Distinct structural brain network properties in children with familial versus non-familial attention-deficit/hyperactivity disorder (ADHD).

Attention-deficit/hyperactivity disorder (ADHD) is among the most prevalent, inheritable, and heterogeneous childhood-onset neurodevelopmental disorders. Children with a hereditary background of ADHD have heightened risk of having ADHD and persistent impairment symptoms into adulthood. These facts suggest distinct familial-specific neuropathological substrates in ADHD that may exist in anatomical components subserving attention and cognitive control processing pathways during development. The objective of this study is to investigate the topological properties of the gray matter (GM) structural brain networks in children with familial ADHD (ADHD-F), non-familial ADHD (ADHD-NF), as well as matched controls. A total of 452 participants were involved, including 132, 165 and 155 in groups of ADHD-F, ADHD-NF and typically developed children, respectively. The GM structural brain network was constructed for each group using graph theoretical techniques with cortical and subcortical structures as nodes and correlations between volume of each pair of the nodes within each group as edges, while controlled for confounding factors using regression analysis. Relative to controls, children in both ADHD-F and ADHD-NF groups showed significantly higher nodal global and nodal local efficiencies in the left caudal middle frontal gyrus. Compared to controls and ADHD-NF, children with ADHD-F showed distinct structural network topological patterns associated with right precuneus (significantly higher nodal global efficiency and significantly higher nodal strength), left paracentral gyrus (significantly higher nodal strength and trend toward significantly higher nodal local efficiency) and left putamen (significantly higher nodal global efficiency and trend toward significantly higher nodal local efficiency). Our results for the first time in the field provide evidence of familial-specific structural brain network alterations in ADHD, that may contribute to distinct clinical/behavioral symptomology and developmental trajectories in children with ADHD-F.

Non-familial White Sponge Nevus, an Innocuous yet Clinically Significant Entity: Report of a Case with Review of the Literature.

White sponge nevus (WSN) is a hereditary mucosal defect that primarily affects the oral mucosa, presenting with asymptomatic velvety, corrugated hyperkeratotic white plaques that do not disappear on stretching the mucosa. In this case report, we present a non-familial case of a WSN occurring in the tongue in a middle-aged female, which was misdiagnosed as verrucous leukoplakia.

Variance of age-specific log incidence decomposition (VALID): a unifying model of measured and unmeasured genetic and non-genetic risks.

BACKGROUND: The extent to which known and unknown factors explain how much people of the same age differ in disease risk is fundamental to epidemiology. Risk factors can be correlated in relatives, so familial aspects of risk (genetic and non-genetic) must be considered. DEVELOPMENT: We present a unifying model (VALID) for variance in risk, with risk defined as log(incidence) or logit(cumulative incidence). Consider a normally distributed risk score with incidence increasing exponentially as the risk increases. VALID's building block is variance in risk, Δ2, where Δ = log(OPERA) is the difference in mean between cases and controls and OPERA is the odds ratio per standard deviation. A risk score correlated r between a pair of relatives generates a familial odds ratio of exp(rΔ2). Familial risk ratios, therefore, can be converted into variance components of risk, extending Fisher's classic decomposition of familial variation to binary traits. Under VALID, there is a natural upper limit to variance in risk caused by genetic factors, determined by the familial odds ratio for genetically identical twin pairs, but not to variation caused by non-genetic factors. APPLICATION: For female breast cancer, VALID quantified how much variance in risk is explained-at different ages-by known and unknown major genes and polygenes, non-genomic risk factors correlated in relatives, and known individual-specific factors. CONCLUSION: VALID has shown that, while substantial genetic risk factors have been discovered, much is unknown about genetic and familial aspects of breast cancer risk especially for young women, and little is known about individual-specific variance in risk.

The Genetic Architecture of Non-Syndromic Rhegmatogenous Retinal Detachment.

