Molecular features driving cellular complexity of human brain evolution.

Human-specific genomic changes contribute to the unique functionalities of the human brain1-5. The cellular heterogeneity of the human brain6,7 and the complex regulation of gene expression highlight the need to characterize human-specific molecular features at cellular resolution. Here we analysed single-nucleus RNA-sequencing and single-nucleus assay for transposase-accessible chromatin with sequencing datasets for human, chimpanzee and rhesus macaque brain tissue from posterior cingulate cortex. We show a human-specific increase of oligodendrocyte progenitor cells and a decrease of mature oligodendrocytes across cortical tissues. Human-specific regulatory changes were accelerated in oligodendrocyte progenitor cells, and we highlight key biological pathways that may be associated with the proportional changes. We also identify human-specific regulatory changes in neuronal subtypes, which reveal human-specific upregulation of FOXP2 in only two of the neuronal subtypes. We additionally identify hundreds of new human accelerated genomic regions associated with human-specific chromatin accessibility changes. Our data also reveal that FOS::JUN and FOX motifs are enriched in the human-specifically accessible chromatin regions of excitatory neuronal subtypes. Together, our results reveal several new mechanisms underlying the evolutionary innovation of human brain at cell-type resolution.

SCA8 RAN polySer protein preferentially accumulates in white matter regions and is regulated by eIF3F.

Spinocerebellar ataxia type 8 (SCA8) is caused by a bidirectionally transcribed CTG·CAG expansion that results in the in vivo accumulation of CUG RNA foci, an ATG-initiated polyGln and a polyAla protein expressed by repeat-associated non-ATG (RAN) translation. Although RAN proteins have been reported in a growing number of diseases, the mechanisms and role of RAN translation in disease are poorly understood. We report a novel toxic SCA8 polySer protein which accumulates in white matter (WM) regions as aggregates that increase with age and disease severity. WM regions with polySer aggregates show demyelination and axonal degeneration in SCA8 human and mouse brains. Additionally, knockdown of the eukaryotic translation initiation factor eIF3F in cells reduces steady-state levels of SCA8 polySer and other RAN proteins. Taken together, these data show polySer and WM abnormalities contribute to SCA8 and identify eIF3F as a novel modulator of RAN protein accumulation.

The effects of compulsory isolation measures during the COVID-19 pandemic: The example of prison workers.

OBJECTIVE: The aim of this research was to identify depression, anxiety, and perceived social support levels among prison workers and to determine the relationship between anxiety and depression and perceived social support. METHODS: The descriptive, cross-sectional research was conducted between 15 November 2020, and 10 February 2021. The study sample consisted of 603 prison workers contacted using the convenience sampling method, consenting to take part in the research, and working under compulsory Covid-19 isolation measures. A questionnaire produced in an electronic environment consisting of a personal information form, the Generalised Anxiety Disorder Scale (GAD), the Patient Health Questionnaire (PHQ), and the Multidimensional Scale of Perceived Social Support (MSPSS) questions was employed. RESULTS: The mean GAD, PHQ and MSPSS scores of the prison workers working under compulsory isolation conditions were 18.38 ± 5.78, 14.30 ± 6.99, and 42.76 ± 20.27, respectively. Of the prison workers in this study, 71.5% exhibited severe depression symptoms and 21.4% moderate depression, while 25.5% exhibited severe anxiety symptoms and 23.4% moderate anxiety symptoms. MSPSS and its subdomains exhibited negative correlation with depression, and the MSPSS friends subdomain was negatively correlated with anxiety. CONCLUSION: Anxiety and depression scores were at high levels in prison workers exposed to compulsory isolation during the Covid-19 pandemic.

Intimate Partner Violence against Women in Turkey during the COVID-19 Pandemic.

