Bone mineral density from early to middle adulthood in persons with Down syndrome.

BACKGROUND: While accelerated ageing is recognised among individuals with Down syndrome (DS), the trajectory of their bone health across adulthood remains poorly understood. METHODS: This study aimed to determine the age-related loss of bone mineral density (BMD) of the lumbar spine in 128 adults with DS aged 18 to 54 years compared with 723 counterparts without DS. RESULTS: Men and women with DS had lower level of BMD than counterparts without DS across age groups. Magnitude of decrement in BMD as reflected in the z-scores was similar between younger and older men with DS. Older women with DS, on the contrary, showed greater decrement in older ages especially in their fourth decade of life. Osteopenia and osteoporosis as defined using age-specific and gender-specific T-scores affected greater number of men with DS (38% and 25%) than women (17% and 17%) aged 40-49 years. CONCLUSIONS: Findings supported adults with DS, especially men, to have early bone mineral testing.

Factor analysis of the Chinese version of the Autism Spectrum Quotient 10 and its association with schizotypal traits in adolescents and young adults in Hong Kong.

BACKGROUND: There is evidence suggesting that autistic traits are associated with schizotypal traits. This study examined the factor structure of the Autism Spectrum Quotient 10 (AQ-10) and its associations with schizotypal traits (measured by the Schizotypal Personality Questionnaire-Brief [SPQ-B]) in a cohort of Chinese adolescents and young adults. METHODS: Invitation letters, stratified by locations and housing types, were randomly sent to individuals aged 15 to 24 years for participation. Assessments were made using face-to-face or online interviews. Autistic traits were assessed using the Chinese version of the AQ-10. Schizotypal personality traits were assessed using the Chinese version of the 22-item SPQ-B. RESULTS: In total, 395 male and 536 female participants (mean age, 19.93 years) were recruited between July 2020 and May 2021. Exploratory factor analysis of the AQ-10 yielded three factors (theory of mind, task switching, and attention deficits) explaining 55.11% of the total variance. Autistic traits were positively correlated with schizotypal traits of disorganised features (r = 0.21, p < 0.001), interpersonal relationship deficits (r = 0.19, p < 0.001), and cognitive-perceptual deficits (r = 0.11, p = 0.001). CONCLUSION: In Chinese adolescents and young adults, autistic traits, especially task switching and attention deficits (compared with theory of mind) are more closely correlated with schizotypal personality traits. Disentangling the overlapping and diametrical structure of autistic traits and schizotypal traits may help understand their aetiologies, assessment, and interventions.

Impacts of duration of untreated psychosis on cognition and negative symptoms in first-episode schizophrenia: a 3-year prospective follow-up study.

BACKGROUND: Cognitive impairment is a core feature of schizophrenia. Its relationship with duration of untreated psychosis (DUP), a potentially malleable prognostic factor, has been less studied, with inconsistent findings being observed in the literature. Previous research investigating such a relationship was mostly cross-sectional and none of those prospective studies had a follow-up duration beyond 2 years. Method A total of 93 Hong Kong Chinese aged 18 to 55 years presenting with first-episode schizophrenia-spectrum disorder were studied. DUP and pre-morbid adjustment were measured using a structured interview incorporating multiple sources of information. Psychopathological evaluation was administered at intake, after clinical stabilization of the first psychotic episode, and at 12, 24 and 36 months. Cognitive functions were measured at clinical stabilization, and at 12, 24 and 36 months. RESULTS: DUP exerted differential effects on various cognitive domains, with memory deficits being the most related to DUP even when potential confounders including pre-morbid adjustment and sex were adjusted. Prolonged DUP was associated with more severe impairment in visual memory at clinical stabilization and verbal memory at 24 and 36 months. Further, patients with a long DUP were found to have worse outcomes on negative symptoms at 36 months. The effects of DUP on verbal memory remained significant even when negative symptoms were taken into consideration. CONCLUSIONS: Our findings provided further supportive evidence that delayed treatment to first-episode psychosis is associated with poorer cognitive and clinical outcomes. In addition, DUP may specifically affect memory function and its adverse impact on verbal memory may only become evident at a later stage of the recovery process.

