Functional correlation between cerebellum and basal ganglia: A parkinsonism model.

INTRODUCTION: The cerebellar response has been studied for years with different models of alteration of other brain structures to understand its complex functioning and its relationship with the rest of the body. Studies in patients with Parkinson's disease (PD) showed that the cerebellar function is modified by deficit of the basal ganglia; which supports the hypothesis that both structures are related anatomically and functionally. METHODS: In our study, the ventrolateral striatum (VLS) of the basal ganglia was altered by an electrolytic lesion, in order to produce a similar jaw frequency of jaw tremor movements presented in parkinsonism, thereafter we analyzed the effect of the lesion on the expression of multiunit activity (MUA) of the cerebellum. RESULTS: We found cerebellar activation during mandibular movements and increment during oral jaw tremor movements. In addition, the amplitude of baseline MUA registered in animals with alteration of the VLS decreased with respect to the intact group. CONCLUSIONS: Accordingly, we conclude that cerebellar changes in MUA may be due to a decrease in the cerebellar inflectional or as a possible compensatory function between cerebellum and basal ganglia.

The synthetic molecule stauprimide impairs cell growth and migration in triple-negative breast cancer.

Stauprimide, a semi-synthetic derivative of staurosporine, is known mainly for its potent differentiation-enhancing properties in embryonic stem cells. Here, we studied the effects of stauprimide in cell growth and migration of triple-negative breast cancer cells in vitro, evaluating its potential antitumoral activity in an orthotopic mouse model of breast cancer in vivo. Our results from survival curves, EdU incorporation, cell cycle analysis and annexin-V detection in MDA-MB-231 cells indicated that stauprimide inhibited cell proliferation, arresting cell cycle in G2/M without induction of apoptosis. A decrease in the migratory capability of MDA-MB-231 was also assessed in response to stauprimide. In this work we pointed to a mechanism of action of stauprimide involving the modulation of ERK1/2, Akt and p38 MAPK signalling pathways, and the downregulation of MYC in MDA-MB-231 cells. In addition, orthotopic MDA-MB-231 xenograft and 4T1 syngeneic models suggested an effect of stauprimide in vivo, increasing the necrotic core of tumors and reducing metastasis in lung and liver of mice. Together, our results point to the promising role of stauprimide as a putative therapeutic agent in triple-negative breast cancer.

Severe smallness as predictor of adverse perinatal outcome in suspected late small-for-gestational-age fetuses: systematic review and meta-analysis.

OBJECTIVE: To investigate the performance of severe smallness in the prediction of adverse perinatal outcome among fetuses with suspected late-onset small-for-gestational age (SGA). METHODS: A systematic search was performed to identify relevant studies in PubMed, Web of Science and Scopus. Late-onset SGA was defined as estimated fetal weight (EFW) or abdominal circumference (AC) < 10th percentile diagnosed at or after 32 weeks' gestation, while severe SGA was defined as EFW or AC < 3rd percentile or < 2 SD. Random-effects modeling was used to generate hierarchical summary receiver-operating-characteristics (HSROC) curves. The performance of severe SGA (as a presumptive diagnosis) in predicting adverse perinatal outcome among singleton pregnancies with suspected late-onset SGA was expressed as area under the HSROC curve (AUC), sensitivity, specificity and positive/negative likelihood ratios. The association between suspected severe SGA and adverse perinatal outcome was also assessed by random-effects modeling using the Mantel-Haenszel method and presented as odds ratio (OR). The non-exposed group was defined as non-severe SGA (EFW ≥ 3rd centile). RESULTS: Twelve cohort studies were included in this systematic review and meta-analysis. The studies included a total of 3639 fetuses with suspected late-onset SGA, of which 1246 had suspected severe SGA. Significant associations were found between suspected severe SGA and composite adverse perinatal outcome (OR, 1.97 (95% CI, 1.33-2.92)), neonatal intensive care unit admission (OR, 2.87 (95% CI, 1.84-4.47)) and perinatal death (OR, 4.26 (95% CI, 1.07-16.93)). However, summary ROC curves showed limited performance of suspected severe SGA in predicting perinatal outcomes, with AUCs of 60.9%, 66.9%, 53.6%, 57.2%, 54.6% and 64.9% for composite adverse perinatal outcome, neonatal intensive care unit admission, neonatal acidosis, Cesarean section for intrapartum fetal compromise, low Apgar score and perinatal death, respectively. CONCLUSION: Although suspected severe SGA was associated with a higher risk of perinatal complications, it performed poorly as a standalone parameter in predicting adverse perinatal outcome. © 2022 International Society of Ultrasound in Obstetrics and Gynecology.

