Descontrol glucémico: desafío de salud pública en prepandemia y pandemia.

OBJETIVO: Comparar el control glucémico entre pacientes con diabetes mellitus tipo 2 prepandemia vs pandemia de Covid-19 que acudieron a unidades de salud de primer nivel de atención de la Ciudad de México. Material y métodos. Se analizaron los registros de 23 912 pacientes con diabetes; 78.7% fueron del grupo prepandemia (2016 a 2020) y 21.3% del grupo pandemia (marzo 2020 a julio 2021). Se calcularon medidas de tendencia central y de dispersión, pruebas t de Student y se ajustó un modelo de regresión logística múltiple. RESULTADOS: La mayoría de los pacientes con diabetes fueron mujeres (66.6 y 62.6%) con edad promedio de 59 y 58 años, respectivamente, y con hemoglobina glucosilada (HbA1) final de 7.7 vs el grupo pandemia (8.0). Las variables asociadas con el descontrol glucémico incluyeron periodo, nivel de HbA1, sobrepeso, obesidad, antecedente de padres con diabetes, número de medicamentos y tipo de insulina. CONCLUSIONES: La mayoría de los pacientes con diabetes en ambos grupos tuvieron descontrol glucémico. Los pacientes del grupo pandemia tuvieron mayor descontrol glucémico de HbA1 comparados con los del grupo prepandemia. Después de recibir atención médica en ambos grupos, los pacientes mejoraron su control glucémico.

A retention-release mechanism based on RAB11FIP2 for AMPA receptor synaptic delivery during long-term potentiation.

It is well--established that Rab11-dependent recycling endosomes drive the activity-dependent delivery of AMPA receptors (AMPARs) into synapses during long-term potentiation (LTP). Nevertheless, the molecular basis for this specialized function of recycling endosomes is still unknown. Here, we have investigated RAB11FIP2 (FIP2 hereafter) as a potential effector of Rab11-dependent trafficking during LTP in rat hippocampal slices. Surprisingly, we found that FIP2 operates independently from Rab11 proteins, and acts as a negative regulator of AMPAR synaptic trafficking. Under basal conditions, FIP2 associates with AMPARs at immobile compartments, separately from recycling endosomes. Using shRNA-mediated knockdown, we found that FIP2 prevents GluA1 (encoded by the Gria1 gene) AMPARs from reaching the surface of dendritic spines in the absence of neuronal stimulation. Upon induction of LTP, FIP2 is rapidly mobilized, dissociates from AMPARs and undergoes dephosphorylation. Interestingly, this dissociation of the FIP2-AMPAR complex, together with FIP2 dephosphorylation, is required for LTP, but the interaction between FIP2 and Rab11 proteins is not. Based on these results, we propose a retention-release mechanism, where FIP2 acts as a gate that restricts the trafficking of AMPARs, until LTP induction triggers their release and allows synaptic delivery.

Sibling astrocytes share preferential coupling via gap junctions.

Astrocytes are organized as communicating cellular networks where each cell is connected to others via gap junctions. These connections are not pervasive and there is evidence for the existence of subgroups composed by preferentially connected cells. Despite being unclear how these are established, we hypothesized lineage might contribute to the establishment of these subgroups. To characterize the functional coupling of clonally related astrocytes, we performed intracellular dye injections in clones of astrocytes labeled with the StarTrack method. This methodology revealed sibling astrocytes are preferentially connected when compared to other surrounding astrocytes. These results suggest the role of the developmental origin in the organization of astrocytes as intercellular networks.

MAP1B Light Chain Modulates Synaptic Transmission via AMPA Receptor Intracellular Trapping.

