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L444P <i>Gba1</i> mutation increases formation and spread of α-synuclein deposits in mice injected with mouse α-synuclein pre-formed fibrils

by Anna Migdalska‐Richards, Michal Wegrzynowicz, Ian F. Harrison, Guglielmo Verona, Vittorio Bellotti, Maria Grazia Spillantini, Anthony H. V. Schapira

Parkinson disease is the most common neurodegenerative movement disorder, estimated to affect one in twenty-five individuals over the age of 80. Mutations in glucocerebrosidase 1 (GBA1) represent the most common genetic risk factor for Parkinson disease. The link between GBA1 mutations and α-synuclein accumulation, a hallmark of Parkinson disease, is not fully understood. Following our recent finding that Gba1 mutations lead to increased α-synuclein accumulation in mice, we have studied the effects of a single injection of mouse α-synuclein pre-formed fibrils into the striatum of Gba1 mice that carry a L444P knock-in mutation. We found significantly greater formation and spread of α-synuclein inclusions in Gba1-transgenic mice compared to wild-type controls. This indicates that the Gba1 L444P mutation accelerates α-synuclein pathology and spread.

Comparing two dry needling interventions for plantar heel pain: a randomised controlled trial

Por: Al-Boloushi · Z. · Gomez-Trullen · E. M. · Arian · M. · Fernandez · D. · Herrero · P. · Bellosta-Lopez · P.
Objectives

To compare the effectiveness of dry needling (DN) versus percutaneous needle electrolysis (PNE) for improving the level of pain, function and quality of life (QoL) of patients suffering from plantar heel pain (PHP) provoked by myofascial trigger points.

Design

A prospective, parallel-group, randomised controlled trial with blinded outcome assessment.

Setting

A single treatment facility in the State of Kuwait.

Participants

118 participants were screened for eligibility. Of these, 102 participants were enrolled (30 men (49.5±8.9 years) and 72 women (48.1±8.8 years)) and 68 of them completed the trial.

Interventions

Two parallel groups, one study arm received DN and a stretching protocol whereas the other arm received percutaneous needling electrolysis with a stretching protocol.

Primary and secondary outcome measures

The primary outcome measure was the Foot Pain domain of the Foot Health Status Questionnaire, with 13 questions related to foot health-related domains. Secondary outcome measures included the 0–10 numerical rating scale pain visual analogue scale (VAS) scores, performed before and after each treatment session. In addition, QoL was measured using the EuroQoL-5 dimensions. All measurements were taken at baseline, at 4, 8, 12, 26 and 52 weeks.

Results

Foot Pain domain improved at all time points for DN group (p

Conclusions

Both PNE and DN were effective for PHP management, reducing mean and maximum pain since the first treatment session, with long lasting effects (52 weeks) and significant differences between groups in the case of QoL at 52 weeks in favour of the PNE group.

Trial registration number

NCT03236779.

An in-depth survey of the microbial landscape of the walls of a neonatal operating room

by Dieunel Derilus, Filipa Godoy-Vitorino, Hebe Rosado, Edgardo Agosto, Maria Gloria Dominguez-Bello, Humberto Cavallin

Bacteria found in operating rooms (ORs) might be clinically relevant since they could pose a threat to patients. In addition, C-sections operations are performed in ORs that provide the first environment and bacterial exposure to the sterile newborns that are extracted directly from the uterus to the OR air. Considering that at least one third of neonates in the US are born via C-section delivery (and more than 50% of all deliveries in some countries), understanding the distribution of bacterial diversity in ORs is critical to better understanding the contribution of the OR microbiota to C-section- associated inflammatory diseases. Here, we mapped the bacteria contained in an OR after a procedure was performed; we sampled grids of 60x60 cm across walls and wall-adjacent floors and sequenced the V4 region of 16S rRNA gene from 260 samples. The results indicate that bacterial communities changed significantly (ANOSIM, p-value

