Embryonic Origin of Postnatal Neural Stem Cells.

Adult neural stem/progenitor (B1) cells within the walls of the lateral ventricles generate different types of neurons for the olfactory bulb (OB). The location of B1 cells determines the types of OB neurons they generate. Here we show that the majority of mouse B1 cell precursors are produced between embryonic days (E) 13.5 and 15.5 and remain largely quiescent until they become reactivated postnatally. Using a retroviral library carrying over 100,000 genetic tags, we found that B1 cells share a common progenitor with embryonic cells of the cortex, striatum, and septum, but this lineage relationship is lost before E15.5. The regional specification of B1 cells is evident as early as E11.5 and is spatially linked to the production of neurons that populate different areas of the forebrain. This study reveals an early embryonic regional specification of postnatal neural stem cells and the lineage relationship between them and embryonic progenitor cells.

Phase and Amplitude Modes in the Anisotropic Dicke Model with Matter Interactions.

Phase and amplitude modes, also called polariton modes, are emergent phenomena that manifest across diverse physical systems, from condensed matter and particle physics to quantum optics. We study their behavior in an anisotropic Dicke model that includes collective matter interactions. We study the low-lying spectrum in the thermodynamic limit via the Holstein-Primakoff transformation and contrast the results with the semi-classical energy surface obtained via coherent states. We also explore the geometric phase for both boson and spin contours in the parameter space as a function of the phases in the system. We unveil novel phenomena due to the unique critical features provided by the interplay between the anisotropy and matter interactions. We expect our results to serve the observation of phase and amplitude modes in current quantum information platforms.

Advancing therapy in people with suboptimally controlled basal insulin-treated type 2 diabetes: Subanalysis of the SoliMix trial in participants in Latin American countries.

AIMS: This subanalysis of the SoliMix trial assessed the efficacy and safety of advancing basal insulin (BI) therapy with iGlarLixi versus BIAsp 30 in people with type 2 diabetes (T2D) living in Latin American (LATAM) countries, i.e. Argentina and Mexico (N = 160). MATERIALS AND METHODS: SoliMix (EudraCT: 2017-003370-13) was a 26-week, open-label, multicentre study, where adults with T2D suboptimally controlled with BI plus one or two oral glucose-lowering drugs and glycated haemoglobin (HbA1c) ≥7.5% to ≤10% were randomized to once-daily iGlarLixi or twice-daily BIAsp 30. Primary efficacy endpoints were non-inferiority in HbA1c reduction (margin 0.3%) or superiority in body weight change for iGlarLixi versus BIAsp 30. RESULTS: Both primary efficacy endpoints were met in the LATAM region. After 26 weeks, HbA1c was reduced by 1.8% with iGlarLixi and 1.4% with BIAsp 30, meeting non-inferiority [least squares mean difference -0.47% (95% confidence interval: -0.82, -0.11); p < .001]. iGlarLixi was superior to BIAsp 30 for body weight change [least squares mean difference -1.27% (95% confidence interval: -2.41, -0.14); p = .028]. iGlarLixi was also superior to BIAsp 30 for HbA1c reduction (p = .010). A greater proportion of participants achieved HbA1c <7% without weight gain and HbA1c <7% without weight gain and without hypoglycaemia with iGlarLixi versus BIAsp 30. Incidence and rates of American Diabetes Association Level 1 and 2 hypoglycaemia were lower with iGlarLixi versus BIAsp 30. CONCLUSIONS: Once-daily iGlarLixi provided better glycaemic control with weight benefit and less hypoglycaemia than twice-daily premix BIAsp 30. iGlarLixi may be a favourable alternative to premix BIAsp 30 in people with suboptimally controlled T2D to advance BI therapy in the LATAM region.

Critical Phenomena in Light-Matter Systems with Collective Matter Interactions.