The regulated transport of AMPA-type glutamate receptors (AMPARs) to the synaptic membrane is a key mechanism to determine the strength of excitatory synaptic transmission in the brain. In this work, we uncovered a new role for the microtubule-associated protein MAP1B in modulating access of AMPARs to the postsynaptic membrane. Using mice and rats of either sex, we show that MAP1B light chain (LC) accumulates in the somatodendritic compartment of hippocampal neurons, where it forms immobile complexes on microtubules that limit vesicular transport. These complexes restrict AMPAR dendritic mobility, leading to the intracellular trapping of receptors and impairing their access to the dendritic surface and spines. Accordingly, increasing MAP1B-LC expression depresses AMPAR-mediated synaptic transmission. This effect is specific for the GluA2 subunit of the AMPAR and requires glutamate receptor interacting protein 1 (GRIP1) interaction with MAP1B-LC. Therefore, MAP1B-LC represents an alternative link between GRIP1-AMPARs and microtubules that does not result in productive transport, but rather limits AMPAR availability for synaptic insertion, with a direct impact on synaptic transmission.SIGNIFICANCE STATEMENT The ability of neurons to modify their synaptic connections, known as synaptic plasticity, is accepted as the cellular basis for learning and memory. One mechanism for synaptic plasticity is the regulated addition and removal of AMPA-type glutamate receptors (AMPARs) at excitatory synapses. In this study, we found that a microtubule-associated protein, MAP1B light chain (MAP1B-LC), participates in this process. MAP1B-LC forms immobile complexes along dendrites. These complexes limit intracellular vesicular trafficking and trap AMPARs inside the dendritic shaft. In this manner, MAP1B restricts the access of AMPARs to dendritic spines and the postsynaptic membrane, contributing to downregulating synaptic transmission.

Association of Muscle Strength, Psychological Factors, and Central Sensitization With Movement-Evoked Pain in Patients With Nonspecific Chronic Low Back Pain: The BACKFIT Project.

BACKGROUND: People with chronic pain might evade certain movements to prevent their experience of pain. Movement-evoked pain (MEP) might induce lower functionality during daily activities. HYPOTHESIS: (1) MEP after physical fitness tests would vary depending on the main musculature involved in the test; (2) physical and psychological factors would be associated with MEP in patients with NSCLBP. STUDY DESIGN: Cross-sectional design. LEVEL OF EVIDENCE: Level 3. METHODS: A total of 104 (69 women) patients aged 51.0 ± 10.3 years with NSCLBP participated. MEP was measured with a visual analog scale (VAS) at baseline and immediately after performing each physical fitness test, that is, the Biering-Sørensen, prone bridging, handgrip, chair-stand, and 8-foot time-up-and-go tests, measuring back extensor, back flexor, upper- and lower-body muscle strength, and motor agility, respectively. Global muscle strength was calculated with normalized index (z-score) procedure. Depression, anxiety, pain catastrophizing, and central sensitization were assessed with the Beck Depression Inventory II, State Trait Anxiety Inventory I, Pain Catastrophizing Scale, and Central Sensitization Inventory (CSI), respectively. RESULTS: Patients showed greater pain after completion of the Biering-Sørensen (mean difference 95% CI, 0.02, 1.11), prone bridging (0.15, 1.21), lower pain after handgrip (-1.46, -0.52), and the 8-foot time-up-and-go (-1.43, 0.46) tests (all P ≤ 0.04). Lower global muscular strength (ß between -0.18 and -0.30), and greater pain catastrophizing (ß = 0.16), and CSI scoring (ß between 0.18 and 0.27) were associated with greater MEP (all P ≤ 0.04). CONCLUSION: Greater MEP was observed after tests measuring core musculature strength than after tests measuring distal (limbs) strength and agility. Greater MEP was overall associated with lower muscle strength, greater pain catastrophizing, and central sensitization. CLINICAL RELEVANCE: Fitness testing might be implemented as a complementary tool for the monitoring of NSCLBP in clinical settings.

Combining Spirometry and the ARISCAT Respiratory Risk Assessment Can Improve Postoperative Outcomes and Reduce Mortality Risk in Mexico.

