Prevalence of causes of secondary osteoporosis and contribution to lower bone mineral density in HIV-infected patients

Summary

Eighty-one percent of human immunodeficiency virus (HIV)-infected patients had one or more of seven evaluated causes of secondary osteoporosis, and this rate increases with age. The type and number of causes were associated with a lower bone mineral density (BMD), and with an increased rate of osteopenia/osteoporosis, regardless of age and body mass index.

Introduction

The objective of this study was to determine whether factors of secondary osteoporosis were associated with lower BMD in HIV.

Methods

This was a cross-sectional study of 285 HIV-infected patients (25 % females) evaluating the impact of seven different factors of reduced BMD: hyperthyroidism, diabetes, chronic viral hepatitis, chronic kidney disease (CKD), hypovitaminosis D, secondary hyperparathyroidism, and hypogonadism. Dual-energy X-ray absorptiometry scan of the femoral neck was obtained at the clinical visit.

Results

Mean age was 45.7 years; osteopenia and osteoporosis were diagnosed in 38 and 6 %, respectively. Overall, 230 patients (81 %) had secondary factors; 107 (38 %) had only 1 cause, 94 (33 %) had 2, and 28 (10 %) had 3 or more, predominantly vitamin D deficiency in 61 %, hepatitis C virus coinfection in 45 %, and secondary hyperparathyroidism in 27 %. The number of secondary factors was closely related to a lower BMD, which is statistically significant for patients having ≥2 causes (0.77 vs 0.73 g/cm², p?=?0.02). The rate of osteopenia ranged from 36 % without any cause to 57 % with three or more, osteoporosis from 0 to 19 %, and Z-score <?2 SD from 0 to 27 %, respectively. In a multivariate linear regression, adjusting by age, body mass index, and HIV-related factors, the number of secondary factors was independently associated with a lower BMD (ß coefficient ?0.134; p?=?0.02), mainly due to patients with hepatitis C virus (HCV) coinfection, secondary hyperparathyroidism, and CKD.

Conclusions

A high prevalence of secondary causes of osteoporosis is observed in HIV-infected patients, and its type and cumulative number determine a lower BMD, after adjusting by age and body mass index.     

Mapping the brain pathways of declarative verbal memory: Evidence from white matter lesions in the living human brain

Understanding the contribution of the brain white matter pathways to declarative verbal memory processes has been hindered by the lack of an adequate model in humans. An attractive and underexplored approach to study white matter region functionality in the living human brain is through the use of non-aprioristic models which specifically search disrupted white matter pathways. For this purpose, we employed voxel-based lesion–function mapping to correlate white matter lesions on the magnetic resonance images of 46 multiple sclerosis patients with their performance on declarative verbal memory storage and retrieval. White matter correlating with storage was in the temporal lobe–particularly lateral to the hippocampus and in the anterior temporal stem–, in the thalamic region and in the anterior limb of the internal capsule, all on the left hemisphere, and also in the right anterior temporal stem. The same volumes were relevant for retrieval, but to them were added temporo-parieto-frontal paramedian bundles, particularly the cingulum and the fronto-occipital fasciculus. These 3D maps indicate the white matter regions most critically involved in declarative verbal memory in humans.     

Myofascial trigger points, neck mobility and forward head posture in unilateral migraine

This paper describes the differences in the presence of myofascial trigger points (TrPs) in the upper trapezius, sternocleidomastoid, temporalis and suboccipital muscles between unilateral migraine subjects and healthy controls, and the differences in the presence of TrPs between the symptomatic side and the non-symptomatic side in migraine subjects. In addition, we assess the differences in the presence of both forward head posture (FHP) and active neck mobility between migraine subjects and healthy controls and the relationship between FHP and neck mobility. Twenty subjects with unilateral migraine without side-shift and 20 matched controls participated. TrPs were identified when there was a hypersensible tender spot in a palpable taut band, local twitch response elicited by the snapping palpation of the taut band and reproduction of the referred pain typical of each TrP. Side-view pictures were taken in both sitting and standing positions to measure the cranio-vertebral angle. A cervical goniometer was employed to measure neck mobility. Migraine subjects showed a significantly greater number of active TrPs (P<0.001), but not latent TrPs, than healthy controls. Active TrPs were mostly located ipsilateral to migraine headaches (P<0.01). Migraine subjects showed a smaller cranio-vertebral angle than controls (P<0.001), thus presenting a greater FHP. Neck mobility in migraine subjects was less than in controls only for extension (P=0.02) and the total range of motion in flexion/extension (P=0.01). However, there was a positive correlation between the cranio-vertebral angle and neck mobility. Nociceptive inputs from TrPs in head and neck muscles may produce continuous afferent bombardment of the trigeminal nerve nucleus caudalis and, thence, activation of the trigeminovascular system. Active TrPs located ipsilateral to migraine headaches might be a contributing factor in the initiation or perpetuation of migraine.     

