Interhemispheric CA1 projections support spatial cognition and are affected in a mouse model of the 22q11.2 deletion syndrome.

Untangling the hippocampus connectivity is critical for understanding the mechanisms supporting learning and memory. However, the function of interhemispheric connections between hippocampal formations is still poorly understood. So far, two major hippocampal commissural projections have been characterized in rodents. Mossy cells from the hilus of the dentate gyrus project to the inner molecular layer of the contralateral dentate gyrus and CA3 and CA2 pyramidal neuron axonal collaterals to contralateral CA3, CA2 and CA1. In contrary, little is known about commissural projection from the CA1 region. Here, we show that CA1 pyramidal neurons from the dorsal hippocampus project to contralateral dorsal CA1 as well as dorsal subiculum. We further demonstrate that the interhemispheric projection from CA1 to dorsal subiculum supports spatial memory and spatial working memory in WT mice, two cognitive functions impaired in male mice from the Df16(A) +/- model of 22q11.2 deletion syndrome (22q11.2DS) associated with schizophrenia. Investigation of the CA1 interhemispheric projections in Df16(A) +/- mice revealed that these projections are disrupted with male mutants showing stronger anatomical defects compared to females. Overall, our results characterize a novel interhemispheric projection from dCA1 to dorsal subiculum and suggest that dysregulation of this projection may contribute to the cognitive deficits associated with the 22q11.2DS.

A perfect recipe for a corticospinal neuron.

A tailored cocktail of genes can reprogram a subset of progenitors to no longer produce glial cells and instead develop into neurons involved in motor control.

Somatic RAP1B gain-of-function variant underlies isolated thrombocytopenia and immunodeficiency.

The ubiquitously expressed small GTPase Ras-related protein 1B (RAP1B) acts as a molecular switch that regulates cell signaling, cytoskeletal remodeling, and cell trafficking and activates integrins in platelets and lymphocytes. The residue G12 in the P-loop is required for the RAP1B-GTPase conformational switch. Heterozygous germline RAP1B variants have been described in patients with syndromic thrombocytopenia. However, the causality and pathophysiological impact remained unexplored. We report a boy with neonatal thrombocytopenia, combined immunodeficiency, neutropenia, and monocytopenia caused by a heterozygous de novo single nucleotide substitution, c.35G>A (p.G12E) in RAP1B. We demonstrate that G12E and the previously described G12V and G60R were gain-of-function variants that increased RAP1B activation, talin recruitment, and integrin activation, thereby modifying late responses such as platelet activation, T cell proliferation, and migration. We show that in our patient, G12E was a somatic variant whose allele frequency decreased over time in the peripheral immune compartment, but remained stable in bone marrow cells, suggesting a differential effect in distinct cell populations. Allogeneic hematopoietic stem cell transplantation fully restored the patient's hemato-immunological phenotype. Our findings define monoallelic RAP1B gain-of-function variants as a cause for constitutive immunodeficiency and thrombocytopenia. The phenotypic spectrum ranged from isolated hematological manifestations in our patient with somatic mosaicism to complex syndromic features in patients with reported germline RAP1B variants.

Gender differences and the association between the phenomenological characteristics of autobiographical memories and psychopathic traits in a university student sample.

The study aimed to analyse the relationship between the dimensions of the triarchic model of psychopathy (meanness, boldness and disinhibition) and the phenomenological characteristics of Autobiographical Memory (AM) in a sample of university students, examining potential gender differences. Participants (N = 260; 55.4% women; aged 18-25) performed an AM task, followed by the Autobiographical Memory Characteristics Questionnaire and the Triarchic Psychopathy Measure. We found gender differences, with men scoring higher than women in meanness and disinhibition as well as in precision, accessibility, sharing and narrative coherence of AM. Correlations showed that boldness was negatively related to the valence and emotional intensity of the memory. Meanness was positively associated with precision, sensory details, accessibility, sharing, narrative coherence, distancing and preoccupation with emotions and negatively with recollection. Disinhibition was positively related to precision, sensory details and accessibility and negatively to intensity, distancing and preoccupation with emotions. Our results suggest that psychopathic traits could predict certain characteristics of AM, highlighting the predictive value of meanness, especially regarding memory quality characteristics (e.g., precision), as well as disinhibition, concerning the emotional content (e.g., preoccupation with emotions). Our results contribute to understanding psychopathy through an autobiographical perspective, showing how psychopathic traits may shape how people remember personal events.

