Description of the immature and mature larvae of Bocchus scobiolae Nagy (Hymenoptera: Dryinidae).

The last immature instar and the mature larva of Bocchus scobiolae are described and illustrated for the first time. The affinities of both immature and mature larvae of Bocchus scobiolae and Mystrophorus formicaeformis are discussed to define larval characters of the subfamily Bocchinae.

Gender role endorsement in first-episode schizophrenia spectrum disorders.

Sex (a biological distinction) and gender (a social construct) are inter-related, but semi-independent measures. The aim of our research was to compare gender role endorsement between first-episode schizophrenia spectrum disorder patients (n=77) and matched controls (n=64). The Bem Sex Role Inventory (BSRI) was used to assess masculinity and femininity scores as separate linear measures. This well-known research instrument also allowed us to examine gender as a categorical measure based on sex-specific cut-off scores calculated for controls as our normative reference sample using a median-split technique. First, we found that both masculinity and femininity scores differed between patients and controls. The distribution of gender as a categorical measure also differed between the two groups. Post-hoc testing with correction for multiple comparisons identified masculinity scores in particular as being lower in both male and female patients compared to controls of the corresponding sex. In conclusion, lower masculinity scores reported for chronic schizophrenia also affects first-episode patients with minimal prior treatment exposure irrespective of their biological sex. Future studies would do well to examine the associations of sex and gender with clinical and treatment outcomes from the perspective of the neurodevelopmental model of schizophrenia as a proposed "disorder of the self".

The effect of the COVID-19 lockdown on the epidemiology of hip fractures in the elderly: a multicentre cohort study.

INTRODUCTION: The COVID-19 pandemic presented extraordinary challenges to the UK healthcare system. This study aimed to assess the impact of the COVID-19 lockdown on the epidemiology, treatment pathways and 30-day mortality rates of hip fractures. Outcomes of COVID-19 positive patients were compared against those who tested negative. METHODS: An observational, retrospective, multicentre study was conducted across six hospitals in the South East of England. Data were retrieved from the National Hip Fracture Database and electronic medical records. Data was collected for the strictest UK lockdown period (period B=23 March 2020-11 May 2020), and the corresponding period in 2019 (period A). RESULTS: A total of 386 patients were admitted during period A, whereas 381 were admitted during period B. Despite the suspension of the 'Best Practice Tariff' during period B, time to surgery, time to orthogeriatric assessment, and 30-day mortality were similar between period A and B. The length of inpatient stay was significantly shorter during period B (11.5 days vs 17.0 days, p<0.001). Comparison of COVID-19 positive and negative patients during period B demonstrated that a positive test was associated with a significantly higher rate of 30-day mortality (53.6% vs 6.7%), surgical delay >36h (46.4% vs 30.8%, p=0.049), and increased length of inpatient stay (15.8 vs 11.7 days, p=0.015). CONCLUSIONS: The COVID-19 lockdown did not alter the epidemiology of hip fractures. A substantially higher mortality rate was observed among patients with a COVID-19 positive test. These findings should be taken into consideration by the healthcare policymakers while formulating contingency plans for a potential 'second wave'.

Fronto-limbic white matter fractional anisotropy and body mass index in first-episode schizophrenia spectrum disorder patients compared to healthy controls.

In this diffusion tensor imaging study, we explored the associations of body mass index (BMI) with white matter microstructure in first-episode schizophrenia spectrum disorder patients (n = 69) versus healthy controls (n = 93). We focused on fractional anisotropy (FA) measures for fronto-limbic white matter tracts known to connect brain regions which form part of a "core eating network". Secondary objectives included the associations of body mass with global illness severity, psychopathology and depressive symptoms. In a multivariate analysis of covariance (MANCOVA) model, there was a significant interaction between BMI and group (patient versus control) across the fronto-limbic white matter tracts of interest (F(1,155)= 4.91, p = 0.03). In a sub-analysis, BMI was significantly inversely correlated with FA measures for the genu and body of the corpus callosum, left and right tapetum, and left superior fronto-occipital fasciculus in controls. In patients, BMI was significantly positively correlated with white matter FA for the genu of the corpus callosum and left tapetum. Lower BMI was significantly correlated with more severe negative symptoms, as was earlier age of illness onset. Body mass may be differentially associated with fronto-limbic white matter microstructure in first-episode schizophrenia spectrum disorder compared to controls.