We study the quantum phase diagram and the onset of quantum critical phenomena in a generalized Dicke model that includes collective qubit-qubit interactions. By employing semiclassical techniques, we analyze the corresponding classical energy surfaces, fixed points, and the smooth Density of States as a function of the Hamiltonian parameters to determine quantum phase transitions in either the ground (QPT) or excited states (ESQPT). We unveil a rich phase diagram, the presence of new phases, and new transitions that result from varying the strength of the qubits interactions in independent canonical directions. We also find a correspondence between the phases emerging due to qubit interactions and those in their absence but with varying the strength of the non-resonant terms in the light-matter coupling. We expect our work to pave the way and stimulate the exploration of quantum criticality in systems combining matter-matter and light-matter interactions.

Immunity and COVID-19 vaccines. Revisiting the bases.

The COVID-19 pandemic is one of the challenges of the 21st century; science and technology were put to the test for the development vaccines, diagnostic techniques and treatments in record time. However, misinformation and misinterpretation have made the safety and efficacy of COVID-19 vaccines a subject of debate. This review addresses concepts on immunization mechanisms and vaccination, as well as evidence supporting that COVID-19 vaccines are immunogenic, efficacious and safe.

La pandemia de COVID-19 es uno de los retos del siglo XXI; la ciencia y la tecnología se pusieron a prueba para desarrollar vacunas, técnicas diagnósticas y tratamientos en tiempo récord. No obstante, la desinformación y mala interpretación han hecho que la seguridad y eficacia de las vacunas contra COVID-19 sean un tema de debate. En esta revisión se abordan conceptos sobre los mecanismos de la inmunización y la vacunación; así como la evidencia que sostiene que las vacunas contra COVID-19 son inmunogénicas, eficaces y seguras.

HPV infection profile in cervical lesions.

INTRODUCTION: The prevalence of the different genotypes of human papillomavirus (HPV) varies depending on lesion severity and geographic region. OBJECTIVE: To identify multiple HPV infections in low- and high-grade cervical lesions in a group of women from the Mexican Bajío region referred with inconclusive cytology. METHODS: Pilot study of women referred from primary care units of Guanajuato, Mexico, with cytology suggestive of cervical lesion. Cervical smears were subjected to DNA extraction and HPV genotyping using microarrays. RESULTS: 100 consecutive cases were collected and 90 were analyzed; HPV positivity was observed in 26% of healthy women, and 62% had some degree of cervical lesion. The most common HPV genotypes were 59, 31, 16 and 51. Multiple infections were found in most samples. CONCLUSIONS: HPV heterogeneity was identified in the samples of the study population in contrast to worldwide reports; furthermore, multiple infections are common in precursor lesions and decrease in high-grade lesions. These data could have an impact on current HPV vaccination programs.

INTRODUCCIÓN: La prevalencia de los diferentes genotipos de virus del papiloma humano (VPH) varía dependiendo de la severidad de la lesión y región geográfica. OBJETIVO: Identificar infecciones múltiples de VPH en lesiones cervicales de bajo y alto grado en un grupo de mujeres del Bajío mexicano referidas con citología no concluyente. MÉTODOS: Estudio piloto de mujeres referidas de unidades del primer nivel de atención de Guanajuato, México, por citología sugerente de lesión cervical. Los raspados cervicales fueron sujetos a extracción de ADN y genotipificación del VPH mediante microarreglos. RESULTADOS: Se colectaron 100 casos consecutivos y fueron analizados 90; se observó 26 % de positividad a VPH en mujeres sanas y 62 % presentó algún grado de lesión. Los genotipos de VPH más frecuentes fueron 59, 31, 16 y 51. En la mayoría de las muestras se encontró infección múltiple. CONCLUSIONES: Se identificó heterogeneidad de VPH en las muestras de la población estudiada en contraste con los reportes internacionales; además, son comunes las infecciones múltiples en lesiones precursoras y disminuyen en las lesiones de alto grado. Estos datos podrían influir en los actuales programas de vacunación anti-VPH.

