Dual disorder: does expert clinical experience support the rationale for cariprazine use?

Comorbid substance use disorder (SUD) in patients with schizophrenia (dual disorder, DD) is a frequent occurrence in the psychiatric clinical practice and is positively associated with poorer outcomes. Despite a very high co-prevalence, clinical guidelines for SUD and severe mental illnesses tend to give limited consideration to co-existing disorders regarding diagnosis and management. This article is the result of a meeting held in February 2023 to discuss common challenges and best clinical practice initiatives for patients with schizophrenia and DD in different treatment settings. The authors identified issues in the clinical approach to DD in schizophrenia spectrum disorders and suggested the most suitable management based on their experience as a group of experts, identifying possible improvement areas. In conclusion, the panel recommends that individuals with DD should be cared for in a single center. Pharmacologic treatment in individuals with DD needing both control of symptoms related to schizophrenia spectrum disorders and substance withdrawal should ideally be based on using a non-sedative antipsychotic with anti-craving activity.

Effect of Water Stress on Reproduction and Colonization of Podosphaera aphanis of Strawberry.

In a number of pathosystems involving the powdery mildews (Erysiphales), plant stress is associated with decreased disease susceptibility and is detrimental to pathogen growth and reproduction. However, in strawberry, anecdotal observations associate severe powdery mildew (Podosphaera aphanis) with water stress. In a 2017 survey of 42 strawberry growers in Norway and California, 40 growers agreed with a statement that water-stressed strawberry plants were more susceptible to powdery mildew compared with nonstressed plants. In repeated in vitro and in vivo experiments, we found that water stress was consistently and significantly unfavorable to conidial germination, infection, and increases in disease severity. Deleterious effects on the pathogen were observed from both preinoculation and postinoculation water stress in the host. Soil moisture content in the range from 0 to 50% was correlated (R2 = 0.897) with germinability of conidia harvested from extant colonies that developed on plants growing at different levels of water stress. These studies confirm that P. aphanis fits the norm for biotrophic powdery mildews and hosts under stress. Mild water stress, compared with a state of optimal hydration, is likely to decrease rather than increase susceptibility of strawberry to P. aphanis. We believe it is possible that foliar symptoms of leaf curling due to diffuse and inconspicuous infection of the lower leaf surfaces by P. aphanis could easily be mistakenly attributed to water stress, which we observed as having a nearly identical leaf curling symptom in strawberry.

Myofibroblasts and increased angiogenesis contribute to periapical cystic injury containment and repair.

BACKGROUND: Myofibroblasts (MF) and angiogenesis are important factors in the development and expansion of cystic lesions, where these cells secrete growth factors and proteases, stimulating angiogenesis, matrix deposition and cell migration, affecting the growth of these periapicopathies. The present study aimed to evaluate the immunohistochemical expression of CD34 and α-SMA in radicular cysts (RC) and residual radicular cysts (RRC), with the purpose of contributing to a better understanding of the expansion and progression of these periapical lesions. MATERIAL AND METHODS: The present study os a descriptive, quantitative and comparative analysis of positive CD34 and α-SMA immunohistochemical expressions in 30 RC and 30 RRC specimens. α-SMA expression was evaluated in the fibrous capsule of the lesions, at 100x magnification below the epithelial lining. A total of 10 higher immunostaining fields were selected and subsequently, positive cells were quantified at 400x magnification, averaged per field. Regarding the angiogenic index, immuno-labeled microvessel counts for the anti-CD34 antibody were performed in 10 fields at 200x magnification. RESULTS: Statistically significant differences regarding α-SMA immunostaining were observed (p = 0.035), as well as a correlation between α-SMA versus CD34 (p = 0.004) in RRC. However, the angiogenic index obtained by immunostaining for CD34 indicated no statistical difference between lesions. Intense inflammatory infiltrates were predominant in RC, while mild and moderate degrees were more commonly observed in RRC (p <0.001). Intense inflammatory infiltrates were also more often noted in larger RRC (p = 0.041). Inflammatory infiltrates showed no significant correlation with α-SMA and CD34 immunostaining. CONCLUSIONS: The results indicate that the significant correlation found between the presence of MF and the angiogenic index are related to the repair process in RRC.

Understanding the Environmental Impact of a Mine Dam Rupture in Brazil: Prospects for Remediation.