Depressive Symptoms and Its Correlates in Undergraduates during the COVID-19 Pandemic.

INTRODUCTION: This study aims to investigate depressive symptoms and its association with resilience, pessimistic bias of COVID-19, lifestyle changes, and family conflicts among undergraduates in a Hong Kong university. METHODS: 1020 undergraduates in The University of Hong Kong completed the online survey between May and August 2020. Severity of depressive symptoms was assessed using the Patient Health Questionnaire-9. Resilience was assessed using the Connor-Davidson Resilience Scale. Pessimistic bias was assessed using two questions on the perceived risks of contracting COVID-19 and of dying from COVID-19. Changes in lifestyles and the presence of family conflicts were measured. Multivariable and mediation analyses were performed to examine association of depressive symptoms with other variables. RESULTS: 61.7% of the respondents reported having mild to severe depressive symptoms. 18.5% of the variance in depressive symptoms was explained by resilience, pessimistic bias, changes in the frequency of sleep, studying at home, and family conflict. Pessimistic bias partially mediated the association between resilience and depressive symptoms. CONCLUSION: The proportion of undergraduates with mild to severe depressive symptoms during the pandemic was high. Measures to reduce family conflict, maintain healthy daily habits, adjust pessimistic bias, and enhance resilience may help to improve the mental well-being of undergraduates during the pandemic.

Cognitive Stimulation for Persons with Dementia: a Systematic Review and Meta-Analysis.

OBJECTIVE: We aim to provide an up-to-date systematic review and meta-analysis of the effects of cognitive stimulation (CS) on cognition, depressive symptoms, and quality of life in persons with dementia. Factors affecting the treatment effect were examined. METHODS: A literature search was performed on databases of MEDLINE, EMBASE, PsycINFO, CINAHL Plus, and Cochrane Library up to 7 March 2019. Only randomised controlled trials investigating the effects of CS in persons with dementia were included. The outcome measures were cognitive function, depressive symptoms, and quality of life. RESULTS: 20 randomised controlled trials with a total of 1251 participants (intervention group: 674; control group: 577) were included for meta-analysis. Most participants had mild to moderate dementia. CS had a significant positive small-to-moderate effect on cognition (Hedges's g = 0.313, p < 0.001). Heterogeneity of CS was low to moderate (Q=30.5854, df=19, p < 0.05, I2 = 37.877%). Inconclusive results were found for depressive symptoms and quality of life. CONCLUSION: CS has a significant positive effect on cognitive function, but its effect on depressive symptoms and quality of life was inconclusive. Future studies with more robust methodology establishing evidence of its efficacy are required.

Induction of manganous superoxide dismutase by tumor necrosis factor: possible protective mechanism.

Manganous superoxide dismutase (MnSOD) scavenges potentially toxic superoxide radicals produced in the mitochondria. Tumor necrosis factor-alpha (TNF-alpha) was found to induce the messenger RNA for MnSOD, but not the mRNAs for other antioxidant or mitochondrial enzymes tested. The increase in MnSOD mRNA occurred rapidly and was blocked by actinomycin D, but not by cycloheximide. Induction of MnSOD mRNA was also observed with TNF-beta, interleukin-1 alpha (IL-1 alpha), and IL-1 beta but not with other cytokines or agents tested. TNF-alpha induced MnSOD mRNA in all cell lines and normal cells examined in vitro and in various organs of mice in vivo. These effects of TNF-alpha and IL-1 on target cells may contribute to their reported protective activity against radiation as well as their ability to induce resistance to cell killing induced by the combination of TNF-alpha and cycloheximide.

Protective roles of cytokines against radiation: induction of mitochondrial MnSOD.