Introduction: Although a major goal of preoperative evaluation is to identify risk factors and improve postoperative outcomes, current clinical guidelines in Mexico indicate that preoperative spirometry should only be performed on patients with pulmonary disease. The aim of this study was to compare the incidence of postoperative complications (POC), mortality, and risk factors among adults who did or did not undergo preoperative spirometry, based on their Assess Respiratory Risk in Surgical Patients in Catalonia (ARISCAT) risk level. Material and methods: An observational, retrospective and comparative study design was used to identify 2059 patients from the General Hospital of Mexico who had an ARISCAT assessment during 2013-2017. Patients were classified in two groups: ARISCAT with spirometry (n = 1306) and ARISCAT without spirometry (n = 753). Chi-square, Fisher's exact test and the Student's t-tests were used to compare groups. Logistic regression was used to identify factors associated with an increased risk of POC and mortality. Results: In the ARISCAT with spirometry group, 11% of patients had POC, compared with 48% of patients in the ARISCAT without spirometry group. High-risk ARISCAT patients who did not receive spirometry had higher mortality (18%), than those who underwent spirometry (0.4%). Logistic regression results indicate that not performing preoperative spirometry increases the probability of POC and mortality. Conclusions: Our findings suggest that the combined use of preoperative spirometry and ARISCAT is associated with reduced POC and mortality. Future clinical guidelines should recommend the use of preoperative spirometry for patients with a moderate or high ARISCAT level in Mexico.

Introducción: La evaluación preoperatoria se centra en identificar los factores de riesgo y mejorar los resultados posoperatorios; las guías clínicas actuales en México indican la espirometría preoperatoria solo en pacientes con enfermedad pulmonar. El objetivo fue comparar la incidencia de complicaciones posoperatorias (CPO), la mortalidad y los factores de riesgo en pacientes clasificados por su nivel de riesgo de la escala de riesgo respiratorio en pacientes quirúrgicos de Cataluña (ARISCAT) sometidos o no a una espirometría preoperatoria. Material y métodos: Estudio observacional, retrospectivo y comparativo. Se clasificaron 2.059 pacientes del Hospital General de México durante 2013 a 2017; en dos grupos: ARISCAT con espirometría (n = 1.306) y ARISCAT sin espirometría (n = 753). Se aplicaron pruebas de X2, f de Fisher y t de Student para comparar los grupos y análisis de regresión logística para identificar los factores asociados a mayor riesgo de CPO y mortalidad. Resultados: Las CPO en el grupo ARISCAT con espirometría se presentaron en 11% de los pacientes, en comparación con el grupo ARISCAT sin espirometría (48%). Los pacientes ARISCAT sin espirometría de alto riesgo tuvieron una mortalidad más elevada (18%), en comparación con los pacientes que sí la realizaron (0.4%). Los resultados de la regresión logística indican que no realizar la espirometría preoperatoria incrementa la probabilidad de CPO y mortalidad. Conclusiones: Nuestros hallazgos sugieren que el uso combinado de espirometría preoperatoria y ARISCAT se asocia con menores CPO y mortalidad. Las guías clínicas futuras deberán recomendar el uso de la espirometría preoperatoria para pacientes con un nivel moderado o alto de ARISCAT en México.

Preoperative risk assessment and spirometry is a cost-effective strategy to reduce post-operative complications and mortality in Mexico.

AIM: Combining preoperative spirometry with the Assess Respiratory Risk in Surgical Patients in Catalunia (ARISCAT) risk scale can reduce post-operative complications and improve patient survival. This study aimed to assess the cost-effectiveness of performing spirometry or not in conjunction with the ARISCAT scale, to reduce post-operative complications and improve survival among adult patients undergoing elective surgery in Mexico. METHODS: A cost-effectiveness analysis (CEA) was performed to compare the specific cost and health outcomes associated with the combined use of the ARISCAT scale and preoperative spirometry (Group 1), and the use of the ARISCAT scale without preoperative spirometry (Group 2). The health outcomes evaluated were post-operative complications and survival. The perspective was from the health care provider (Hospital General de México) and direct medical costs were reported in 2019 US dollars. A decision tree with a time horizon of eight months was used for each health outcome and ARISCAT risk level. RESULTS: The combined use of the ARISCAT scale and spirometry is more cost-effective for reducing post-operative complications in the low and moderate-risk levels and is cost-saving in the high-risk level, than use of the ARISCAT scale without spirometry. To improve patient survival, ARISCAT and spirometry are also more cost-effective at the moderate risk level, and cost-saving for high-risk patients, than using the ARISCAT scale alone. CONCLUSIONS: The use of preoperative spirometry among patients with a high ARISCAT risk level was cost-saving, reduced post-operative complications, and improved survival. Our findings indicate an urgent need to implement spirometry as part of preoperative care in Mexico, which is already the standard of care in other countries.

Contribution of Membrane Lipids to Postsynaptic Protein Organization.