The rupture of the Fundão mine dam in Mariana municipality, Minas Gerais State, Brazil, spilled the tailings across the Doce River basin. These tailings, composed of residues discarded from the beneficiation of iron ore, are rich in SiO and AlO, as well as some ether amine compounds and NaOH. The aim of this study was to assess the distribution of these sediments, as well as their effect on the riparian zones reached, as compared with preserved sites. Sediment deposition in the river resulted in a morphological change from a meandering profile to a braided aspect. The nutrient and mineral content (P, K, Ca, Mg, Cu, Fe, Mn, Zn, and NO) and soil organic matter of the sediments were depleted, whereas NH, Na, and pH increased. A random presence of ether amines in the sediments was confirmed by quantitative and chromatographic analyses, with concentrations ranging from 0 to 57.8 mg kg; Na reached values as high as 150 mg kg. The impact of the dam tailings on biota was assessed by estimating total microbial biomass (phospholipid fatty acids), which were depleted in sediments relative to soils from preserved sites. Overall plant mortality, as well as a low resilience capacity, were also observed. Ether amines and Na present in the sediments had a strong toxic effect in the environment. Identification of these substances as the main impact factors will help guide future remediation efforts.

Cost-effectiveness of a multicomponent primary care program targeting frail elderly people.

BACKGROUND: Over the last 20 years, integrated care programs for frail elderly people aimed to prevent functional dependence and reduce hospitalization and institutionalization. However, results have been inconsistent and merely modest. To date, evidence on the cost-effectiveness of these programs is scarce. We evaluated the cost-effectiveness of the CareWell program, a multicomponent integrated care program for frail elderly people. METHODS: Economic evaluation from a healthcare perspective embedded in a cluster controlled trial of 12 months in 12 general practices in (the region of) Nijmegen. Two hundred and four frail elderly from 6 general practices in the intervention group received care according to the CareWell program, consisting of multidisciplinary team meetings, proactive care planning, case management, and medication reviews; 165 frail elderly from 6 general practices in the control group received usual care. In cost-effectiveness analyses, we related costs to daily functioning (Katz-15 change score i.e. follow up score minus baseline score) and quality adjusted life years (EQ-5D-3 L). RESULTS: Adjusted mean costs directly related to the intervention were €456 per person. Adjusted mean total costs, i.e. intervention costs plus healthcare utilization costs, were €1583 (95% CI -4647 to 1481) higher in the intervention group than in the control group. Incremental Net Monetary Benefits did not show significant differences between groups, but on average tended to favour usual care. CONCLUSIONS: The CareWell primary program was not cost-effective after 12 months. From a cost-effectiveness perspective, widespread implementation of the program in its current form cannot be recommended. TRIAL REGISTRATION: The study was registered in the ClinicalTrials.govProtocol Registration System: ( NCT01499797 ; December 26, 2011). Retrospectively registered.

Unravelling complex primary-care programs to maintain independent living in older people: a systematic overview.

OBJECTIVES: Complex interventions are criticized for being a "black box", which makes it difficult to determine why they succeed or fail. Recently, nine proactive primary-care programs aiming to prevent functional decline in older adults showed inconclusive effects. The aim of this study was to systematically unravel, compare, and synthesize the development and evaluation of nine primary-care programs within a controlled trial to further improve the development and evaluation of complex interventions. STUDY DESIGN AND SETTING: A systematic overview of all written data on the nine proactive primary-care programs was conducted using a validated item list. The nine proactive primary-care programs involved 214 general practices throughout the Netherlands. RESULTS: There was little or no focus on the (1) context surrounding the care program, (2) modeling of processes and outcomes, (3) intervention fidelity and adaptation, and (4) content and evaluation of training for interventionists. CONCLUSIONS: An in-depth analysis of the context, modeling of the processes and outcomes, measurement and reporting of intervention fidelity, and implementation of effective training for interventionists is needed to enhance the development and replication of future complex interventions.

The association between implementation and outcome of a complex care program for frail elderly people.

Background: Over the last 20 years, the effectiveness of complex care programs aiming to prevent adverse outcomes in frail elderly people has been disappointing. Recently, we found no effectiveness of the CareWell primary care program. It is largely unknown to what extent incomplete implementation of these complex interventions influences their outcomes. Objective: To examine the association between the degree of implementation of the CareWell program and the prevention of functional decline in frail elderly people. Methods: Quantitative process evaluation conducted alongside a cluster-controlled trial. Two hundred and four frail elderly participants from six general practitioner practices in the Netherlands received care according to the CareWell program, consisting of four key components: multidisciplinary team meetings, proactive care planning, case management and medication reviews. We measured time registrations of team meetings, case management and medication reviews and care plan data as stored in a digital information portal. These data were aggregated into a total implementation score (TIS) representing the program's overall implementation. We measured functional decline with the Katz-15 change score (follow-up score at 12 months minus the baseline score). The association between TIS and functional decline was analyzed with linear mixed model analyses. Results: We found no statistically significant differences in functional decline between TIS groups (F = 1.350, P = 0.245). In the groups with the highest TISs, we found more functional decline. Conclusion: A higher degree of implementation of the CareWell program did not lead to the prevention of functional decline in frail elderly people.