Rhegmatogenous retinal detachment (RRD) is the most common form of retinal detachment (RD), affecting 1 in 10,000 patients per year. The condition has significant ocular morbidity, with a sizeable proportion of patients obtaining poor visual outcomes. Despite this, the genetics underpinning Idiopathic Retinal Detachment (IRD) remain poorly understood; this is likely due to small sample sizes in relevant studies. The majority of research pertains to the well-characterised Mende lian syndromes, such as Sticklers and Wagners, associated with RRD. Nevertheless, in recent years, there has been an increasing body of literature identifying the common genetic mutations and mechanisms associated with IRD. Several recent Genomic Wide Association Studies (GWAS) studies have identified a number of genetic loci related to the development of IRD. Our review aims to provide an up-to-date summary of the significant genetic mechanisms and associations of Idiopathic RRD.

[The coincidence of benign non-familial infantile seizures type 2 with osteogenesis imperfecta type 1]. / Sochetanie dobrokachestvennykh nesemeinykh infantil'nykh pristupov 2-go tipa s nesovershennym osteogenezom 1-go tipa.

A clinical case of a patient with neonatal epilepsy at the age of 5 months, with impaired bone formation, early osteoporosis and frequent limb fractures is described. Panel sequencing confirmed by Sanger sequencing revealed two independent hereditary diseases - osteogenesis imperfect type 1, associated with a mutation in the COL1A1 gene (c.2010delT) and benign non-familial infantile seizures associated with a mutation in the PRRT2 gene (c.649dupC). A unique clinical case of a combination of these diseases is presented.

Distinct Thalamic and Frontal Neuroanatomical Substrates in Children with Familial vs. Non-Familial Attention-Deficit/Hyperactivity Disorder (ADHD).

Attention-deficit/hyperactivity disorder (ADHD) is a highly prevalent, inheritable, and heterogeneous neurodevelopmental disorder. Children with a family history of ADHD are at elevated risk of having ADHD and persisting its symptoms into adulthood. The objective of this study was to investigate the influence of having or not having positive family risk factor in the neuroanatomy of the brain in children with ADHD. Cortical thickness-, surface area-, and volume-based measures were extracted and compared in a total of 606 participants, including 132, 165, and 309 in groups of familial ADHD (ADHD-F), non-familial ADHD (ADHD-NF), and typically developed children, respectively. Compared to controls, ADHD probands showed significantly reduced gray matter surface area in the left cuneus. Among the ADHD subgroups, ADHD-F showed significantly increased gray matter volume in the right thalamus and significantly thinner cortical thickness in the right pars orbitalis. Among ADHD-F, an increased volume of the right thalamus was significantly correlated with a reduced DSM-oriented t-score for ADHD problems. The findings of this study may suggest that a positive family history of ADHD is associated with the structural abnormalities in the thalamus and inferior frontal gyrus; these anatomical abnormalities may significantly contribute to the emergence of ADHD symptoms.

Soluble interleukin-2 receptor as a predictive and prognostic marker for patients with familial breast cancer.

The incidence of breast cancer increases annually, and it has become common within families of breast cancer patients. Interleukin-2 activates cytotoxic T lymphocytes, which are important for cancer immunity. To identify markers of increased familial breast cancer risk, soluble interleukin-2 receptor levels and immunologic factors were investigated in familial breast cancer and non-familial breast cancer patients. Of 106 untreated breast cancer patients in this study, 24 had familial breast cancer and 82 had non-familial breast cancer. The patients' soluble interleukin-2 receptor, interleukin-10, vascular endothelial growth factor, interleukin-17, regulatory T cell, myeloid-derived suppressor cell, white blood cell, and C-reactive protein levels, and their neutrophil-to-lymphocyte ratios were measured, and their prognoses were compared according to the soluble interleukin-2 receptor levels. Additionally, postoperative tissues from the patients with high soluble interleukin-2 receptor levels were stained with programmed cell death ligand 1 and cluster of differentiation 8. The soluble interleukin-2 receptor level in the familial breast cancer patients was significantly higher, and it showed significantly stronger correlations with the neutrophil-to-lymphocyte ratio and the interleukin-10, vascular endothelial growth factor, interleukin-17, regulatory T cell, myeloid-derived suppressor cell, white blood cell, and C-reactive protein levels, than in the non-familial breast cancer patients. The regulatory T cell and myeloid-derived suppressor cell levels were significantly higher in the patients with high soluble interleukin-2 receptor levels, and the overall survival and disease-free-survival rates were significantly worse for the familial breast cancer patients than for the non-familial breast cancer patients. Triple-negative breast cancer tissues from the familial breast cancer patients with high soluble interleukin-2 receptor levels stained well for programmed cell death ligand 1 and cluster of differentiation 8. Soluble interleukin-2 receptor levels can be used to predict the prognosis of familial breast cancer patients. Prospectively identifying patients who are less likely to have non-familial breast cancer is vital for improving their overall survival.

