Evolutionary history and systematics of European blind mole rats (Rodentia: Spalacidae: Nannospalax): Multilocus phylogeny and species delimitation in a puzzling group.

Species delimitation is a powerful approach to assist taxonomic decisions in challenging taxa where species boundaries are hard to establish. European taxa of the blind mole rats (genus Nannospalax) display small morphological differences and complex chromosomal evolution at a shallow evolutionary divergence level. Previous analyses led to the recognition of 25 'forms' in their distribution area. We provide a comprehensive framework to improve knowledge on the evolutionary history and revise the taxonomy of European blind mole rats based on samples from all but three of the 25 forms. We sequenced two nuclear-encoded genetic regions and the whole mitochondrial cytochrome b gene for phylogenetic tree reconstructions using concatenation and coalescence-based species-tree estimations. The phylogenetic analyses confirmed that Aegean N. insularis belongs to N. superspecies xanthodon, and that it represents the second known species of this superspecies in Europe. Mainland taxa reached Europe from Asia Minor in two colonisation events corresponding to two superspecies-level taxa: N. superspecies monticola (taxon established herewith) reached Europe c. 2.1 million years ago (Mya) and was followed by N. superspecies leucodon (re-defined herewith) c. 1.5 Mya. Species delimitation allowed the clarification of the taxonomic contents of the above superspecies. N. superspecies monticola contains three species geographically confined to the western periphery of the distribution of blind mole rats, whereas N. superspecies leucodon is more speciose with six species and several additional subspecies. The observed geographic pattern hints at a robust peripatric speciation process and rapid chromosomal evolution. The present treatment is thus regarded as the minimum taxonomic content of each lineage, which can be further refined based on other sources of information such as karyological traits, crossbreeding experiments, etc. The species delimitation models also allowed the recognition of a hitherto unnamed blind mole rat taxon from Albania, described here as a new subspecies.

Association Between Metastatic Pattern and Prognosis in Stage IV Gastric Cancer: Potential for Stage Classification Reform.

PURPOSE: This study aims to clarify the association between metastatic pattern and prognosis in stage IV gastric cancer, with a focus on patients presenting with metastases limited to nonregional lymph nodes. METHODS: In this retrospective cohort study, the National Cancer Database was used to identify patients ≥ 18 years of age diagnosed with stage IV gastric cancer between 2016 and 2019. Patients were stratified according to pattern of metastatic disease at diagnosis: nonregional lymph nodes only ("stage IV-nodal"), single systemic organ ("stage IV-single organ"), or multiple organs ("stage IV-multi-organ"). Survival was assessed by Kaplan-Meier curves and multivariable Cox models in unadjusted and propensity score-matched samples. RESULTS: Overall, 15,050 patients were identified, including 1,349 (8.7%) stage IV-nodal patients. Most patients in each group received chemotherapy [68.6% of stage IV-nodal patients, 65.2% of stage IV-single organ patients, and 63.5% of stage IV-multi-organ patients (p = 0.003)]. Stage IV-nodal patients exhibited better median survival (10.5 months, 95% CI 9.7-11.9, p < 0.001) than single organ (8.0, 95% CI 7.6-8.2) and multi-organ (5.7, 95% CI 5.4-6.0) patients. In the multivariable Cox model, stage IV-nodal patients also exhibited better survival (HR 0.79, 95% CI 0.73-0.85, p < 0.001) than single organ (reference) and multi-organ (HR 1.27, 95% CI 1.22-1.33, p < 0.001) patients. CONCLUSIONS: Nearly 9% of clinical stage IV gastric cancer patients have their distant disease confined to nonregional lymph nodes. These patients were managed similarly to other stage IV patients but experienced a better prognosis, suggesting opportunities to introduce M1 staging subclassifications.

[Lou Salomé - the woman with whom Nietzsche,Rilke and Freud were in love].

Lou Salomé (1861-1937) left her native Russia at the age of nineteen and began her university studies in Zurich. During her long life, the famous and less famous men who came into contact with her almost without exception came under her influence. Some had passionate love, some had platonic love, and some had a "more than" master and student relationship. Was she a muse or a femme fatale? An analysis of her special life path provides an answer to the question.

The impact of 3D printed models on spatial orientation in echocardiography teaching.