Multicomponent Program to Reduce Functional Decline in Frail Elderly People: A Cluster Controlled Trial.

BACKGROUND: The increasing number of community-dwelling frail elderly people poses a challenge to general practice. We evaluated the effectiveness of a general practitioner-led extensive, multicomponent program integrating cure, care, and welfare for the prevention of functional decline. METHODS: We performed a cluster controlled trial in 12 general practices in Nijmegen, the Netherlands. Community-dwelling frail elderly people aged ≥70 years were identified with the EASY-Care two-step older persons screening instrument. In 6 general practices, 287 frail elderly received care according to the CareWell primary care program. This consisted of proactive care planning, case management, medication reviews, and multidisciplinary team meetings with a general practitioner, practice and/or community nurse, elderly care physician, and social worker. In another 6 general practices, 249 participants received care as usual. The primary outcome was independence in functioning during (instrumental) activities of daily living (Katz-15 index). Secondary outcomes were quality of life [EuroQol (EQ5D+C) instrument], mental health and health-related social functioning (36-item RAND Short Form survey instrument), institutionalization, hospitalization, and mortality. Outcomes were assessed at baseline and at 12 months, and were analyzed with linear mixed-model analyses. RESULTS: A total of 204 participants (71.1%) in the intervention group and 165 participants (66.3%) in the control group completed the study. No differences between groups regarding independence in functioning and secondary outcomes were found. CONCLUSION: We found no evidence for the effectiveness of a multifaceted integrated care program in the prevention of adverse outcomes in community-dwelling frail elderly people. Large-scale implementation of this program is not advocated.

Associations of birth weight, linear growth and relative weight gain throughout life with abdominal fat depots in adulthood: the 1982 Pelotas (Brazil) birth cohort study.

BACKGROUND: Several studies have reported on associations of size at birth and early growth with general and central obesity; however, few have examined the potential effects of birth weight and postnatal growth on separate abdominal fat compartments. We investigated the effects of size at birth, linear growth and relative weight gain from birth to adulthood on visceral (VFT) and subcutaneous abdominal (SAFT) fat thicknesses at age 30 years. METHODS: A total of 2663 participants from the 1982 Pelotas (Brazil) birth cohort study had complete information on ultrasound measures of abdominal fat at age 30 years, and anthropometric measurements for at least five visits (0/2/4/23/30 years). We estimated weight and height Z-score changes, conditional relative weight gain and conditional height at several ages. RESULTS: In both men and women, VFT and SAFT showed positive associations with conditional relative weight gain during all age periods beyond 2 years and birth, respectively (all P⩽0.01). Women born with intrauterine growth restriction (IUGR) had greater VFT than other women (difference=0.15 s.d., 95% CI: 0.01-0.29), and they showed a stronger positive influence of infant weight gain 0-2 years on VFT (IUGR: ß=0.17 s.d., 95% CI: 0.05-0.29; non-IUGR: ß=0.01 s.d., 95% CI: -0.04 to 0.06; Pinteraction=0.02). Stunting at 2 years was associated with lower SAFT but not VFT, and it modified the influence of weight gain 2-4 years on SAFT in both sexes (both Pinteraction<0.05). CONCLUSIONS: Our findings reinforce the advantages of being born with an appropriate birth weight, and the hazards of rapid postnatal gains in weight relative to linear growth, particularly after the critical window of the first 1000 days.

Size at birth and abdominal adiposity in adults: a systematic review and meta-analysis.