Diagnostic validity Polish language version of the questionnaire MINI-KID (Mini International Neuropsychiatry Interview for Children and Adolescent)

Objective

Since over forty years structuralized interviews for clinical and epidemiological research in child and adolescent psychiatry are being developed that should increase validity and reliability of diagnoses according to classification systems (DSM and ICD). The aim of the study is to assess the validity of the Polish version of MINI-KID (Mini International Neuropsychiatric Interview for Children and Adolescents) in comparison to clinical diagnosis made by a specialist in the field of child and adolescent psychiatry.

Materials and methods

There were 140 patients included in the study (93 boys, 66.4%, mean age 11.8 ± 3.0 and 47 girls 33.5%, mean age 14.0 ± 2.9). All the patients were diagnosed by the specialist in the field of child and adolescent psychiatry according to ICD-10 criteria and by the independent interviewer with the Polish version of MINI-KID (version 2.0, 2001).

Results

There was higher agreement between clinical diagnoses and diagnoses based on MINI-KID interview with respect to eating disorders and externalizing disorders (κ 0.43–0.56) and lower in internalizing disorders (κ 0.13–0.45). In the clinical interview, there was smaller number of diagnostic categories (maximum 3 diagnoses per one patient) in comparison to MINI-KID (maximum 10 diagnoses per one patient), and the smaller percentage of patients with one diagnosis (65,7%) in comparison to MINI-KID interview (72%).

Conclusion

Our study has shown satisfactory validity parameters of MINI-KID questionnaire, promoting its use for clinical and epidemiological settings.

Implications and contribution

The Mini International Neuropsychiatry Interview for Children and Adolescent (MINI-KID) is the first structuralized diagnostic interview for assessing mental status in children and adolescents, which has been translated into Polish language. Our validation study demonstrated satisfactory psychometric properties of the questionnaire, enabling its use in clinical practice and in research projects.     

Recognition of Pain as Another Deficit in Young Males with High Callous-Unemotional Traits

Prior research on callous-unemotional (CU) traits supports a deficit in recognizing fear in faces and body postures. Difficulties recognising others’ emotions may impair the typical behavioural inhibition for violent behaviour. However, recent research has begun to examine other distress cues such as pain. The present study examined emotion recognition skills, including pain, of school-excluded boys aged 11–16 years (N = 50). Using dynamic faces and body poses, we examined the relation between emotion recognition and CU traits using the youth psychopathic traits inventory (YPI) and the inventory of CU traits. Violent delinquency was covaried in regression analyses. Although fearful facial and fearful bodily expressions were unrelated to CU traits, recognition of dynamic pain facial expressions was negatively related to CU traits using the YPI. The failure to replicate a fear and sad deficit are discussed in relation to previous research. Also, findings are discussed in support of a general empathy deficit for distress cues which may underlie the problem behaviour of young males with CU traits.     

Do patient and ward-related characteristics influence the use of coercive measures? Results from the EUNOMIA international study

Purpose

This study aims to identify whether selected patient and ward-related factors are associated with the use of coercive measures. Data were collected as part of the EUNOMIA international collaborative study on the use of coercive measures in ten European countries.

Methods

Involuntarily admitted patients (N = 2,027) were divided into two groups. The first group (N = 770) included patients that had been subject to at least one of these coercive measures during hospitalization: restraint, and/or seclusion, and/or forced medication; the other group (N = 1,257) included patients who had not received any coercive measure during hospitalization. To identify predictors of use of coercive measures, both patients’ sociodemographic and clinical characteristics and centre-related characteristics were tested in a multivariate logistic regression model, controlled for countries’ effect.

Results

The frequency of the use of coercive measures varied significantly across countries, being higher in Poland, Italy and Greece. Patients who received coercive measures were more frequently male and with a diagnosis of psychotic disorder (F20–F29). According to the regression model, patients with higher levels of psychotic and hostility symptoms, and of perceived coercion had a higher risk to be coerced at admission. Controlling for countries’ effect, the risk of being coerced was higher in Poland. Patients’ sociodemographic characteristics and ward-related factors were not identifying as possible predictors because they did not enter the model.

