Rubus urticifolius Compounds with Antioxidant Activity, and Inhibition Potential against Tyrosinase, Melanin, Hyaluronidase, Elastase, and Collagenase.

In our study, using chromatographic techniques, we isolated three bioactive compounds, which were structurally elucidated as (E)-2-(3-(3,4-dimethoxyphenyl)acrylamido)-N-methylbenzamide (1), 4-Hydroxyquinoline-2-carboxylic acid (2), and (E)-2-Cyano-3-(4-hydroxyphenyl)acrylic acid (3), using spectroscopic methods. The anti-melanogenic, anti-inflammatory, antioxidant, and anti-aging properties were evaluated in vitro by measuring the activity of pharmacological targets including tyrosinase, melanin, NF-κB, hyaluronidase, elastase, collagenase, and Nrf2. Our results show that compound 1 is the most active with IC50 values of 14.19 µM (tyrosinase inhibition), 22.24 µM (melanin inhibition), 9.82-12.72 µM (NF-κB inhibition), 79.71 µM (hyaluronidase inhibition), 80.13 µM (elastase inhibition), 76.59 µM (collagenase inhibition), and 116-385 nM (Nrf2 activation) in the THP-1, HEK001, WS1, and HMCB cells. These findings underscore the promising profiles of the aqueous extract of R. urticifolius at safe cytotoxic concentrations. Additionally, we report, for the first time, the isolation and characterisation of these nitrogenous compounds in the R. urticifolius species. Finally, compound 1, isolated from R. urticifolius, is a promising candidate for the development of more effective and safer compounds for diseases related to skin pigmentation, protection against inflammation, and oxidative stress.

Nerve Injury Triggers Time-dependent Activation of the Locus Coeruleus, Influencing Spontaneous Pain-like Behavior in Rats.

BACKGROUND: Dynamic changes in neuronal activity and in noradrenergic locus coeruleus (LC) projections have been proposed during the transition from acute to chronic pain. Thus, the authors explored the cellular cFos activity of the LC and its projections in conjunction with spontaneous pain-like behavior in neuropathic rats. METHODS: Tyrosine hydroxylase:Cre and wild-type Long-Evans rats, males and females, were subjected to chronic constriction injury (CCI) for 2 (short-term, CCI-ST) or 30 days (long-term, CCI-LT), evaluating cFos and Fluoro-Gold expression in the LC, and its projections to the spinal cord (SC) and rostral anterior cingulate cortex (rACC). These tests were carried out under basal conditions (unstimulated) and after noxious mechanical stimulation. LC activity was evaluated through chemogenetic and pharmacologic approaches, as were its projections, in association with spontaneous pain-like behaviors. RESULTS: CCI-ST enhanced basal cFos expression in the LC and in its projection to the SC, which increased further after noxious stimulation. Similar basal activation was found in the neurons projecting to the rACC, although this was not modified by stimulation. Strong basal cFos expression was found in CCI-LT, specifically in the projection to the rACC, which was again not modified by stimulation. No cFos expression was found in the CCI-LT LCipsilateral (ipsi)/contralateral (contra)→SC. Chemogenetics showed that CCI-ST is associated with greater spontaneous pain-like behavior when the LCipsi is blocked, or by selectively blocking the LCipsi→SC projection. Activation of the LCipsi or LCipsi/contra→SC dampened pain-like behavior. Moreover, Designer Receptor Exclusively Activated by Designer Drugs (DREADDs)-mediated inactivation of the CCI-ST LCipsi→rACC or CCI-LT LCipsi/contra→rACC pathway, or intra-rACC antagonism of α-adrenoreceptors, also dampens pain-like behavior. CONCLUSIONS: In the short term, activation of the LC after CCI attenuates spontaneous pain-like behaviors via projections to the SC while increasing nociception via projections to the rACC. In the long term, only the projections from the LC to the rACC contribute to modulate pain-like behaviors in this model.

Risk factors for suicide reattempt: a systematic review and meta-analysis.