Intergenerational Commensality: A Critical Discussion on Non-Familial Age Groups Eating Together.

Connecting intergenerational relationships and commensality has been a neglected area in research and conceptual development within both food and life-course studies. This has been especially true of relations beyond the family. Here, public and private settings are explored in order to examine the relationship between eating together and generationally intelligent empathy. This is to help the discovery of spaces where different generations can interact positively around food and mealtimes. Contemporary social and public health challenges include: to adapt to increased longevity and to build solidarity between generations; to repair the relations between generations arising from institutional segregation; and to increase experiences of generational connection and social inclusion. As age-based cohorts are led to see themselves as separate from each other, we must find ways of building and negotiating new complementary roles for different parts of the life-course. Commensality, eating together at the same table provides an important cultural location and opportunity around which complementary understandings between generations may be built. A new framework is proposed to help identify and critically examine the variables underpinning non-familial intergenerational commensal spaces.

Non-familial Juvenile Polyposis Syndrome Presenting as Rectal Prolapse: An Unusual Presentation of a Rare Disease.

Juvenile polyposis syndrome is a rare inherited disorder that afflicts the gastrointestinal system. It usually occurs as a result of gene mutations; to date, several gene mutations, including those involving the bone morphogenetic protein receptor type IA (BMPR1A) gene, have been implicated in heralding the onset of the ailment. The disease is characterized by the infiltration of the gastrointestinal system with numerous hamartomas, which are predominantly benign. However, if left untreated, the hamartomas can undergo malignant transformations. Timely diagnosis and prompt surgical intervention are, therefore, imperative in portending favorable disease outcomes. We hereby delineate the case of a patient who presented with rectal prolapse and bleeding per rectum. Further diagnostic workup revealed the presence of polyps throughout the colon and the rectum, thereby insinuating a diagnosis of non-familial juvenile polyposis syndrome. The patient was managed through open surgery and continues to do well with no indications of disease recurrence.

Beyond Just Giving Care: Exploring the Role of Culture in Chinese American Personal Care Aides' Work.

As the number of older Chinese Americans with immigration background increases, there is a growing need for Chinese American personal care aides (CA-PCAs) to assist them with aging at home by providing culturally congruent and linguistically competent service. However, little is known about how culture factors into the caregiving process and influences CA-PCAs' well-being. In this study, two focus groups were conducted with ten immigrant CA-PCAs and conventional content analysis was used to analyze the qualitative data. Seven cultural themes were identified, including guanxi (relationship), renqing (favor), mianzi/lian (face), hierarchy and authority, communication, harmony, and elder respect. By drawing attention to the idiosyncratic cultural landscape and entailed challenges faced by underrepresented CA-PCAs, the investigators corroborate the importance of cultural sensitivity for working with ethnic minority non-familial caregivers. The findings shed light on cultural factors that can be targeted by culturally sensitive direct practices, programs, and policies.

Genetic characteristics of non-familial epilepsy.

