Adult male patient with severe intellectual disability caused by a homozygous mutation in the HNMT gene

Histamine is involved in various physiological functions like sleep-wake cycle and stress regulation. The histamine N-methyltransferase (HNMT) enzyme is the only pathway for termination of histamine neurotransmission in the central nervous system. Experiments with HNMT knockout mice generated aggressive behaviours and dysregulation of sleep-wake cycles. Recently, seven members of two unrelated consanguineous families have been reported in whom two different missense HNMT mutations were identified. All showed severe intellectual disability, delayed speech development and mild regression from the age of 5 years without, however, any dysmorphisms or congenital abnormality. A diagnosis of mental retardation, autosomal recessive 51 was made. Here, we describe a severely mentally retarded adolescent male born from second cousins with a homozygous mutation in HNMT. His phenotypic profile comprised aggression, delayed speech, autism, sleep disturbances and gastro-intestinal problems. At early age, regression occurred. Treatment with hydroxyzine combined with a histamine-restricted diet resulted in significant general improvement

Українська ветеринарна лексика 20-30-х років ХХ ст.

Метою написання статті є розгляд української ветеринарної лексики, що функціонувала у 20-30-х роках 20 століття.Целью написания статьи является рассмотрение украинской ветеринарной лексики, что функционировала в 20-30-х годах 20 века

Validation of a novel multivariate method of defining HIV-associated cognitive impairment

Background. The optimum method of defining cognitive impairment in virally suppressed people living with HIV is unknown. We evaluated the relationships between cognitive impairment, including using a novel multivariate method (NMM), patient– reported outcome measures (PROMs), and neuroimaging markers of brain structure across 3 cohorts. Methods. Differences in the prevalence of cognitive impairment, PROMs, and neuroimaging data from the COBRA, CHARTER, and POPPY cohorts (total n = 908) were determined between HIV-positive participants with and without cognitive impairment defined using the HIV-associated neurocognitive disorders (HAND), global deficit score (GDS), and NMM criteria. Results. The prevalence of cognitive impairment varied by up to 27% between methods used to define impairment (eg, 48% for HAND vs 21% for NMM in the CHARTER study). Associations between objective cognitive impairment and subjective cognitive complaints generally were weak. Physical and mental health summary scores (SF-36) were lowest for NMM-defined impairment (P < .05). There were no differences in brain volumes or cortical thickness between participants with and without cognitive impairment defined using the HAND and GDS measures. In contrast, those identified with cognitive impairment by the NMM had reduced mean cortical thickness in both hemispheres (P < .05), as well as smaller brain volumes (P < .01). The associations with measures of white matter microstructure and brain-predicted age generally were weaker. Conclusion. Different methods of defining cognitive impairment identify different people with varying symptomatology and measures of brain injury. Overall, NMM-defined impairment was associated with most neuroimaging abnormalities and poorer selfreported health status. This may be due to the statistical advantage of using a multivariate approac

Possible pathophysiological roles of neurotransmitter systems in men with lifelong premature ejaculation: a scoping review

This scoping review will combine two types of studies to provide an overview of neurotransmitter systems as the pathophysiological cause of LPE. There is potential for the identification of one or multiple targets to develop a targeted strategy for further genetic research

Men with subjective premature ejaculation have a similar lognormal IELT distribution as men in the general male population and differ mathematically from males with lifelong premature ejaculation after an IELT of 1.5 minutes (Part 2)

Men with Subjective premature ejaculation (PE) have complaints of PE but have normal intravaginal ejaculation latency time (IELT) durations. We found two previously published large epidemiological stopwatch-mediated IELT studies to encompass IELT details of men with Subjective PE, albeit this term was not mentioned in both studies or in reviews of them. In the current study we developed the mathematical formula of the IELT distribution of men with complaints of PE, as diagnosed by a clinician on basis of the DSM-IV-TR definition of PE, as reported in the two studies performed in the USA and Europe, respectively. The formula was calculated by investigation of the fitness of various well-known mathematical Probability Density distributions into the IELT distribution of the PE men and non-PE men of the two studies. The better the fitness the lower is the Goodnes of Fit (GOF). Another aim of the study was to investigate whether the IELT distribution of men with "complaints" of PE (Subjective PE) differs mathematically from the IELT distribution of the general male population and that of Lifelong PE. The overlap of the area under the curve (AUC) of the IELT distribution of the men with PE complaints and that of the general male population was calculated together with the cut-off point at which the AUC equals 10%. We found that the IELT distributions of the PE men in both studies were Lognormal distributions and that at the cut-off point at which the AUC is equal to 10% (p = 0.10) the IELT is 1.5 min, indicating that after 1.5 min the IELT distribution of males with complaints of PE becomes mathematically identical to that of the general male population. In conclusion, there is hard mathematical evidence that the IELT distribution of men with complaints of PE with normal IELT values (e.g., the Lognormal IELT distribution of Subjective PE) and the IELT distribution of men with Lifelong PE (e.g. the Gumbel Max IELT distribution) belong to two independent populations. According to the applied mathematical calculations Subjective PE starts after an IELT of 1.5 min and encompasses all higher IELT values. It may imply that the current IELT cut-off point in Lifelong PE should be 1.5 min instead of the approximate 1 min, as has previously been stated by ISSM and DSM 5