BACKGROUND: Suicide is one of the main external causes of death worldwide. People who have already attempted suicide are at high risk of new suicidal behavior. However, there is a lack of information on the risk factors that facilitate the appearance of reattempts. The aim of this study was to calculate the risk of suicide reattempt in the presence of suicidal history and psychosocial risk factors and to estimate the effect of each individual risk factor. METHODS: This systematic review and meta-analysis were conducted following the PRISMA-2020 guidelines. Studies on suicide reattempt that measured risk factors were searched from inception to 2022. The risk factors studied were those directly related to suicide history: history of suicide prior to the index attempt, and those that mediate the transition from suicidal ideation to attempt (alcohol or drug misuse, impulsivity, trauma, and non-suicidal self-injury). RESULTS: The initial search resulted in 11 905 articles. Of these, 34 articles were selected for this meta-analysis, jointly presenting 52 different effect sizes. The pooled effect size across the risk factors was significant (OR 2.16). Reattempt risk may be increased in presence of any of the following risk factors: previous history, active suicidal ideation, trauma, alcohol misuse, and drug misuse. However, impulsivity, and non-suicidal self-injury did not show a significant effect on reattempt. CONCLUSION: Most of the risk factors traditionally associated with suicide are also relevant when talking about suicide reattempts. Knowing the traits that define reattempters can help develop better preventive and intervention plans.

Exploring Pathways and Obstacles to Well-Being in Victims of Terrorism: A Qualitative Approach.

On March 11, 2004, Madrid suffered one of the worst terrorist attacks in the history of Spain, leaving more than 190 dead and 2,000 injured. For years, the psychological consequences of the attacks have been studied; however, its long-term effects on symptomatology and especially on well-being remains unknown. This study aims to explore, through a qualitative approach, pathways and obstacles to the well-being of those affected directly or indirectly by the attacks of March 11 in Madrid. Two focus groups were held, one for indirect victims and one for direct victims. Subsequently, a thematic analysis of the materials obtained was carried out. More than 10 years after the attacks, most of the participants reported great difficulty in achieving well-being. Acceptance and victims' associations seemed to act as key facilitators, while symptoms, political institutions and the media were the main obstacles. Direct and indirect victims presented similar data although aspects such as guilt and family relationships played a different role in their well-being.

Factors associated with having COVID-19 among unvaccinated pregnant and non-pregnant women in Metro Manila, Philippines: a multicentre longitudinal cohort study.

OBJECTIVE: To determine the potential risk factors associated with having COVID-19 among unvaccinated pregnant and non-pregnant women. DESIGN: A multicentre prospective cohort study among eligible women in Metro Manila, Philippines, from 2020 to 2022. SETTING: Five national and local hospital research sites altogether recruited and screened 500 consenting eligible individuals. PARTICIPANTS: Pregnant and non-pregnant participants meeting the eligibility criteria were admitted for a reverse-transcription PCR determination of SARS-CoV-2, pregnancy testing and ultrasound, and an interview with an administered questionnaire. EXPOSURES: Primary exposure was pregnancy; secondary exposures involve sociodemographic, lifestyle and obstetric-gynaecologic factors. OUTCOME MEASURE: Outcome being measured was COVID-19 status. RESULTS: The significant COVID-19 risk factors were: pregnancy (PR=1.184, 95% CI 1.096, 1.279), having a white-collar job (PR=1.123, 95% CI 1.02, 1.235), travelling abroad (PR=1.369, 95% CI 1.083, 1.173) and being infected by at least one vaccine-preventable disease (VPD) (PR=1.208, 95% CI 1.113, 1.310). Protective factors included having graduate-level education (PR=0.787, 95% CI 0.649, 0.954), immunisation against a VPD (PR=0.795, 95% CI 0.733, 0.862) and practising contraception (PR=0.889, 95% CI 0.824, 0.960). CONCLUSION: This study is the first in the country to determine the risks influencing COVID-19 infection among unvaccinated pregnant and non-pregnant women. Pregnancy is a significant risk for COVID-19 among women in Metro Manila. Educational attainment and positive health behaviours seem to confer protection. Occupations and activities that increase the frequency of interactions, as well as history of communicable diseases may predispose women to COVID-19. Further studies are needed to elucidate the development of the disease in pregnant women, including the maternal and neonatal effects of COVID-19 via potential vertical mechanisms of transmission.

Short mindfulness meditation training: does it really reduce perceived stress?

To study whether an 8-week mindfulness meditation training program truly reduces perceived stress without designing a stress reduction program. An experimental study was performed in which we studied the effects of 8 weeks of MM training on attention and awareness, as measured by the MAAS (mindfulness attention awareness scale) and perceived stress, as measured by the PSQ (perceived stress questionnaire), in 80 volunteers from the general public recruited by email from university centers. An increase in the individual's dispositional capacity to be attentive and aware of the experience of the present moment in everyday life was observed in the experimental group versus the control group; F (2, 156) = 14.30, p = .000, η2 partial = .155. Perceived stress showed no significant differences between groups in: social acceptance; F (2, 156) = 2.30, p = .103, overload; F (2, 156) = 2.32, p = .101, irritability, tension and fatigue; F (2, 156) = 2.27, p = .106, energy and joy; F (2, 156) = 2.79, p = .065. MM practice for 8 weeks of training increases the individual's dispositional capacity to be attentive and aware of the experience of the present moment in everyday life but may not reduce perceived stress.