Conclusions

The use of coercive measures varied significantly in the participating countries. Clinical factors, such as high levels of psychotic symptoms and high levels of perceived coercion at admission were associated with the use of coercive measures, when controlling for countries’ effect. These factors should be taken into consideration by programs aimed at reducing the use of coercive measures in psychiatric wards.     

Glutamate Excitotoxicity Activates the MAPK/ERK Signaling Pathway and Induces the Survival of Rat Hippocampal Neurons In Vivo

Current knowledge concerning the molecular mechanisms of the cellular response to excitotoxic insults in neurodegenerative diseases is insufficient. Although glutamate (Glu) has been widely studied as the main excitatory neurotransmitter and principal excitotoxic agent, the neuroprotective response enacted by neurons is not yet completely understood. Some of the molecular participants have been revealed, but the signaling pathways involved in this protective response are just beginning to be identified. Here, we demonstrate in vivo that, in response to the cell damage and death induced by Glu excitotoxicity, neurons orchestrate a survival response through the extracellular signal-regulated kinase (ERK) signaling pathway by increasing ERK expression in the rat hippocampal (CA1) region, allowing increased neuronal survival. In addition, this protective response is specifically reversed by U0126, an ERK inhibitor, which promotes cell death only when it is administered together with Glu. Our findings demonstrate that the ERK signaling pathway has a neuroprotective role in the response to Glu-induced excitotoxicity in hippocampal neurons. Therefore, the ERK signaling pathway may be activated as a cellular response to excitotoxic injury to prevent damage and neural loss, representing a novel therapeutic target in the treatment of neurodegenerative diseases.     

The diverse roles and multiple forms of focal adhesion kinase in brain

Although it was originally characterized as a constituent of focal adhesions in fibroblasts, focal adhesion kinase (FAK) is now considered to be not only a mediator of adhesion processes but also a crucial regulator of guidance and a modulator of gene expression. FAK is the main transducer of the integrin signaling required to stabilize the actin cytoskeleton. However, additional activities have been described over the years. In the brain, FAK deserves particular attention as it is found in various alternatively spliced forms – these distributed in multiple subcellular compartments or bound to multiple partners. Moreover, its signaling involves not only phosphorylation but also ubiquitination and proteolysis. Several experimental cell models demonstrate that FAK increases or decreases migration, participates in differentiation and contributes to plasticity events. In addition, this kinase is linked to cell survival in cancer and apoptosis. This review focuses on the diversity of events involving brain‐located forms of FAK.     

Impact of CYP1A1, GSTM1, and GSTT1 polymorphisms in overall and specific prostate cancer survival

ObjectivePrognostic biomarkers that distinguish between patients with good or poor outcome can be used to guide decisions of whom to treat and how aggressively. In this sense, several groups have proposed genetic polymorphisms as potential susceptibility and prognostic biomarkers; however, their validity has not been proven. Thus, the main goal of the present work was to investigate the potential role of single and combined CYP1A1, GSTM1, and GSTT1 genotypes as modifiers of cancer survival in Chilean patients with prostate cancer.Methods and materialsA total of 260 histologically confirmed patients were recruited from a voluntary screening, and genomic DNA was obtained from their blood samples for genotyping analyses to detect the CYP1A1*2A polymorphism and GSTM1 and GSTT1 deletions. The progression of illness and mortality were estimated with a median follow-up of 8.82 years. Adjusted estimated genotype risks were evaluated by hazard ratio and 95% CI using the Cox proportional model. In addition, the Kaplan-Meier survival method and log-rank test were used to evaluate patient survival with regard to genotype.ResultsThe 9-year overall and specific survival rates were 67.6% and 36.6% in the GSTT1null group, 67.6% and 58.7% in the GSTM1non-null group, 69.0% and 51.6% in the *1A/*2A group, 63.9% and 61.5% in the *2A/*2A group vs. 76.2% and 62.3% in the GSTT1non-null group, 82.3% and 50% in the GSTM1null group, and 83.7% and 56.3% in the *1A/*1A group, respectively. The hazard ratios and the Kaplan-Meier curve results demonstrate that the GSTM1non-null, GSTT1null, and CYP1A1*2A genotypes are significantly associated with mortality. Our study has two main limitations: a relatively small sample size and a low global mortality percentage (25.4%); thus, we need to continue the follow-up to confirm these findings.ConclusionsOur results suggest that the GSTM1non-null, GSTT1null, and CYP1A1*2A genotypes may be good prognosis markers, particularly in patients with high-risk tumors.