Oxidative stress such as radiation can trigger the production of cytokines including tumor necrosis factor (TNF) and lymphotoxin (LT). The increased cytokine levels may in turn induce the synthesis of protein(s) that protect against subsequent killing by oxidative stress. Indeed, pretreatment of animals with TNF or LT can protect them against lethal doses of radiation and the alopecia that results from anticancer drugs. TNF or LT can specifically and selectively induce the expression of manganous superoxide dismutase (MnSOD). MnSOD, identified as one of the protective proteins, is a mitochondrial enzyme that scavenges superoxide radicals (O2-). TNF-R1 but not TNF-R2 is responsible for TNF and LT's induction of MnSOD. Paradoxically, the TNF-R1 is also the receptor that mediates the production of oxygen free radicals and apoptosis. Overexpression of MnSOD but not CuZn-SOD or EC-SOD enhances cellular resistance to radiation. Conversely, overexpression of antisense MnSOD RNA diminishes resistance. Transfection of cells with MnSOD lacking the mitochondrial matrix signal does not provide protection against radiation. However, insertion of the mitochondrial signal sequence into CuZn-SOD or EC-SOD results in significant protection. TNF or LT does not induce MnSOD in tumor cells; nor do they protect these cells against radiation. Actually, TNF or LT pretreatment can sensitize tumor cells to killing by radiation.

Interferon-gamma enhances the expression of the major histocompatibility class I antigens on mouse pancreatic beta cells.

Cell surface antigens of the major histocompatibility complex (MHC) play a crucial role in the initiation of immune reactions. To investigate whether the expression of MHC antigens on pancreatic islet cells could be altered, we have cultured mouse islets in the presence of interferon-gamma (IFN-gamma) and subsequently examined the levels of MHC antigen by indirect immunofluorescence using monoclonal antibodies. IFN-gamma induced a 10-fold increase in H-2K antigen expression on islet cells, the percentage of cells with detectable H-2K expression increasing from 24% to 98%. The effects of IFN-gamma on H-2D and la antigen expression were less marked, with only a twofold increase in mean fluorescence levels, the percentage of cells with detectable levels of expression increasing from 10% to 48% and 5% to 16%, respectively. Using double-indirect immunofluorescence, it was demonstrated that IFN-gamma enhanced expression of H-2K and H-2D antigens on beta-cells. However la-positive beta-cells were undetectable in the presence or absence of IFN-gamma. The ability of IFN-gamma to induce increased expression of H-2 antigens on beta-cells may represent a mechanism for targeting immune (cytotoxic) reactions to beta-cells, e.g., in autoimmune insulitis or allograft rejection.

Oral health status of chinese paediatric and adolescent oncology patients with chemotherapy in Hong Kong: a pilot study.

AIM: To study the oral health status of Chinese children and adolescents undergoing chemotherapy in Hong Kong. METHOD: All Chinese children and adolescent oncology patients aged 18 or below attending the Children's Centre for Cancer and Blood Disease at a hospital for chemotherapy were invited and parental consent was sought before they were accepted into the study. The study comprised of 1) a parental questionnaire, 2) the collection of medical history and 3) a clinical examination for tooth decay (caries) and mucosal status. RESULTS: A total of 69 patients were invited, and they all participated in this study. Their mean age was 9.2±5.0 and 44 (64%) were males. Twenty-six patients (38%) had no caries experience (DMFT and/or dmft = 0). Higher caries experience was detected in participants that were not born in Hong Kong, had completed active chemotherapy, participated in school dental care service and whose parents had low educational levels. There were 41 patients with active chemotherapy, 24 of whom were diagnosed with acute leukaemia, 5 with haematological malignancies other than leukaemia and 11 with solid tumours. Antimetabolites, cytotoxic antibiotics, alkylating agents and plant alkaloids were administered in 49%, 32%, 24% and 22% of them, respectively. Twenty-six (63%) patients showed no mucosal complications. The most common oral complication was oral mucositis (24%) followed by petechiae (10%). CONCLUSION: About two-thirds of paediatric and adolescent cancer patients had caries experience, which was more common among those who had completed chemotherapy. Oral mucositis followed by petechiae were the two most common complications of receiving chemotherapy.

Regulation of transplacental virus infection by developmental and immunological factors: studies with lactate dehydrogenase-elevating virus.