¿Es el colesterol no-HDL un indicador de riesgo cardiovascular en las personas con diabetes mellitus? / Is non-HDL cholesterol a risk marker for cardiovascular atherosclerotic disease in diabetes mellitus?

La diabetes mellitus tipo 2 (DM2) es un factor de riesgo cardiovascular (FRCV) mayor. La DM confiere dos a cuatro veces más riesgo cardiovascular (RCV). El riesgo es aún más elevado en el paciente con DM2 que ha sufrido un infarto agudo de miocardio (IAM) o un accidente cerebrovascular (ACV). La dislipidemia de la DM2 consiste en triglicéridos elevados de ayuno, con mayor excursión posprandial, bajos niveles de HDLc, y alteraciones cuantitativas y cualitativas de LDLc y HDLc. El control glucémico apropiado en DM2 mejora en gran medida las alteraciones lipoproteicas. La terapia hipolipemiante es clave para reducir el RCV en la DM2. La reducción del RCV que se consigue con estatinas se basa en la reducción del LDLc y sus efectos pleiotrópicos. En pacientes que persisten con el perfil lipídico alterado, a pesar de dosis altas de estatinas, se debe considerar el agregado de otros agentes hipolipemiantes para reducir las lipoproteínas aterogénicas.

Type 2 diabetes (T2D) is a major cardiovascular risk factor (CVRF). Diabetes confers two to four times more cardiovascular risk (CVR). The risk is even higher in patients with T2D who have suffered an acute myocardial infarction (AMI) or cerebrovascular accident (CVA). The dyslipidemia of T2D consists of high fasting triglycerides, with greater postprandial excursion, low levels of HDLc and qualitative alterations of LDLc and HDLc. Appropriate glycemic control in T2D greatly improves lipoprotein abnormalities. Lipid-lowering therapy is key to reducing CVR in T2D. The CVR reduction achieved with statins is based on the reduction of LDLc. In patients who persist with an altered lipid profile despite highdose statins, the addition of other lipid-lowering agents to reduce atherogenic lipoproteins may be considered.

¿Cómo individualizar el tratamiento de la hipertensión arterial en las personas con diabetes mellitus tipo 2? / How to individualize arterial hypertension treatment in type 2 diabetes mellitus?

En las personas con diabetes mellitus (DM) e hipertensión arterial (HTA), los objetivos de presión arterial (PA) deben individualizarse considerando el riesgo cardiovascular, los potenciales efectos adversos de los fármacos antihipertensivos, y el costo y las preferencias de los pacientes. En personas con DM y elevado riesgo cardiovascular un objetivo de PA <130/80 mmHg sería apropiado si puede lograrse con seguridad. Si el riesgo cardiovascular es bajo, tratar la HTA con un objetivo <140/90 mmHg. En embarazadas con DM gestacional (DMG) e HTA preexistente, se sugiere un objetivo de PA de 110-135/85 mmHg con la finalidad de reducir el riesgo de eclampsia y minimizar el retraso de crecimiento intrauterino.

In patients with diabetes mellitus (DM) and hypertension (HP), blood pressure (BP) goals should be individualized considering cardiovascular risk, potential adverse effects of antihypertensive medications, cost, and patient preferences. In people with DM and high cardiovascular risk, a BP target <130/80 mmHg would be appropriate if it can be achieved safely. If cardiovascular risk is low, treat hypertension with a target <140/90 mmHg. In pregnant women with gestational diabetes mellitus (GDM) and preexisting hypertension, a BP target of 110-135/85 mmHg is suggested to reduce the risk of eclampsia and minimize intrauterine growth restriction.

