[Clinical and genetic spectrum of 6 cases with asparagine synthetase deficiency].

Objective: To explore the clinical and genetic characteristics of asparagine synthase deficiency. Methods: Case series studies. Retrospective analysis and summary of the clinical data of 6 cases with asparagine synthase deficiency who were diagnosed by genetic testing and admitted to the Third Affiliated Hospital of Zhengzhou University from May 2017 to April 2023 were analyzed retrospectively. The main clinical features, laboratory and imaging examination characteristics of the 6 cases were summarized, and the gene variation sites of them were analyzed. Results: All of the 6 cases were male, with onset ages ranging from 1 month to 1 year and 4 months. All of the 6 cases had cognitive and motor developmental delay, with 3 cases starting with developmental delay, 3 cases starting with convulsions and later experiencing developmental arrest or even regression. All of 6 cases had epilepsy, in whom 2 cases with severe microcephaly developed epileptic encephalopathy in the early stages of infancy with spasms as the main form of convulsions, 4 cases with mild or no microcephaly gradually evolved into convulsions with no fever after multiple febrile convulsions with focal seizures, tonic clonic seizures and tonic seizure as the main forms of convulsions. Three cases of 4 gradually developed into stagnation or even regression of development and ataxia after multiple convulsions with no fever. There were normal cranial imaging in 2 cases, dysplasia of the brains in 1 cases, frontal lobe apex accompanied by abnormal white matter signal in the frontal lobe and thin corpus callosum in 1 case, thin corpus callosum and abnormal lateral ventricular morphology in 1 case, and normal in early stage, but gradually developing into cerebellar atrophy at the age of 5 years and 9 months in 1 case. Two cases underwent visual evoked potential tests, the results of which were both abnormal. Three cases underwent auditory evoked potential examination, with 1 being normal and 2 being abnormal. All of 6 cases had variations in the asparagine synthase gene, with 2 deletion variations and 7 missense variations. The variations of 2 cases had not been reported so far, including c.1341_1343del and c.1283A>G, c.1165_1167del and c.1075G>A. The follow-up time ranged from 3 months to 53 months. Two cases who had severe microcephaly died in infancy, while the other 4 cases with mild or no microcephaly were in survival states until the follow-up days but the control of epilepsy was poor. Conclusions: Asparagine synthase deficiency has a certain degree of heterogeneity in clinical phenotype. Children with obvious microcephaly often present as severe cases, while children with mild or no microcephaly have relatively mild clinical manifestations. The variation of asparagine synthetase gene is mainly missense variation.

Activities of daily living performance in dementia.

OBJECTIVE: To explore the activities of daily living ADL performance profile of community-living people with dementia and to investigate its relationship with dementia severity. MATERIALS & METHODS: ADL performance of 86 subjects were evaluated using Barthel Index (BI), Lawton and Brody's Instrumental Activities Daily Living (IADL) and Assessment of Motor and Process Skills (AMPS). Dementia severity was measured by Clinical Dementia Rating (CDR). RESULTS: Subjects were able to perform most basic ADL (BI mean = 16.4) and some IADL (Lawton and Brody's IADL mean = 4.3). The AMPS process ability measure and the Lawton and Brody's IADL were significantly correlated with CDR (P < 0.01). CONCLUSIONS: Subjects with mild dementia were able to perform mostly all basic ADL and some IADL. The AMPS process ability measure and the Lawton and Brody's IADL could provide useful information on their ability to live independently in the community.

Development and validation of the interview version of the Hong Kong Chinese WHOQOL-BREF.

INTRODUCTION: The Hong Kong Chinese version of the WHOQOL-BREF was designed as a self-administered questionnaire and has limitations in clinical application on subjects who have limitations in reading or writing. An interview version is therefore needed to avoid sampling biases in clinical studies. Since there are significant differences in the written Chinese and spoken Cantonese, which is a dialect commonly spoken among people in Hong Kong, and adaptation process for converting the written Chinese into spoken Cantonese was necessary. The interview version was designed to allow administration in both face-to-face interview and telephone interview mode. METHODS: Three members of the research team translated the formal written Chinese in the self-administered version of the WHOQOL-BREF(HK) into colloquial Cantonese separately. Brief notes extracted from the facet definitions of the WHOQOL-100 were added in brackets after some questions to further explain the intention of the questions. Two series of focus groups were conducted and subsequently the field test version was produced. 329 subjects were recruited by convenient sampling method for the field test. RESULTS: The interview version and the self-administered version was found equivalent. The ICC values of the domain scores ranged from 0.73 in the environment domain to 0.83 in the psychological domain. The face-to-face interview and telephone interview mode of administration were also found equivalent. The ICC for the domain scores ranged from 0.76 in the social interaction domain to 0.84 in the psychological domain. The other psychometric properties of the interview version were found comparable to the self-administered version. CONCLUSION: The self-administered and the interview version of the WHOQOL-BREF are regarded as identical in group comparison. The authors advise that it is acceptable to use different versions on different subjects in the same study, provided that the same version is applied on the same subject throughout the study.