BACKGROUND: Knowledge of the genetic etiology of epilepsy can provide essential prognostic information and influence decisions regarding treatment and management, leading us into the era of precision medicine. However, the genetic basis underlying epileptogenesis or epilepsy pharmacoresistance is not well-understood, particularly in non-familial epilepsies with heterogeneous phenotypes that last until or start in adulthood. METHODS: We sought to determine the contribution of known epilepsy-associated genes (EAGs) to the causation of non-familial epilepsies with heterogeneous phenotypes and to the genetic basis underlying epilepsy pharmacoresistance. We performed a multi-center study for whole exome sequencing-based screening of 178 selected EAGs in 243 non-familial adult patients with primarily focal epilepsy (122 drug-resistant and 121 drug-responsive epilepsies). The pathogenicity of each variant was assessed through a customized stringent filtering process and classified according to the American College of Medical Genetics and Genomics guidelines. RESULTS: Possible causal genetic variants of epilepsy were uncovered in 13.2% of non-familial patients with primarily focal epilepsy. The diagnostic yield according to the seizure onset age was 25% (2/8) in the neonatal and infantile period, 11.1% (14/126) in childhood and 14.7% (16/109) in adulthood. The higher diagnostic yields were from ion channel-related genes and mTOR pathway-related genes, which does not significantly differ from the results of previous studies on familial or early-onset epilepsies. These potentially pathogenic variants, which were identified in genes that have been mainly associated with early-onset epilepsies with severe phenotypes, were also linked to epilepsies that start in or last until adulthood in this study. This finding suggested the presence of one or more disease-modifying factors that regulate the onset time or severity of epileptogenesis. The target hypothesis of epilepsy pharmacoresistance was not verified in our study. Instead, neurodevelopment-associated epilepsy genes, such as TSC2 or RELN, or structural brain lesions were more strongly associated with epilepsy pharmacoresistance. CONCLUSIONS: We revealed a fraction of possible causal genetic variants of non-familial epilepsies in which genetic testing is usually overlooked. In this study, we highlight the importance of earlier identification of the genetic etiology of non-familial epilepsies, which leads us to the best treatment options in terms of precision medicine and to future neurobiological research for novel drug development. This should be considered a justification for physicians determining the hidden genetics of non-familial epilepsies that last until or start in adulthood.

Health Literacy among Non-Familial Caregivers of Older Adults: A Study Conducted in Tuscany (Italy).

Many older adults who live at home depend on a caregiver. When familial support cannot provide the necessary care, paid caregivers are frequently hired. Health literacy (HL) is the knowledge and competence required of people to meet the complex demands of health in modern society. The aim of this study is to assess the HL level of paid non-familial caregivers who were enrolled through two different sources: from the homes of assisted people in two Tuscan health districts (first sample) and during job interviews in a home care agency operating in Florence (second sample). The two different recruitment contexts allow us to provide a broader view of the phenomenon, presenting a picture of the HL level of those who are already working and those who are looking for a new job in this field. One-on-one face-to-face interviews, which include the administration of the Newest Vital Sign (NVS) to measure HL, were conducted. Recruitment resulted in 84 caregivers in the first sample and 68 in the second sample. In the first sample, the mean age was 51.2 ± 9 years; 94% of the participants were women. A high likelihood or likelihood of inadequate HL (i.e., a low level of HL) was found in 73.8% of cases. In the second sample, the mean age was 43.7 ± 11.5 years; 83.8% of the participants were women, and 80.9% had a low level of HL. In both samples, HL was statistically associated with the level of understanding of the Italian language. In conclusion, inadequate HL is an under-recognized problem among non-familial caregivers. Educational programs that aim to increase HL skills could be an effective approach to improving the qualification of informal healthcare professionals.

Non-familial paid caregivers as potential flu carriers and cause of spread: the primary prevention of flu measured through their adhesion to flu vaccination campaigns-A Florentine experience.

Introduction: Influenza vaccination is recommended for caregivers of elderly people. In a study aimed at assessing the level of health literacy (HL) in a sample non-familial caregivers in the Florence Health District (Tuscany), data were collected regarding access and adherence to the flu vaccination campaigns. Methods: The sample consists of 47 non-familial paid caregivers. We collected information regarding socio-demographic characteristics, services provided and daily work time, whether or not influenza vaccination was administered for the 2016/2017 season and in the previous three years. The level of HL was assessed through the Newest Vital Sign. Results: 63.8% of non-familial caregivers have not joined the flu campaigns over the last four years, 14.9% have been vaccinated only sometimes (in some epidemic seasons), and 21.3% have received a flu shot in all the seasons investigated. Most of the non-familial caregivers who do not get vaccinated (27.7%) do not perceive that they are in direct contact with a person at-risk; those who get the vaccine regularly (12.8%) reported they want to protect the assisted person as motivation for vaccine uptake. Vaccination was not associated with HL. Conclusion: Adhesion to anti-flu vaccination campaigns for these homecare workers has been resulted rather poor. Coverage does not seem to be related with HL level. It seems appropriate to promote extensively flu vaccination among family carers by actively offering the vaccination in appropriate forms, places and times, to avoid serious consequences on elderly people with higher risk of comorbidity and frailty.