A systematic review of long-term patient reported outcomes for the treatment of anterior cruciate ligament injuries in the skeletally immature.

PURPOSE: To systematically review the available literature regarding outcomes for the treatment of anterior cruciate ligament (ACL) injuries in the skeletally immature at skeletal maturity or more than five years after surgery. METHODS: A systematic search was performed of seven online databases for literature reporting patient reported outcomes for the treatment of ACL injuries in the skeletally immature. A systematic review of this literature was performed examining the outcomes and their association with skeletal immaturity and treatment techniques. RESULTS: A total of 18 articles reported the outcomes of 425 subjects. The mean age at surgery ranged from 10.3 to 15 years. Mean follow-up ranged from 36 to 163 months. Ten studies followed up subjects until skeletal maturity. Mean outcome scores were similar for extraphyseal (Lysholm 96.2 (95.7 to 97.4), Tegner 6.75, IKDC 95.4 (94 to 100)) and transphyseal surgery (Lysholm 94.3 (84.6-100), Tegner 7.6 (6 to 8.7), International Knee Documentation Committee (IKDC) 93.6 (84 to 99)). However, the lower range boundary for Lysholm and IKDC was worse for the transphyseal group. The results for non-surgical treatments were worse (Lysholm 63.2, Tegner 4.8, IKDC 87). No significant differences were found in the incidence of limb-length discrepancy (p = 0.32), coronal plane growth disturbance (p = 0.48), graft rupture (p = 0.88) and persistent symptomatic instability (p = 0.11) with transphyseal and extraphyseal surgical techniques. CONCLUSION: Both transphyseal and extraphyseal reconstructive techniques produced good patient reported outcomes, with no significant differences in the incidence of limb-length discrepancy, coronal plane growth disturbance, graft rupture and persistent symptomatic instability. They compare favourably with the repair techniques reviewed and the natural history of the condition. Further high-quality studies comparing the transphyseal and extraphyseal techniques are required. LEVEL OF EVIDENCE: Level IV.

Use of diffusion-weighted imaging to evaluate the initial response of progressive multifocal leukoencephalopathy to highly active antiretroviral therapy: early experience.

BACKGROUND AND PURPOSE: IRIS occurs in a small percentage of patients with AIDS following the initiation of HAART. Because PML lesions have a characteristic DWI/ADC appearance, our purpose was to determine if DWI/ADC measurements of PML lesions can be used to follow HAART treatment response and/or identify patients at risk for IRIS. MATERIALS AND METHODS: Six patients with AIDS and PML who had recently started HAART were retrospectively identified. On the basis of clinical history, patients were classified as having slow (non-IRIS) or rapid (IRIS) progression. Images were obtained at pre-HAART (time point 1) and post-HAART (time point 2). ADC parameters were measured and compared by using the 2-tailed t test. RESULTS: Seven lesions (4 rapidly progressing, 3 slowly progressing) were identified. Lesions from patients with rapid clinical progression had higher maximal ADC ratios at time point 1. There were also significant correlations between ADC parameters, time to clinical deterioration, and JCV titers. CONCLUSIONS: The ADC parameters of PML lesions were different for patients with rapid-versus-slow clinical progression. In our preliminary experience, ADC was helpful in diagnosing rapid clinical progression and IRIS. ADC values may correlate with the pathologic changes in PML lesions following HAART therapy.

Targeting RANK/RANKL in the treatment of solid tumours and myeloma.

Cancers which damage the human skeleton include multiple myeloma, where the primary tumour colonises bone directly, or breast and prostate cancer, where malignant cells travel from the primary tumour to form clonal outgrowths within the bone. Owing to the interaction of tumour cells with those normally found in the bone microenvironment, such as osteoclasts and osteoblasts, these cancers affect the closely linked processes of bone formation and resorption. As a result, these twin processes contribute to the clinical manifestations of cancer metastasis, including bone pain and pathological fractures. A critical component of physiologically normal bone remodelling, the RANK/RANKL/OPG pathway, has been implicated in the formation of osteolytic, and possibly osteoblastic, lesions, which characterise the bone disease associated with these malignancies. In these cancers that affect the skeleton in this way the abnormally regulated RANK/RANKL system appears to be the final effector pathway. As a result, there has been much research focused upon targeting these molecules using OPG constructs, peptidomimetics, soluble receptor constructs and antibodies to RANKL, in pre-clinical studies. The success of these studies has paved the way for a clinical programme, the success of which is likely to lead to a new therapeutic approach to treating cancers that develop in the skeleton.