This study aims to determine the prevalence of and risk factors for intimate partner violence (IPV) during the COVID-19 pandemic. The cross-sectional study was conducted with 1,036 women in Turkey who were either married or had an intimate partner. The data were collected between June 20 and July 10, 2020. Experience of any form of IPV (physical (10.1%), sexual (4.0%), psychological (32.2%) or economic (11.5%) was reported by 35.5% of the participants. Regression analyses revealed that exposure to IPV during the pandemic was significantly associated with being married, having children, unemployment, poor marital/relationship satisfaction, an increased workload in the household and the negative effect of quarantine on mood (p < 0.05). Educational programs need to be prepared for the prevention of IPV during the COVID-19 pandemic and for the acquisition of protective behaviors toward women victims of IPV.

Effect of childbirth education on the perceptions of childbirth and breastfeeding self-efficacy and the obstetric outcomes of nulliparous women*,**,**.

In this quasi-experimental and prospective study, we aimed to determine the effect of education about childbirth on the perceptions of nulliparous women regarding the experience of childbirth, obstetric outcomes (e.g., type of delivery, use of induction, and instrument-assisted delivery), and breastfeeding self-efficacy. The study population comprised 121 women, of whom 64 and 57 were classified into the education and control groups, respectively. Study data were collected using a participant identification form, the Perception of Birth Scale, Visual Analog Scale, and Breastfeeding Self-Efficacy Scale-Short Form. Compared to the control group, participants in the education group held significantly more positive birth-related perceptions (p = 0.000) and experienced a lower level of pain during delivery (p = 0.016). However, education did not affect the obstetric outcomes. During the first month postpartum, a higher level of breastfeeding self-efficacy was reported by mothers in the education group than by those in the control group. In conclusion, systematic childbirth education positively affected the mothers' perceptions of the childbirth experience and their breastfeeding self-efficacy, but had no effect on the type of delivery or other birth-related obstetric interventions.

Effectiveness of external cold and vibration for procedural pain relief during peripheral intravenous cannulation in pediatric patients.

The aim of this study was to investigate the effect of external cold and vibration stimulation via Buzzy on the pain and anxiety level of children during peripheral intravenous (IV) cannulation. This study was a prospective, randomized controlled trial. The sample consisted of 176 children ages 7 to 12 years who were randomly assigned to two groups: a control group that received no peripheral IV cannulation intervention and an experimental group that received external cold and vibration via Buzzy. The same nurse conducted the peripheral IV cannulation in all the children, and the same researcher applied the external cold and vibration to all the children. The external cold and the vibration were applied 1 minute before the peripheral IV cannulation procedure and continued until the end of the procedure. Preprocedural anxiety was assessed using the Children's Fear Scale, along with reports by the children, their parents, and an observer. Procedural anxiety was assessed with the Children's Fear Scale and the parents' and the observer's reports. Procedural pain was assessed using the Wong Baker Faces Scale and the visual analog scale self-reports of the children. Preprocedural anxiety did not differ significantly. Comparison of the two groups showed significantly lower pain and anxiety levels in the experimental group than in the control group during the peripheral IV cannulation. Buzzy can be considered to provide an effective combination of coldness and vibration. This method can be used during pediatric peripheral IV cannulation by pediatric nurses.

The Association Between Witnessing Interparental Violence and Adolescents' Anger Expression Styles.

The purpose of this research was to determine the association between witnessing interparental violence and anger expression styles in adolescents. Previous studies have generally focused on the attitudes to violence of individuals witnessing it. However, the present research specifically investigated the association between witnessing interparental violence and anger. The research was performed as a descriptive and correlational study. The research sample consisted of 1,000 adolescents aged 15 to 19 contacted via social media platforms using the convenience sample method. An online data collection form containing questions was prepared to determine adolescents' sociodemographic characteristics and contained questions from the Witnessing Interparental Violence Scale and Trait Anger Expression Inventory. Statistical analysis was performed on SPSS 21.0 software. In all, 446 (44.6%) adolescents had witnessed interparental violence. Trait, externalized, and internalized anger scores were higher among adolescents who had witnessed interparental violence compared to those who had not. This research shows that witnessing interparental violence has significant effects on the individual's trait anger and anger expression styles. We recommend that the effects of exposure to violence and witnessing interparental violence be compared and that witnessing violence in different cultural environments be evaluated in future studies.