Recomendaciones para la práctica clínica: hipoglucemia en personas con diabetes mellitus / Recommendations for clinical practice: hypoglycemia in people with diabetes mellitus

En la hipoglucemia secundaria, el tratamiento de la diabetes mellitus (DM) se define ante un valor de glucemia por debajo de 70 mg/dl, pudiendo manifestarse por síntomas autonómicos y neuroglucopénicos, con consecuencias a corto y largo plazo, como el deterioro de las funciones cognitivas y el aumento del riesgo cardiovascular, entre otras. La hipoglucemia en personas con DM1 es más frecuente que en aquellas con DM2. Los factores que incrementan su riesgo son: el retraso en la ingesta de comida, el alcohol, el ejercicio intenso, el ayuno y la neuropatía autonómica. Por otro lado, las hipoglucemias inadvertidas se asocian con un mayor riesgo de hipoglucemia grave. Los niños y adultos mayores son un grupo vulnerable a estos eventos que, en muchos casos, presentan síntomas difíciles de distinguir. A su vez, la hipoglucemia durante el embarazo se asocia con mayor riesgo de complicaciones. Otro grupo importante para detectar estos episodios son los pacientes hospitalizados a fin de disminuir la morbimortalidad asociada a los mismos. La calidad de vida está claramente afectada en los pacientes que sufren episodios de hipoglucemia, por lo cual resulta esencial instaurar estrategias de prevención como la educación, el monitoreo glucémico, realizar modificaciones en la dieta y el ejercicio, y ajustar la medicación. El tratamiento, en caso de no presentar pérdida de conciencia, será por vía oral, de lo contrario, se recurrirá a glucosa endovenosa o glucagón intramuscular.

Hypoglycemia due to treatment of diabetes mellitus (DM) is defined by a blood glucose value below 70 mg/dl, which can manifest itself by autonomic and neuroglycopenic symptoms, with short- and long-term consequences, such as impaired cognitive functions and increased cardiovascular risk, among others. Hypoglycemia in people with DM1 is more frequent than in those with DM2. Factors that increase its risk are: delayed food intake, alcohol, intense exercise, fasting and autonomic neuropathy. On the other hand, inadvertent hypoglycemia is associated with an increased risk of severe hypoglycemia. Children and older adults are a vulnerable group to these events that, in many cases, present symptoms that are difficult to distinguish. Hypoglycemia during pregnancy is associated with an increased risk of complications. Another important group to detect these episodes are hospitalized patients in order to reduce the morbimortality associated with them. Quality of life is clearly affected in patients who suffer episodes of hypoglycemia, so it is essential to implement prevention strategies such as education, glycemic monitoring, dietary and exercise modifications, and medication adjustment. Treatment, if there is no loss of consciousness, will be oral, otherwise, intravenous glucose or intramuscular glucagon will be used.

Maduración pulmonar fetal en diabetes mellitus pregestacional y complicaciones crónicas / Fetal lung maturation in pregestational diabetes mellitus and chronic complications

Las pacientes embarazadas con diabetes mellitus (DM) pregestacional y complicaciones micro y macroangiopáticas tienen mayor riesgo de empeoramiento de las mismas y de presentar otros trastornos asociados al embarazo. La progresión de la retinopatía diabética ocurre durante el embarazo y el posparto. La nefropatía se asocia con un mayor riesgo de preeclampsia, parto prematuro, restricción del crecimiento fetal y mortalidad perinatal. Cuando hay enfermedad de arterias coronarias o gastroparesia se observa un aumento de la morbilidad materna y fetal. El parto prematuro es una condición prevalente en pacientes con DM. La maduración pulmonar fetal con corticosteroides fue extensamente estudiada, con numerosas pruebas controladas, hasta convertirse en una de las más importantes terapias prenatales basadas en evidencias para reducir la mortalidad perinatal y el síndrome de dificultad respiratoria, la hemorragia intraventricular y la enterocolitis necrosante en los niños prematuros. Sin embargo, en dicha evidencia no se han incluido a embarazadas con DM, por lo cual no se conocen resultados perinatales en este grupo de pacientes.

Pregnant patients with pregestational diabetes mellitus (DM) and micro and macroangiopathic complications have a higher risk of their worsening and of presenting other pregnancyassociated disorders. The progression of diabetic retinopathy occurs during pregnancy and postpartum. Nephropathy is associated with an increased risk of preeclampsia, preterm delivery, fetal growth restriction, and perinatal mortality. When there is coronary artery disease or gastroparesis, an increase in maternal and fetal morbidity is observed Preterm delivery is a prevalent condition in diabetic patients. Corticosteroid fetal lung maturation has been extensively studied, with numerous controlled trials, to become one of the most important evidence-based prenatal therapies to reduce perinatal mortality and decrease respiratory distress syndrome, intraventricular hemorrhage, and necrotizing enterocolitis, in premature infants. Nevertheless, this evidence did not include patients with DM, for this reason perinatal results are not known in this group of patients.

¿Es el colesterol no-HDL un indicador de riesgo cardiovascular en las personas con diabetes mellitus? / Is non-HDL cholesterol a risk marker for cardiovascular atherosclerotic disease in diabetes mellitus?