Diagnostic journey in Spinal Muscular Atrophy: Is it still an odyssey?

by Maria Carmela Pera, Giorgia Coratti, Beatrice Berti, Adele D’Amico, Maria Sframeli, Emilio Albamonte, Roberto de Sanctis, Sonia Messina, Michela Catteruccia, Giorgia Brigati, Laura Antonaci, Simona Lucibello, Claudio Bruno, Valeria A. Sansone, Enrico Bertini, Danilo Tiziano, Marika Pane, Eugenio Mercuri

Background

The advent of new therapies has increased the need to achieve early diagnosis in Spinal Muscular Atrophy (SMA). The aim of the present study was to define the age of diagnosis in the three main types of SMA with pediatric-onset and the timing between the recognition of clinical signs and confirmed genetic diagnosis.

Methods

All patients with a confirmed diagnosis of type I, II, III SMA followed in 5 Italian centers were included in this study, assessing age at symptoms onset, presenting sign or symptom, age at diagnosis, interval between clinical onset and diagnosis and type of medical investigations conducted in order to obtain the diagnosis.

Results

The cohort included 480 patients, 191 affected by SMA type I, 210 by type II and 79 by type III. The mean age at diagnosis was 4.70 months (SD ±2.82) in type I, 15.6 months (SD±5.88) in type II, and 4.34 years (SD±4.01) in type III.The mean time between symptom onset and diagnosis was 1.94 months (SD±1.84) in type I, 5.28 months (SD±4.68) in type II and 16.8 months (SD±18.72) in type III.

Conclusions

Our results suggest that despite improved care recommendations there is still a marked diagnostic delay, especially in type III. At the time new therapies are becoming available more attention should be devoted to reducing such delay as there is consistent evidence of the benefit of early treatment.

Randomised controlled trial to investigate the relationship between mild hypercapnia and cerebral oxygen saturation in patients undergoing major surgery

Por: Wong · C. · Churilov · L. · Cowie · D. · Tan · C. O. · Hu · R. · Tremewen · D. · Pearce · B. · Pillai · P. · Karalapillai · D. · Bellomo · R. · Weinberg · L.
Objectives

The effects of hypercapnia on regional cerebral oxygen saturation (rSO2) during surgery are unclear. We conducted a randomised controlled trial to investigate the relationship between mild hypercapnia and rSO2. We hypothesised that, compared with targeted normocapnia (TN), targeted mild hypercapnia (TMH) during major surgery would increase rSO2.

Design

A prospective, randomised, controlled trial in adult participants undergoing elective major surgery.

Setting

A single tertiary centre in Heidelberg, Victoria, Australia.

Participants

40 participants were randomised to either a TMH or TN group (20 to each).

Interventions

TMH (partial pressure of carbon dioxide in arterial blood, PaCO2, 45–55 mm Hg) or TN (PaCO2 35–40 mm Hg) was delivered via controlled ventilation throughout surgery.

Primary and secondary outcome measures

The primary endpoint was the absolute difference between the two groups in percentage change in rSO2 from baseline to completion of surgery. Secondary endpoints included intraoperative pH, bicarbonate concentration, base excess, serum potassium concentration, incidence of postoperative delirium and length of stay (LOS) in hospital.

Results

The absolute difference between the two groups in percentage change in rSO2 from the baseline to the completion of surgery was 19.0% higher in both hemispheres with TMH (p2 was greater in the TMH group than the TN group throughout the duration of surgery. The difference between the groups became more noticeable over time. Furthermore, postoperative delirium was higher in the TN group (risk difference 0.3, 95% CI 0.1 to 0.5, p=0.02). LOS was similar between groups (5 days vs 5 days; p=0.99).

Conclusion

TMH was associated with a stable increase in rSO2 from the baseline, while TN was associated with a decrease in rSO2 in both hemispheres in patients undergoing major surgery. This resulted in a clear separation of percentage change in rSO2 from the baseline between TMH and TN over time. Our findings provide the rationale for larger studies on TMH during surgery.