Exome sequencing in 51 early onset non-familial CRC cases.

BACKGROUND: Colorectal cancer (CRC) cases with an age of onset <40 years suggests a germline genetic cause. In total, 51 simplex cases were included to test the hypothesis of CRC as a mendelian trait caused by either heterozygous autosomal dominant or bi-allelic autosomal recessive pathogenic variants. METHODS: The cohort was whole exome sequenced (WES) at 100× coverage. Both a dominant- and recessive model were used for searching predisposing genetic factors. In addition, we assayed recessive variants of potential moderate risk that were enriched in our young-onset CRC cohort. Variants were filtered using a candidate cancer gene list or by selecting variants more likely to be pathogenic based on variant type (e.g., loss-of-function) or allele frequency. RESULTS: We identified one pathogenic variant in PTEN in a patient subsequently confirmed to have a hereditary hamartoma tumor syndrome (Cowden syndrome) and one patient with a pathogenic heterozygous variant in PMS2 that was originally not identified by WES due to low quality reads resulting from pseudogenes. In addition, we identified three heterozygous candidate missense variants in known cancer susceptibility genes (BMPR1A, BRIP1, and SRC), three truncating variants in possibly novel cancer genes (CLSPN, SEC24B, SSH2) and four candidate missense variants in ACACA, NR2C2, INPP4A, and DIDO1. We also identify five possible autosomal recessive candidate genes: ATP10B, PKHD1, UGGT2, MYH13, TFF3. CONCLUSION: Two clear pathogenic variants were identified in patients that had not been identified clinically. Thus, the chance of detecting a hereditary cancer syndrome in patients with CRC at young age but without family history is 2/51 (4%) and therefore the clinical benefit of genetic testing in this patient group is low. Of note, using stringent filtering, we have identified a total of ten candidate heterozygous variants and five possibly biallelic autosomal recessive candidate genes that warrant further study.

Etiology of short stature in Indian children and an assessment of the growth hormone-insulin-like growth factor axis in children with idiopathic short stature.

Background Our objectives were to evaluate the etiology of short stature, assess the prevalence of idiopathic short stature (ISS) and assess the growth hormone (GH)-insulin-like growth factor (IGF) axis in children with ISS. Methods A stepwise diagnostic evaluation was done in 394 children aged 4-16 years with short stature. Children with no definitive etiology were labeled as ISS. In these children, baseline IGF-1, IGF binding protein-3 (IGFBP-3) and stimulated IGF-1 after administration of GH for 4 days were measured. Results Hypothyroidism (in 18.1%) and ISS (in 15.5%) were the commonest causes of short stature. In children with ISS (n=61), the mean baseline and stimulated IGF-1 standard deviation scores (SDSs) were -1.2±1.0 and -0.3±1.4, respectively, with levels below -2 SDS in 13 (21%) and six (10%) children, respectively. In 33 (54%) of the ISS patients, response to GH was suboptimal (increment in the IGF-1 level <40%). There was no difference in the mean peak GH, IGFBP-3 and baseline and stimulated IGF-1 levels between children with familial and non-familial ISS. A significant positive correlation of height SDS with baseline IGF-1 SDS (r=0.28, p=0.026), stimulated IGF-1 SDS (r=0.32, p=0.010) and ΔIGF-1 SDS (r=0.26, p=0.036) was observed in children with ISS. Conclusions Hypothyroidism and ISS were the commonest etiologies for short stature. The baseline IGF-1 was below -2 SDS in 21% and the increment after GH stimulation was suboptimal in 54% of children, indicating that a substantial proportion of children with ISS had an impaired GH-IGF axis.

Drug use disorders and post-traumatic stress disorder over 25 adult years: role of psychopathology in relational networks.