Risk factors for falls in hospitalized older medical patients.

BACKGROUND: The incidence of falls among older hospitalized patients is higher than that of community-dwelling older persons. Prevention is important, but factors associated with these falls are less well studied than falls occurring in the community or nursing homes. METHODS: This study was conducted in an acute-care general hospital in Hong Kong. During November 1995 to March 1997, all older inpatients who fell during hospitalization were assessed by a geriatrician, a physiotherapist, and an occupational therapist. A standardized protocol to study the clinical and performance-oriented functional factors was employed. A sex- and age-matched hospital control was recruited for each case. In total, 51 cases and controls (mean ages 77.8 +/- 7.3 years and 77.5 +/- 7.0 years, respectively) were studied. RESULTS: Among the multiple clinical and functional risk factors for falls identified, lower limb weakness (i.e., power less than MRC grade 4 in one or both lower limbs) and poor tandem walk ability emerged as two significant predictive factors for falls in the hospital. The overall classification accuracy of fallers and nonfallers was 79%. The sensitivity was 84% and specificity was 75%. Clinical factors were the underlying causes for the lower limb weakness and poor tandem walk performance. CONCLUSIONS: Among clinical and functional risk factors for falls in the older medical patient, lower limb weakness and poor tandem walk ability were most predictive. Falls prevention programs in hospitals should employ these two tests as screening instruments.

Environmental carcinogenesis and biotechnology.

Numerous environmental and host factors, some of which are known and some unknown, contribute to cancer development. While data and studies abound, our current understanding of the relation between cancer and the environment is still very limited. Understanding environmental carcinogenesis is critical to its effective management. Biotechnology has revolutionalized the study of biological and biomedical sciences. This minireview provides an overview of environmental carcinogenesis with emphasis on the contributions and prospects of biotechnology in advancing an understanding of environmental carcinogenesis for its prevention and intervention.

Oxidation of low-spin iron(II) porphyrins by molecular oxygen. An outer sphere mechanism.

Hexacoordinate low-spin iron(II) porphyrins are oxidized by molecular oxygen in amine solvents at room temperature by a process that is acid dependent. The visible and NMR spectra of solutions of the iron complexes and the influence of axial ligands upon the rate of oxidation are consistent with an outer sphere mechanism that entails the dissociation of a protonated 1:1 iron porphyrin-oxygen pi complex as the rate-limiting step.

The acid-catalyzed decompostion of phenacylcobalamin: evidence for the formation of an enol-Co(III) pi-complex intermediate.

Phenacylcobalamin has been synthesized and characterized by thin-layer chromatography and uv-visible spectroscopy, as well as identification of the cobalt-containing and organic products of its cleavage in acid and base and by aerobic photolysis. The major organic product from all three cleavage reactions is acetophenone and the cobalt-containing product is aquacobalamin (or hydroxocobalamin, its conjugate base). In aqueous acidic solution (pH 0 to 7.3, ionic strength 1.0 M, and 25.0 degrees C), the kinetics of the formation of aquacobalamin are biphasic representing the linear sum of two exponential terms. The pH dependence of the first-order rate constant of both phases shows a first-order dependence on proton concentration but with an inflection point ot pH 3.55 for the faster phase and at pH 4.03 for the slower phase. This behavior is interpreted in terms of the specific acid catalyzed formation of an intermediate from both "base on" and "base off" phenacylcobalamin with different second-order rate constants for each form, followed by an intermediate decompotion step with a similar formal mechanism. The nature of the intermediate is discussed and it is concluded to be a pi-complex between cob(III)alamin and the enol of acetophenone.