Phenotypic variations of TRAIL sensitivity in cloned populations of prostate cancer cells.

Factors that regulate the induction of apoptosis of tumour cells are potential candidates for therapeutic intervention for the majority of cancers. Studying modifiers of apoptotic responses, such as members of the tumour necrosis factor receptor superfamily, may give clues as to how induction of apoptosis in tumours could be maximized to enhance the benefit of treatment regimes. Tumour necrosis factor-related apoptosis-inducing ligand (TRAIL) is a promising anti-tumour molecule since its activity is specific for tumour cell populations. TRAIL binds to death receptors, inducing apoptosis in susceptible cells. The mechanisms which determine whether tumour cells are susceptible to TRAIL are unclear, and several mechanisms have been proposed, including expression of osteoprotegerin (OPG), decoy receptors, and factors that affect intracellular signalling of pro-apoptotic molecules, such as c-FLIP. Here we show that experiments to modulate the activity of one of these factors, OPG, by over-expression and also by stable knockdown of OPG expression, alters the TRAIL sensitivity of PC3 prostate cancer cells. However we show that some observed effects, which appear to support the hypothesis that OPG prevents TRAIL-induced apoptosis of tumour cells, may be due to variation of the TRAIL response of sub-clones of tumour cells, even within a cloned population. These results highlight potential limitations of experiments designed to test contribution of factors affecting intrinsic apoptosis susceptibility using cloned tumour cell populations.

A new xenograft model of myeloma bone disease demonstrating the efficacy of human mesenchymal stem cells expressing osteoprotegerin by lentiviral gene transfer.

We describe a new model of myeloma bone disease in which beta2m NOD/SCID mice injected with KMS-12-BM cells develop medullary disease after tail vein administration. Micro-computed tomography analysis demonstrated significant bone loss in the tibiae and vertebrae of diseased animals compared to controls, with loss of cortical bone (P<0.01), as well as trabecular bone volume, thickness and number (P<0.05 for all). Bone marrow of diseased animals demonstrated an increase in osteoclasts (P<0.01) and reduction in osteoblasts (P<0.01) compared to control animals. Both bone loss and osteoclast increase correlated with the degree of disease involvement. Mesenchymal stem cells (MSCs) were lentivirally transduced to express human osteoprotegerin (hOPG). Systemic administration of OPG expressing MSC reduced osteoclast activation (P<0.01) and trabecular bone loss in the vertebrae (P<0.05) and tibiae of diseased animals, to levels comparable to non-diseased controls. Because of its predominantly medullary involvement and quantifiable parameters of bone disease, the KMS-12-BM xenogeneic model provides unique opportunities to test therapies targeted at the bone marrow microenvironment.

Identification of candidate genes for psychosis in rat models, and possible association between schizophrenia and the 14-3-3eta gene.

Although the genetic contribution to schizophrenia is substantial, positive findings in whole-genome linkage scans have not been consistently replicated. We analyzed gene expression in various rat conditions to identify novel candidate genes for schizophrenia. Suppression subtraction hybridization (SSH), with polyA mRNA from temporal and frontal cortex of rats, was used to identify differentially expressed genes. Expression of mRNA was compared between adult Lewis and Fischer 344 (F344) rats, adult and postnatal day 6 (d6) F344, and adult F344 treated with haloperidol or control vehicle. These groups were chosen because each highlights a particular aspect of schizophrenia: differences in strain vulnerability to behavioral analogs of psychosis; factors that may relate to disease onset in relation to CNS development; and improvement of symptoms by haloperidol. The 14-3-3 gene family, as represented by 14-3-3gamma and 14-3-3zeta isoforms in the SSH study, and SNAP-25 were among the candidate genes. Genetic association between schizophrenia and the 14-3-3eta gene, positioned close to a genomic locus implicated in schizophrenia, and SNAP-25 genes was analyzed in 168 schizophrenia probands and their families. These findings address three different genes in the 14-3-3 family. We find a significant association with schizophrenia for two polymorphisms in the 14-3-3eta gene: a 7 bp variable number of tandem repeats in the 5' noncoding region (P=0.036, 1 df), and a 3' untranslated region SNP (753G/A) that is an RFLP visualized with Ava II (P=0.028). There was no significant genetic association with SNAP-25. The candidate genes identified may be of functional importance in the etiology, pathophysiology or treatment response of schizophrenia or psychotic symptoms. This is to our knowledge the first report of a significant association between the 14-3-3eta-chain gene and schizophrenia in a family-based sample, strengthening prior association reports in case-control studies and microarray gene expression studies.