Psychosocial interventions aimed at family members caring for patients with cancer in the palliative period: A systematic review.

AIM: The purpose of this systematic review is to examine evidence-based psychosocial intervention research aimed at family members caring for patients with cancer in the palliative period. METHOD: In this systematic review, randomized controlled psychosocial intervention studies for the family member caring for patients with cancer published between January 1, 2016 and July 30, 2021 were reviewed. PubMed (including MEDLINE), Cochrane, APA PsycNet, ProQuest, Science Direct, TR Index, and Wiley Online Library databases were scanned. Eight publications were identified following a database review for English language articles published from 2016 to 2021. Sample, methods, content, and outcomes of included interventions are summarized. RESULTS: Only eight of the 4652 articles examined met the inclusion criteria. Psychosocial interventions such as mindfulness exercises, stress management, acceptance and commitment therapy, cognitive behavioral intervention, and meaning-centered psychotherapy for cancer caregivers were applied for relatives caring for patients with cancer in the palliative period. CONCLUSION: Psychosocial interventions applied to family members caring for patients with cancer during the palliative period lead to improvements in depressive symptoms, stress levels, the caregiver burden, quality of life, self-efficacy, coping skills, and awareness levels.

Cell type specific roles of FOXP1 during early neocortical murine development.

Cortical development is a tightly controlled process and any deviation during development may increase the susceptibility to neurodevelopmental disorders, such as autism spectrum disorders (ASD). Numerous studies identified mutations in FOXP1, a transcription factor enriched in the neocortex, as causal for ASD and FOXP1 syndrome. Our group has shown that Foxp1 deletion in the mouse cortex leads to overall reduced cortex thickness, alterations in cortical lamination, and changes in the relative thickness of cortical layers. However, the developmental and cell type-specific mechanisms underlying these changes remained unclear. This work characterizes the developmental requirement of neocortical Foxp1 at key embryonic and perinatal ages using a conditional knock-out of Foxp1. We find that Foxp1 deletion results in accelerated pseudo-age during early neurogenesis, increased cell cycle exit during late neurogenesis, altered gene expression and chromatin accessibility, and selective migration deficits in a subset of upper-layer neurons. These data explain the postnatal differences observed in cortical layers and relative cortical thickness. We also highlight genes regulated by FOXP1 and their enrichment with high-confidence ASD or synaptic genes. Together, these results underscore a network of neurodevelopmental disorder-related genes that may serve as potential modulatory targets for postnatal modification relevant to ASD and FOXP1 syndrome.

Psychometric testing and the predictive validity of the Postpartum Depression Predictors Inventory-Revised (PDPI-R): A longitudinal study with Turkish women.

OBJECTIVE: The aim of this study was to investigate the validity and reliability of the prenatal and postnatal versions of the Postpartum Depression Predictors Inventory-Revised (PDPI-R) and to examine the predictive validity of PDPI-R in Turkish women, considering two gold standards to determine postpartum depression (PPD). METHODS: This prospective longitudinal study was conducted between August 2021 and September 2023. A total of 301 pregnant women participated in the study. Participants completed the PDPI-R during the third trimester of pregnancy (T1) and at 4 weeks postpartum (T2). At T2, participants also completed the Edinburgh Postnatal Depression Scale (EPDS), and women were interviewed using the Structured Clinical Interview for DSM-IV Disorders. RESULTS: The prenatal version of the PDPI-R predicted PPD with 64% (R:0.64) accuracy on the basis of the EPDS and 78% accuracy (R:0.78) according to DSM IV criteria. The postnatal version of the PDPI-R predicted PPD with 71% (R:0.71) accuracy on the basis of the EPDS and 81% accuracy (R:0.781) based on DSM IV criteria. The cut-off points exhibited the highest sensitivity and specificity values at 8.5 for the prenatal version and 10.5 for the postnatal version. CONCLUSIONS: The PDPI-R is a valid and reliable screening tool for identifying Turkish women at high risk of developing PPD and for estimating the psychosocial risk associated with PPD.