Theory of a rotationally shearing interferometer.

We developed a general theory about the performance of a rotational shearing interferometer. We apply the aberration theory to the detection of planets outside our planet system. We considered cases when the mutual coherence functions of the on-axis and the off-axis system are 0 and 1.

Adenosine augments the production of IL-10 in cervical cancer cells through interaction with the A2B adenosine receptor, resulting in protection against the activity of cytotoxic T cells.

Cervical cancer (CeCa) produces large amounts of IL-10, which downregulates the major histocompatibility complex class I molecules (HLA-I) in cancer cells and inhibits the immune response mediated by cytotoxic T lymphocytes (CTLs). In this study, we analyzed the ability of CeCa cells to produce IL-10 through the CD73-adenosine pathway and its effect on the downregulation of HLA-I molecules to evade CTL-mediated immune recognition. CeCa cells cultured in the presence of ≥10 µM AMP or adenosine produced 4.5-6 times as much IL-10 as unstimulated cells. The silencing of CD73 or the blocking of A2BR with the specific antagonist MRS1754 reversed this effect. In addition, IL-10 decreased the expression of HLA-I molecules, resulting in the protection of CeCa cells against the cytotoxic activity of CTLs. The addition of MRS1754 or anti-IL-10 reversed the decrease in HLA-I molecules and favored the cytotoxic activity of CTLs. These results strongly suggest the presence of a feedback loop encompassing the adenosinergic pathway, the production of IL-10, and the downregulation of HLA-I molecules in CeCa cells that favors immune evasion and thus tumor progression. This pathway may have clinical importance as a therapeutic target.

The big challenge of SARS-CoV-2 latency: testes as reservoir.

In the efforts to explain COVID-19 pathophysiology, studies are being carried out on the correspondence between the expression of SARS-CoV-2 cell receptors and viral sequences. ACE2, CD147 and TMPRSS2 receptors expression could indicate poorly explored potential infection targets. For the genomic analysis of SARS-CoV-2 receptors, using BioGPS information was decided, which is a portal that centralizes genetic annotation resources, in combination with that of The Human Protein Atlas, the largest portal of human transcriptome and proteome data. We also reviewed the most recent articles on the subject. RNA and viral receptor proteins expression was observed in numerous anatomical sites, which partially coincides with the information reported in the literature. High expression in testicular cells markedly stood out, and it would be therefore important ruling out whether this anatomical site is a SARS-CoV-2 reservoir; otherwise, germ cell damage, as it is observed in infections with other RNA viruses, should be determined.

En el afán por explicar la fisiopatogenia de COVID-19 se están realizando estudios en torno a la correspondencia entre la expresión de receptores celulares de SARS-CoV-2 y las secuencias virales. La expresión de los receptores ACE2, CD147 y TMPRSS2 podría indicar blancos de infección poco explorados. Para el análisis genómico de los receptores de SARS-CoV-2 se optó por utilizar la información del BioGPS, un portal que centraliza los recursos de anotación genética, en combinación con la de The Human Protein Atlas, el portal más grande de datos del transcriptoma y proteoma humanos. También se revisaron los artículos más recientemente respecto al tema. En numerosos sitios anatómicos se observó la expresión de ARN y proteínas de los receptores del virus, que coinciden parcialmente con la información reportada en la literatura. Resaltó la alta expresión en las células de los testículos, por lo que sería importante descartar si este sitio anatómico es un reservorio de SARS-CoV-2; de no ser así, determinar el daño en las células germinales, tal como sucede en infecciones por otros virus ARN.

Development and validation of a predictive model for incident type 2 diabetes in middle-aged Mexican adults: the metabolic syndrome cohort.