PURPOSE: During our transthoracic echocardiography (TTE) courses, medical students showed difficulty in spatial orientation. We implemented the use of 3D printed cardiac models of standard TTE views PLAX, PSAX, and A4C and assessed their efficacy in TTE-teaching. METHODS: One hundred fifty-three participants were split into two groups. A pre-test-retest of anatomy, 2D -, and 3D orientation was conducted. The intervention group (n = 77) was taught using 3D models; the control group (n = 76) without. Both were comparable with respect to baseline parameters. Besides test-scores, a Likert scale recorded experiences, difficulties, and evaluation of teaching instruments. RESULTS: From the 153 students evaluated, 123 improved, 20 did worse, and ten achieved the same result after the course. The median overall pre-test score was 29 of 41 points, and the retest score was 35 (p < 0.001). However, the intervention group taught with the 3D models, scored significantly better overall (p = 0.016), and in 2D-thinking (p = 0.002) and visual thinking (p = 0.006) subtests. A backward multivariate linear regression model revealed that the 3D models are a strong individual predictor of an excellent visual thinking score. In addition, our study showed that students with difficulty in visual thinking benefited considerably from the 3D models. CONCLUSION: Students taught using the 3D models significantly improved when compared with conventional teaching. Students regarded the provided models as most helpful in their learning process. We advocate the implementation of 3D-printed heart models featuring the standard views for teaching echocardiography. These findings may be transferable to other evidence based medical and surgical teaching interventions.

Long-Term Follow-Up of Survivors of Extracorporeal Life Support Therapy for Cardiogenic Shock: Are They Really Survivors?

Background and Objectives: Cardiogenic shock (CS) is a medical emergency associated with a high mortality rate. Veno-arterial extracorporeal membrane oxygenation (VA-ECMO) has become an accepted therapy for CS. Despite widely available data for short-term survival rates, there are only limited data available regarding long-term outcomes following successful VA-ECMO therapy. Materials and Methods: We analyzed the demographics, past medical history, adverse events, and outcomes of survivors who received VA-ECMO support for CS at our center from January 2012 to December 2019. Post-cardiotomy cases were excluded. Results: A total of 578 VA-ECMO implantations on 564 consecutive patients due to CS were identified during the study period. Successful weaning was achieved in 207 (36.7%) patients. Among the survivors, 126 (63%) patients received VA-ECMO therapy without preceding cardiac surgery during their current admission. A follow-up exceeding 12 (mean: 36 ± 20.9) months was available in a total of 55 (43.7%) survivors. The mean VA-ECMO perfusion time was 10.9 (±7.7) days with a mean intensive care unit (ICU) stay of 38.2 (±29.9) days and a mean hospital stay of 49.9 (±30.5) days. A total of 3 deaths were recorded during long-term follow-up (mean survival of 26 ± 5.3 months). Conclusions: Despite the high mortality associated with VA-ECMO therapy, a long-term follow-up with an acceptably low rate of negative cardiac events can be achieved in many survivors. We observed an acceptable low rate of new cardiac events. Further evaluation, including a quality-of-life assessment and a close follow-up for rarer complications in these patients, is needed to elucidate the longer-term outcomes for survivors of invasive VA-ECMO therapy.

Treatment of Complex Two-Vessel Coronary Heart Disease with Single Left Internal Mammary Artery as T-Graft with Itself-A Retrospective Double Center Analysis of Short-Term Outcomes.

Background and Objectives: The strategy of revascularization may be constrained in patients with insufficient bypass grafts and with increased risk of wound healing disorders. Among those with complex left-sided double-vessel disease in whom a percutaneous coronary intervention (PCI), as well as the surgical procedure of minimally invasive coronary artery bypass grafting via left minithoracotomy (MICS CABG), is not a treatment option, CABG using the left internal mammary artery as a T-graft with itself may be an effective treatment strategy. Materials and Methods: We reviewed the data from patients treated in Cologne and Tuebingen from 2019 to 2022. We included 40 patients who received left internal mammary artery (LIMA) grafting, and additional T-graft with the LIMA itself. The objective was focused on intraoperative and short-term outcomes. Results: A total of 40 patients were treated with the LIMA-LIMA T-graft procedure with a Fowler score calculated at 20.1 ± 3.0. A total of 37.5% of all patients had lacking venous graft material due to prior vein stripping, and 21 patients presented severe vein varicosis. An overall of 2.6 ± 0.5 distal anastomoses (target vessels were left anterior descending, diagonal, intermediate branch, and/or left marginal ramus) were performed, partly sequentially. Mean flow of LIMA-Left anterior descending (LAD) anastomosis was 59.31 ± 11.04 mL/min with a mean PI of 1.21 ± 0.18. Mean flow of subsequent T-Graft accounted for 51.31 ± 3.81 mL/min with a mean PI of 1.39 ± 0.47. Median hospital stay was 6.2 (5.0; 7.5) days. No incidence of postoperative wound healing disorders was observed, and all patients were discharged. There was one 30-day readmission with a diagnosis of pericardial effusion (2.5%). There was no 30-day mortality within the cohort. Conclusions: Patients requiring surgical myocardial revascularization due to complex two-vessel coronary artery disease (CAD) can be easily managed with LIMA alone, despite an elevated Fowler score and a promising outcome. A prospective study needs to be conducted, as well as longer term surveillance, to substantiate and benchmark the long-term results, as well as the patency rates.