Trial registration number

The Australian New Zealand Clinical Trials Registry (ACTRN12616000320459).

Education as a strategy for managing occupational-related musculoskeletal pain: a scoping review

Por: Palsson · T. S. · Boudreau · S. · Hogh · M. · Herrero · P. · Bellosta-Lopez · P. · Domenech-Garcia · V. · Langella · F. · Gagni · N. · Christensen · S. W. · Villumsen · M.
Background

Musculoskeletal (MSK) pain is the primary contributor to disability worldwide. There is a growing consensus that MSK pain is a recurrent multifactorial condition underpinned by health and lifestyle factors. Studies suggest that education on work-related pain and individualised advice could be essential and effective for managing persistent MSK pain.

Objective

The objective of this scoping review was to map the existing educational resources for work-related MSK (WRMSK) pain, and the effects of implementing educational strategies in the workplace on managing WRMSK pain.

Methods

This scoping review assessed original studies that implemented and assessed education as a strategy to manage WMSK pain. Literature search strategies were developed using thesaurus headings (ie, MeSH and CINAHL headings) and free-text search including words related to MSK in an occupational setting. The search was carried out in PubMed, CINAHL, Cochrane Library and Web of Science in the period 12–14 February 2019.

Results

A total of 19 peer-reviewed articles were included and the study design, aim and outcomes were summarised. Of the 19 peer-reviewed articles, 10 randomised controlled trial (RCT) studies assessed the influence of education on work-related MSK pain. Many studies provided a limited description of the education material and assessed/used different methods of delivery. A majority of studies concluded education positively influences work-related MSK pain. Further, some studies reported additive effects of physical activity or ergonomic adjustments.

Conclusions

There is a gap in knowledge regarding the best content and delivery of education of material in the workplace. Although beneficial outcomes were reported, more RCT studies are required to determine the effects of education material as compared with other interventions, such as exercise or behavioural therapy.

A multidisciplinary approach to mental illness: do inflammation, telomere length and microbiota form a loop? A protocol for a cross-sectional study on the complex relationship between inflammation, telomere length, gut microbiota and psychiatric disorders

Por: Manchia · M. · Paribello · P. · Arzedi · C. · Bocchetta · A. · Caria · P. · Cocco · C. · Congiu · D. · Cossu · E. · Dettori · T. · Frau · D. V. · Garzilli · M. · Manca · E. · Meloni · A. · Montis · M. A. · Mura · A. · Nieddu · M. · Noli · B. · Pinna · F. · Pisanu · C. · Robledo · R. · Severino
Introduction

Severe psychiatric disorders are typically associated with a significant reduction in life expectancy compared with the general population. Among the different hypotheses formulated to explain this observation, accelerated ageing has been increasingly recognised as the main culprit. At the same time, telomere shortening is becoming widely accepted as a proxy molecular marker of ageing. The present study aims to fill a gap in the literature by better defining the complex interaction/s between inflammation, age-related comorbidities, telomere shortening and gut microbiota in psychiatric disorders.

Methods and analysis

A cross-sectional study is proposed, recruiting 40 patients for each of three different diagnostic categories (bipolar disorder, schizophrenia and major depressive disorder) treated at the Section of Psychiatry and at the Unit of Clinical Pharmacology of the University Hospital Agency of Cagliari (Italy), compared with 40 age-matched and sex-matched non-psychiatric controls. Each group includes individuals suffering, or not, from age-related comorbidities, to account for the impact of these medical conditions on the biological make-up of recruited patients. The inflammatory state, microbiota composition and telomere length (TL) are assessed.