BACKGROUND: Type 2 diabetes mellitus (T2D) is a leading cause of morbidity and mortality in Mexico. Here, we aimed to report incidence rates (IR) of type 2 diabetes in middle-aged apparently-healthy Mexican adults, identify risk factors associated to ID and develop a predictive model for ID in a high-risk population. METHODS: Prospective 3-year observational cohort, comprised of apparently-healthy adults from urban settings of central Mexico in whom demographic, anthropometric and biochemical data was collected. We evaluated risk factors for ID using Cox proportional hazard regression and developed predictive models for ID. RESULTS: We included 7636 participants of whom 6144 completed follow-up. We observed 331 ID cases (IR: 21.9 per 1000 person-years, 95%CI 21.37-22.47). Risk factors for ID included family history of diabetes, age, abdominal obesity, waist-height ratio, impaired fasting glucose (IFG), HOMA2-IR and metabolic syndrome. Early-onset ID was also high (IR 14.77 per 1000 person-years, 95%CI 14.21-15.35), and risk factors included HOMA-IR and IFG. Our ID predictive model included age, hypertriglyceridemia, IFG, hypertension and abdominal obesity as predictors (Dxy = 0.487, c-statistic = 0.741) and had higher predictive accuracy compared to FINDRISC and Cambridge risk scores. CONCLUSIONS: ID in apparently healthy middle-aged Mexican adults is currently at an alarming rate. The constructed models can be implemented to predict diabetes risk and represent the largest prospective effort for the study metabolic diseases in Latin-American population.

EUS-Guided Choledochoduodenostomy for Distal Malignant Biliary Obstruction Using Electrocautery-Enhanced Lumen-Apposing Metal Stents: First US, Multicenter Experience.

BACKGROUND AND AIMS: EUS-guided biliary drainage has emerged as a technique to enable endobiliary drainage in failed ERCP. A newer model, lumen-apposing metal stents (LAMS), with a cautery-enhanced delivery system became available in the USA in late 2015. This cautery-tipped version may facilitate EUS-guided choledochoduodenostomy (EUS-CD), but data using this model are lacking. METHODS: We reviewed outcomes of attempted EUS-CD using cautery-enhanced LAMS from 6, US centers. The following data were collected: patient and procedure details, technical success, adverse events, clinical success (resolution of jaundice or improvement in bilirubin > 50%), and biliary re-interventions. RESULTS: EUS-CD was attempted in 67 patients (mean age 68.8) with malignant obstruction after failed ERCP between September 2015 and April 2018. EUS-CD was technically successful in 64 (95.5%). A plastic or metal stent was inserted through the lumen of the deployed LAMS in 50 of 64 (78.1%) patients to maintain a non-perpendicular LAMS axis into the bile duct. Adverse events occurred in 4 (6.3%) and included: abdominal pain (n = 2), peritonitis that responded to antibiotics (n = 1), and bleeding requiring transfusion (n = 1). Among 40 patients with follow-up of > 4 weeks, clinical success was achieved in 100%. Biliary re-interventions for obstruction were needed in 7(17.5%), in 3 of 6 (50.0%) that underwent EUS-CD with LAMS alone versus 4 of 34 (5%) with LAMS plus an axis-orienting stent (p = 0.02). CONCLUSION: EUS-CD using LAMS with cautery-enhanced delivery systems has high technical and clinical success rates, with a low rate of adverse events. Inserting an axis-orienting stent through the lumen of the LAMS may reduce the need for biliary re-interventions.

A non-invasive tool for detecting cervical cancer odor by trained scent dogs.

