Detecting Neuroimaging Biomarkers for Schizophrenia: A Meta-Analysis of Multivariate Pattern Recognition Studies

Multivariate pattern recognition approaches have recently facilitated the search for reliable neuroimaging-based biomarkers in psychiatric disorders such as schizophrenia. By taking into account the multivariate nature of brain functional and structural changes as well as their distributed localization across the whole brain, they overcome drawbacks of traditional univariate approaches. To evaluate the overall reliability of neuroimaging-based biomarkers, we conducted a comprehensive literature search to identify all studies that used multivariate pattern recognition to identify patterns of brain alterations that differentiate patients with schizophrenia from healthy controls. A bivariate random-effects meta-analytic model was implemented to investigate the sensitivity and specificity across studies as well as to assess the robustness to potentially confounding variables. In the total sample of n=38 studies (1602 patients and 1637 healthy controls), patients were differentiated from controls with a sensitivity of 80.3% (95% CI: 76.7–83.5%) and a specificity of 80.3% (95% CI: 76.9–83.3%). Analysis of neuroimaging modality indicated higher sensitivity (84.46%, 95% CI: 79.9–88.2%) and similar specificity (76.9%, 95% CI: 71.3–81.6%) of rsfMRI studies as compared with structural MRI studies (sensitivity: 76.4%, 95% CI: 71.9–80.4%, specificity of 79.0%, 95% CI: 74.6–82.8%). Moderator analysis identified significant effects of age (p=0.029), imaging modality (p=0.019), and disease stage (p=0.025) on sensitivity as well as of positive-to-negative symptom ratio (p=0.022) and antipsychotic medication (p=0.016) on specificity. Our results underline the utility of multivariate pattern recognition approaches for the identification of reliable neuroimaging-based biomarkers. Despite the clinical heterogeneity of the schizophrenia phenotype, brain functional and structural alterations differentiate schizophrenic patients from healthy controls with 80% sensitivity and specificity.     

Immunohistochemical characterization of the inflammatory infiltrate in placental Chagas' disease: a qualitative and quantitative analysis

Chagas' disease, a systemic illness endemic to some regions of South America, is caused by the protozoan Trypanosoma cruzi. Transplacental infection may occur during any phase and cause fetal death. This study is the first to characterize the inflammatory cells in chagasic villitis by immunohistochemistry. Paraffin sections of 8 placentas with villitis by T. cruzi (4 live births and 4 stillbirths), as well as 8 control placentas without inflammation, were stained with hematoxylin and eosin, monoclonal antibodies for CD45RO, CD20, CD45RO/OPD4, CD8, HNKI, CD15, MAC387, and CD68 proteins, and a polyclonal antibody for S-100 protein. Quantification of positive cells was performed in 3 different high-power fields. In all cases of chagasic villitis, the inflammatory infiltrate was composed mainly of CD68+ macrophages, T lymphocytes, and a few natural killer cells. Among T cells, CD8+ cells outnumbered CD4+ cells in all placentas (CD4+:CD8+ ratios ranged from 0.04 to 0.38). B cells were absent or rare. In stillbirths, villitis was diffuse and severe with numerous T. cruzi, while in live births it was focal with few parasites. Other features that characterized villitis in stillbirths were 1) frequent trophoblastic necrosis, 2) presence of MAC387+ macrophages and CD15+ granulocytes attached to the sites of trophoblastic necrosis, 3) low CD4+: CD8+ ratios in most cases, 4) increased numbers of S-100 positive cells in the villous stroma. In conclusion, CD68+ macrophages and CD8+ T lymphocytes were the major cell population in villitis caused by T. cruzi. However, the pattern of inflammatory reaction differed between stillbirths and live births and was probably related to the number of parasites in the placental villi.     

The validity and reliability of the sixth-year internal medical examination administered at the King Abdulaziz University Medical College

Background

Exams are essential components of medical students’ knowledge and skill assessment during their clinical years of study. The paper provides a retrospective analysis of validity evidence for the internal medicine component of the written and clinical exams administered in 2012 and 2013 at King Abdulaziz University’s Faculty of Medicine.

Methods

Students’ scores for the clinical and written exams were obtained. Four faculty members (two senior members and two junior members) were asked to rate the exam questions, including MCQs and OSCEs, for evidence of content validity using a rating scale of 1–5 for each item.Cronbach’s alpha was used to measure the internal consistency reliability. Correlations were used to examine the associations between different forms of assessment and groups of students.