19 pandemic and obsessive compulsive disorder. How does the COVID-19 pandemic influence symptoms in obsessive compulsive disorder patients?

The COVID-19 pandemic had a significant psychological impact on the mental state of both healthy and psychiatric patients. The authors involved 34 obsessive-compulsive patients in their study. The patient group included both patients with and without symptoms of contamination, patients with and without COVID-19 infection, and patients with and without continuous, available therapy. Changes in general condition as a result of the pandemic that had existed for nearly two years, adherence to health standards, and changes in compulsive symptoms were assessed. The results show that the non-specific stress effect of the pandemic significantly less affected those patients who are under care compared to those who did not receive therapy. However, the characteristics of the symptomatic picture and the fact of COVID infection did not significantly affect the general condition of the patients, their adherence to the health regulations, and the change in compulsive symptoms. The main finding of the study is that psychiatric, psychotherapeutic patient follow-up is the most important factor in the prevention of deterioration, and neither the symptomatic dimension (symptomatic subgroup) nor COVID infection played a significant role. The results support that in such an acute and persistent stress situation as a pandemic, the continuous availability of professional help and the appropriate therapeutic relationship is one of the most important protective factors in relapse prevention.

Exploring Mentoring Experiences, Perceptions, and Needs of General Internal Medicine Clinician Educators Navigating Academia: a Mixed-Methods Study.

BACKGROUND: Few studies examined specific mentoring needs and preferences of clinician educators (CEs). Further research on CEs' perceptions of mentoring adequacy, as related to educational development and career advancement, is needed. OBJECTIVE: The study aims were to (1) explore general internal medicine CEs' experiences as mentees within various mentoring models; (2) examine the perceived quality, nature, and impact of mentoring on career development; and (3) determine whether specific models of mentoring impact their attitudes towards mentoring. DESIGN: Sequential mixed methods study design answered the study questions. PARTICIPANTS: Society of General Internal Medicine members identifying themselves as CEs. MAIN MEASURES/APPROACH: Participants completed an anonymous online survey and a subsample participated in two semi-structured focus group discussions. Outcomes of interest were perceptions of mentoring experiences, and perspectives on quality of mentoring as well as mentoring needs specific to clinician educators. KEY RESULTS: One hundred thirty-nine participants completed the survey (37% response rate) with 20 participants in focus group discussions. Among CEs with perceived high-quality mentor relationships (e.g., reporting strongly agree), peer mentorship was viewed as adequate mentorship (45% (n = 17) vs 24% (n = 24), p < 0.05), as beneficial for career development (77% (n = 40) vs 48% (n = 41), p < 0.01) and as being challenged to become a better CE (58% (n = 30) vs 35% (n = 29), p < 0.05), compared to reporting agree or lower. Qualitative analysis generated four themes: (1) A mentoring team promotes career advancement, (2) peer mentors are important at every stage of a CE's career, (3) there is inadequate mentoring specific to CE needs, and (4) mentoring needs protected time and skill development. CONCLUSIONS: The traditional dyadic mentoring relationship may not adequately address all professional needs of CEs. A mentoring team can provide valuable perspectives on career goals. Peer mentoring can be powerful for professional growth. Mentoring needs change at different career stages and training in mentoring skills is essential.

Characterizing the nuclease accessibility of DNA in human cells to map higher order structures of chromatin.