The precise subsynaptic organization of proteins at the postsynaptic membrane controls synaptic transmission. In particular, postsynaptic receptor complexes are concentrated in distinct membrane nanodomains to optimize synaptic signaling. However, despite the clear functional relevance of subsynaptic receptor organization to synaptic transmission and plasticity, the mechanisms that underlie the nanoscale organization of the postsynaptic membrane remain elusive. Over the last decades, the field has predominantly focused on the role of protein-protein interactions in receptor trafficking and positioning in the synaptic membrane. In contrast, the contribution of lipids, the principal constituents of the membrane, to receptor positioning at the synapse remains poorly understood. Nevertheless, there is compelling evidence that the synaptic membrane is enriched in specific lipid species and that deregulation of lipid homeostasis in neurons severely affects synaptic functioning. In this review we focus on how lipids are organized at the synaptic membrane, with special emphasis on how current models of membrane organization could contribute to protein distribution at the synapse and synaptic transmission. Finally, we will present an outlook on how novel technical developments could be applied to study the dynamic interplay between lipids and proteins at the postsynaptic membrane.

KIF13A drives AMPA receptor synaptic delivery for long-term potentiation via endosomal remodeling.

The regulated trafficking of AMPA-type glutamate receptors (AMPARs) from dendritic compartments to the synaptic membrane in response to neuronal activity is a core mechanism for long-term potentiation (LTP). However, the contribution of the microtubule cytoskeleton to this synaptic transport is still unknown. In this work, using electrophysiological, biochemical, and imaging techniques, we have found that one member of the kinesin-3 family of motor proteins, KIF13A, is specifically required for the delivery of AMPARs to the spine surface during LTP induction. Accordingly, KIF13A depletion from hippocampal slices abolishes LTP expression. We also identify the vesicular protein centaurin-α1 as part of a motor transport machinery that is engaged with KIF13A and AMPARs upon LTP induction. Finally, we determine that KIF13A is responsible for the remodeling of Rab11-FIP2 endosomal structures in the dendritic shaft during LTP. Overall, these results identify specific kinesin molecular motors and endosomal transport machinery that catalyzes the dendrite-to-synapse translocation of AMPA receptors during synaptic plasticity.

Influence of climatic variables on chronic obstructive pulmonary disease patient attendance to a pulmonary rehabilitation program.

PURPOSE: Implementing adherence to pulmonary rehabilitation (PR) programs is key to obtaining the best results. The objective of our study was to evaluate the influence of weather conditions (humidity, temperature, and precipitation) on attendance to a PR program in chronic obstructive pulmonary disease (COPD) patients. METHODS: This prospective observational study, carried out in Seville (Spain), included COPD patients who participated in a 36-session outpatient mixed (strength and endurance) training program for 12 weeks. The program included educational sessions as well. The attendance at the program scheduled sessions during 1 year was evaluated in relation to the meteorological conditions of relative humidity in percentage (%), temperature in degree centigrade (°C), and precipitation in millimeters (mm) according to the data from the State Meteorological Agency (AEMET) and the meteorological center of La Rinconada. RESULTS: A total of 81 COPD patients who underwent 2903 sessions were analyzed. The annual average attendance of the program was 78.6%. No differences were found in the attendance to the program depending on the climatic conditions evaluated throughout the year. CONCLUSIONS: In a specific geographical area such as Seville, meteorological conditions are not a determining factor of attendance to the PR program for COPD patients.

A kinesin 1-protrudin complex mediates AMPA receptor synaptic removal during long-term depression.

The synaptic removal of AMPA-type glutamate receptors (AMPARs) is a core mechanism for hippocampal long-term depression (LTD). In this study, we address the role of microtubule-dependent transport of AMPARs as a driver for vesicular trafficking and sorting during LTD. Here, we show that the kinesin-1 motor KIF5A/C is strictly required for LTD expression in CA3-to-CA1 hippocampal synapses. Specifically, we find that KIF5 is required for an efficient internalization of AMPARs after NMDA receptor activation. We show that the KIF5/AMPAR complex is assembled in an activity-dependent manner and associates with microsomal membranes upon LTD induction. This interaction is facilitated by the vesicular adaptor protrudin, which is also required for LTD expression. We propose that protrudin links KIF5-dependent transport to endosomal sorting, preventing AMPAR recycling to synapses after LTD induction. Therefore, this work identifies an activity-dependent molecular motor and the vesicular adaptor protein that executes AMPAR synaptic removal during LTD.