Actigraphy-assessed sleep duration and quality and executive function in a sample of typically developing preschoolers.

Sleep is essential for cognitive development and brain maturation during early childhood. Studies focused on preschool populations using objective measures of sleep are still scarce. The objective of this study was to examine the associations between objective measures of sleep duration and quality with executive functioning in a 133 non-clinical sample of Spanish participants (Mage = 60.33 months, SD = 9.04; ages 41-77 months; 51.1% girls). Sleep was assessed for five weeknights using actigraphy; Shape School task was applied to assess inhibition and cognitive flexibility; and Word Span task was used to assess working memory. The results revealed that relation between sleep and executive functioning was significant for inhibition and working memory. Preschoolers with higher sleep efficiency showed better results in executive functioning tasks after controlling for the effect of age. Additionally, age and sleep duration and quality variables were predictive of inhibition, working memory, and cognitive flexibility. These results suggest that the different dimensions of sleep could play an important role in the development of executive functions during preschool age. Therefore, improving sleep could lead to an improvement in children's executive functioning in both clinical and educational contexts.

Early cortical GABAergic interneurons determine the projection patterns of L4 excitatory neurons.

During cerebral cortex development, excitatory pyramidal neurons (PNs) establish specific projection patterns while receiving inputs from GABAergic inhibitory interneurons (INs). Whether these inhibitory inputs can shape PNs' projection patterns is, however, unknown. While layer 4 (L4) PNs of the primary somatosensory (S1) cortex are all born as long-range callosal projection neurons (CPNs), most of them acquire local connectivity upon activity-dependent elimination of their interhemispheric axons during postnatal development. Here, we demonstrate that precise developmental regulation of inhibition is key for the retraction of S1L4 PNs' callosal projections. Ablation of somatostatin INs leads to premature inhibition from parvalbumin INs onto S1L4 PNs and prevents them from acquiring their barrel-restricted local connectivity pattern. As a result, adult S1L4 PNs retain interhemispheric projections responding to tactile stimuli, and the mice lose whisker-based texture discrimination. Overall, we show that temporally ordered IN activity during development is key to shaping local ipsilateral S1L4 PNs' projection pattern, which is required for fine somatosensory processing.

Evaluation of the association between excessive screen use, sleep patterns and behavioral and cognitive aspects in preschool population. A systematic review.

In this review, we analyzed the possible relationship between the excessive use of screens and sleep patterns, and how this may affect certain behavioral and cognitive factors in preschool children. The selection, extraction and synthesis of the data were conducted according to PRISMA guidelines. The search was carried out in the electronic databases Medline (PubMed), PsycINFO (American Psychological Association), Scopus and Web of Science (WOS). Of the 597 articles initially identified, 13 met the inclusion criteria. The risk of bias of the articles selected was evaluated using a specific scale created for this purpose. The results found indicate that excessive use of screens is associated with a negative impact on the duration and quality of sleep-in preschoolers, and this worsening of sleep in infancy is related with a greater probability of the appearance of internalizing and externalizing behavioral problems and certain cognitive problems. The results also suggest that sleep could play a mediating or moderating role as a bioregulatory system that attenuates or increases the onset of behavioral and cognitive difficulties in those children most exposed to digital devices.

Language and autobiographical memory development from 5 to 12 years: A longitudinal perspective.