Ethics and dissemination

The study protocol was approved by the Ethics Committee of the University Hospital Agency of Cagliari (PG/2018/11693, 5 September 2018). The study is conducted in accordance with the principles of good clinical practice and the Declaration of Helsinki, and in compliance with the relevant Italian national legislation. Written, informed consent is obtained from all participants. Participation in the study is on a voluntary basis only. Patients will be part of the dissemination phase of the study results, during which a local conference will be organised and families of patients will also be involved. Moreover, findings will be published in one or more research papers and presented at national and international conferences, in posters or oral communications.

What are the benefits and risks of sharing patients diagnostic radiological images with them? A cross-sectional study of the perceptions of patients and clinicians in the UK

Por: Cox · W. A. S. · Cavenagh · P. · Bello · F.
Objectives

The objective for this work was to assess clinical experts’ and patients’ opinions on the benefits and risks of sharing patients’ diagnostic radiological images with them.

Setting

This study was conducted outside of the primary and secondary care settings. Clinical experts were recruited at a UK national imaging and oncology conference, and patients were recruited via social media.

Participants

121 clinical experts and 282 patients completed the study. A further 73 patient and 10 clinical expert responses were discounted due to item non-response. Individuals were required to be a minimum of 18 years of age at the time of participation.

Primary and secondary outcome measures

This study was exploratory in nature. As such, the outcomes to be measured for demonstration of the successful completion of this study were generated organically through the process of the investigation itself. These were: (1) the delineation of the benefits available from, and the risks posed by, widening access to diagnostic radiological images; (2) establishment of the level and nature of demand for access to diagnostic radiological images; and (3) the identification of stakeholder requirements for accessing available benefit from diagnostic radiological images.

Results

403 usable questionnaires were returned consisting of responses from clinical experts (n=121) and patients (n=282). Both groups acknowledge the potential benefits of this practice. Examples included facilitating communication, promoting patient engagement and supporting patients in accepting health information shared with them. However, both groups also recognised risks associated with image sharing, such as the potential for patients to be upset or confused by their images.

Conclusions

There is a demand from patients for access to their diagnostic radiological images alongside acknowledgement from clinical experts that there may be benefits available from this. However, due to the acknowledged risks, there is also a need to carefully manage this interaction.

Trial registration number

187752.

Dementia among migrants and ethnic minorities in Italy: rationale and study protocol of the ImmiDem project

Por: Canevelli · M. · Lacorte · E. · Cova · I. · Cascini · S. · Bargagli · A. M. · Angelici · L. · Giusti · A. · Pomati · S. · Pantoni · L. · Vanacore · N. · On behalf of the ImmiDem Study Group · Bacigalupo · Bellomo · Gervasi · Marchetti · Mayer · Mazzola · Palazzesi · Piscopo · Porrel
Introduction

Due to the ongoing demographic and epidemiological transitions, estimating the phenomenon of dementia in migrants and minority groups, exploring its characteristics and challenges and implementing dedicated healthcare policies, constitute emerging and urgent matters for Western countries. In the present paper we describe the rationale and design of the ‘Dementia in immigrants and ethnic minorities living in Italy: clinical-epidemiological aspects and public health perspectives" (ImmiDem) project.

Methods and analysis

Three main aims will be pursued by the ImmiDem project. First, a survey of all Italian dementia services will be conducted with dedicated questionnaires in order to estimate and describe the proportion and characteristics of migrants seeking help for cognitive disturbances. The different clinical approaches for diagnosing dementia and the challenges encountered in the assessment of cognitive functioning and in the provision of care in these groups of individuals will also be investigated. Second, record linkage procedures of data routinely collected in regional Health Information Systems will be conducted in order to identify and monitor migrant individuals with dementia living in the Lazio region. Third, tailored national and local care-coordination pathways and/or good practices dedicated to migrants affected by dementia and cognitive disorders will be identified and promoted.

Ethics and dissemination

The study protocol was approved by the Ethics Committee of the Italian National Institute of Health (protocol 10749; 5 April 2018). The project was launched in November 2018 and will end in November 2021. The findings of the project will be disseminated through scientific peer-reviewed journals as well as to the public via the Dementia Observatory website (https://demenze.iss.it).