Resumen La diabetes mellitus tipo 2 (DM2) es un factor de riesgo cardiovascular (FRCV) mayor. La DM confiere dos a cuatro veces más riesgo cardiovascular (RCV). El riesgo es aún más elevado en el paciente con DM2 que ha sufrido un infarto agudo de miocardio (IAM) o un accidente cerebrovascular (ACV). La dislipidemia de la DM2 consiste en triglicéridos elevados de ayuno, con mayor excursión posprandial, bajos niveles de HDLc, y alteraciones cuantitativas y cualitativas de LDLc y HDLc. El control glucémico apropiado en DM2 mejora en gran medida las alteraciones lipoproteicas. La terapia hipolipemiante es clave para reducir el RCV en la DM2. La reducción del RCV que se consigue con estatinas se basa en la reducción del LDLc y sus efectos pleiotrópicos. En pacientes que persisten con el perfil lipídico alterado, a pesar de dosis altas de estatinas, se debe considerar el agregado de otros agentes hipolipemiantes para reducir las lipoproteínas aterogénicas.

Abstract Type 2 diabetes (T2D) is a major cardiovascular risk factor (CVRF). Diabetes confers two to four times more cardiovascular risk (CVR). The risk is even higher in patients with T2D who have suffered an acute myocardial infarction (AMI) or cerebrovascular accident (CVA). The dyslipidemia of T2D consists of high fasting triglycerides, with greater postprandial excursion, low levels of HDLc and qualitative alterations of LDLc and HDLc. Appropriate glycemic control in T2D greatly improves lipoprotein abnormalities. Lipid-lowering therapy is key to reducing CVR in T2D. The CVR reduction achieved with statins is based on the reduction of LDLc. In patients who persist with an altered lipid profile despite highdose statins, the addition of other lipid-lowering agents to reduce atherogenic lipoproteins may be considered.

¿Cómo individualizar el tratamiento de la hipertensión arterial en las personas con diabetes mellitus tipo 2? / How to individualize arterial hypertension treatment in type 2 diabetes mellitus?

Resumen En las personas con diabetes mellitus (DM) e hipertensión arterial (HTA), los objetivos de presión arterial (PA) deben individualizarse considerando el riesgo cardiovascular, los potenciales efectos adversos de los fármacos antihipertensivos, y el costo y las preferencias de los pacientes. En personas con DM y elevado riesgo cardiovascular un objetivo de PA <130/80 mmHg sería apropiado si puede lograrse con seguridad. Si el riesgo cardiovascular es bajo, tartar la HTA con un objetivo <140/90 mmHg. En embarazadas con DM gestacional (DMG) e HTA preexistente, se sugiere un objetivo de PA de 110-135/85 mmHg con la finalidad de reducir el riesgo de eclampsia y minimizar el retraso de crecimiento intrauterino.

Abstract In patients with diabetes mellitus (DM) and hypertension (HP), blood pressure (BP) goals should be individualized considering cardiovascular risk, potential adverse effects of antihypertensive medications, cost, and patient preferences. In people with DM and high cardiovascular risk, a BP target <130/80 mmHg would be appropriate if it can be achieved safely. If cardiovascular risk is low, treat hypertension with a target <140/90 mmHg. In pregnant women with gestational diabetes mellitus (GDM) and preexisting hypertension, a BP target of 110-135/85 mmHg is suggested to reduce the risk of eclampsia and minimize intrauterine growth restriction.

Recomendaciones para la práctica clínica: hipoglucemia en personas con diabetes mellitus / Recommendations for clinical practice: hypoglycemia in people with diabetes mellitus

Resumen En la hipoglucemia secundaria, el tratamiento de la diabetes mellitus (DM) se define ante un valor de glucemia por debajo de 70 mg/dl, pudiendo manifestarse por síntomas autonómicos y neuroglucopénicos, con consecuencias a corto y largo plazo, como el deterioro de las funciones cognitivas y el aumento del riesgo cardiovascular, entre otras. La hipoglucemia en personas con DM1 es más frecuente que en aquellas con DM2. Los factores que incrementan su riesgo son: el retraso en la ingesta de comida, el alcohol, el ejercicio intenso, el ayuno y la neuropatía autonómica. Por otro lado, las hipoglucemias inadvertidas se asocian con un mayor riesgo de hipoglucemia grave. Los niños y adultos mayores son un grupo vulnerable a estos eventos que, en muchos casos, presentan síntomas difíciles de distinguir. A su vez, la hipoglucemia durante el embarazo se asocia con mayor riesgo de complicaciones. Otro grupo importante para detectar estos episodios son los pacientes hospitalizados a fin de disminuir la morbimortalidad asociada a los mismos. La calidad de vida está claramente afectada en los pacientes que sufren episodios de hipoglucemia, por lo cual resulta esencial instaurar estrategias de prevención como la educación, el monitoreo glucémico, realizar modificaciones en la dieta y el ejercicio, y ajustar la medicación. El tratamiento, en caso de no presentar pérdida de conciencia, será por vía oral, de lo contrario, se recurrirá a glucosa endovenosa o glucagón intramuscular.