Are Oral Mucosal Changes a Sign of COVID-19? A Cross-Sectional Study at a Field Hospital. / ¿Son las alteraciones en la mucosa oral un signo de COVID-19? Estudio transversal en un Hospital de Campaña.

BACKGROUND: Coronavirus disease 19 (COVID-19) has many manifestations, including respiratory, thrombotic, neurologic, digestive, and cutaneous ones. Cutaneous manifestations have been classified into 5 clinical patterns: acro-ischemic (pseudo-chilblain), vesicular, urticarial, maculopapular, and livedoid. Oral manifestations have also been reported, but much less frequently. PATIENTS AND METHODS: We performed a cross-sectional study in which we examined the oral mucosa of 666 patients with COVID-19 at the IFEMA field hospital in Madrid in April 2020. RESULTS: Seventy-eight patients (11.7%) had changes involving the oral mucosa. The most common were transient anterior U-shaped lingual papillitis (11.5%) accompanied or not by tongue swelling (6.6%), aphthous stomatitis (6.9%), a burning sensation in the mouth (5.3%), mucositis (3.9%), glossitis with patchy depapillation (3.9%), white tongue (1.6%), and enanthema (0.5%). Most of the patients also reported taste disturbances. CONCLUSION: COVID-19 also manifests in the oral cavity. The most common manifestations are transient U-shaped lingual papillitis, glossitis with patchy depapillation, and burning mouth syndrome. Mucositis with or without aphthous ulcers or enanthema may also be observed. Any these findings may be key clues to a diagnosis of COVID-19.

Doppler changes in umbilical artery, middle cerebral artery, cerebroplacental ratio and ductus venosus during open fetal microneurosurgery for intrauterine open spina bifida repair.

OBJECTIVE: To describe changes in fetal Doppler parameters during a novel technique for open fetal microneurosurgery for open spina bifida (OSB) repair. METHODS: This was a prospective study of 44 fetuses undergoing open fetal surgery for OSB repair using a novel microneurosurgery approach that is characterized by a mini-hysterotomy (diameter of 15 mm), minimal fetal manipulation and maintenance of a constant normal amniotic fluid volume throughout the procedure. Doppler velocimetry of the umbilical artery (UA), fetal middle cerebral artery (MCA) and ductus venosus (DV) was performed before the start of surgery and at prespecified timepoints during fetal surgery. UA pulsatility index (PI) > 95th percentile, DV-PI > 95th percentile, MCA-PI < 5th percentile and cerebroplacental ratio (CPR) < 5th percentile were considered abnormal. RESULTS: Median gestational age at fetal surgery was 25.2 weeks (range, 22.9-27.9 weeks). Doppler recordings were successfully obtained in all cases during all timepoints throughout the surgery. As compared with Doppler values before surgery, there was a significant increase in the proportion of fetuses with MCA-PI < 5th percentile (63.6% vs 13.6%; P < 0.001), CPR < 5th percentile (65.9% vs 15.9%; P < 0.001) and DV-PI > 95th percentile (22.7% vs 0%; P = 0.01) and a non-significant increase in the proportion of fetuses with UA-PI > 95th percentile (11.4% vs 0%; P = 0.12) during fetal surgery. None of the fetuses showed absent or reversed end-diastolic velocity in the UA or absent or reversed DV a-wave at any stage during OSB repair. All abnormal Doppler parameters returned to normal after surgery. CONCLUSIONS: During open fetal surgery for OSB repair, a small hysterotomy, reduced fetal manipulation and maintenance of a normal amniotic fluid volume seem to prevent severe fetal Doppler abnormalities. The mild Doppler changes observed during fetal surgery could be a manifestation of fetal adaptation to the stress of fetal surgery. © 2020 International Society of Ultrasound in Obstetrics and Gynecology.