Impact of Ramadan fasting on kidney function and related outcomes in patients with chronic kidney disease: a systematic review protocol

Por: Bello · A. K. · Kurzawa · J. · Osman · M. A. · Olah · M. E. · Lloyd · A. · Wiebe · N. · Habib · S. · Qarni · U. · Shojai · S. · Pauly · R. P.
Introduction

Fasting during the month of Ramadan is a significant Islamic religious practice that involves abstinence from food, drink and medication from dawn to dusk. As just under a quarter of the world’s population identifies as Muslim, the effect of fasting on chronic conditions, such as chronic kidney disease (CKD) is a topic of broad relevance. To date, the information in this area has been mixed, with many limitations of previous studies. This study aims to synthesise the evidence of the effect of Ramadan fasting on changes on kidney function, risk factors, episodes of acute kidney injury and impact on the quality of life in patients with CKD or kidney transplant.

Methods and analysis

A systematic review of the literature will be conducted, using electronic databases such as MEDLINE, Embase, Global Health, CINAHL and Scopus. Original research and grey literature on the effect of Ramadan fasting in adult patients with CKD or renal transplantation will be included. Two reviewers will independently screen articles for inclusion in the review and independently assess the methodology of included studies using a customised checklist. Mean difference or risk ratio will be reported for continuous or dichotomous outcomes and results will be pooled using a random-effects model where heterogeneity is reasonable. If possible, subgroups (CKD status, setting, season and risk of bias) will be analysed for effect modification with fasting and the outcomes of interest. Risk of bias will be assessed using the Downs and Black checklist.

Ethics and dissemination

The results will be disseminated using a multifaceted approach to engage all stakeholders (patients, practitioners and community leaders). Research ethics board approval is not required as this is a systematic review of previously published research.

PROSPERO registration number

CRD42018088973.

National health information systems for achieving the Sustainable Development Goals

Por: Suthar · A. B. · Khalifa · A. · Joos · O. · Manders · E.-J. · Abdul-Quader · A. · Amoyaw · F. · Aoua · C. · Aynalem · G. · Barradas · D. · Bello · G. · Bonilla · L. · Cheyip · M. · Dalhatu · I. T. · De Klerk · M. · Dee · J. · Hedje · J. · Jahun · I. · Jantaramanee · S. · Kamocha · S. · Lereb
Objectives

Achieving the Sustainable Development Goals will require data-driven public health action. There are limited publications on national health information systems that continuously generate health data. Given the need to develop these systems, we summarised their current status in low-income and middle-income countries.

Setting

The survey team jointly developed a questionnaire covering policy, planning, legislation and organisation of case reporting, patient monitoring and civil registration and vital statistics (CRVS) systems. From January until May 2017, we administered the questionnaire to key informants in 51 Centers for Disease Control country offices. Countries were aggregated for descriptive analyses in Microsoft Excel.

Results

Key informants in 15 countries responded to the questionnaire. Several key informants did not answer all questions, leading to different denominators across questions. The Ministry of Health coordinated case reporting, patient monitoring and CRVS systems in 93% (14/15), 93% (13/14) and 53% (8/15) of responding countries, respectively. Domestic financing supported case reporting, patient monitoring and CRVS systems in 86% (12/14), 75% (9/12) and 92% (11/12) of responding countries, respectively. The most common uses for system-generated data were to guide programme response in 100% (15/15) of countries for case reporting, to calculate service coverage in 92% (12/13) of countries for patient monitoring and to estimate the national burden of disease in 83% (10/12) of countries for CRVS. Systems with an electronic component were being used for case reporting, patient monitoring, birth registration and death registration in 87% (13/15), 92% (11/12), 77% (10/13) and 64% (7/11) of responding countries, respectively.