Packaging of DNA into chromatin regulates DNA accessibility and consequently all DNA-dependent processes. The nucleosome is the basic packaging unit of DNA forming arrays that are suggested, by biochemical studies, to fold hierarchically into ordered higher-order structures of chromatin. This organization has been recently questioned using microscopy techniques, proposing an irregular structure. To address the principles of chromatin organization, we applied an in situ differential MNase-seq strategy and analyzed in silico the results of complete and partial digestions of human chromatin. We investigated whether different levels of chromatin packaging exist in the cell. We assessed the accessibility of chromatin within distinct domains of kb to Mb genomic regions, performed statistical analyses and computer modelling. We found no difference in MNase accessibility, suggesting no difference in fiber folding between domains of euchromatin and heterochromatin or between other sequence and epigenomic features of chromatin. Thus, our data suggests the absence of differentially organized domains of higher-order structures of chromatin. Moreover, we identified only local structural changes, with individual hyper-accessible nucleosomes surrounding regulatory elements, such as enhancers and transcription start sites. The regulatory sites per se are occupied with structurally altered nucleosomes, exhibiting increased MNase sensitivity. Our findings provide biochemical evidence that supports an irregular model of large-scale chromatin organization.

ECMO implantation training: Needle penetration in 3D printable materials and porcine aorta.

AIM: Patients with cardiogenic shock or ARDS, for example, in COVID-19/SARS-CoV-2, may require extracorporeal membrane oxygenation (ECMO). An ECLS/ECMO model simulating challenging vascular anatomy is desirable for cannula insertion training purposes. We assessed the ability of various 3D-printable materials to mimic the penetration properties of human tissue by using porcine aortae. METHODS: A test bench for needle penetration and piercing in sampled porcine aorta and preselected 3D-printable polymers was assembled. The 3D-printable materials had Shore A hardness of 10, 20, and 50. 17G Vygon 1.0 × 1.4 mm × 70 mm needles were used for penetration tests. RESULTS: For the porcine tissue and Shore A 10, Shore A 20, and Shore A 50 polymers, penetration forces of 0.9036 N, 0.9725 N, 1.0386 N, and 1.254 N were needed, respectively. For piercing through the porcine tissue and Shore A 10, Shore A 20, and Shore A 50 polymers, forces of 0.8399 N, 1.244 N, 1.475 N, and 1.482 N were needed, respectively. ANOVA showed different variances among the groups, and pairwise two-tailed t-tests showed significantly different needle penetration and piercing forces, except for penetration of Shore A 10 and 20 polymers (p = 0.234 and p = 0.0857). Significantly higher forces were required for all other materials. CONCLUSION: Shore A 10 and 20 polymers have similar needle penetration properties compared to the porcine tissue. Significantly more force is needed to pierce through the material fully. The most similar tested material to porcine aorta for needle penetration and piercing in ECMO-implantation is the silicon Shore A 10 polymer. This silicon could be a 3D-printable material in surgical training for ECMO-implantation.

Exploring factors of diagnostic delay for patients with bipolar disorder: a population-based cohort study.

BACKGROUND: Bipolar disorder if untreated, has severe consequences: severe role impairment, higher health care costs, mortality and morbidity. Although effective treatment is available, the delay in diagnosis might be as long as 10-15 years. In this study, we aim at documenting the length of the diagnostic delay in Hungary and identifying factors associated with it. METHODS: Kaplan-Meier survival analysis and Cox proportional hazards model was employed to examine factors associated with the time to diagnosis of bipolar disorder measured from the date of the first presentation to any specialist mental healthcare institution. We investigated three types of factors associated with delays to diagnosis: demographic characteristics, clinical predictors and patient pathways (temporal sequence of key clinical milestones). Administrative data were retrieved from specialist care; the population-based cohort includes 8935 patients from Hungary. RESULTS: In the sample, diagnostic delay was 6.46 years on average. The mean age of patients at the time of the first bipolar diagnosis was 43.59 years. 11.85% of patients were diagnosed with bipolar disorder without any delay, and slightly more than one-third of the patients (35.10%) were never hospitalized with mental health problems. 88.80% of the patients contacted psychiatric care for the first time in outpatient settings, while 11% in inpatient care. Diagnostic delay was shorter, if patients were diagnosed with bipolar disorder by non-specialist mental health professionals before. In contrast, diagnoses of many psychiatric disorders received after the first contact were coupled with a delayed bipolar diagnosis. We found empirical evidence that in both outpatient and inpatient care prior diagnoses of schizophrenia, unipolar depression without psychotic symptoms, and several disorders of adult personality were associated with increased diagnostic delay. Patient pathways played an important role as well: the hazard of delayed diagnosis increased if patients consulted mental healthcare specialists in outpatient care first or they were hospitalized. CONCLUSIONS: We systematically described and analysed the diagnosis of bipolar patients in Hungary controlling for possible confounders. Our focus was more on clinical variables as opposed to factors controllable by policy-makers. To formulate policy-relevant recommendations, a more detailed analysis of care pathways and continuity is needed.