Abstract Hypoglycemia due to treatment of diabetes mellitus (DM) is defined by a blood glucose value below 70 mg/dl, which can manifest itself by autonomic and neuroglycopenic symptoms, with short- and long-term consequences, such as impaired cognitive functions and increased cardiovascular risk, among others. Hypoglycemia in people with DM1 is more frequent than in those with DM2. Factors that increase its risk are: delayed food intake, alcohol, intense exercise, fasting and autonomic neuropathy. On the other hand, inadvertent hypoglycemia is associated with an increased risk of severe hypoglycemia. Children and older adults are a vulnerable group to these events that, in many cases, present symptoms that are difficult to distinguish. Hypoglycemia during pregnancy is associated with an increased risk of complications. Another important group to detect these episodes are hospitalized patients in order to reduce the morbimortality associated with them. Quality of life is clearly affected in patients who suffer episodes of hypoglycemia, so it is essential to implement prevention strategies such as education, glycemic monitoring, dietary and exercise modifications, and medication adjustment.

Maduración pulmonar fetal en diabetes mellitus pregestacional y complicaciones crónicas / Fetal lung maturation in pregestational diabetes mellitus and chronic complications

Resumen Las pacientes embarazadas con diabetes mellitus (DM) pregestacional y complicaciones micro y macroangiopáticas tienen mayor riesgo de empeoramiento de las mismas y de presentar otros trastornos asociados al embarazo. La progresión de la retinopatía diabética ocurre durante el embarazo y el posparto. La nefropatía se asocia con un mayor riesgo de preeclampsia, parto prematuro, restricción del crecimiento fetal y mortalidad perinatal. Cuando hay enfermedad de arterias coronarias o gastroparesia se observa un aumento de la morbilidad materna y fetal. El parto prematuro es una condición prevalente en pacientes con DM. La maduración pulmonar fetal con corticosteroides fue extensamente estudiada, con numerosas pruebas controladas, hasta convertirse en una de las más importantes terapias prenatales basadas en evidencias para reducir la mortalidad perinatal y el síndrome de dificultad respiratoria, la hemorragia intraventricular y la enterocolitis necrosante en los niños prematuros. Sin embargo, en dicha evidencia no se han incluido a embarazadas con DM, por lo cual no se conocen resultados perinatales en este grupo de pacientes.

Abstract Pregnant patients with pregestational diabetes mellitus (DM) and micro and macroangiopathic complications have a higher risk of their worsening and of presenting other pregnancyassociated disorders. The progression of diabetic retinopathy occurs during pregnancy and postpartum. Nephropathy is associated with an increased risk of preeclampsia, preterm delivery, fetal growth restriction, and perinatal mortality. When there is coronary artery disease or gastroparesis, an increase in maternal and fetal morbidity is observed Preterm delivery is a prevalent condition in diabetic patients. Corticosteroid fetal lung maturation has been extensively studied, with numerous controlled trials, to become one of the most important evidence-based prenatal therapies to reduce perinatal mortality and decrease respiratory distress syndrome, intraventricular hemorrhage, and necrotizing enterocolitis, in premature infants. Nevertheless, this evidence did not include patients with DM, for this reason perinatal results are not known in this group of patients.

A comparative study of climacteric symptoms among two populations of mid-aged women.