Results

A total of 824 students completed the internal medicine course and took the exam. The numbers of rated questions were 320 and 46 for the MCQ and OSCE, respectively. Significant correlations were found between the MCQ section, the OSCE section, and the continuous assessment marks, which include 20 long-case presentations during the course; participation in daily rounds, clinical sessions and tutorials; the performance of simple procedures, such as IV cannulation and ABG extraction; and the student log book.Although the OSCE exam was reliable for the two groups that had taken the final clinical OSCE, the clinical long- and short-case exams were not reliable across the two groups that had taken the oral clinical exams. The correlation analysis showed a significant linear association between the raters with respect to evidence of content validity for both the MCQ and OSCE, r?=?.219 P?<?.001 and r?=?.678 P?<?.001, respectively, and r?=?.241 P?<?.001 and r?=?.368 P?=?.023 for the internal structure validity, respectively. Reliability measured using Cronbach’s alpha was greater for assessments administered in 2013.

Conclusion

The pattern of relationships between the MCQ and OSCE scores provides evidence of the validity of these measures for use in the evaluation of knowledge and clinical skills in internal medicine. The OSCE exam is more reliable than the short- and long-case clinical exams and requires less effort on the part of examiners and patients.

     

Diagnostic and treatment recommendations on perianal Crohn's disease.

Treatment of perianal fistulas in Crohn's disease should be defined on an individual basis. A combined medical and surgical approach is the optimal treatment. Adequate management of perianal fistula disease is based on the presence or absence of active proctitis, anatomic location, and fistula type. Furthermore, the presence of perianal abscesses must be ruled out. This evaluation includes digital rectal examination, endoscopy, and examination under anesthesia combined with pelvic magnetic resonance imaging or anorectal endoscopy ultrasonography findings.     

Who are the older Australians referred for a bone density scan? Data from the Barwon region

Summary

This study aimed to estimate the incidence rate of hip fracture during 2008–2010 in Shiraz, Iran. Overall, the standardized age-related incidence were 329.6/100,000 in men and 1,589.7/100,000 in women. The incidence rate in females was remarkably higher than the previous studies in Iran.

Purpose

This study aims to determine the incidence rate of hip fracture and its possible changes during 2008–2010 in Shiraz, Iran.

Materials and methods

This study reviewed and abstracted the hospital records, demographic, and clinical data of 1,923 patients aged 50 years or older with first time hip fracture admitted to private and public hospitals of Shiraz, Iran during 2008–2010 The age-adjusted incidence rate of hip fracture was determined along with association between gender, age, site of fracture, and socioeconomic status (SES) with the incidence rate.

Results

The mean age of subjects was 74.7 years (±10.6 years). Age-adjusted incidence rates for hip fracture, standardized to the 2000 US white male and female populations were 329.57 and 1,589.71 per 10⁵, respectively, while totally it was 461.1 per 10⁵. The incidence rate of hip fracture in females was higher than that of males in their 60s (1,229.2 versus 793.3), 70s (4,130.3 versus 2,835.3), and early 80s (4,506.8 versus 3,820.5) per 100,000. The hip fracture incidence in high SES area (157.1 per 100,000) followed by low SES regions (152.5 per 100,000) were higher compared to middle SES area (38.1 per 100,000) and towns around Shiraz (27.7 per 100,000) with fracture of the neck of femur being the most frequent affliction (391 per 100,000).

Conclusions

The rate of hip fracture is increasing in the area under study particularly in women and to a greater extent in those aged 60 years or older. Therefore, it is necessary to pay special attention to primary and secondary prevention of hip fracture.     

Relationship Between Diet and Mental Health in Children and Adolescents: A Systematic Review

