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BACKGROUND The impact of biological sex and social determinants of health (gender) on the prevalence of cardiovascular (CV) risk factors such as diabetes mellitus (DM) may vary by culture and health systems. In this study, we aimed to elucidate how sex and gender influence access to care and CV outcomes of individuals with DM across different countries. METHODS AND RESULTS Data from the Canadian Community Health Survey (2015-16) (N=109,659, 53.7% Females, 8.4% DM) and the European Health Interview Survey (N=316,333, 51.3% Females, 7.3% DM), were analyzed. A composite measure of socio-cultural gender was constructed (score range: 0-1; higher score identifying characteristics traditionally ascribed to women). The relationship between the gender score, antihyperglycemic care, complications and hospitalization of individuals with DM was assessed with a logistic regression model. European countries were stratified based on their Gender Inequality Index (GII); which quantifies gender disparity and inequity amongst various countries in the world, from low-GII (GII =0.1635). Characteristics traditionally ascribe to women (i.e., higher gender score) included greater stress level, being widowed or divorced, larger household size, higher education, good sense of belonging to community, and lower income in Canadians; while being divorced or widowed, having greater household size, lower education and lower income were found in Europeans. Sex and gender significantly influenced the standard care of patients with diabetes including periodic glucose and HbA1C monitoring. Canadian diabetic females were more likely to check their HbA1c (OR: 1.29, 95%CI:1.03-1.6), while European counterparts were less likely to check their blood sugar (OR: 0.89, 95%CI:0.79-0.99). A higher gender score in both populations was associated with less frequent monitoring of HbA1C and blood glucose levels (Table 1). When stratifying by GII, DM patients in countries with medium and high GII were less likely to check their blood glucose levels compared to low GII countries (Table1). Additionally, higher gender scores independent of sex were associated with higher risk of heart disease, stroke and hospitalization in all countries albeit European countries with medium to high GII, conferred a higher risk of all complications and hospitalization rates (Table1). CONCLUSION Regardless of biological sex, diabetic individuals with characteristics typically ascribed to women and those living in countries with greater gender inequality, exhibited poorer antihyperglycemic care, greater risk of cardiovascular complications, and higher hospitalization rates. Country-specific gender related factors and gender disparity must be targeted for improving health status and access to care of patients with DM.

In the past, functional changes in the circuitry of the basal ganglia that occur in Parkinson's disease were primarily analyzed with electrophysiological and 2-deoxyglucose measurements. The increased activity of the subthalamic nucleus (STN) observed has been attributed to a reduction in inhibition mediated by the external segment of the globus pallidus (GPe), secondary to the loss of dopaminergic-neuron influence on D2-receptor-bearing striato-pallidal neurons. More recently, in situ hybridization studies of cytochrome oxidase subunit I have confirmed the overactivity of the STN in the parkinsonian state. In addition, this technique has provided evidence that the change in STN activity is owing not only to decreased inhibition from the GPe but to hyperactivity of excitatory inputs from the parafascicular nucleus of the thalamus and the pedunculopontine nucleus in the brainstem.

The origins and terminations of entorhinal cortical projections in the rat were analyzed in detail with retrograde and anterograde tracing techniques. Retrograde fluorescent tracers were injected in different portions of olfactory, medial frontal (infralimbic and prelimbic areas), lateral frontal (motor area), temporal (auditory), parietal (somatosensory), occipital (visual), cingulate, retrosplenial, insular, and perirhinal cortices. Anterograde tracer injections were placed in various parts of the rat entorhinal cortex to demonstrate the laminar and topographical distribution of the cortical projections of the entorhinal cortex. The retrograde experiments showed that each cortical area explored receives projections from a specific set of entorhinal neurons, limited in number and distribution. By far the most extensive entorhinal projection was directed to the perirhinal cortex. This projection, which arises from all layers, originates throughout the entorhinal cortex, although its major origin is from the more lateral and caudal parts of the entorhinal cortex. Projections to the medial frontal cortex and olfactory structures originate largely in layers II and III of much of the intermediate and medial portions of the entorhinal cortex, although a modest component arises from neurons in layer V of the more caudal parts of the entorhinal cortex. Neurons in layer V of an extremely laterally located strip of entorhinal cortex, positioned along the rhinal fissure, give rise to the projections to lateral frontal (motor), parietal (somatosensory), temporal (auditory), occipital (visual), anterior insular, and cingulate cortices. Neurons in layer V of the most caudal part of the entorhinal cortex originate projections to the retrosplenial cortex. The anterograde experiments confirmed these findings and showed that in general, the terminal fields of the entorhinal-cortical projections were densest in layers I, II, and III, although particularly in the more densely innervated areas, labeling in layer V was also present. Comparably distributed, but much weaker projections reach the contralateral hemisphere. Our results show that in the rat, hippocampal output can reach widespread portions of the neocortex through a relay in a very restricted part of the entorhinal cortex. However, most of the hippocampal-cortical connections will be mediated by way of entorhinal-perirhinal-cortical connections. We conclude that, in contrast to previous notions, the overall organization of the hippocampal-cortical connectivity in the rat is largely comparable to that in the monkey.