BACKGROUND: Cervical Cancer (CC) has become a public health concern of alarming proportions in many developing countries such as Mexico, particularly in low income sectors and marginalized regions. As such, an early detection is a key medical factor in improving not only their population's quality of life but also its life expectancy. Interestingly, there has been an increase in the number of reports describing successful attempts at detecting cancer cells in human tissues or fluids using trained (sniffer) dogs. The great odor detection threshold exhibited by dogs is not unheard of. However, this represented a potential opportunity to develop an affordable, accessible, and non-invasive method for detection of CC. METHODS: Using clicker training, a male beagle was trained to recognize CC odor. During training, fresh CC biopsies were used as a reference point. Other samples used included cervical smears on glass slides and medical surgical bandages used as intimate sanitary pads by CC patients. A double-blind procedure was exercised when testing the beagle's ability to discriminate CC from control samples. RESULTS: The beagle was proven able to detect CC-specific volatile organic compounds (VOC) contained in both fresh cervical smear samples and adsorbent material samples. Beagle's success rate at detecting and discriminating CC and non-CC odors, as indicated by specificity and sensitivity values recorded during the experiment, stood at an overall high (>90%). CC-related VOC in adsorbent materials were detectable after only eight hours of use by CC patients. CONCLUSION: Present data suggests different applications for VOC from the uterine cervix to be used in the detection and diagnosis of CC. Furthermore, data supports the use of trained dogs as a viable, affordable, non-invasive and, therefore, highly relevant alternative method for detection of CC lesions. Additional benefits of this method include its quick turnaround time and ease of use while remaining highly accurate and robust.

Balloon valvuloplasty for annular- and leaflet-level tricuspid stenosis: Report of cases and literature review.

Congenital tricuspid valve stenosis is extremely rare. We describe 2 cases of patients with adult congenital heart disease with hypoplastic tricuspid valve annulus who were symptomatic from annular- and leaflet-level tricuspid stenosis. The patients underwent transcatheter balloon valvuloplasty with good clinical outcomes. An extensive literature review and analysis of various procedural strategies suggests that percutaneous balloon valvuloplasty may be a reasonable therapeutic choice as a first-line therapy or when open surgical repair is associated with prohibitively high mortality. This procedure can be performed either as a destination therapy or as a bridge to valve replacement.

Influence of Alternative Prey on the Functional Response of a Predator in Two Contexts: With and without Intraguild Predation.

In biological control, joint releases of predators and parasitoids are standard. However, intraguild predation (IGP) can occur when a predator attacks a parasitoid, potentially affecting pest control dynamics. In addition to the focal prey (FP), Trialeurodes vaporariorum, the intraguild predator (IG-predator) Geocoris punctipes can consume the parasitoid Eretmocerus eremicus (IG-prey). In this IGP context with multiple prey, an alternative prey (AP), like the aphid Myzus persicae, may influence interactions. Theory predicts that, in simple interactions, a predator's functional response (FR) to the FP changes with the presence of an AP. However, whether this holds in an IGP context is unknown. In this study, we empirically tested that prediction. Our results show that without IGP, G. punctipes exhibits a generalized FR with and without AP. Nevertheless, with IGP, the predator exhibited a Type II FR at low and high AP densities, increasing pressure on the FP and potentially favoring short-term biological control strategies. However, when 25 AP were offered, the predator's response shifted, underscoring the importance of monitoring AP densities to prevent potential disruptions in FP control. In both contexts, the increase in AP produced a handling time increase and a decrease in consumption rate. These results indicate that the theoretical prediction of the effect of AP on the FR is met only under specific conditions, and the complexity of multitrophic interactions must be considered.

Cultivable Microbiome Approach Applied to Cervical Cancer Exploration.

Traditional microbiological methodology is valuable and essential for microbiota composition description and microbe role assignations at different anatomical sites, including cervical and vaginal tissues; that, combined with molecular biology strategies and modern identification approaches, could give a better perspective of the microbiome under different circumstances. This pilot work aimed to describe the differences in microbiota composition in non-cancer women and women with cervical cancer through a culturomics approach combining culture techniques with Vitek mass spectrometry and 16S rDNA sequencing. To determine the possible differences, diverse statistical, diversity, and multivariate analyses were applied; the results indicated a different microbiota composition between non-cancer women and cervical cancer patients. The Firmicutes phylum dominated the non-cancer (NC) group, whereas the cervical cancer (CC) group was characterized by the predominance of Firmicutes and Proteobacteria phyla; there was a depletion of lactic acid bacteria, an increase in the diversity of anaerobes, and opportunistic and non-typical human microbiota isolates were present. In this context, we hypothesize and propose a model in which microbial composition and dynamics may be essential for maintaining the balance in the cervical microenvironment or can be pro-oncogenesis microenvironmental mediators in a process called Ying-Yang or have a protagonist/antagonist microbiota role.