Improving Antimicrobial Properties of GelMA Biocomposite Hydrogels for Regenerative Endodontic Treatment.

Regenerative endodontics is a developing field involving the restoration of tooth structure and re-vitality of necrotic pulp. One of the most critical clinical considerations for regenerative endodontic procedures is the disinfection of the root canal system, since infection interferes with regeneration, repair, and stem cell activity. In this study, we aimed to provide the synthesis of injectable biopolymeric tissue scaffolds that can be used in routine clinical and regenerative endodontic treatment procedures using Gelatin methacryloyl (GelMA), and to test the antimicrobial efficacy of Gelatin methacryloyl/Silver nanoparticles (GelMA/AgNP), Gelatin methacryloyl/Hyaluronic acid (GelMA/HYA), and Gelatin methacryloyl/hydroxyapatite (GelMA/HA) composite hydrogels against microorganisms that are often encountered in stubborn infections in endodontic microbiology. Injectable biocomposite hydrogels exhibiting effective antimicrobial activity and non-cytotoxic behavior were successfully synthesized. This is also promising for clinical applications of regenerative endodontic procedures with hydrogels, which are proposed based on the collected data. The GelMA hydrogel loaded with hyaluronic acid showed the highest efficacy against Enterococcus faecalis, one of the stubborn bacteria in the root canal. The GelMA hydrogel loaded with hydroxyapatite also showed a significant effect against Candida albicans, which is another bacteria responsible for stubborn infections in the root canal.

A community-based study in the central district of Giresun: COVID-19 vaccine hesitancy.

Thanks to immunization strategies, which is a multistakeholder process that includes scientific, political, and nongovernmental organizational pillars, deaths and the risk of severe disease caused by COVID-19 infection are prevented. However, to prevent the losses caused by vaccine hesitancy, it is important to reveal the causes. We aimed to determine the frequency of vaccine hesitancy in individuals registered in the central district of Giresun, Turkey, and to investigate the related factors. In this cross-sectional study, the sample was selected from the population aged over 18 years, who were eligible for COVID-19 vaccination but had not been vaccinated. The systematic sampling method was used to select the participants (n = 422) from a list of the entire population (n = 12,055). The dependent variable was "COVID-19 vaccine hesitancy." Data were analyzed using the SPSS 22 software; descriptive, Chi-square, and logistic regression analyses were conducted. The rate of vaccine hesitancy was 58.9%. Vaccine hesitancy was higher in those who were old, employed, and had not been infected with COVID-19. After being given information, 55.8% of those who hesitated and 12.4% of those who resisted were convinced. Distrust in vaccines was the most frequent cause of vaccine hesitancy (32.5%). It was found that vaccine hesitancy was two times higher in those who had not had COVID-19 [OR = 1.95; 95% CI: 1.13-3.369], and 1.7 times higher in those who were employed [OR = 1.70; 95% CI: 1.06-2.74]. The fight against vaccine hesitancy and resistance must be based on active information, guidance, confidence, and a thorough understanding of the reasons.

Examination of risk assessment tools developed to evaluate risks in mental health areas: A systematic review.