The main aim of this study, with two repeated measurements, was to analyze the development of autobiographical memory in a sample of 78 Spanish participants at ages 5 (Time 1; M = 62.43 months, range: 50-74 months) and 12 (Time 2; M = 142.71 months, range: 132-155 months). Data were collected on autobiographical memory and verbal functions. We analyzed the relation between language and autobiographical memory specificity from a longitudinal perspective and assessed the indirect effect of vocabulary in the relationship between age and specific memory at both temporal moments. The results showed that language skills were positively related with autobiographical memory specificity at preschool age, but not at the second measurement. Furthermore, vocabulary scores appear to mediate the relationship between age and autobiographical specificity when children are in the preschool years, but not later. These findings agree with previous research that consider preschool age to be a crucial period for the development of autobiographical memory and its relations with language, but once basic command of language is acquired, linguistic differences impact much less on individual differences in autobiographical specificity.

Pessary with perineal suture for treatment of pelvic organ prolapse: description and benefit of the technique.

INTRODUCTION AND HYPOTHESIS: Vaginal pessaries are used as a conservative treatment for POP in women who do not want or are not candidates for surgery, or as a preliminary step to surgery. Our goals are: evaluate the evolution of patients with advanced POP and repeated expulsion of the pessary, who underwent perineal suture to try to maintain the device. Describe the epidemiological characteristics of patients treated with pessaries in our environment, with or without perineal closure. METHODS: Observational, descriptive and prospective study (October 2016-March 2021) that includes 352 women with advanced-stage POP treated with a pessary, of which 55, after repeated expulsion of the pessary, were treated with a pessary and perineal suture. RESULTS: After pessary insertion associated with perineal closure, 26 patients (47.2%) expelled the pessary and underwent surgery, and 29 (52.8%) kept the device, avoiding surgery. Regarding the women who required perineal suture: The mean age was higher than in the group of patients who did not need this intervention (75.3 vs. 68.3 years), 94.5% had POP ≥ grade III and 100% had a perineal width > 2.5 cm. CONCLUSIONS: Treatment with pessary and perineal closure avoids surgery in women with advanced age and repeated expulsion. Although age should not be an independent factor that limits surgical treatment or the type of intervention, it would be useful to have scales to quantify the frailty of patients, being able to standardize perineal closure in elderly and/or frail women, and in those who do not want or have contraindications for surgery.

Relation between resilience and personality traits: The role of hopelessness and age.

Resilience refers to the process by which individuals use the ability to cope with challenges to successfully adapt to adverse situations, inclining towards the future and hope. The main aim of this study was to analyze the relation between resilience, personality traits, and hopelessness. Furthermore, we conducted comparisons between two age groups: young and older adults. The sample comprised 439 Spanish participants (66.7% women; M = 43.73, SD = 26.41; age range = 18-98 years). The Connor-Davidson Resilience Scale, NEO-Five Factor Inventory, and Beck Hopelessness Scale were used to measure the main study variables. The results revealed a negative relation between resilience and neuroticism, and a positive association with the other personality traits. Additionally, levels of resilience were found to be negatively related to hopelessness. The group of older adults showed significantly lower resilience levels than the young adults, although age was not a significant predictor of resilience. Neuroticism, extraversion, openness, and hopelessness were the only predictors of resilience for the current study. This work contributes to the study of resilience and related factors, by attempting to understand the role of resilience and resistance to risk and how individuals tackle challenges over time, with important implications for mental health.

Effects of the use of autobiographical photographs on emotional induction in older adults: a systematic review.

There is evidence to support the positive contribution of autobiographical recall based techniques on individuals' quality of life, mood and cognitive functioning. In this review, we analyzed the effects of the use of personal photographs in interventions based on autobiographical memory in older people with and without cognitive impairment. The PRISMA guidelines for systematic reviews were followed. The search was carried out in the electronic databases Web of Sciences (WOS), Medline (PubMed), SCIELO and PsycInfo (American Psychological Association). The articles based on clinical trials selected were evaluated using the PEDRo scale, which is specific to this type of article. Of the 1098 articles initially found, 6 met the inclusion criteria. The final articles focused their intervention on the use of autobiographical photographs as a means of stimulation. The results show that the use of photographs in different autobiographical recall stimulation techniques is associated with higher scores on well-being and quality of life, as well as with improvements in personal identity and cognitive functioning. This suggests that using personal photographs shows promise in enhancing the effect of these types of interventions in healthy or cognitively impaired older adults.