Four consecutive injections (s.c.) of apomorphine (Apo) were given to 5 parkinsonian monkeys after i.v. MPTP administration. The minimal effective dose (MED) of Apo was defined as that capable of reducing motor disability by 50% or more for a minimum period of 30 min. Repeated apomorphine injections were given with an interval of 30 min after the motor effect of the previous injection had worn off or with a separation of 3 h between injections. The doses used in different experiments were the MED (2.4 micrograms/kg), 4 MED and 8 MED. In every experiment the duration of motor benefit was longest with the first Apo injection. There was a decay in the duration of the response elicited by consecutive Apo injections when given 30 min after the previous effect had waned. This was significant for the MED and 4 MED (ANOVA, P0.01). When Apo boluses were given with an interval of 3 h there was a significant reduction in the duration of the response elicited by the MED, 4 MED and 8 MED of apomorphine. For the MED the reduction in the duration of the motor response was significantly greater for injections given with a 30-min interval than 3-h interval. These findings indicate that behavioral hyposensitivity to repeated Apo administration in parkinsonian monkeys occurs preferentially when near threshold doses are given with short intervals.

The relationship between homocysteine (Hc) and vascular diseases has been known for more than 30 years. Lately, Hc has also been related to cognitive and motor impairment. In Parkinson's disease (PD), chronic treatment with levodopa could induce higher levels of Hc, and thus may increase risk of cognitive impairment.To confirm that PD patients treated with levodopa have higher levels of Hc and to establish a relationship between Hc, folic acid and vitamin B12 levels. Also, we studied a possible link between those variables and cognitive function.58 patients with diagnosis of PD were included (45 under treatment with levodopa). Basal levels of Hc, vitamin B12 and folic acid were determined. Forty five patients underwent neuropsychological evaluation.Hc levels were significantly higher in patients taking levodopa and were not related to levodopa dosage or treatment duration. There was a negative correlation between Hc levels and those of vitamin B12 and folic acid in men but we found no such correlation in women. Entacapone was not found to reduce Hc levels. Hc levels were significantly higher in patients with cognitive impairment (9 out of 45 patients).Our study confirms presence of high levels of Hc in PD patients under treatment with levodopa, more evident in patients with cognitive impairment.

The body temperature and locomotor activity rhythms of seven 1-Methyl, 4-phenyl, 1,2,3,6-tetrahydropyridine (MPTP)-treated cynomolgous monkeys were registered over a week on two separate occasions over an interval of 2 months. Motor disability was absent in two animals and present in five: it was mild in one, moderate in two and severe in two. Both temperature and motor activity were recorded every minute using a radio telemetry system. Analysis of circadian rhythms revealed less robustness of the 24-hour circadian components of body temperature and locomotor activity with increasing motor impairment, and a fragmentation of the body temperature rhythm into 8 hour-period components. Both total activity and daytime activity correlated inversely with the degree of motor impairment. On the contrary, the monkeys did not show differences in night time activity. The proportions of variance accounted for by the body temperature and locomotor activity of 24 h + 12 h + 8 h components were correlated. Also, the average levels at which the circadian rhythm varies between body temperature and locomotor activity were correlated. The results were almost identical in the two 1-week recording sessions. The present study confirms individual differences in the vulnerability to MPTP of the nigrostriatal system of monkeys, suggesting that if a cumulative dose does not provoke stable motor alterations, this cumulative dose will not produce circadian body temperature and locomotor activity rhythm alterations either. Similarly, if a dose is able to produce motor impairment, this dose will also be able to produce circadian rhythm alterations.

Introduccion. La relacion entre homocisteina (Hc) y enfermedades vasculares se conoce desde hace mas de 30 anos. En los ultimos anos se ha relacionado tambien con deterioro cognitivo y motor. En la enfermedad de Parkinson (EP), el tratamiento cronico con levodopa puede inducir un incremento en los niveles de Hc, implicando un riesgo anadido para el deterioro cognitivo. Objetivos. Confirmar la elevacion de los niveles de Hc en pacientes con EP tratados con levodopa, su relacion con los niveles de vitamina B12 y folato, y si podia existir una relacion entre dichas variables y la funcion cognitiva. Pacientes y metodos. Se incluyeron 58 pacientes diagnosticados de EP (45 en tratamiento con levodopa), se determinaron los niveles basales de Hc, vitamina B12 y folato, y se realizo una evaluacion neuropsicologica en 45 de los pacientes. Resultados. El nivel de Hc estaba significativamente mas elevado en los pacientes en tratamiento con levodopa, sin relacion con la dosis ni el tiempo en tratamiento. Existia una correlacion negativa entre los valores de Hc y vitamina B12 y folato en los hombres, que no se observo en las mujeres. Tomar entacapona no redujo los niveles de Hc. El nivel de Hc estaba significativamente mas elevado en los pacientes con deterioro cognitivo (9 de los 45 evaluados). Conclusiones. Nuestro estudio confirma la elevacion de los niveles de Hc en pacientes con EP en tratamiento con levodopa, y de forma mas evidente en los pacientes con deterioro cognitivo.

MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine) was incidentally administered to pregnant marmosets during the whole gestational period, except for the last 15 days before term. The infant monkeys were killed 5 months after birth, and dopamine and its metabolites were measured in the striatum and the nucleus accumbens. Prenatal exposure to MPTP produced a marked dopamine depletion in these brain regions of the offspring, showing that MPTP is able to cross the placental barrier in primates.