The Beliefs of Non-Psychiatric Doctors about the Causes, Treatments and Prognosis of Schizophrenia

Objectives To examine the causal beliefs about schizophrenia of non‐psychiatric doctors and whether differential belief in biogenetic vs. psychosocial causes influences doctors’ views about treatments and prognosis. Design and methods Three hundred and five non‐psychiatric doctors working in outpatient community centres completed the ‘Opinions on mental disorders Questionnaire’ after reading a clinical description of people with schizophrenia. Results The factors most frequently reported as causes of schizophrenia were heredity (65.2%) and use of street drugs (54.1%). Seventy‐five per cent of participants endorsed both one or more biological causal factors and one or more psychosocial causal factors. Of the 264 participants who expressed their opinion about the most important cause of schizophrenia, 53.8% indicated a biogenetic cause. Fifty‐two per cent of respondents thought it ‘completely true’ that drugs are useful in schizophrenia, and 33.9% thought it ‘completely true’ that people with schizophrenia must take drugs all their life. Participants stating that the most important cause was biogenetic more frequently recommended a psychiatrist and less frequently a psychologist. Compared to doctors who indicated a psychosocial cause as the most important one, those who indicated a biogenetic cause were more sceptical about recovery, more confident in the usefulness of drugs, and more convinced of the need of lifelong pharmacological treatments in schizophrenia. Conclusions These findings suggest the need to provide some doctors with training on the multiple, interacting causes of schizophrenia and the efficacy of the broad range of available treatments. The education of health professionals regarding stigma and its effects on clinical practice is also needed

Parps: Rapidly Evolving Weapons in the War against Viral Infection

Post-translational protein modifications such as phosphorylation and ubiquitinylation are common molecular targets of conflict between viruses and their hosts. However, the role of other post-translational modifications, such as ADP-ribosylation, in host-virus interactions is less well characterized. ADP-ribosylation is carried out by proteins encoded by the PARP (also called ARTD) gene family. The majority of the 17 human PARP genes are poorly characterized. However, one PARP protein, PARP13/ZAP, has broad antiviral activity and has evolved under positive (diversifying) selection in primates. Such evolution is typical of domains that are locked in antagonistic 'arms races' with viral factors. To identify additional PARP genes that may be involved in host-virus interactions, we performed evolutionary analyses on all primate PARP genes to search for signatures of rapid evolution. Contrary to expectations that most PARP genes are involved in 'housekeeping' functions, we found that nearly one-third of PARP genes are evolving under strong recurrent positive selection. We identified a >300 amino acid disordered region of PARP4, a component of cytoplasmic vault structures, to be rapidly evolving in several mammalian lineages, suggesting this region serves as an important host-pathogen specificity interface. We also found positive selection of PARP9, 14 and 15, the only three human genes that contain both PARP domains and macrodomains. Macrodomains uniquely recognize, and in some cases can reverse, protein mono-ADP-ribosylation, and we observed strong signatures of recurrent positive selection throughout the macro-PARP macrodomains. Furthermore, PARP14 and PARP15 have undergone repeated rounds of gene birth and loss during vertebrate evolution, consistent with recurrent gene innovation. Together with previous studies that implicated several PARPs in immunity, as well as those that demonstrated a role for virally encoded macrodomains in host immune evasion, our evolutionary analyses suggest that addition, recognition and removal of ADP-ribosylation is a critical, underappreciated currency in host-virus conflicts

Nuclear poly(ADP-ribose) activity is a therapeutic target in amyotrophic lateral sclerosis

Abstract Amyotrophic lateral sclerosis (ALS) is a devastating and fatal motor neuron disease. Diagnosis typically occurs in the fifth decade of life and the disease progresses rapidly leading to death within ~ 2–5 years of symptomatic onset. There is no cure, and the few available treatments offer only a modest extension in patient survival. A protein central to ALS is the nuclear RNA/DNA-binding protein, TDP-43. In > 95% of ALS patients, TDP-43 is cleared from the nucleus and forms phosphorylated protein aggregates in the cytoplasm of affected neurons and glia. We recently defined that poly(ADP-ribose) (PAR) activity regulates TDP-43-associated toxicity. PAR is a posttranslational modification that is attached to target proteins by PAR polymerases (PARPs). PARP-1 and PARP-2 are the major enzymes that are active in the nucleus. Here, we uncovered that the motor neurons of the ALS spinal cord were associated with elevated nuclear PAR, suggesting elevated PARP activity. Veliparib, a small-molecule inhibitor of nuclear PARP-1/2, mitigated the formation of cytoplasmic TDP-43 aggregates in mammalian cells. In primary spinal-cord cultures from rat, Veliparib also inhibited TDP-43-associated neuronal death. These studies uncover that PAR activity is misregulated in the ALS spinal cord, and a small-molecular inhibitor of PARP-1/2 activity may have therapeutic potential in the treatment of ALS and related disorders associated with abnormal TDP-43 homeostasis

Epidemiology of foot deformities in Southern Italy: focus on Pes Planus and Pes Cavus