Effect of popular songs from the reminiscence bump as autobiographical memory cues in aging: a preliminary study using EEG.

Introduction: Music has the capacity to evoke emotions and memories. This capacity is influenced by whether or not the music is from the reminiscence bump (RB) period. However, research on the neural correlates of the processes of evoking autobiographical memories through songs is scant. The aim of this study was to analyze the differences at the level of frequency band activation in two situations: (1) whether or not the song is able to generate a memory; and (2) whether or not the song is from the RB period. Methods: A total of 35 older adults (22 women, age range: 61-73 years) listened to 10 thirty-second musical clips that coincided with the period of their RB and 10 from the immediately subsequent 5 years (non-RB). To record the EEG signal, a brain-computer interface (BCI) with 14 channels was used. The signal was recorded during the 30-seconds of listening to each music clip. Results: The results showed differences in the activation levels of the frequency bands in the frontal and temporal regions. It was also found that the non-retrieval of a memory in response to a song clip showed a greater activation of low frequency waves in the frontal region, compared to the trials that did generate a memory. Discussion: These results suggest the importance of analyzing not only brain activation, but also neuronal functional connectivity at older ages, in order to better understand cognitive and emotional functions in aging.

Effects of affectively-loaded childhood-related photos from the IAPS on the induction of involuntary autobiographical memories in young and older adults.

Objective: Aging produces changes in emotional reactivity and the retrieval of autobiographical memories. The main aim of this study was to assess age-related differences, comparing emotion induction and autobiographical memory recall using photos from the International Affective Picture System (IAPS) that are thematically related to childhood. Method: A cross-sectional observational study was conducted, with the participation of 327 individuals (168 young adults and 159 older adults) with no cognitive impairment and aged between 18 and 88 years. We showed the participants a set of five pictures from the IAPS, the affective content of which was related to childhood. Two of these were considered to be positive images, two negative and one neutral, according to the valence of these pictures in the literature. The main study variables were the reactions associated with emotional valence or pleasure, arousal and dominance, after viewing the photos, and the autobiographical memories retrieved by the participants. Results: The younger adults retrieved a larger number of memories than their older counterparts. As regards the responses to the five affective pictures (IAPS) on valence, arousal and dominance (IAPS), statistically significant differences were only found for pictures 2,345 (BlackEye), with a more positive valence in the group of older adults and higher arousal in the young ones, and 2,312 (Mother), with a more positive valence in the group of older persons. A greater number of memories were retrieved for the photos that generated higher levels of pleasure, greater relaxation and greater emotional control. Conclusion: Of the variables that may be associated with the elicitation of involuntary autobiographical memories, the most significant are age and a positive stimulus.

Initial management of hydatidiform mole

Introduction: Hydatidiform mole is a type of gestational trophoblastic disease that results from the abnormal fertilization of an oocyte and causes nonspecific symptoms such as amenorrhea, metrorrhagia, and enlarged uterus. Although rare, its most characteristic symptoms include hyperemesis, early-onset pre-eclampsia, anemia, and respiratory distress. Case presentation: A 47-year-old Moroccan woman consulted the emergency department of the Hospital Clínico Universitario in Valladolid (Spain) after a month of persistent coughing and emesis. The patient reported epigastralgia and amenorrhoea for two months, as well as scant vaginal bleeding two days prior to consultation. Taking into account that the patient tested positive for pregnancy, that a heterogeneous intrauterine mass measuring 124x120mm was observed on transvaginal ultrasound, that no abnormal findings were reported on Doppler ultrasound, and that her serum ßhCG levels reached a value of 772.110 mIU/mL, a diagnosis of hydatidiform mole was suspected. Once informed about the possible therapeutic options, the patient decided to undergo a total hysterectomy, as she stated that she had already fulfilled her desire to be a mother. After the procedure, the patient's clinical condition improved, and the pathology report of the mass confirmed the diagnosis of partial hydatidiform mole. Conclusion: Early diagnosis of hydatidiform mole is paramount in order to provide adequate treatment and improve the prognosis of these patients. Therefore, despite its low incidence and non-specific clinical manifestations, it should be considered as a differential diagnosis for first-trimester metrorrhagia.