The purpose of this research was to identify and examine risk assessment tools evaluating at least two risk dimensions to evaluate the risk assessments of patients in mental health areas in a more comprehensive and standard manner. This systematic review was prepared according to the PRISMA guidelines. The databases to be scanned and the keywords to be entered were identified before scanning the literature. The keywords risk assessment, risk management, mental health, psychiatry, risk assessment scales, and risk assessment tools were scanned. The CINAHL, EMBASE, PsycInfo, Medline, APA PsycNET, Science Direct, Pubmed, ProQuest, and Google Scholar databases were searched. All full-text articles published between December 30th, 1970, and January 1st, 2020, were examined. A total of 7385 papers were investigated using the keywords listed above, and 18 studies meeting the inclusion criteria were identified. The tools involved were SPC, FACE, Clinical Risk Management, Threshold Assessment Grid, Risk Assessment for People with Mental Health Problems, Psychogeriatric and Risk Behavior Assessment Scale, Sainsbury Risk Assessment Tool, Risk Assessment Management and Audit Systems, Generic Integrated Risk Assessment for Forensic Environments, FRAME, Brief Risk Assessment, Clinical Assessment of Risks to Self & Others, RIO, The Risk Assessment and Management, Risk Assessment and Management Self-Efficacy Study, Galatean Risk and Safety Tool, Short-Term Assessment of Risk and Treatability, and Psychiatric Risk Assessment Scale.

Nuclei isolation from surgically resected human hippocampus.

Single-nucleus RNA sequencing (snRNA-seq), where nuclear transcriptomes are a proxy to cellular transcriptomes, has been used to profile human brain. snRNA-seq is sensitive to tissue processing, tissue quality, postmortem interval time, and cellular debris. This protocol outlines steps for the isolation of high-quality nuclei from surgically resected human brain tissue followed by a sucrose gradient yielding neuronal and non-neuronal nuclei enabling unbiased analysis of various cell types. For complete details on the use and execution of this protocol, please refer to Ayhan et al. (2021).

Resolving cellular and molecular diversity along the hippocampal anterior-to-posterior axis in humans.

The hippocampus supports many facets of cognition, including learning, memory, and emotional processing. Anatomically, the hippocampus runs along a longitudinal axis, posterior to anterior in primates. The structure, function, and connectivity of the hippocampus vary along this axis. In human hippocampus, longitudinal functional heterogeneity remains an active area of investigation, and structural heterogeneity has not been described. To understand the cellular and molecular diversity along the hippocampal long axis in human brain and define molecular signatures corresponding to functional domains, we performed single-nuclei RNA sequencing on surgically resected human anterior and posterior hippocampus from epilepsy patients, identifying differentially expressed genes at cellular resolution. We further identify axis- and cell-type-specific gene expression signatures that differentially intersect with human genetic signals, identifying cell-type-specific genes in the posterior hippocampus for cognitive function and the anterior hippocampus for mood and affect. These data are accessible as a public resource through an interactive website.

Gene-expression correlates of the oscillatory signatures supporting human episodic memory encoding.

In humans, brain oscillations support critical features of memory formation. However, understanding the molecular mechanisms underlying this activity remains a major challenge. Here, we measured memory-sensitive oscillations using intracranial electroencephalography recordings from the temporal cortex of patients performing an episodic memory task. When these patients subsequently underwent resection, we employed transcriptomics on the temporal cortex to link gene expression with brain oscillations and identified genes correlated with oscillatory signatures of memory formation across six frequency bands. A co-expression analysis isolated oscillatory signature-specific modules associated with neuropsychiatric disorders and ion channel activity, with highly correlated genes exhibiting strong connectivity within these modules. Using single-nucleus transcriptomics, we further revealed that these modules are enriched for specific classes of both excitatory and inhibitory neurons, and immunohistochemistry confirmed expression of highly correlated genes. This unprecedented dataset of patient-specific brain oscillations coupled to genomics unlocks new insights into the genetic mechanisms that support memory encoding.

Regulatory genes and pathways disrupted in autism spectrum disorders.