The purpose of this study was to compare climacteric symptoms associated with health-related quality of life (HRQOL) among women from Madrid (Spain) and Belgrade (Serbia). A cross-sectional study included 461 women from Madrid and 513 women from Belgrade aged 40-65 years. Climacteric symptoms and HRQOL were examined using the Menopause Rating Scale (MRS). There were no differences in MRS total score (p = 0.873), somato-vegetative and urogenital domain scores regarding country groups. However, women from Belgrade had poorer psychological domain score than women from Madrid (p = 0.027). Madrilenian women were more likely to have worse MRS score if they were coupled, had gynaecological complaints and longer duration of amenorrhoea. In Belgradian women, having higher level of education and using hormone-replacement therapy was associated with worse MRS score. Midlife women from Madrid and Belgrade had similar perception of intensity of urogenital and somato-vegetative climacteric symptoms. Belgradian women, however, perceived psychological symptoms as more severe.IMPACT STATEMENTWhat is already known on this subject? Social and cultural meanings of menopause vary across countries. It is quite delicate to strike a balance between two or more populations of women that can be compared, but also have specific features that are unique to their area. Similarities such as position of women in the society, access to education, contraception and safe induced abortion can facilitate this comparison.What do the results of this study add? Spanish and Serbian women rated similarly somato-vegetative and urogenital complaints, but Serbian women had worse psychological symptoms compared to Spanish women. Spanish women were more likely to endure climacteric symptoms until they withdraw spontaneously. Serbian women of higher education were more likely to use hormone-replacement therapy to manage climacteric complaints.What are the implications of these findings for clinical practice and/or further research? This study is the first to compare climacteric symptoms between women in Spain and Serbia. Despite the universality of menopause, culture seems to play a major role in differences in the perception of specific climacteric symptoms. Examination of quality of life in menopausal transition is an important measure of health status and should become a part of the routine health care in midlife.

Nerve injury induces transient locus coeruleus activation over time: role of the locus coeruleus-dorsal reticular nucleus pathway.

ABSTRACT: The transition from acute to chronic pain results in maladaptive brain remodeling, as characterized by sensorial hypersensitivity and the ensuing appearance of emotional disorders. Using the chronic constriction injury of the sciatic nerve as a model of neuropathic pain in male Sprague-Dawley rats, we identified time-dependent plasticity of locus coeruleus (LC) neurons related to the site of injury, ipsilateral (LCipsi) or contralateral (LCcontra) to the lesion, hypothesizing that the LC→dorsal reticular nucleus (DRt) pathway is involved in the pathological nociception associated with chronic pain. LCipsi inactivation with lidocaine increased cold allodynia 2 days after nerve injury but not later. However, similar blockade of LCcontra reduced cold allodynia 7 and 30 days after inducing neuropathy but not earlier. Furthermore, lidocaine blockade of the LCipsi or LCcontra reversed pain-induced depression 30 days after neuropathy. Long-term pain enhances phosphorylated cAMP-response element binding protein expression in the DRtcontra but not in the DRtipsi. Moreover, inactivation of the LCcontra→DRtcontra pathway using dual viral-mediated gene transfer of designer receptor exclusively activated by designer drugs produced consistent analgesia in evoked and spontaneous pain 30 days postinjury. This analgesia was similar to that produced by spinal activation of α2-adrenoreceptors. Furthermore, chemogenetic inactivation of the LCcontra→DRtcontra pathway induced depressive-like behaviour in naïve animals, but it did not modify long-term pain-induced depression. Overall, nerve damage activates the LCipsi, which temporally dampens the neuropathic phenotype. However, the ensuing activation of a LCcontra→DRtcontra facilitatory pain projection contributes to chronic pain, whereas global bilateral LC activation contributes to associated depressive-like phenotype.

Pain and depression comorbidity causes asymmetric plasticity in the locus coeruleus neurons.

There is strong comorbidity between chronic pain and depression, although the neural circuits and mechanisms underlying this association remain unclear. By combining immunohistochemistry, tracing studies and western blotting, with the use of different DREADDS (designer receptor exclusively activated by designer drugs) and behavioural approaches in a rat model of neuropathic pain (chronic constriction injury), we explore how this comorbidity arises. To this end, we evaluated the time-dependent plasticity of noradrenergic locus coeruleus neurons relative to the site of injury: ipsilateral (LCipsi) or contralateral (LCcontra) locus coeruleus at three different time points: short (2 days), mid (7 days) and long term (30-35 days from nerve injury). Nerve injury led to sensorial hypersensitivity from the onset of injury, whereas depressive-like behaviour was only evident following long-term pain. Global chemogenetic blockade of the LCipsi system alone increased short-term pain sensitivity while the blockade of the LCipsi or LCcontra relieved pain-induced depression. The asymmetric contribution of locus coeruleus modules was also evident as neuropathy develops. Hence, chemogenetic blockade of the LCipsi→spinal cord projection, increased pain-related behaviours in the short term. However, this lateralized circuit is not universal as the bilateral chemogenetic inactivation of the locus coeruleus-rostral anterior cingulate cortex pathway or the intra-rostral anterior cingulate cortex antagonism of alpha1- and alpha2-adrenoreceptors reversed long-term pain-induced depression. Furthermore, chemogenetic locus coeruleus to spinal cord activation, mainly through LCipsi, reduced sensorial hypersensitivity irrespective of the time post-injury. Our results indicate that asymmetric activation of specific locus coeruleus modules promotes early restorative analgesia, as well as late depressive-like behaviour in chronic pain and depression comorbidity.