Use of hyaluronic acid gel in the management of cicatricial ectropion: results and complications.

AIMS: To report our experience using hyaluronic acid gel injection in the lower eyelid to treat cicatricial ectropion. METHODS: Clinical records and literature review. RESULTS: Between November 2009 and June 2011, 12 lower eyelids of 11 patients with cicatricial ectropion were treated with hyaluronic acid gel. All 11 patients demonstrated improvement in the eyelid position after treatment but only 3 patients (27.3%) experimented total correction after injection. Although the correction was partial in the majority of the patients, the signs and symptoms associated with conjunctival and corneal exposure improved in all patients. Seven patients (63.7%) developed irregular fullness which resolved over time, but in 4 patients (36.3%) fullness persisted for one year. CONCLUSIONS: In our experience, hyaluronic acid gel is a nonsurgical, minimally invasive and safe technique that improves cicatricial ectropion, but with a poor cosmetic result that limits its use. This treatment could be considered only in patients who decline surgery or are poor surgical candidates, as the aesthetic result would not be acceptable to many.

Use of carotid compression in a patient with arteriovenous malformation.

We report a case of a patient with a high flow arteriovenous malformation (AVM)i n the orbit, who developed a severe compartment syndrome, and was successfully treated with manual carotid compressions. The patient suffered a progressive proptosis, restriction of ocular motility and decreased of the visual acuity of the right eye. Embolization had a high risk of serious complications due to fistula location, so an alternative treatment consisting in carotid compressions was prescribed. Manual carotid compression is a non-invasive alternative technique to treat AVMs in patients with high risk of embolization episodes.

Endoscopic resection of GI stromal tumor using full-thickness resection device: tips and tricks.

Video 1R0 endoscopic resection of gastric GI stromal tumor using a dedicated gastroduodenal full-thickness resection device.

The immune response of the whitefly Trialeurodes vaporariorum (Hemiptera: Aleyrodidae) when parasitized by Eretmocerus eremicus (Hymenoptera: Aphelinidae).

In insects, the innate immune system is subdivided into cellular and humoral defenses. When parasitoids attack insects, both reactions can be activated and notably, the phenoloxidase (PO) cascade and lytic activity are part of both cellular and humoral defenses. However, to our knowledge, no study has characterized any immune response of the whitefly Trialeurodes vaporariorum (Hemiptera: Aleyrodidae) to the attack of Eretmocerus eremicus (Hymenoptera: Aphelinidae). Therefore, the first objective of the present study was to determine whether whitefly nymphs recently parasitized by E. eremicus exhibit any immune response. For this, we estimate the level of prophenoloxidase (proPO), phenoloxidase (PO), and lytic activity by colorimetric assays. A second objective was to assess whether the observed whitefly immune response could be related to a previously reported preference of the predator Geocoris punctipes (Hemiptera: Lygaeidae) for non-parasitized nymphs. We therefore offered non-parasitized and recently parasitized nymphs to the predator. Our results show that parasitism of whitefly nymphs by E. eremicus induced a highly estimated level of proPO and PO, and a lower level of lytic activity. In addition, we found that G. punctipes did not show a preference for non-parasitized over recently parasitized nymphs. The nymphs of T. vaporariorum activated the PO pathway against E. eremicus; however, the increase in proPO and PO levels was traded-off with decreased lytic activity. In addition, the previously reported preference for non-parasitized nymphs was not seen in our experiments, indicating that the induced immune response did not affect predator behavior by G. punctipes.