectiveness and safety, and compare them with other series. MATERIAL AND METHODS: Retrospective study in ten consecutive patients, whose variables were age, gender, location of the lesions, clinical, radiological, and histopathological diagnoses, complications, and mortality, for analysis using descriptive statistics and tests of concordance and diagnostic validity. RESULTS: Lesions were pontine in seven cases, and pontomedullary in three occasions, with histopathological diagnoses of four Grade II astrocytomas, two Grade IV astrocytomas, two infectious process, one neuroblastic tumor, and one cavernous malformation, whose frequency differs from the previous reports (χ2 = 0.07). The clinical-radiological concordance was poor (κ = 0.20). The validity of the clinical diagnosis had intermediate values (Sn = 66.7%, Sp = 75%), while radiological studies were more sensitive (Sn = 100%, Sp = 25%). A definitive diagnosis was obtained in all procedures, with no permanent morbidity or mortality because of the surgery. CONCLUSION: The SBB technique for posterior fossa implemented in our hospital shows high diagnostic yield, as well as absolute safety for the patient.

OBJETIVO: Describir nuestra técnica de biopsia cerebral estereotáctica (SBB) para lesiones intraaxiales de fosa posterior, evaluar su eficacia y seguridad y compararlas con otras series. MATERIAL Y MÉTODOS: Estudio retrospectivo en 10 pacientes consecutivos, cuyas variables fueron edad, sexo, localización de las lesiones, diagnósticos clínicos, radiológicos e histopatológicos, complicaciones y mortalidad, para análisis mediante estadística descriptiva y pruebas de concordancia y validez diagnóstica. RESULTADOS: Las lesiones fueron pontinas en 7 casos y pontomedulares en 3 ocasiones, con diagnósticos histopatológicos de 4 astrocitomas grado II, 2 astrocitomas grado IV, 2 procesos infecciosos, 1 tumor neuroblástico y 1 malformación cavernosa, cuya frecuencia difiere de reportes previos (χ2 = 0.07). La concordancia clínico-radiológica fue mala (κ = 0.20). La validez del diagnóstico clínico tuvo valores intermedios (Sn = 66.7%, Sp = 75%), mientras que los estudios radiológicos fueron más sensibles (Sn = 100%, Sp = 25%). Se obtuvo un diagnóstico definitivo en todos los procedimientos, sin morbimortalidad permanente por la cirugía. CONCLUSIÓN: La técnica SBB para fosa posterior implementada en nuestro hospital muestra un alto rendimiento diagnóstico, así como una seguridad absoluta para el paciente.

[Transmural rectal endometriosis as a cause of chronic constipation. A case report and literature review]. / Endometriosis transmural rectal como causa de estreñimiento crónico. Reporte de un caso y revisión de la bibliografía.

The incidence of intestinal endometriosis is reported between 5.3 and 12% of cases and of these, between 70 and 93% are located in the rectum and sigmoid. We report the case of a 32-year-old with constipation and bloating and cramping pain during the last 2 years. The pain increased in frequency during the past 6 months. From the data obtained from physical examination and imaging studies may be suspected pelvic endometriosis with infiltration of anterior rectal wall. Resection of the low anterior rectum with colo-rectal anastomosis was performed, with adequate surgical outcome and resolution of symptoms. In patients of childbearing age with abdominal or pelvic pain, constipation of recent onset or occlusive bowel, which may or may not be related to the menstrual cycle should be considered transmural infiltration by endometrial tissue.

Real-Time and Wireless Assessment of Adherence to Antiretroviral Therapy With Co-Encapsulated Ingestion Sensor in HIV-Infected Patients: A Pilot Study.

Adherence with antiretroviral therapy is important for preventing disease progression and HIV transmission. The co-encapsulated pill sensor system sends a signal through a cutaneous patch and allows real-time monitoring of pill ingestion. A 16-week pilot study used a sensor system in 15 HIV-infected individuals with real-time monitoring of pill-taking with a personalized short message system text. System acceptability was assessed by survey at weeks 4, 8, 12, and 16. Follow-up occurred in 80% of subjects through 8 weeks. The system effectively collected measures of pill ingestion, which triggered text message reminders. Only 2 of 14 participants stated that co-encapsulated pills were "unable to take" or "poorly tolerated." At least 75% of respondents stated at each visit that the patch was very or somewhat comfortable. With regard to text message reminders, only 10-15% of the participants at any visit did not find the messages to be helpful. Larger studies will define the utility of this system to assess antiretroviral adherence relative to standard measures.

Pharmacokinetics of Coencapsulated Antiretrovirals with Ingestible Sensors.

We investigated the use of a system with an ingestible sensor (Proteus Digital Health Feedback system) coencapsulated with antiretrovirals (ARVs) to measure real-time adherence. To assess the safety and impact, if any, coencapsulation might have on ARV concentrations, we evaluated the pharmacokinetics of ARVs coencapsulated with an ingestible sensor for eight commonly used fixed-dose combination ARVs: emtricitabine (FTC)/tenofovir disoproxil fumarate (TDF); FTC/tenofovir alafenamide (TAF); efavirenz (EFV)/FTC/TDF; abacavir (ABC)/lamivudine (3TC); dolutegravir (DTG)/ABC/3TC; rilpivirine (RPV)/TAF/FTC; elvitegravir (EVG)/cobicistat (COBI)/FTC/TAF; and bictegravir (BIC)/FTC/TAF. The steady-state apparent peak plasma concentration (Cmax) and area under the concentration-time curve (AUC) were determined from plasma concentrations measured at predose, 1, 2, 4, and 6 h postdose, and compared with literature values. A total of 49 unique patients on stable regimens for at least 12 weeks with undetectable viral loads were recruited. Cmax and AUC values were not statistically significantly different from literature values for all of the formulations except the Cmax of FTC/TDF, Cmax of BIC, and the Cmax of RPV. In a subsequent evaluation of FTC/TDF and BIC/FTC/TAF using a crossover design, the geometric mean ratio (GMR) between the coencapsulated and the unencapsulated formulations for FTC/TDF were the following: FTC, 84.6% (90% confidence interval [CI] 66.6-107.4) for AUC and 77.5% (60.1-99.9) for Cmax. For tenofovir (TFV), the GMR was 96.2% (90% CI 89.2-103.8) for AUC and 87.3% (64.2-118.7) for Cmax. The GMR for BIC (from the BIC/FTC/TAF formulation) was 98.0% (90% CI 84.5-113.5) for AUC and 89.9% (84.5-95.7) for Cmax. The observed deviation in FTC/TDF (Truvada) may be due to participant characteristics, fasted/fed conditions, and/or random variation and may warrant further investigations with a larger sample size. These findings provide assurance for use of coencapsulated ARVs for future HIV treatment-adherence research.