Introducción. La mola hidatiforme es un tipo de enfermedad trofoblástica gestacional que se presenta como resultado de la fertilización anormal de un ovocito y que ocasiona síntomas inespecíficos como amenorrea, metrorragia y aumento del tamaño del útero. Aunque infrecuentes, sus síntomas más característicos incluyen hiperémesis, preeclampsia de inicio temprano, anemia y distrés respiratorio. Presentación del caso. Mujer marroquí de 47 años que consultó al servicio de urgencias del Hospital Clínico Universitario de Valladolid debido a que había presentado tos y vómitos por un mes. La paciente refirió haber sufrido epigastralgia y amenorrea por dos meses, así como escaso sangrado vaginal en los últimos dos días. Teniendo en cuenta que la paciente dio positivo en una prueba de embarazo, que en la ecografía transvaginal se observó una masa intrauterina heterogénea de 124x120mm, que no se reportaron hallazgos anormales en la ecografía Doppler y que sus niveles séricos de ßhCG alcanzaron un valor de 772.110 mUI/mL, se sospechó un diagnóstico de mola hidatiforme. Una vez informada sobre las posibles alternativas terapéuticas, la paciente decidió someterse a una histerectomía total, pues refirió que ya había cumplido su deseo de ser madre. Luego de realizar procedimiento, la condición clínica de la paciente mejoró; además, el informe de patología de la masa permitió confirmar el diagnóstico de mola hidatiforme parcial. Conclusiones. El diagnóstico temprano de la mola hidatiforme es de gran importancia para ofrecer un tratamiento adecuado y, de esta forma, mejorar el pronóstico de estas pacientes. Por tanto, a pesar de su baja incidencia y sus manifestaciones clínicas inespecíficas, se debe considerar como diagnóstico diferencial de las metrorragias del primer trimestre.

Maternal and perinatal outcomes in women ≥40 years undergoing induction of labor compared with women <35 years: Results from 4027 mothers.

AIM: Cesarean section is known to be increased with advanced maternal age in women undergoing induction of labor (IOL), but there is less information regarding other possible adverse maternal and fetal outcomes. METHODS: Retrospective cohort study of singleton, nulliparous, at-term women undergoing IOL between January 2007 and September 2020. Outcomes studied were: cesarean section, failed induction rate, fetal distress, post-partum hemorrhage, post-partum hysterectomy, and need of transfusion. Neonatal variables analyzed were: Apgar score, umbilical cord pH, need of admission to neonatal intensive care unit, and mortality. RESULTS: A total of 4027 women met the inclusion criteria; 1968 (48.9%) of mothers were <35 years, 1283 (31.9%) were 35-39 years, 658 (16.3%) were 40-44 years, and 118 (2.9%) were ≥45 years. Results showed a significantly increased incidence of c-section in women ≥35 years, with an OR 1.79 (95% CI 1.50-2.14) for women 40-44 years and OR 3.95 (95% CI 2.66-5.98) for women ≥45 years. The main indication for cesarean delivery was failed IOL, and this risk was also significantly increased in women ≥40 years. These differences remained significant after adjustment for confounding factors. No other adverse maternal or fetal outcomes showed an association with age. CONCLUSION: Maternal age ≥40 years was associated with an increased risk of c-section after IOL at term compared with younger women, mainly because of failed induction, but no association with other adverse maternal or neonatal outcomes were found in our population. Risks and benefits of IOL in older women should be individually evaluated and adequately discussed with mothers.

Relation between nighttime sleep duration and executive functioning in a nonclinical sample of preschool children.