Background Pes cavus and Pes Planus are two foot deformities and could be detected through baropodometrical digital techniques. In our study, we used computerized baropodometric analysis to make diagnosis of Pes planus and Pes cavus in the population of Foggia (Apulia Region, Southern Italy). The aim of our study was to calculate the prevalence of these deformities and to show significant differences due to gender or age. Methods We conducted a cross sectional study from January 2011 to August 2016, in the Orthopaedic Ambulatory of the LHU of Foggia, Italy. The patients were asked to sign a consent form to participate in the study. The baropodometric analysis was performed to diagnose Pes planus and Pes cavus, and additional information (gender and age) were recorded. We calculated percentages, means and standard deviation. The Chi-square test, and the calculation of Odds Ratio were used to identify differences due to these variables (sex and age). Results We performed 7816 baropodometric tests, and 978 patients were screened for suspected foot deformities: 668 cases of Pes cavus and 310 of Pes Planus were diagnosed. There is a statistically significant difference in the prevalence of Pes cavus and Pes Planus (p < 0.01) due to age: the young age is a risk factor for Pes Planus (OR = 1.61 CI 95% 1.22 - 2.11) but protective for Pes cavus (OR = 0.62 CI 95% 0.47- 0.81). There is a statistically significant difference (p < 0.01) due to sex in the prevalence of hollow feet (OR = 0.44 CI 95% 0.33 - 0.59) and flat feet (OR = 2.23 CI 95% 1.68 - 2.98): beinga man reduces the risk for hollow feet, but increases the risk for flat feet. Conclusions Pes Planus and Pes cavus are not so spread in the general population but they represent an underestimated public health problem because these deformities negatively influence the productivity of workers. It would be interesting to continue our study evaluating also the impact of these problems on the quality of life of affected patients. Key messages: Pes cavus and Pes Planus are two foot deformities and the baropodometrical digital techniques are fundamental for their detection. Pes Planus and Pes cavus are not so spread in general population but they represent an underestimated public health problem

Disabled students and the quality of relationships within the class

An investigation of the quality of peer relationships of disabled students within regular classes was conducted. A total of 496 students participated in the study, 40 of which disabled, enrolled in 27 public elementary and middle schools. The students filled in the “Loneliness and Social Dissatisfaction Scale” (Asher, 1984) and responded to three questions of a sociometric test. Disabled students significantly felt lonelier in class compared to the students with no disability. They were also often rejected or left out during play activities, and probably due to the rejection experienced in class, over the years disabled students increasingly expect rejection from their peers

Clinical and functional outcomes after type B-C(AO/OTA) distal humeral fractures treated with locking compression plates: A retrospective study

BACKGROUND: B-C (AO/OTA) fractures of distal humerus are lesions difficult to treat with results that are not always satisfactory. The aim of this study was to evaluate the outcome of patients with this type of fractures treated at our institute. METHODS: A retrospective study considering 32 patients with mean age of 57.1 years (19-85) treated with open reduction and internal fixation (ORIF) for distal humerus articular fractures, 5 type B1, 1 type B2, 12 type C1, 4 type C2, 10 type C3 (AO/OTA), 29 closed fractures, 2 with grade I-II (Gustillo) of exposure, 1 with point exposure. Surgical exposures used are triceps-on and olecranon osteotomy, while the synthesis was performed with locking compression plates. The average follow-up was 42.7 months (79-9). The radiograms performed during the standard controls were evaluated and the Mayo Elbow Performance Score was used for functional evaluation. RESULTS: Average MEPS of 90.6 (55-100), excellent in 68.8%, good 18.7%, fair, 6.3% and poor 6.3%. Average flexion of 125.1 ° (40-140°) with an average deficiency of 11 ° (0-40°). All olecranial osteotomies healed, no pseudoarthrosis was found. Registered complications: 2 wound dehiscences, 7 cases with residual hypoesthesia in the territory of the ulnar nerve, 1 mobilization of a healed fracture screw, 3 cases with presence of joint ossifications and marked rigidity with subsequent surgical revision. CONCLUSIONS: ORIF with orthogonal construct and locking compression plates is an optimal technique for the treatment of distal humerus articular fractures. Associated with an early mobilization leads to an excellent functional result with a minimum rate of complications

Clinical and radiographical outcome after surgical treatment of periprosthetic type B proximal femur fractures: a retrospective study

Purpose Periprosthetic fractures after hip prosthesis represent a constantly increasing clinical problem and a challenging complication to treat surgically. Among these, type B proximal femur fractures should be diagnosed correctly to be treated surgically. The aim of this study was to re-evaluate the type of surgical treatment of periprosthetic fractures. Methods We examined the cases treated between January 2012 and February 2018, classifying them according to the U.C.S. AO/OTA. We evaluated the radiographic outcome according to the Beals and Tower criteria. Patients still alive were also re-evaluated according to the H.H.S. and the WOMAC score. Results We treated 48 patients (12 men, 35 women, average age 81 years), divided into 24 type B1, 14 type B2 and 10 type B3 fractures. The overall consolidation rate was 95.4%, while the major complication (implant dislocation, pseudoarthrosis and deep infection) rate was 12.5%. Clinically, it was possible to reassess 34 patients with a mean follow-up of 38.4 months, an average HHS of 75.89 and a mean WOMAC score of 79.93. Conclusions Periprosthetic type B fractures are difficult to manage and require careful preoperative planning and appropriate intraoperative management. However, the overall clinical and radiographic result was satisfactory, although patients should still be aware of the risk of complications associated with this type of fractur