Conclusions

Most responding countries have a solid foundation for policy, planning, legislation and organisation of health information systems. Further evaluation is needed to assess the quality of data generated from systems. Periodic evaluations may be useful in monitoring progress in strengthening and harmonising these systems over time.

Effectiveness of complex multiple-risk lifestyle interventions in reducing symptoms of depression: a study protocol for a systematic review and meta-analysis of randomised controlled trials

Por: Gomez-Gomez · I. · Motrico · E. · Moreno-Peral · P. · Rigabert · A. · Conejo-Ceron · S. · Ortega-Calvo · M. · Recio · J.-I. · Bellon · J. A.
Introduction

Many studies have explored the impact of lifestyle interventions on depression. However, little is known about the effectiveness of complex multiple-risk lifestyle interventions in reducing symptoms of depression. Our objective is to assess the effectiveness of complex multiple-risk lifestyle interventions in reducing depressive symptoms in the adult population by the acquisition of at least two healthy habits—healthy diet, physical activity and/or smoking cessation. For such purpose, a systematic review and meta-analysis of randomised controlled trials will be conducted.

Method and analysis

MEDLINE (through Ovid and PubMed), Scopus, Cochrane Central Register of Controlled Trials, Web of Science, PsycINFO, OpenGrey Register (System for Information on Grey Literature in Europe) and the International Clinical Trials Registry Platform will be searched for relevant articles. Additionally, a supplementary manual search will be performed using lists of references, references to expert authors and other systematic reviews and/or meta-analyses. Study selection, data extraction (target habits, country, target populations, conditions and statistical data to name a few) and assessment of the risk of bias will be performed separately by two independent researchers. The primary outcome measure will be the reduction of depression symptoms, as measured by validated instruments. We will calculate pooled standardised mean differences and 95% CIs using random-effect models. Heterogeneity, sensitivity and publication bias will be assessed, and sub-group analysis will be performed. Heterogeneity will be explored by random-effects meta-regression analysis.

Ethics and dissemination

Ethical approval is not required for this study. The results of this systematic review and meta-analysis will be presented in relevant conferences and published in a peer-review journal. The findings of this study could have important clinical and scientific implications for the improvement of symptoms of depression.

PROSPERO registration number

CRD42018100253; Pre-results.

Cuáles son los efectos de la relajación sobre los niveles de depresión en mujeres con embarazos de alto riesgo

Se llevó a cabo la revisión crítica a través de CASPe1 como lista de comprobación para ensayo clínico aleatorizado, el estudio presenta un aporte relevante puesto que permite apropiarse de una técnica de relajación para disminuir el riesgo de depresión en mujeres embarazadas de alto riesgo obstétrico [Fragmento de texto].

Historia de Violencia y Violencia de Compañero Íntimo en mujeres embarazadas. Resultados en salud

Objetivos: examinar la frecuencia de Historia de Violencia (HV) en mujeres embarazadas; estudiar las características sociodemográficas asociadas e identificar los resultados en salud. Metodología: estudio transversal (Andalucía, España) con 754 mujeres embarazadas con cuestionario autoadministrado, incluyendo variables sociodemográficas, estado de salud y violencia. Se calculó la prevalencia de HV y modelos de regresión logística multivariable. Resultados: el 9% refirió HV, el 4,8% Violencia de Compañero Íntimo actual y el 1,9% durante su embarazo. La HV se asoció significativamente con mala percepción del estado de salud (ORa 2,54; IC95%: 1,46-4,43), morbilidad psíquica (ORa 2,82; IC95%:1,56-5,07) y uso de medicación en el embarazo (ORa 2,36 IC95%: 1,14-4,87). Conclusión principal: la HV tiene un impacto en los resultados de salud de las gestantes. Dada la alta tasa de cobertura sanitaria durante el embarazo, este se convierte en un momento idóneo para poner en marcha las recomendaciones de los protocolos.

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