Autism spectrum disorder (ASD) is a highly prevalent and complex genetic disorder. The complex genetic make-up of ASD has been extensively studied and both common and rare genetic variants in up to 1000 genes have been linked to increased ASD risk. While these studies highlight the genetic complexity and begin to provide a window for delineating pathways at risk in ASD, the pathogenicity and specific contribution of many mutations to the disorder are poorly understood. Defining the convergent pathways disrupted by this large number of ASD-associated genetic variants will help to understand disease pathogenesis and direct future therapeutic efforts for the groups of patients with distinct etiologies. Here, we review some of the common regulatory pathways including chromatin remodeling, transcription, and alternative splicing that have emerged as common features from genetic and transcriptomic profiling of ASD. For each category, we focus on one gene (CHD8, FOXP1, and RBFOX1) that is significantly linked to ASD and functionally characterized in recent years. Finally, we discuss genetic and transcriptomic overlap between ASD and other neurodevelopmental disorders.

Genomics of autism spectrum disorder: approach to therapy.

Autism spectrum disorder (ASD) is a highly prevalent neurodevelopmental condition with no current treatment available. Although advances in genetics and genomics have identified hundreds of genes associated with ASD, very little is known about the pathophysiology of ASD and the functional contribution of specific genes to ASD phenotypes. Improved understanding of the biological function of ASD-associated genes and how this heterogeneous group of genetic variants leads to the disease is needed in order to develop therapeutic strategies. Here, we review the current state of ASD research related to gene discovery and examples of emerging molecular mechanisms (protein translation and alternative splicing). In addition, we discuss how patient-derived three-dimensional brain organoids might provide an opportunity to model specific genetic variants in order to define molecular and cellular defects that could be amenable for developing and screening personalized therapies related to ASD.

Gentamicin release from photopolymerized PEG diacrylate and pHEMA hydrogel discs and their in vitro antimicrobial activities.

Hydrogels based on poly(ethylene glycol)-diacrylate (PEG-DA) and 2-hydroxyethyl methacrylate (HEMA) were polymerized with cross-linking agent ethylene glycol diacrylate (EGDMA) under mild photoinitiating conditions. PEG-DA and HEMA concentrations of disks with 1 +/- 0.3 mm thickness were 30% and 50% w/w and 40% and 60% w/w, respectively. Gentamicin sulphate was incorporated into the hydrogel during photopolymerization and its release kinetics were tested by spectrophotometric method at 255 nm wavelength in phosphate buffer (pH 7.4) and citrate buffer (pH 2.2). The drug release in citrate buffer was faster compared with to phosphate buffer. The release of drug from 40% HEMA containing hydrogel showed Fickian diffusion mechanisms in phosphate buffer (pH 7.4). Antimicrobial efficiency of the samples was tested by agar diffusion method in two different bacterial cultures (Pseudomonas aeruginosa [ATCC 10145], Staphylococcus aureus [ATCC 25923]). Inhibition zone diameter (mm) surrounding each sample was measured after 24 hr incubation of drug loaded disks onto agar plates at 37 degrees C. Inhibition zone formation also confirms that gentamicin sulphate preserves its antimicrobial activity after subjected to photopolymerization conditions.

RAN Translation Regulated by Muscleblind Proteins in Myotonic Dystrophy Type 2.

Several microsatellite-expansion diseases are characterized by the accumulation of RNA foci and RAN proteins, raising the possibility of a mechanistic connection. We explored this question using myotonic dystrophy type 2, a multisystemic disease thought to be primarily caused by RNA gain-of-function effects. We demonstrate that the DM2 CCTG⋅CAGG expansion expresses sense and antisense tetrapeptide poly-(LPAC) and poly-(QAGR) RAN proteins, respectively. In DM2 autopsy brains, LPAC is found in neurons, astrocytes, and glia in gray matter, and antisense QAGR proteins accumulate within white matter. LPAC and QAGR proteins are toxic to cells independent of RNA gain of function. RNA foci and nuclear sequestration of CCUG transcripts by MBNL1 is inversely correlated with LPAC expression. These data suggest a model that involves nuclear retention of expansion RNAs by RNA-binding proteins (RBPs) and an acute phase in which expansion RNAs exceed RBP sequestration capacity, are exported to the cytoplasm, and undergo RAN translation. VIDEO ABSTRACT.