We systematically reviewed 12 epidemiological studies to determine whether an association exists between diet quality and patterns and mental health in children and adolescents; 9 explored the relationship using diet as the exposure, and 3 used mental health as the exposure.We found evidence of a significant, cross-sectional relationship between unhealthy dietary patterns and poorer mental health in children and adolescents. We observed a consistent trend for the relationship between good-quality diet and better mental health and some evidence for the reverse. When including only the 7 studies deemed to be of high methodological quality, all but 1 of these trends remained.Findings highlight the potential importance of the relationship between dietary patterns or quality and mental health early in the life span.The role of habitual diet in the development of depressive disorders and symptoms has become a recent research focus over the past decade. Data from adult populations have indicated that better-quality diet is associated with better mental health outcomes.1–5 In fact, new meta-analyses have confirmed the inverse association between healthy diets and depression.4,5 A habitually poor diet (e.g., increased consumption of Western processed foods) is also independently associated with a greater likelihood of or risk for depression1,6,7 and anxiety.1 Although stress and depression can promote unhealthy eating, recent longitudinal studies have suggested that reverse causality is a less likely explanation for long-term associations.8However, our understanding of these associations earlier in the life span remains unclear. To date, much of the research around this relationship has focused on dietary intake and externalizing behaviors (particularly hyperactivity). For example, poor nutritional quality is independently associated with symptoms of attention-deficit hyperactivity disorder.9 However, the relationship between dietary intake in childhood and adolescence and internalizing behaviors, which represent depressive symptoms, low mood, or anxiety, has received comparably less attention. Given that the previous literature in adults regarding diet and mental health has focused on the common mental disorders, depression and anxiety, examination of these same mental health parameters in children and adolescents is needed. In terms of what evidence is available to date, findings remain inconsistent. For example, although some studies have observed a dose–response relationship between diet quality and mental health in young adolescents,10 others have shown no significant association.11 The evidence is even less comprehensive for the relationship between dietary intake and anxiety symptoms.12To our knowledge, no systematic reviews to date have specifically investigated the association between diet, measured using diet quality scores, dietary pattern analysis, or both and internalizing behaviors that characterize low or depressive mood and anxiety symptoms in child and adolescent populations.     

Listening to the Voices of Native Hawaiian Elders and ‘Ohana Caregivers: Discussions on Aging,Health, and Care Preferences

Native Hawaiians, the indigenous people of Hawai’i, are affected by varying social and health disparities that result in high prevalence of chronic disease, early onset of disability, and shorter life expectancy compared to other ethnic groups in Hawai’i. Six listening meetings were conducted, involving 41 community-dwelling kūpuna (Native Hawaiian elders) and ‘ohana (family) caregivers to investigate health and care preferences that offer the potential for improving well-being in later life for Native Hawaiian elders. As background, we provide three explanatory perspectives and theories—life course perspective, minority stress theory, and historical trauma—that guided the design of this study and provided the study’s context. A number of overarching themes and subthemes were identified, some of which point to universal concerns with age and caregiving (such as challenges and costs associated with growing old and caregiving) and others that are culturally specific (such as influence of culture and social stressors, including discrimination, on health needs and care preferences). Results give further support to the urgency of affordable, accessible, and acceptable programs and policies that can respond to the growing health and care needs of native elders and family caregivers.     

Synthesis of Isosteric Triterpenoid Derivatives and Antifungal Activity

Dermatomycoses are among the most widespread and common superficial and cutaneous fungal infections in humans. There is an urgent need to develop efficient and non‐toxic antimycotic agents with a specific spectrum of activity. Triterpenes have been demonstrated to exhibit a wide range of biological activities, including antifungal activities. In this study, through hemisynthesis, we aimed to obtain triterpene‐isosteric molecules from betulinic and ursolic acids to improve the antifungal activity and spectrum of action of these compounds. Six compounds were resynthesized and tested against eleven mucocutaneous and cutaneous mycotic agents. The results of the susceptibility assays were expressed as the minimal inhibitory concentration (MIC). The MIC values of the piperazinyl derivatives of ursolic and betulinic acids that were active against pathogenic yeasts were in the range of 16–32 μg/mL and 4–16 μg/mL, respectively, whereas fungicidal effects were observed at concentrations ranging from 16 to 128 μg/mL and 8 to 128 μg/mL, respectively. The piperazinyl derivative of betulinic acid exhibited an antifungal profile similar to that of terbinafine and was the most effective derivative against dermatophytes. This strategy led to a promising candidate for the development of a new antifungal agent.     

Functional performance and quality of life related to training and detraining of community-dwelling elderly

Purpose.?Despite clear evidence of physiological declines during detraining, the effects of detraining on functional performance and quality of life have not often been investigated. The purpose of this study was to investigate functional performance and quality of life measures after a training and detraining programme with community-dwelling elderly.

Method.?Twenty-three subjects took part in a combined programme of muscle strengthening and aerobic conditioning twice a week and were assessed at baseline, after training, and after one, two, and three months of detraining. Functional performance was assessed by gait speed and by the rate of ascending and descending stairs, while quality of life was evaluated by the Nottingham Health Profile.

Results.?Repeated measures ANOVA showed that gains observed in measures of gait speed, ascending, and descending stairs returned to baseline after one, two, and three months of detraining, respectively. However, the gains in quality of life remained unchanged.

Conclusions.?One-month detraining was enough to show functional decline, with gait speed the most sensitive parameter to detect these changes and QL measure most resilient, beneficial factor during the detraining process. Based on these findings, it is recommended that programmes devised for elderly should not be interrupted, to maintain the acquired benefits.