[The next psychoactive drugs: From imipramine to ketamine]. / Psychotropes du futur : de l'imipramine à la kétamine.

Since the 1950s, the therapeutic arsenal against depression has grown considerably. From the discovery of monoamine oxidase inhibitors (MAOI) to the antidepressant effect of ketamine, these pharmacological breakthroughs made the history of psychiatry. They also guided the research about the pathophysiology of depression, one of the most devasting diseases, which affects between 10 and 20 % of general population. In this article, we offer a short historical review of the various therapeutic options developed over the past century and the consequences of these innovations. We then review the most recent one, ketamine (and its enantiomer S, esketamine). Ketamine's effects are spectacular both in terms of their very short onset time, and because they are observed even in treatment-resistant depression. Just as MAOIs and tricyclic antidepressants allowed the "monoaminergic hypothesis of depression" to emerge, to unravel the mechanisms of ketamine's antidepressant effects should allow the understanding of the role of glutamatergic system, or that of neuro-inflammation, in the neurobiology of depression. Ketamine might also help to refine our understanding of the cognitive pathophysiology of depression, or even to deeply transform the clinical representations about what depression is.

Olfactory conditioned same-sex partner preference in female rats: Role of ovarian hormones.

The dopamine D2-type receptor agonist quinpirole (QNP) facilitates the development of conditioned same-sex partner preference in males during cohabitation, but not in ovariectomized (OVX) females, primed with estradiol benzoate (EB) and progesterone (P). Herein we tested the effects of QNP on OVX, EB-only primed females. Females received a systemic injection (every four days) of either saline (Saline-conditioned) or QNP (QNP-conditioned) and then cohabited for 24h with lemon-scented stimulus females (CS+), during three trials. In test 1 (female-female) preference was QNP-free, and females chose between the CS+ female and a novel female. In test 2 (male-female) they chose between the CS+ female and a sexually experienced male. In test 1 Saline-conditioned females displayed more hops & darts towards the novel female, but QNP-conditioned females displayed more sexual solicitations towards the CS+ female. In test 2 Saline-conditioned females displayed a clear preference for the male, whereas QNP-conditioned females displayed what we considered a bisexual preference. We discuss the effect of dopamine and ovarian hormones on the development of olfactory conditioned same-sex preference in females.

Vulnerability of mixotrophic algae to nutrient pulses and UVR in an oligotrophic Southern and Northern Hemisphere lake.

Nutrient inputs and ultraviolet radiation (UVR) are global factors affecting the structure and functioning of aquatic ecosystems, particularly clear-water ecosystems. We performed experiments in two model lakes highly exposed to UVR fluxes in order to test the effect that future increases in mineral nutrients transported by dust aerosol might exert on primary producers depending on the likelihood of atmospheric inputs. Lake La Caldera (Northern Hemisphere) has been receiving recurrent dust inputs from the Sahara Desert while lake Los Cántaros (Southern Hemisphere) has been less affected by dust aerosol. UVR × Nutrient synergistically stimulated primary production (PP), chlorophyll a (Chl a), with a smaller increase in phytoplanktonic biomass in La Caldera, but not in Los Cántaros, where nutrient addition unmasked the UVR inhibitory effect on phytoplankton. The proportional decrease of mixotrophic nanoflagellates (MNFs) after the nutrient pulse (in Los Cántaros) and the long-term decline of MNFs in La Caldera associated with the increase in aerosol-dust intrusions from the Sahara during the last 40 years suggest that a future scenario of intensified aerosol events from desert and desertified areas would not only reduce functional diversity with the decline of MNFs, but would ultimately alter the C flux towards the grazing chain in oligotrophic ecosystems.