Aging and neuroinflammation: Changes in immune cell responses, axon integrity, and motor function in a viral model of progressive multiple sclerosis.

Although aggravated multiple sclerosis (MS) disability has been reported in aged patients, the aging impact on immune cells remodeling within the CNS is not well understood. Here, we investigated the influence of aging on immune cells and the neuroinflammatory and neurodegenerative processes that occur in a well-established viral model of progressive MS. We found an anomalous presence of CD4+ T, CD8+ T, B cells, and cells of myeloid lineage in the CNS of old sham mice whereas a blunted cellular innate and adaptive immune response was observed in Theiler's murine encephalomyelitis virus (TMEV) infected old mice. Microglia and macrophages show opposite CNS viral responses regarding cell counts in the old mice. Furthermore, enhanced expression of Programmed Death-ligand 1 (PD-L1) was found in microglia isolated from old TMEV-infected mice and not in isolated CNS macrophages. Immunocytochemical staining of microglial cells confirms the above differences between young and old mice. Age-related axonal loss integrity in the mouse spinal cord was found in TMEV mice, but a less marked neurodegenerative process was present in old sham mice compared with young sham mice. TMEV and sham old mice also display alterations in innate and adaptive immunity in the spleen compared to the young mice. Our study supports the need of new or adapted pharmacological strategies for MS elderly patients.

Level of physical activity and barriers to exercise in adults with type 2 diabetes.

INTRODUCTION: Physical activity (PA) is an important element in type 2 diabetes mellitus (T2DM) management. The aims of this study were to assess the percentage of adults with T2DM who perform PA, according to the intensity level and to describe barriers to exercise and the association between metabolic control and other clinical variables. METHODS: Multicenter, observational, cross-sectional study. Data were collected through the International PA Questionnaire (IPAQ) and the PA Barrier Questionnaire. Adults (18-65 years old) with T2DM from 17 Argentine diabetes centers were included, from May to July 2018. RESULTS: A total of 270 men (54.9 ± 9.8 years) and 225 women (55.3 ± 9.6 years) were included. Duration of diabetes: 8.2 ± 6.3 years. The BMI in men was 32 ± 10.6 kg/m2, whereas that in women was 32.5 ± 7.2 kg/m2. The last two HbA1c values were 7.6 ± 1.7% and 7.5 ± 1.6. Results also showed that 12.7% had clinical heart disease, 13.7% had nephropathy, 20.8% had neuropathy, 6.1% had diabetic foot and 14.1% had retinopathy. The level of PA was low in 52.3% of the patients studied and moderate in 30.5%. The most frequent barriers were: "lack of will" (59.6%) and "lack of energy" (37.2%). The low level of PA was associated with age (OR: 1.05 per year of age; p < 0.001), HbA1c (OR: 1.16 per 1%; p < 0.05), BMI (OR: 1.06 per kg/m2; p < 0.001) and sex (OR: 1.69 for women; p < 0.01). CONCLUSIONS: PA in a cornerstone in management T2DM. Nevertheless, in this study, 52.3% of T2DM adults showed low level of PA. The main barriers reported were related to low personal motivation. These factors should be taken into account to implement programs to promote physical activity.

Women in a situation of homelessness and violence: a single-case study using the photo-elicitation technique.

BACKGROUND: Violence against women places them in a vulnerable position with regard to homelessness. Although sometimes invisible, women's homelessness is a complex reality shrouded in dramatic biographies that should be sensitively addressed to avoid revictimization. METHODS: With the aim of understanding the chaotic discourse of homeless women's experiences of violence, a qualitative single-case study was conducted using the photo-elicitation technique. Data were analyzed in accordance with grounded theory. RESULTS: The participant's discourse could be summarized in the following categories: "Living in a spiral of violence", "Confronting vulnerability and violence", "Being a strong woman", "New family networks", "Re-building mother-child relationships", and "Nurturing spiritual wellbeing". CONCLUSIONS: Supporting homelessness women requires an approach that focuses on the prevention of re-victimization and the consequences of violence in terms of physical and mental health. Shelters are spaces of care for recovery and represent referential elements for the re-construction of self.