Placental and fetal infections with lactate dehydrogenase-elevating virus (LDV) were determined by virus titration, indirect fluorescence antibody (IFA), and in situ hybridization with cDNA probes. Experiments were designed to determine the effects of gestational age, timing of maternal LDV infection, and immunological (antibody and cytokine) factors on mouse placental and fetal LDV infection. Virus infection of the placenta was detected at high levels (almost all placentas infected) within 24 h post-maternal infection (p.m.i.), whereas fetal LDV infection was detected only at a low level by 24 h p.m.i. The percentage of fetuses becoming LDV infected progressively increased between 24 and 72 h p.m.i. When fetal infection was studied at 72 h p.m.i., earlier gestational ages (9-11 days) were associated with fetal resistance to infection, whereas between 12.5 and 15 days of gestation, virus infection was detected in 50-71% of fetuses. Maternal treatment with interferon-gamma (IFN-gamma) or anti-LDV monoclonal antibodies was associated with reduced rates of fetal, but not placental, LDV infection. These results demonstrate that both developmental and immunological factors are important in the regulation of transplacental LDV infection.

Tumor necrosis factor and lymphotoxin: protection against oxidative stress through induction of MnSOD.

Tumor necrosis factor (TNF) and lymphotoxin (LT) are related cytokines produced in response to infection or oxidative insults such as radiation. These cytokines bind to the same receptors and have pleiotropic effects on a variety of cell types. TNF or LT pretreatment, which can induce the synthesis of "protective" proteins such as mitochondrial manganese superoxide dismutase (MnSOD), protects animals from lethal doses of radiation or the chemotherapeutic drug doxorubicin. In contrast, TNF or LT pretreatment of tumor cells, which do not express MnSOD, results in sensitization to these insults. Therefore, radio- or chemoprotection of normal cells may act partially through enhanced expression of MnSOD. On the other hand, tumor sensitization may result from activation of "killing" proteins such as interleukin-1 beta converting enzyme (ICE) or other ICE-like proteases, possibly through TNF/LT-induced oxygen free radicals. In addition to their originally described anti-tumor activity, these cytokines may have new therapeutic indications in protecting normal cells while sensitizing tumor cells to radiation or chemotherapeutic drugs.

T-cell-lymphokines and the production and function of accessory cells.

The recent purification and cloning of T cell-derived growth factors, should lead to rapid progress in delineating their role in the generation of accessory cells and the regulation of their function. The techniques that have allowed detailed in vitro studies of the T-dependent mast cells, should be generally applicable to other bone-marrow-derived cells. Although the T-dependent mast cell (i.e. P cells) of the mouse appear to have a special propensity to persist in vitro and special techniques that promote the emergence of immortalized clones will probably be necessary to grow useful quantities of other cell-types in vitro using PSF, it should prove possible to develop factor-dependent lines of various bone-marrow-derived accessory cells such as dendritic cells and Langerhans cells. The availability of clonal populations will permit analysis of the interaction of factors such as haematopoietic growth factors, interferon, glucocorticoids and other mediators involved in inflammatory reactions such as the prostaglandins and leukotrienes - not only in the regulation of Ia-antigen expression but also in modulation of other accessory cell functions such as the secretion of IL-1 and perhaps ultimately the processing and presentation of antigens.

Inhibition of virus-induced age-dependent poliomyelitis by interferon-gamma.

Age-dependent poliomyelitis (ADPM) is a neuroparolytic disease which results from combined infection of susceptible mice with lactate dehydrogenase-elevating virus (LDV) and murine leukemia virus (MuLV). The present study examined the effects of interferon-gamma (IFN-gamma) treatment on the incidence of ADPM, replication of LDV and MuLV and anti-LDV immunity. IFN-gamma treatment of ADPM-susceptible C58/M mice protected them from paralytic disease, but had no detectable effect on the IgG anti-LDV response or LDV viremia. IFN-gamma-mediated protection from ADPM correlated with reduced expression of LDV RNA, but not MuLV RNA, in the spinal cords of C58/M mice. These results confirm that spinal cord LDV replication is the determinant of ADPM and demonstrate that cytokine-mediated inhibition of LDV replication in the central nervous system prevents neuroparalytic disease.

Cytokine regulation of lactate dehydrogenase-elevating virus: inhibition of viral replication by interferon-gamma.