Polymorphisms in dopamine receptors: what do they tell us?

Many genetic studies have focussed on dopamine receptors and their relationship to neuropsychiatric disease. Schizophrenia, bipolar disorder, and substance abuse have been the most studied, but no conclusive linkage or association has been found. The possible influence of dopamine receptor variants on drug response has not received as much attention. While there is some evidence that polymorphisms and mutations in dopamine receptors can alter functional activity and pharmacological profiles, no conclusive data link these gene variants to drug response or disease. The lack of unequivocal findings may be related, in part, to the subtle changes in receptor pharmacology that these polymorphisms and mutations mediate. These subtle effects may be obscured by the influence of genes controlling drug metabolism and kinetics. Further insight into the pharmacogenetics of dopamine receptors may require not just more studies, but novel approaches to the study of complex genetic traits and diseases.

The use of non-prescription sleep products in the elderly.

UNLABELLED: While sleep disorders are common in the elderly, the use of non-prescription products for sleep in this population has not been fully evaluated. The objectives of this project were to assess the use, perceived effectiveness and toxicity of non-prescription sleep products in an ambulatory elderly population. METHODS: A self-administered 20-question survey was distributed to seniors, aged 60 years or more, during hospital or pharmacy visits. RESULTS: Of the total respondents (N=176, mean age 74+/-7 years, 59% female), 84 (48%) indicated that they had used one or more therapies for sleep within the past year. These included non-prescription products (50% of therapies), prescription products (17%) and non-drug activities such as walking or drinking milk (34%). For those individuals who had used a non-prescription product in the past year (N=47, 27% of total respondents), the most frequently used products were: dimenhydrinate (21%), acetaminophen (19%), diphenhydramine (15%), alcohol (13%) and herbal products (11%). Most took them at least 1 day per week (79%) and 32% took them daily. These products subjectively improved sleep latency (mean 32 vs 61 minutes, p<0.001), number of nocturnal awakenings (mean 2 vs 3 awakenings, p<0.001) and total hours of sleep (mean 6.6 vs 5.4 hours, p<0.001). Mild side-effects were reported by 35 respondents (75%), the most common being dry mouth (N=22) and daytime drowsiness (N=13). Respondents were taking an average of four (SD+/-3, range 0-10) other medications currently. CONCLUSIONS: Non-prescription products are widely used by this population of ambulatory elderly for sleep disturbances. Most of the products were not marketed for sleep; however, they were perceived to be efficacious with low toxicity. The potential for drug interaction is high. Further research is warranted to evaluate the safety and effectiveness of non-prescription sleep products in the elderly.

Increased chromosomal breakage in Tourette syndrome predicts the possibility of variable multiple gene involvement in spectrum phenotypes: preliminary findings and hypothesis.

Increased chromosomal breakage was found in 12 patients with DSM-IV Tourette syndrome (TS) as compared with 10 non-TS control individuals with respect to untreated, modified RPM1-, and BrdU treated lymphocyte cultures (P < 0.001 in each category). A hypothesis is proposed that a major TS gene is probably connected to genetic instability, and associated chromosomal marker sites may be indicative of the localization of secondary genes whose altered expression could be responsible for associated comorbid conditions. This concept implies that genes influencing higher brain functions may be situated at or near highly recombigenic areas allowing enhanced amplification, duplication and recombination following chromosomal strand breakage. Further studies on a larger sample size are required to confirm the findings relating to chromosomal breakage and to analyze the possible implications for a paradigmatic shift in linkage strategy for complex disorders by focusing on areas at or near unstable chromosomal marker sites.