Extended resection of a cardiac paraganglioma-A rare neuroendocrine manifestation of the heart.

BACKGROUND: Cardiac paragangliomas are rare tumors that develop from neural crest cells. They account for about 2% of all paragangliomas and there is only limited evidence of malignant transformation. CASE PRESENTATION: We present a young woman with atypical symptoms, which are related to the mass effect of the 40 × 49mm cardiac tumor on top of the left atrium. The patient underwent an extensive resection of the tumor including the root of the pulmonary trunk, the ascending aorta, and the left main artery. CONCLUSIONS: The present case is of great importance showing the need for multidisciplinary approach in the management of cardiac tumors that infiltrate multiple anatomic structures.

Video assisted thoracoscopic sympathectomy for intractable recurrent VT after minimal-invasive LVAD implantation.

BACKGROUND: Recurrent ventricular tachycardia (VT) can occur after left ventricular assist device (LVAD) implantation. In this case, medical treatment might be insufficient. We report a case of a left-sided thoracoscopic sympathectomy as a feasible treatment escalation in intractable VT. CASE REPORT: A 72-year-old patient underwent an internal cardioverter defibrillator (ICD) implantation as primary prophylaxis for VTs in the setting of staged heart failure therapy. Afterwards, due to a progressive dilative cardiomyopathy he underwent a minimal-invasive LVAD implantation (HeartWare, Medtronic). After an uneventful minimal-invasive LVAD-implantation the patient was discharged to a rehabilitation program. However, after 7 weeks he developed recurrent VTs which were successfully terminated by ICD shocks deliveries leading to severe discomfort and frequent hospitalizations. Eventually, the patient was admitted with an electrical VT storm. Successful endocardial catheter ablation of all inducible VTs were performed combined with multiple rearrangements of his oral antiarrhythmic medication. However, all these treatments could not suppress further occurrence of VTs. After an interdisciplinary discussion the patient agreed to a left-sided video-assisted thoracoscopic sympathectomy. After a follow up of 150 days the patient was free from VTs apart from one short event. CONCLUSION: We believe video-assisted thoracoscopic sympathectomy might be a surgical treatment option in patients with intractable recurrent VTs after catheter ablation of VT reentrant substrate even after minimal-invasive LVAD implantation.

Is it Safe for Patients with Left Ventricular Assist Devices to Undergo Non-Cardiac Surgery?

Background and Objectives: Since the first use of ventricular assist devices (VADs) as bridge to recovery and bridge to cardiac transplantation in the early 1990s, significant technological advances have transformed VAD implantation into a routine destination therapy. With improved survival, many patients present for cardiac surgery for conditions not directly related to their permanent mechanical circulatory support. The aim of this study was to analyze the indications and outcomes of non-cardiac surgeries (NCSs) of left ventricular assist device (LVAD) patients in tertiary center. Material and Methods: We present a single-center experience after 151 LVAD implantations in 138 consecutive patients between 2012-2019 who had to undergo NCS during a follow-up period of 37 +/- 23.4 months on left ventricular assist device (LVAD). Results: A total of 105 procedures was performed in 63 LVAD recipients, resulting in peri-operative mortality of 3.8%. Twenty-five (39.7%) of patients underwent multiple surgeries. We found no significant difference in cumulative survival associated with the performed surgical interventions (p = 0.469). Conclusion: We demonstrated good overall clinical outcomes in LVAD patients undergoing NCS. With acceptable peri-operative mortality, NCS can be safely performed in LVAD patients on long-term support.

Alu element-containing RNAs maintain nucleolar structure and function.

Non-coding RNAs play a key role in organizing the nucleus into functional subcompartments. By combining fluorescence microscopy and RNA deep-sequencing-based analysis, we found that RNA polymerase II transcripts originating from intronic Alu elements (aluRNAs) were enriched in the nucleolus. Antisense-oligo-mediated depletion of aluRNAs or drug-induced inhibition of RNA polymerase II activity disrupted nucleolar structure and impaired RNA polymerase I-dependent transcription of rRNA genes. In contrast, overexpression of a prototypic aluRNA sequence increased both nucleolus size and levels of pre-rRNA, suggesting a functional link between aluRNA, nucleolus integrity and pre-rRNA synthesis. Furthermore, we show that aluRNAs interact with nucleolin and target ectopic genomic loci to the nucleolus. Our study suggests an aluRNA-based mechanism that links RNA polymerase I and II activities and modulates nucleolar structure and rRNA production.