The mechanisms which regulate the replication of lactate dehydrogenase-elevating virus (LDV), a persistent murine model virus which infects macrophages, are unclear. For this study, the effects of murine recombinant interferon-gamma (IFN-gamma) and tumor necrosis factor-alpha (TNF-alpha) on LDV replication were examined. LDV permissiveness was reduced in macrophages obtained from uninfected mice treated with IFN-gamma prior to cell harvest and in vitro LDV infection. Virus inhibition by IFN-gamma was also observed when neonatal LDV-infected mice were injected with this cytokine prior to macrophage harvest and analysis of LDV replication-positive cells. Persistently LDV-infected mice demonstrated an increase in viremia levels following treatment with TNF-alpha. Neither IFN-gamma nor TNF-alpha had any direct in vitro effect on LDV replication in cultured macrophages, suggesting that the actions of these cytokines required secondary or accessory in vivo events. These results provide evidence for cytokine-mediated regulation of LDV infection and support a role for the immune system in the LDV-host relationship.

Tumor necrosis factor promotes motor functional recovery in crushed peripheral nerve.

The potential benefits of tumor necrosis factor pretreatment in promoting motor functional recovery of peripheral nerve following low load crush injury were examined. Using a specially designed crush device, rat sciatic nerve was subjected to a low load crush injury of 2-h duration. Recombinant murine tumor necrosis factor and saline were intraperitoneally injected into the experimental and control animals, respectively, prior to nerve crushing. Subsequent motor function was evaluated at intervals by measurement of the sciatic functional index. There was significantly (P < 0.05 to < 0.01) more rapid recovery in the tumor necrosis factor pretreated group as compared to the controls between day 14 and day 28. The sciatic functional index in the tumor necrosis factor group improved to -69.3 +/- 5.3 at day 14 and to nearly normal at day 21. In contrast, the sciatic functional index in the control group was -95.5 +/- 3.1% at day 14 and did not approach normal until day 42. Histological results paralleled the functional findings. The results suggest that tumor necrosis factor pretreatment has the potential to attenuate neurostructural damage and promote motor functional recovery in rat peripheral nerve.

Effect of sugars and metabolic intermediates on the attachment of Treponema pallidum to rabbit cells.

The effect of various energy sources and metabolic intermediates on the attachment of Treponema pallidum to baby rabbit genital organ (BRGO) cells in culture was examined. Pyruvate and glucose enhanced the motility of T. pallidum in vitro. Pyruvate increased significantly the attachment of treponemes to BRGO cells when compared with the other substrates but all substrates tested stimulated DNA synthesis by cultured BRGO cells. Thus, the effect of pyruvate on attachment may be due to an effect on the treponemes. Prior exposure of the BRGO cells to the glucose analogue 2-deoxyglucose greatly inhibited the attachment of T. pallidum whereas three other analogues had no effect. The inhibitory effect of 2-deoxyglucose was partially reversed by the presence of pyruvate in the attachment assay. These results suggest that energy metabolism of both T. pallidum and host cells may be required for the initial interaction of T. pallidum with its host in vivo.

Effect of serum concentration and metabolic inhibitors on the attachment of Treponema pallidum to rabbit cells.

The effect of host-cell metabolism on the attachment of Treponema pallidum to mammalian cells in vitro was studied. The growth of baby rabbit genital organ (BRGO) cells was enhanced by increasing the concentration of serum ("serum shift-up") in the growth medium. Cells starved for 24 h in serum-free medium showed a burst of DNA synthesis when shifted to fresh medium containing 20% serum. In aerobic conditions, they were much more heavily coated with attached T. pallidum than cells shifted to 20% serum after maintenance at serum concentrations of 2.5%, 5% or 10%. This effect was very pronounced during the first few hours of co-incubation. In microaerophilic conditions, the extent of T. pallidum adherence also paralleled the increase in DNA synthesis by BRGO cells. Cycloheximide and methotrexate greatly inhibited DNA and protein synthesis in BRGO cells, but did not affect the motility of T. pallidum. When BRGO cell metabolism was inhibited by these two drugs, attachment of T. pallidum was significantly decreased. These results indicate that T. pallidum attaches best to actively growing BRGO cells in tissue culture. This may explain the apparently preferential parasitism of actively growing tissues by T. pallidum in syphilis in man.