We performed a systematic literature review on the associations between birth size and abdominal adiposity in adults, while also investigating the role of the adjustment for adult body mass index (BMI). MEDLINE, Scopus, Web of Science, LILACS and SciELO databases were searched for articles published up to February 2013. Only prospective studies were included. After screening 2,570 titles, we selected 31 publications for the narrative synthesis, of which 13 were considered to be of high methodological quality. Six main indicators of birth size were identified, and birth weight (BW) was the most extensively studied. Most studies relied on anthropometric measurements as proxies for abdominal fatness or as indicators of body fat distribution. Few studies assessed abdominal adiposity through imaging methods, generally with small sample sizes. Eleven articles could be included in the meta-analyses. BW was found to be positively associated with waist circumference in adulthood, but the association disappeared after adjustment for adult BMI. In contrast, there was no association between BW and waist-to-hip ratio, whereas a strong negative association became evident after controlling for adult BMI. In conclusion, BW seems to be associated with larger adult size in general, including both waist and hip circumferences. The marked change in coefficients after adjustment for adult BMI suggests that post-natal growth strongly affects relative central adiposity, whereas BW per se does not play a role. Given the potential impact of post-natal growth, further research is needed to identify different growth trajectories that lead to abdominal adiposity, as well as studies on interactions of foetal and post-natal growth patterns.

The CareWell-primary care program: design of a cluster controlled trial and process evaluation of a complex intervention targeting community-dwelling frail elderly.

BACKGROUND: With increasing age and longevity, the rising number of frail elders with complex and numerous health-related needs demands a coordinated health care delivery system integrating cure, care and welfare. Studies on the effectiveness of such comprehensive chronic care models targeting frail elders show inconclusive results. The CareWell-primary care program is a complex intervention targeting community-dwelling frail elderly people, that aims to prevent functional decline, improve quality of life, and reduce or postpone hospital and nursing home admissions of community dwelling frail elderly. METHODS/DESIGN: The CareWell-primary care study includes a (cost-) effectiveness study and a comprehensive process evaluation. In a one-year pragmatic, cluster controlled trial, six general practices are non-randomly recruited to adopt the CareWell-primary care program and six control practices will deliver 'care as usual'. Each practice includes a random sample of fifty frail elders aged 70 years or above in the cost-effectiveness study. A sample of patients and informal caregivers and all health care professionals participating in the CareWell-primary care program are included in the process evaluation. In the cost-effectiveness study, the primary outcome is the level of functional abilities as measured with the Katz-15 index. Hierarchical mixed-effects regression models/multilevel modeling approach will be used, since the study participants are nested within the general practices. Furthermore, incremental cost-effectiveness ratios will be calculated as costs per QALY gained and as costs weighed against functional abilities. In the process evaluation, mixed methods will be used to provide insight in the implementation degree of the program, patients' and professionals' approval of the program, and the barriers and facilitators to implementation. DISCUSSION: The CareWell-primary care study will provide new insights into the (cost-) effectiveness, feasibility, and barriers and facilitators for implementation of this complex intervention in primary care. TRIAL REGISTRATION: The CareWell-primary care study is registered in the ClinicalTrials.gov Protocol Registration System: NCT01499797.

DHM in human-centered product design: a case-study on public transport vehicle.

The goal of this paper is to present the advantages on the use of 3D Digital Human Models (DHM) on the design of public transport vehicles. In this case, the subjects were scanned using the WBX Cyberware 3D Whole Body Scanner, with functional and daily postures according to the use of public transportation and some especial cases, such as a mother with her offspring or a business man with his valise, so the volume of the person would be taken in consideration. A data collection was created to simulate several situations of the daily use of the vehicle.

Prevalence of red ear syndrome in juvenile primary headaches.

BACKGROUND: Previous studies have suggested a relationship between 'red ear syndrome' (RES) and pediatric migraine. Aims of this study were (i) to assess the frequency, specificity and sensitivity of RES in a population of pediatric migraineurs and (ii) to establish the pathophysiological mechanisms of RES associated with migraine. METHODS AND RESULTS: A total of 226 children suffering from headache (aged 4-17 years) were enrolled. One hundred and seventy-two (76.4%) were affected by migraine, the remaining 54 (23.6%) by other primary headaches. RES was followed significantly more frequently by migraine (23.3%; p < .0001), and was characterized by high specificity and positive predictive value (96.3 and 95.3%, respectively). According to the univariate statistical analysis, RES showed a statistically significant association with male gender, throbbing quality of the pain, vomiting and phonophobia. It was confirmed by a multivariate stepwise logistic regression model only for the throbbing quality of the pain, vomiting and male gender. CONCLUSIONS: Our study showed that (i) in children, RES is a highly specific sign for migraine. In addition, the evidence of an association of RES with some migraine features partially provoked by the parasympathetic system supports the hypothesis of a shared pathophysiological background (e.g. via the activation of the trigeminal-autonomic reflex).

Spermatic cell characteristics in Gymnotiformes (Teleostei: Ostariophysi) and their phylogenetic meaning.