Evidencias del uso de la musicoterapia y la memoria del adulto mayor / Evidence of the use of music theraphy and memory of the elderly

Con el avance del envejecimiento se observa undecline parcial de las funciones cognitivas, aunqueno es un hecho generalizado, un porcentajerelativamente alto de personas experimentan cambioscognitivos, principalmente problemas de memoria.En los últimos años, la musicoterapia ha ganado unmayor reconocimiento dentro de las intervencionesno farmacológicas. En el campo de la geriatría lamusicoterapia es capaz de modular factores dela cognición implicando diversas funciones cognitivas.El objetivo de la presente revisión es examinar lasevidencias del uso de la musicoterapia para elfortalecimiento de la memoria en la población adultamayor. Como resultado de la presente revisión seencontró que la musicoterapia ha sido utilizada envarias ocasiones como terapéutica complementariaen adultos mayores, sobre todo en aquellos quepresentan algún tipo de alteración cognitiva relevante,los efectos reportados sugieren mejoría en la funcióncognitiva de la memoria. Sin embargo, hace faltaevidencia de esta intervención en adultos mayoressanos cognitivamente

Pericranial nerve blockade as a preventive treatment for migraine: Experience in 60 patients. / Bloqueo anestésico de nervios pericraneales como tratamiento preventivo de migraña: experiencia en una serie de 60 pacientes.

INTRODUCTION: Anaesthetic blockade of pericranial nerves is frequently used to treat headache disorders. There is no evidence on indication of this treatment for migraine. We aim to evaluate its effectiveness as a preventive treatment for migraine using specific indication criteria. METHODS: Between January 2009 and May 2013 we offered pericranial nerve blockade to migraine patients with a history of preventive drug intolerance or failure. We selected patients with tenderness to palpation of at least one greater occipital nerve (GON) or supraorbital nerve (SON). Responses at 3 months were categorised as complete response (no pain), partial response (reduction of at least 50% in severity or frequency of headache episodes), or no response. RESULTS: Anaesthetic blockade was performed in 60 patients (52 females, 8 males; mean age 40.6 ± 12.4 years, range 19-76). The most common procedure was blockade of GON and SON on both sides. Complete response lasting at least 2 weeks was recorded in 23 patients (38.3%), with partial response in 24 patients (40%), and no response in 13 (21.7%). In the group presenting complete response, age and length of history of migraine were significantly lower. No severe side effects were detected. Response time ranged from 2 weeks to 3 months. CONCLUSIONS: Pericranial nerves blockade using tenderness to palpation as an inclusion criterion is safe and potentially effective as prophylactic treatment for migraine. The best responses in our series were observed in younger patients with shorter histories of migraine.

Quantitative nanoscale electrostatics of viruses.

Electrostatics is one of the fundamental driving forces of the interaction between biomolecules in solution. In particular, the recognition events between viruses and host cells are dominated by both specific and non-specific interactions and the electric charge of viral particles determines the electrostatic force component of the latter. Here we probe the charge of individual viruses in liquid milieu by measuring the electrostatic force between a viral particle and the Atomic Force Microscope tip. The force spectroscopy data of co-adsorbed ϕ29 bacteriophage proheads and mature virions, adenovirus and minute virus of mice capsids is utilized for obtaining the corresponding density of charge for each virus. The systematic differences of the density of charge between the viral particles are consistent with the theoretical predictions obtained from X-ray structural data. Our results show that the density of charge is a distinguishing characteristic of each virus, depending crucially on the nature of the viral capsid and the presence/absence of the genetic material.

Efficacy of lycopene-enriched virgin olive oil for treating burning mouth syndrome: a double-blind randomised.

