Mutations in Human Accelerated Regions Disrupt Cognition and Social Behavior.

Comparative analyses have identified genomic regions potentially involved in human evolution but do not directly assess function. Human accelerated regions (HARs) represent conserved genomic loci with elevated divergence in humans. If some HARs regulate human-specific social and behavioral traits, then mutations would likely impact cognitive and social disorders. Strikingly, rare biallelic point mutations-identified by whole-genome and targeted "HAR-ome" sequencing-showed a significant excess in individuals with ASD whose parents share common ancestry compared to familial controls, suggesting a contribution in 5% of consanguineous ASD cases. Using chromatin interaction sequencing, massively parallel reporter assays (MPRA), and transgenic mice, we identified disease-linked, biallelic HAR mutations in active enhancers for CUX1, PTBP2, GPC4, CDKL5, and other genes implicated in neural function, ASD, or both. Our data provide genetic evidence that specific HARs are essential for normal development, consistent with suggestions that their evolutionary changes may have altered social and/or cognitive behavior. PAPERCLIP.

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.

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.

Development and plasticity of the corpus callosum.

The corpus callosum (CC) connects the cerebral hemispheres and is the major mammalian commissural tract. It facilitates bilateral sensory integration and higher cognitive functions, and is often affected in neurodevelopmental diseases. Here, we review the mechanisms that contribute to the development of CC circuits in animal models and humans. These species comparisons reveal several commonalities. First, there is an early period of massive axonal projection. Second, there is a postnatal temporal window, varying between species, in which early callosal projections are selectively refined. Third, sensory-derived activity influences axonal refinement. We also discuss how defects in CC formation can lead to mild or severe CC congenital malformations.

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.

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.

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.

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).

A multi-method comparison of autobiographical memory impairments amongst younger and older adults.

Objectives: Research indicates that, compared to younger adults, older adults have difficulty recalling memories of specific past events (those lasting less than 24 h) and this difficulty is associated with depression. These studies are largely confined to a single measure of specific memory recall and there are conflicting findings when alternative measures are used. This investigation provides the first comparison of memory specificity between younger and older adults using several different measures.Method: Older (n = 105) and younger (n = 88) adults completed the Autobiographical Memory Test (AMT), Autobiographical Memory Interview (AMI) and Sentence Completion for Events from the Past Test (SCEPT) and the number of specific memories was quantified for each measure. Participants also completed the Beck Depression Inventory Version II (BDI-II).Results: Compared to younger adults, older adults recalled fewer specific memories in the AMT and more specific memories in the AMI. This latter effect was particularly pronounced for memories related to childhood. There was no group difference in responses in the SCEPT. There was no evidence of an association between memory specificity and depression for any of the measures.Conclusion: Older adults have difficulty retrieving specific memories after cuing by nouns and adjectives, as in the AMT, but they have enhanced recall of specific memories after cuing by life periods, as in the AMI, and this is particularly true of memories related to childhood. Individual differences in memory specificity are not related to depression symptoms in healthy samples.

T-cell defects in patients with ARPC1B germline mutations account for combined immunodeficiency.

ARPC1B is a key factor for the assembly and maintenance of the ARP2/3 complex that is involved in actin branching from an existing filament. Germline biallelic mutations in ARPC1B have been recently described in 6 patients with clinical features of combined immunodeficiency (CID), whose neutrophils and platelets but not T lymphocytes were studied. We hypothesized that ARPC1B deficiency may also lead to cytoskeleton and functional defects in T cells. We have identified biallelic mutations in ARPC1B in 6 unrelated patients with early onset disease characterized by severe infections, autoimmune manifestations, and thrombocytopenia. Immunological features included T-cell lymphopenia, low numbers of naïve T cells, and hyper-immunoglobulin E. Alteration in ARPC1B protein structure led to absent/low expression by flow cytometry and confocal microscopy. This molecular defect was associated with the inability of patient-derived T cells to extend an actin-rich lamellipodia upon T-cell receptor (TCR) stimulation and to assemble an immunological synapse. ARPC1B-deficient T cells additionally displayed impaired TCR-mediated proliferation and SDF1-α-directed migration. Gene transfer of ARPC1B in patients' T cells using a lentiviral vector restored both ARPC1B expression and T-cell proliferation in vitro. In 2 of the patients, in vivo somatic reversion restored ARPC1B expression in a fraction of lymphocytes and was associated with a skewed TCR repertoire. In 1 revertant patient, memory CD8+ T cells expressing normal levels of ARPC1B displayed improved T-cell migration. Inherited ARPC1B deficiency therefore alters T-cell cytoskeletal dynamics and functions, contributing to the clinical features of CID.