BACKGROUND: In traumatized populations, drug use disorders and post-traumatic stress disorder (PTSD) persist for many years. Relational factors that mediate this persistence have rarely been systematically examined. Our aim is to examine the relative effects of psychopathology in familial and non-familial networks on the persistence of both disorders over adulthood. METHODS: We utilized longitudinal data from an epidemiologically ascertained sample of male Vietnam veterans (n=642). Measures included DSM-IV drug use disorders, other psychiatric disorders, network problem history and time-varying marital and employment characteristics. Longitudinal measures of veterans' psychopathology and social functioning were retrospectively obtained for each year over a 25 year period. We used generalized estimating equations (GEE) to estimate the relative effects of network problems on veteran's drug use disorders and PTSD after adjusting for covariates. RESULTS: Veterans' mean age was 47 years in 1996. Prevalence of illicit drug disorders declined from 29.8% in 1972 to 8.3% in 1996, but PTSD remained at 11.7% from 13.2% in 1972. While 17.0% of veterans reported a familial drug use problem, 24.9% reported a non-familial drug use problem. In full GEE models, a non-familial drug problem was a significant predictor of illicit drug use disorders over 25 years (OR=2.21, CI=1.59-3.09), while both familial depression (OR=1.69, CI=1.07-2.68) and non-familial drinking problem (OR=1.66, CI=1.08-2.54) were significant predictors of PTSD over 25 years. CONCLUSIONS: Familial and non-familial problems in networks differentially affect the persistence of drug use disorders and PTSD in traumatized male adults.

Non-familial Acrokeratosis Verruciformis of Hopf.

Acrokeratosis verruciformis of Hopf is a rare genodermatosis with an autosomal dominant mode of inheritance. It is a disorder of keratinization, characterized by multiple, flat-topped, skin-colored keratotic lesions resembling plane warts typically observed on the dorsum of the hands and feet. Histopathologically, the lesion shows considerable hyperkeratosis, acanthosis, and papillomatosis, mimicking a "church spire", and a thickened granular layer. It arises in early life, often at birth or infancy. Herein, we report on a rare sporadic case of acrokeratosis verruciformis of Hopf. A 44-year-old Caucasian man presented with multiple, grouped, hyperkeratotic, whitish, flat papules on his shins and feet, which had been present for more than one year. Histopathological examination showed typical findings of acrokeratosis verruciformis of Hopf. Our case is unique in that the patient had no familial history of similar skin lesions.

Non-familial Acrokeratosis Verruciformis of Hopf

Acrokeratosis verruciformis of Hopf is a rare genodermatosis with an autosomal dominant mode of inheritance. It is a disorder of keratinization, characterized by multiple, flat-topped, skin-colored keratotic lesions resembling plane warts typically observed on the dorsum of the hands and feet. Histopathologically, the lesion shows considerable hyperkeratosis, acanthosis, and papillomatosis, mimicking a "church spire", and a thickened granular layer. It arises in early life, often at birth or infancy. Herein, we report on a rare sporadic case of acrokeratosis verruciformis of Hopf. A 44-year-old Caucasian man presented with multiple, grouped, hyperkeratotic, whitish, flat papules on his shins and feet, which had been present for more than one year. Histopathological examination showed typical findings of acrokeratosis verruciformis of Hopf. Our case is unique in that the patient had no familial history of similar skin lesions.

Non-familial Generalized Hypotrichosis Simplex / 대한피부과학회지

Hypotrichosis simplex is a descriptive term of hair loss without other ectodermal or systemic abnormalities. Hypotrichosis simplex with non-familial and generalized types has been seldom reported. A 30-year-old man visited our clinic complaining of scalp hair loss since birth. There was no hair on the arms, axillae and legs. He had relatively scanty eyebrows and pubic hairs. None of his family members had known health problems or any hereditary disease. Hair shaft examination based on electron microscopy did not reveal any structural abnormalities. Microscopic examination of a scalp biopsy specimen showed a reduced number of hair follicles with vellus hairs replacing terminal hairs. Herein we report a rare and interesting case of non-familial generalized hypotrichosis simplex.

Extensive Cornifying Darier's Disease without a Family History / 대한피부과학회지

Darier's disease is an uncommon inheritable genodermatosis that is characterized by recurrent waxy, hyperkeratotic papules that usually occur over the seborrheic areas. The characteristic histopathological changes are acantholysis leading to the formation of lacunae and dyskeratosis with corps ronds and grain, which are diagnostic clues of the disease along with the typical clinical features. A 50-year-old Korean male patient presented with an extensive involvement of whitish thick hyperkeratotic fissures, verrucoid plaques with oozing and foul odor over the skin for about 30 years. We report here on an unusual case of extensive cornifying Darier's disease in a patient who has no family history of this disease.