[Potential directions of development of the Hungarian Mental Health System].

The provision and coordination of good quality care in mental health represents a major challenge worldwide. The direct and indirect costs of psychiatric disorders, including costs due to substance use disorders are very high in the countries of the European Union. The prevalence of both mental disorders and substance use disorders is significant in Hungary. Leaders of the psychiatric profession joined forces and assembled a complex plan for the development of mental health care in Hungary. The National Programme of Mental Health represents both challenges and opportunities for this area. The main objective is a stepped care and collaborative care model for individuals with psychiatric disorders that incorporates the primary care system (general practitioners) and the community psychiatry providers. Primary care needs to develop competence to identify and treat people with common mental disorders, supported by a new care model of clinical psychologist counseling services. The tasks of these psychologists include screening (assessment interviews), giving information, leading patients to the optimal therapeutic pathways, psychoeducation and low-intensity psychological interventions. The psychologist represents a bridge between the family doctor and psychiatric care. The programme aims to shift mental health services from hospitals to community mental health facilities services. However there is a parallel organization of health and social care systems in Hungary that inhibits the complex care of patients. It is necessary to develop a closer coordination (or collaboration) of out-patient psychiatric care and the community-based services, to provide more and better facilities for reintegration of patients. Continuity of care can beestablished by psychiatrists being responsible for treatment plans and pathways, including the frequency of follow-up visits or the need for transferring patients to family doctors or to psychiatric hospitals. In some areas there is an important need for the development of specialized teams or units (for example crisis intervention service, forensic psychiatric unit, mother-child unit, psychiatric emergency rooms, high security wards). Human resources represent a major problem, the numbers of psychiatric nurses and psychiatrists are insufficient. The dysfunctional distribution of human resources leads to the deterioration of services. This is principally financial question. In the future the psychiatry should take advantage of the possibilities offered by digital technology. In this paper we present the main elements of the National Programme of Mental Health. We hope that the programme can be realized in the coming years with financial support of the Hungarian Government.

[Psychiatric disorder of Sylvia Plath].

Sylvia Plath was one of the most famous American poets in the twentieth century. Plath was diagnosed with depression after her first suicide attempt when she was 20 years old. Her major depression (without psychotic symptoms) recurred several times. Plath never had a manic episode, but there were probable hypomanic periods in her life. She died by violent suicide when she was 30. Sylvia Plath took a bottle of sleeping pills and stuck her head in a gas oven. Several factors may have contributed to Plath's psychiatric disorder and suicide. The author reviews the etiological factors and course of psychiatric disorder based on the Unabridged Journals of Sylvia Plath and the literature. Her family history was positive and her premorbid personality was vulnerable to depression. There were histrionic, narcissistic and borderline features in her personality. The probable diagnoses of Plath were bipolar II. affective disorder and mixed personality disorder.

Evaluating CHARGE syndrome in congenital hypogonadotropic hypogonadism patients harboring CHD7 variants.

PURPOSE: Congenital hypogonadotropic hypogonadism (CHH), a rare genetic disease caused by gonadotropin-releasing hormone deficiency, can also be part of complex syndromes (e.g., CHARGE syndrome). CHD7 mutations were reported in 60% of patients with CHARGE syndrome, and in 6% of CHH patients. However, the definition of CHD7 mutations was variable, and the associated CHARGE signs in CHH were not systematically examined. METHODS: Rare sequencing variants (RSVs) in CHD7 were identified through exome sequencing in 116 CHH probands, and were interpreted according to American College of Medical Genetics and Genomics guidelines. Detailed phenotyping was performed in CHH probands who were positive for CHD7 RSVs, and genotype-phenotype correlations were evaluated. RESULTS: Of the CHH probands, 16% (18/116) were found to harbor heterozygous CHD7 RSVs, and detailed phenotyping was performed in 17 of them. Of CHH patients with pathogenic or likely pathogenic CHD7 variants, 80% (4/5) were found to exhibit multiple CHARGE features, and 3 of these patients were reclassified as having CHARGE syndrome. In contrast, only 8% (1/12) of CHH patients with nonpathogenic CHD7 variants exhibited multiple CHARGE features (P = 0.01). CONCLUSION: Pathogenic or likely pathogenic CHD7 variants rarely cause isolated CHH. Therefore a detailed clinical investigation is indicated to clarify the diagnosis (CHH versus CHARGE) and to optimize clinical management.

[Three neuralgic points of psychiatric services: suicide prevention, treatment of dementia and the care of homeless psychiatric patients].

No abstract available.