PlexinD1 and Sema3E determine laminar positioning of heterotopically projecting callosal neurons.

The corpus callosum is the largest bundle of commissural fibres that transfer information between the two cerebral hemispheres. Callosal projection neurons (CPNs) are a diverse population of pyramidal neurons within the neocortex that mainly interconnect homotopic regions of the opposite cortices. Nevertheless, some CPNs are involved in heterotopic projections between distinct cortical areas or to subcortical regions such as the striatum. In this study, we showed that the axon guidance receptor PlexinD1 is expressed by a large proportion of heterotopically projecting CPNs in layer 5A of the primary somatosensory (S1) and motor (M1) areas. Retrograde tracing of M1 CPNs projecting to the contralateral striatum revealed the presence of ectopic neurons aberrantly located in layers 2/3 of Plxnd1 and Sema3e mutant cortices. These results showed that Sema3E/PlexinD1 signalling controls the laminar distribution of heterotopically projecting CPNs.

Impact of aging on obstetric outcomes: defining advanced maternal age in Barcelona.

BACKGROUND: Women of advanced maternal age (AMA) are a growing population, with higher obstetric risks. The Mediterranean population has specific characteristics different from other areas. Thus, the objective of this study was to establish a cut-off to define AMA in a selected mediterranean population coming from a tertiary referral private/mutual health hospital in Barcelona. METHODS: Retrospective cohort of euploid singleton pregnancies delivered from January 2007 to June 2017. Main maternal outcomes were: gestational diabetes, preeclampsia, placenta previa, c-section and prolonged hospitalization (≥ 7 days). Main adverse perinatal outcomes were: stillbirth, prematurity, preterm prelabor rupture of membranes, low birth weight, need of admission at a neonatal intensive care unit and perinatal mortality. Adjustment for confounding factors (smoking, previous comorbilities, parity, assisted reproductive techniques (ART) and obesity) was performed. RESULTS: A total of 25054 pregnancies were included. Mean maternal age was 34.7 ± 4.2 years, with 2807 patients in the group of age between 40 and 44 years (11.2%) and 280 patients ≥45 years (1.1%). Women at AMA had higher incidence of previous comorbilities (compared to the reference group of women < 30 years): prior c-section, chronic hypertension and obesity. In addition, they were more likely to use ART. After adjusting for confounding factors, maternal age was an independent and statistically significant risk factor for gestational diabetes (OR 1.66/2.80/3.14) for ages 30-39, 40-44 and ≥ 45 years respectively, c-section (OR 1.28/2.41/7.27) and placenta previa (OR 2.56/4.83) for ages 40-44 and ≥ 45 years respectively, but not for preeclampsia (neither early-onset nor late-onset). Risk of emergency c-section was only increased in women ≥45 years (OR, 2.03 (95% CI, 1.50-2.74). In the other groups of age, the increase in c-section rate was because of elective indications. Age ≥ 45 years was associated with iatrogenic prematurity < 37 weeks (OR 2.62, 95% CI 1.30-5.27). No other relevant associations between AMA and maternal or neonatal outcomes were found. CONCLUSIONS: Maternal age is an independent risk factor for adverse obstetric outcomes. Age ≥ 40 years was associated to relevant increased risks and reveals to be an adequate cut-off to define AMA in our population.