Results of a pilot study on the use of third-party donor mesenchymal stromal cells in cord blood transplantation in adults.

BACKGROUND AIMS: Cord blood (CB) transplants with co-infusion of third-party donor (TPD) mobilized hematopoietic stem cells (MHSC) have been shown to result in 'bridge' engraftment with prompt neutrophil recovery and high final rates of CB engraftment and full chimerism. This strategy overcomes the limitation posed by low cellularity of CB units for unrelated transplants in adults. Enhancement of adaptive immunity reconstitution without increasing risks of graft-versus-host disease (GvHD) is required to optimize results further. Our objectives were to evaluate co-infusion of mesenchymal stromal cells (MSC) from the same TPD regarding tolerance, CB engraftment and effects on acute (a)GvHD, both preventive and therapeutic. METHODS: Ex vivo-expanded bone marrow MSC were infused at the time of the transplant or the in case of refractory aGvHD. RESULTS: Nine patients received 1.04 - 2.15 x 10(6)/kg (median 1.20) MSC immediately after CB and TPD MHSC. Neither immediate adverse side-effects nor significant differences regarding CB engraftment or aGvHD development were observed. Four patients developed grade II aGvHD, refractory to steroids in two. These reached complete remission after therapeutic infusions of MSC. CONCLUSIONS: In recipients of 'dual CB/TPD MHSC transplants', MSC infusions were therapeutically effective for severe aGvHD but no significant differences in CB engraftment and incidence of severe aGvHD were observed following their prophylactic use. Although results of this study alone cannot conclusively determine the application of MSC in CB transplantation, we believe that, in this setting, the best use of MSC could be as pre-emptive treatment for aGvHD.

Depressive symptoms, physical activity, and weight gain in premenopausal Latina and White women.

OBJECTIVES: Describe changes and examine the association between depressive symptoms, physical activity, body mass index (BMI), and perceived health among Latina (n=81) and White (n=151) women in the first year of the late-premenopausal stage. METHODS: Longitudinal study focused on the biopsychosocial health of midlife women (ages 40-50 years) with regular menstrual cycles and not taking hormones. Frequency of depressive symptoms, BMI, waist to hip ratios, and self-reported physical activity levels were obtained at 6-month intervals and perceived health at 12 months. Results are reported here for 232 women who remained premenopausal (low FSH/regular cycles) for the first 12 months. RESULTS: Depressive symptoms were similar for Latinas (11.1+/-9.8) and Whites (11.1+/-8.2) and increased by 2.3 points over time for all women. Latinas had higher BMI (28+/-5.7, p<0.01) than Whites (26+/-5.7). Body weight increased an average of 1.2 lbs over 12 months for both groups. Both groups reported sub-optimal levels of physical activity that did not change over time, but Latinas reported higher levels at all 3 time points. Controlling for age and ethnicity, women in service or agricultural occupations reported higher activity levels than women in other roles. Better perceived health at 12 months was predicted by lower baseline BMI (r=0.43, p<0.01) and fewer depressive symptoms (r=0.38, p<0.01). CONCLUSIONS: Depressive symptoms, weight gain and physical inactivity among women in the late-premenopausal stage point to the need for interventions focused on causal factors other than hormonal changes and menopause.

Industrial processing of condiments and seasonings and its implications for micronutrient fortification.

Opportunities exist for micronutrient fortification of condiments and seasonings to combat vitamin or mineral deficiencies. This paper reviews the available technologies for industrial processing of condiments and seasonings and their fortification with micronutrients. The industrial processes to manufacture commonly consumed condiments and seasonings, such as soy sauce, bouillon cubes, fish sauce, spices, and other relevant products, are described. The impact of processing on fortification is evaluated, considering both the type of vehicle and the fortificant used. The analyzed technologies represent effective strategies for mineral fortification, particularly with iodine and iron. However, fortification with vitamins has been more challenging, owing to sensory changes of the finished product and a poor stability of the fortificant when using certain vehicles. Therefore, more studies are needed in this area in collaboration with governments, the food industry, and vitamin suppliers. Despite the technical difficulties encountered, the current processing technologies for the production of condiments and seasonings can be adapted and refined to allow their successful fortification with micronutrients.