Sleep is a support for cognitive development in childhood. Most of the studies in the field have focused on school-age children and sleep problems, but less research focuses on the relation between the normative course of sleep and executive functions in preschoolers. Thus, the aim of the present study was to analyze the association between nighttime sleep duration and executive functioning in a 158 non-clinical sample of Spanish participants (Mage = 56.35 months, SD = 11.24; ages 38-78 months; 48.1% girls). Sleep habits were measured by parents' self-reports; Shape School task was applied to assess inhibition and cognitive flexibility; Word Span task was used to assess working memory; and Vocabulary subtest from the Wechsler Preschool and Primary Scale of Intelligence-III was used to assess verbal ability. The findings revealed that the relation between sleep and executive functioning was only significant in the cases of inhibition and working memory. Further, age and verbal ability were related and were predictors of inhibition, working memory, and cognitive flexibility. We consider it necessary to continue researching in this area given the importance of forming a correct sleep habit during the preschool age and its impact on health, cognition, and well-being in childhood. In short, our results represent the first approach to the subject under study, which should be completed with objective sleep measures.

Role of Nrp1 in controlling cortical inter-hemispheric circuits.

Axons of the corpus callosum (CC) mediate the interhemispheric communication required for complex perception in mammals. In the somatosensory (SS) cortex, the CC exchanges inputs processed by the primary (S1) and secondary (S2) areas, which receive tactile and pain stimuli. During early postnatal life, a multistep process involving axonal navigation, growth, and refinement, leads to precise CC connectivity. This process is often affected in neurodevelopmental disorders such as autism and epilepsy. We herein show that in mice, expression of the axonal signaling receptor Neuropilin 1 (Nrp1) in SS layer (L) 2/3 is temporary and follows patterns that determine CC connectivity. At postnatal day 4, Nrp1 expression is absent in the SS cortex while abundant in the motor area, creating a sharp border. During the following 3 weeks, Nrp1 is transiently upregulated in subpopulations of SS L2/3 neurons, earlier and more abundantly in S2 than in S1. In vivo knock-down and overexpression experiments demonstrate that transient expression of Nrp1 does not affect the initial development of callosal projections in S1 but is required for subsequent S2 innervation. Moreover, knocking-down Nrp1 reduces the number of S2L2/3 callosal neurons due to excessive postnatal refinement. Thus, an exquisite temporal and spatial regulation of Nrp1 expression determines SS interhemispheric maps.

Accuracy of dynamic implant navigation surgery performed by a novice operator.

AIM: The main objective was to evaluate the accuracy of dynamic navigation-guided surgery (DNGS) for implant positioning performed by a novice operator. The secondary objectives were to analyze the operator's learning curve and identify possible complications deriving from the technique. MATERIALS AND METHODS: Twenty-five implants were placed in eight partially edentulous human heads. Preoperative CBCT scans were imported to planning software to determine the implant positions. Implants were placed using a dynamic navigation system. Postoperative CBCTs were superimposed onto the implant planning images. Discrepancies between the virtually planned implant positions and the postoperative positions were evaluated by measuring horizontal platform deviation, apex deviation, apicocoronal (vertical) deviation, and angular deviation. RESULTS: Mean platform, apex, vertical, and angle deviations were 1.55 ± 0.81 mm, 2.45 ± 0.84 mm, 1.59 ± 0.70 mm, and 5.56 ± 4.03 degrees, respectively. No significant differences were found between the maxilla and mandible or between anterior and posterior sites. A flat learning curve was observed, with the exception of the implant platform, where a tendency toward improvement in accuracy was observed between the 8th and the 17th implant placed. No complications were reported. CONCLUSIONS: Based on the results of a study performed by a novice operator on a cadaveric model, DNGS allows accurate implant placement within a 2-mm safety margin in terms of implant platform and vertical positions, and a 3-mm margin in apical vicinities. The technique requires practice to learn the required eye-hand coordination. (Int J Comput Dent 2022;25(4):377-0; doi: 10.3290/j.ijcd.b2588207).