Correction to: Influence of surface treatment on osseointegration of dental implants: histological, histomorphometric and radiological analysis in vivo.

Dear Professor Dr. Matthias Hannig. Editor-in-Chief Clinical Oral Investigations. Following the publication of our paper by Calvo Guirado et al, 2015 [1] in Clinical Oral Investigations, it came to light that a certain part of the text at the materials and methods and results sections were similar.

Autobiographical memory specificity across life periods in people with schizophrenia.

OBJECTIVE: Because the well-known relationship between autobiographical memory (AM) with social functioning and psychopathology can manifest itself in a different way for memories of different life periods, the current work assesses AM specificity deficits across different life stages in people with schizophrenia. METHOD: This cross-sectional study compares the performance of specific AM in people with a diagnosis of schizophrenia (n = 53, 78% male, 39.03 mean age) and controls ( n = 69, 88% male, 36.65 mean age) for four life periods (childhood, adolescence, early adulthood, and the year preceding the assessment) using the Autobiographical Memory Enquiry. RESULTS: The results revealed worse AM performance in people with schizophrenia, especially for memory of events occurring over the preceding year, and the use of overgeneral memory style for life periods succeeding childhood. CONCLUSION: These results highlight the need for systematic assessment of difficulties in retrieving specific memories across life periods in people with schizophrenia.

Effects of analytical (abstract) versus experiential (concrete) induced rumination of negative self defining memories on schizotypic symptoms.

Repetitive thought may have adaptive and functional consequences, depending on, among other things, the interpretation of the content: analytical or abstract (general and decontextualized) and experiential or concrete (specific, contextual and incidental). Studies experimentally manipulating repetitive thought have shown both the constructive consequences of the experiential mode and the dysfunctional consequences of the analytical mode. The aim of the current study is to observe the effect of analytical and experiential rumination of negative self-defining memories on schizotypic symptoms. A sample of 111 university students were randomly assigned to one of the two experimental conditions of induced rumination, "analytical" or "experimental." The participants completed a series of questionnaires (anomalous perception of reality, preoccupation and depression) and a negative self-defining memory was obtained to be used as the content of the induced rumination. Following the rumination induction, participants in the experiential condition significantly decreased their scores on anomalous perception of reality compared with those in the analytical condition. We also observed that post-induction scores on self-reported sadness significantly increased in both experimental conditions while scores on self-reported happiness decreased. Our results show that the concrete/experiential rumination, focused here on negative self-defining memories, have positive consequences on schizotypic symptoms, such as decreased anomalous perception of reality.

Zirconia with laser-modified microgrooved surface vs. titanium implants covered with melatonin stimulates bone formation. Experimental study in tibia rabbits.

OBJECTIVES: The aim of the study was to evaluate if zirconia implants with micro-grooved surfaces supplemented with melatonin enhance the bone-to-implant contact (BIC) vs. titanium implants with the same coating. MATERIALS AND METHODS: Eighty implants divided in four groups were inserted in the tibia of 20 New Zealand rabbits as follows: (group A) 20 titanium implants; (group B) 20 micro-grooved zirconia implants; (group C) 20 titanium implants supplemented with melatonin and (group D) 20 micro-grooved zirconia implants supplemented with melatonin. Histometric and SEM evaluation of BIC were evaluated after 1 and 4 weeks. RESULTS: At 1 week, group C (29.7 ± 2.4%) and group D (28.9 ± 1.3%) implants showed higher BIC% compared with group A and B (P < 0.05). After 4 weeks, group D showed higher BIC compared with all the groups (47.5 ± 2.2%) (P < 0.05). Also Connective tissue was higher in groups B (78.9 ± 2.1%) and D (88.7 ± 1.2%) related to titanium and zirconia melatonin untreated at 4 weeks (P < 0.05). CONCLUSIONS: Within the limitations of this pilot study in rabbits, we can conclude that the local application of melatonin increases the BIC values in titanium and in zirconia implants at 1 week.