Unraveling Cajal's view of the olfactory system.

The olfactory system has a highly regular organization of interconnected synaptic circuits from the periphery. It is therefore an excellent model for understanding general principles about how the brain processes information. Cajal revealed the basic cell types and their interconnections at the end of the XIX century. Since his original descriptions, the observation and analysis of the olfactory system and its components represents a major topic in neuroscience studies, providing important insights into the neural mechanisms. In this review, we will highlight the importance of Cajal contributions and his legacy to the actual knowledge of the olfactory system.

Inhibition of acid secretion by the nonsteroidal anti-inflammatory drugs diclofenac and piroxicam in isolated gastric glands: analysis of a multifocal mechanism.

In nonstimulated rabbit gastric glands, acetylsalicylic acid (10-500 microM) and indomethacin (3-300 microM) did not significantly modify the basal rate of acid secretion, whereas diclofenac and piroxicam (10-1,000 microM each) caused a marked and dose-dependent inhibitory effect (EC(50) = 138 and 280 microM, respectively). In gastric glands stimulated by histamine (100 microM), diclofenac also reduced the rate of acid formation in a dose-dependent manner. In contrast, acetylsalicylic acid, indomethacin, and piroxicam exerted a biphasic effect; thus low concentrations (3-100 microM) of these three agents significantly increased the rate of histamine-stimulated acid secretion (10-20% over the corresponding control value) by a cAMP-independent mechanism, whereas higher concentrations reduced the rate of acid formation. With respect to underlying biochemical mechanisms that could mediate inhibitory effects of NSAIDs on gastric acid formation, it was observed that both diclofenac and piroxicam, but not acetylsalicylic acid or indomethacin, decreased the glandular content of ATP, inhibited hydrolytic activity of gastric gland microsomal H(+)-K(+)-ATPase, and reduced the rate of H(+)-K(+)-ATPase-dependent proton transport across microsomal membranes in a dose-dependent manner. Furthermore, diclofenac and piroxicam also significantly increased passive permeability of microsomal membranes to protons. In conclusion, our work shows that diclofenac and piroxicam cause a significant reduction in the rate of basal and histamine-stimulated acid formation in isolated rabbit gastric glands at concentrations that can be attained in the gastric lumen of patients treated with these drugs. Mechanisms involved in these inhibitory effects appear to be multifocal and include different steps of stimulus-secretion coupling.

Auto anti M.N.P1 en un donante de sangre sin evidencia de estímulo antigénico / Auto anti M.N. P1 in blood donor without evidence of antigenic stimuli

Se presenta un caso de un donante voluntario de sangre, no embarazada y no transfundida, mestiza. Los estudios inmunohematológicos revelan la presencia de anticuerpos del tipo Anti M Anti N y Anti P1. Se describen las propiedades fisico-químicas de dichos anticuerpos y se señalan los probables riesgos que este tipo de personas pueden presentar, como donante o como receptor de sangre

Prevalencia de signos y síntomas de los trastornos temporomandibulares en un grupo de adultos mayores / Prevalence of signs and symptoms of temporomandibular joint disorders in a group of older adults

Se realizó un estudio observacional, prospectivo, transversal y descriptivo de 37 ancianos de 60 a 80 años para conocer los signos y síntomas de los trastornos temporomandibulares que se presentan con mayor frecuencia en este grupo etario. Los signos y síntomas que se valoraron fueron: dolor, ruidos articulares, bloqueos, limitación funcional de la apertura mandibular, desgaste dental, pérdida de dientes, dimensión vertical, colapso posterior de la mordida y rehabilitación prostésica, entre otros. El 46 por ciento (n=17) de la población presentó patología dolorosa de la ATM acompañada por los menos con un síntoma , por ej. chasquido, bruxismo o apertura limitada; el 43.2 por ciento (n=16) tiene signos positivos de pérdida de la dimensión vertical; el 81 por ciento (n=30) presenta colapso de la mordida; el 54 por ciento (n=20) de los ancianos que no presentó dolor, está expuesto por lo menos a un factor de riesgo