Spermatic characteristics were studied in representatives of the families Rhamphichthyidae, Sternopygidae and Apteronotidae, and compared with pre-existent data from Gymnotidae and Hypopomidae. The spermatic characteristics found in Gymnotiformes were also compared with data from other Ostariophysi spermatic cells. The spermatic characteristics as the type of spermiogenesis and the structural pattern of the sperm, considering nuclear form, pattern of chromatin condensation, nuclear fossa and its relation with the centriolar complex, form and localization of mitochondria, form of midpiece, presence or absence of cytoplasmic canal and cytoplasmic sleeve, and flagellar fins were utilized. The comparative analysis of the spermatic cell of Gymnotiformes better support the previous proposals for the order considering Gymnotidae as a derived group, than the more recent ones that located Gymnotidae in a basal position as the sister group of the remaining Gymnotiformes. Regarding the Ostariophysi, the comparative analyses based on the spermatic cell characteristics is consistent with a recent systematic proposal that consider Gymnotiformes as a sister group of Characiformes.

Ultrastructure of spermiogenesis and spermatozoa of Gymnotus cf. anguillaris and Brachyhypopomus cf. pinnicaudatus (Teleostei: Gymnotiformes).

The ultrastructure of spermiogenic stages and spermatozoa of representatives of two gymnotiform families, Gymnotus cf. anguillaris (Gymnotidae) and Brachyhypopomus cf. pinnicaudatus (Hypopomidae) were studied. Spermiogenesis of both species is characterized by lateral development of the flagellum and formation of a nuclear fossa. Some differences were found between these species, such as whether (B. cf. pinnicaudatus) or not (G. cf. anguillaris) nuclear rotation occurs, permanence of the cytoplasmic channel, and type and localization of the nuclear fossa. In the G. cf. anguillaris spermatozoon the nucleus is spherical with highly condensed chromatin. The nuclear fossa is shallow and lateral and is associated with the centriolar complex through stabilizing fibrils. The midpiece is short, with many vesicles, a cytoplasmic channel, and elongate mitochondria. In the B. cf. pinnicaudatus spermatozoon the ovoid nucleus is elongated lateral and posterior to the centriolar complex, and has highly condensed chromatin. The eccentric nuclear fossa is of the moderate type, and contains the entire centriolar complex. The midpiece is long, with numerous vesicles, elongate mitochondria, and no cytoplasmic channel. In both species the flagella are laterally disposed in relation to the nucleus and comprise of the classical 9+2 axoneme. Most of the characteristics found in the spermatozoa of these two species of Gymnotiformes are shared with species of Characiformes, whereas only a few are also found in Siluriformes. This suggests that Gymnotiformes and Characiformes may be more closely related than previously proposed.

Nonextensive models for earthquakes.

We have revisited the fragment-asperity interaction model recently introduced by Sotolongo-Costa and Posadas [Phy. Rev. Lett. 92, 048501 (2004)] by considering a different definition for mean values in the context of Tsallis nonextensive statistics and introducing a scale between the earthquake energy and the size of fragment epsilon proportional to r3. The energy-distribution function (EDF) deduced in our approach is considerably different from the one obtained in the above reference. We have also tested the viability of this EDF with data from two different catalogs (in three different areas), namely, the NEIC and the Bulletin Seismic of the Revista Brasileira de Geofísica. Although both approaches provide very similar values for the nonextensive parameter , other physical quantities, e.g., energy density, differ considerably by several orders of magnitude.

[Nasal rhinosporidiosis in children]. / Rinosporidiose nasal na infância.

Rhinosporidiosis is a rare fungal disease resulting from infection by Rhinosporidium seeberi. There seems to be a relationship between the disease and agriculture, suggesting that Rhinosporidium lives in soil, and many authors agree that water is a necessary medium of transmission. The sites of infection are the nose (most common), eye, nasopharynx, penile urethra and external ear. Nasal cases generally present obstruction, epistaxis, watery or mucopurulent discharge, presence of tumoral pedunculated polypoid mass, generally with septal implantation. Histological examination presents characteristic sporangia in large numbers and in the submucosa a granulomatous host response. The treatment is by surgical excision (recurrence occurs in 10% of cases), and medical treatment used diaminodiphenylsulfone or Amphotericin B to avoid recurrent cases. We present a case of Rhinosporidiosis in a 10 years-old child, female, with 3 months history of nasal obstruction, epistaxis and presence of nasal mass in left nasal cavity that was submitted to surgical excision.