Burning mouth syndrome (BMS) is an intensive chronic oral mucosal pain condition of unknown aetiology. The aim of this study was to evaluate the clinical performance of lycopene-enriched virgin olive oil used to treat the condition, comparing this with a placebo. This study took the form of a double-bind, randomised clinical trial. A total of 60 patients with BMS were randomly divided into two groups: Group I (n = 30) treated with lycopene-enriched virgin olive oil (300 ppm) (1.5 mL three times a day) and Group II (n=treated with a placebo (1.5 mL three times a day). Evaluations were made before and after 12 weeks of product/placebo application. Symptoms were evaluated by VAS, whilst patient psychological profiles were assessed using the HAD scale and patient quality of life using the Oral Health Impact Profile-14 (OHIP-14) and the Medical Outcome Short Form Health Survey questionnaire (SF36). Fifty patients completed the 12-week treatment (26 in Group I and 24 in Group II). Visual analogue scale pain values improved in both groups but without statistically significant differences between the groups (P = 0.57). Oral quality of life also improved. Four patients in Group I (treatment) left the study and six left Group II (placebo). No patients experienced any adverse effects resulting from treatment at any of the evaluation times. Patients were lost from the sample due to lack of compliance. It was found that the lipid profile did not change during the 3-month study period as a result of the application of lycopene-enriched olive oil (Group I); nor did any change occur in the placebo group (Group II). In this way, the placebo effect was seen to be strong. The topical lycopene-enriched virgin olive oil is a very safe and an effective similar way that the placebo for treating patients with BMS. However, future studies are required to establish the treatment for patients with chronic and painful syndrome.

Prospective registry of symptomatic severe aortic stenosis in octogenarians: a need for intervention.

OBJECTIVE: To study the factors associated with choice of therapy and prognosis in octogenarians with severe symptomatic aortic stenosis (AS). STUDY DESIGN: Prospective, observational, multicenter registry. Centralized follow-up included survival status and, if possible, mode of death and Katz index. SETTING: Transnational registry in Spain. SUBJECTS: We included 928 patients aged ≥80 years with severe symptomatic AS. INTERVENTIONS: Aortic-valve replacement (AVR), transcatheter aortic-valve implantation (TAVI) or conservative therapy. MAIN OUTCOME MEASURES: All-cause death. RESULTS: Mean age was 84.2 ± 3.5 years, and only 49.0% were independent (Katz index A). The most frequent planned management was conservative therapy in 423 (46%) patients, followed by TAVI in 261 (28%) and AVR in 244 (26%). The main reason against recommending AVR in 684 patients was high surgical risk [322 (47.1%)], other medical motives [193 (28.2%)], patient refusal [134 (19.6%)] and family refusal in the case of incompetent patients [35 (5.1%)]. The mean time from treatment decision to AVR was 4.8 ± 4.6 months and to TAVI 2.1 ± 3.2 months, P < 0.001. During follow-up (11.2-38.9 months), 357 patients (38.5%) died. Survival rates at 6, 12, 18 and 24 months were 81.8%, 72.6%, 64.1% and 57.3%, respectively. Planned intervention, adjusted for multiple propensity score, was associated with lower mortality when compared with planned conservative treatment: TAVI Hazard ratio (HR) 0.68 (95% confidence interval [CI] 0.49-0.93; P = 0.016) and AVR HR 0.56 (95% CI 0.39-0.8; P = 0.002). CONCLUSION: Octogenarians with symptomatic severe AS are frequently managed conservatively. Planned conservative management is associated with a poor prognosis.

Medical education in Ecuador.

BACKGROUND: Ecuador, the smallest of the Andean countries, is located in the northwest portion of South America. The nation's 14.5 million people have a tremendous need for high quality primary care. AIMS: To describe the profound advances as well as the persistent needs in medical education in Ecuador that have occurred with globalization and with the modernization of the country. METHODS: Through an extensive search of the literature; medical school data; reports from the Ecuador Ministry of Public Health and Ministry of Education; and information from the National Secretary of Higher Education, Science, and Innovation (SENESCYT), the medical education system in Ecuador has been thoroughly examined. RESULTS: The National System of Higher Education in Ecuador has experienced significant growth over the last 20 years. As of 2009 the system boasts 19 medical schools, all of which offer the required education needed to obtain the title of Physician, but only 12 of which offer postgraduate clinical training. Of these 19 universities, nine are public, five are private and self-financed, and five are private and co-financed. Post-graduate options for medical students include: (1) Clinical specialization, (2) Higher diploma, (3) Course specialization, (4) Master's degree, and (5) PhD degree. CONCLUSION: The rapid growth of Ecuador's system of medical education has led to inevitable gaps that threaten its ability to sustain itself. Chief among these is the lack of well-trained faculty to supply its medical schools. To ensure an adequate supply of faculty exists, the creation of sufficient postgraduate, sub-specialization, and PhD training positions must be created and maintained.