Fibrillar form of α-synuclein-specific scFv antibody inhibits α-synuclein seeds induced aggregation and toxicity

Synucleinopathies including Parkinson’s disease (PD), dementia with Lewy bodies (DLB), and multiple system atrophy (MSA) are characterized by pathological accumulation of α-synuclein (α-syn). Amongst the various approaches attempting to tackle the pathological features of synucleinopathies, antibody-based immunotherapy holds much promise. However, the large size of antibodies and corresponding difficulty in crossing the blood-brain barrier has limited development in this area. To overcome this issue, we engineered single-chain variable fragments (scFvs) against fibrillar α-syn, a putative disease-relevant form of α-syn. The purified scFvs showed specific activity towards α-syn fibrils and oligomers in comparison to monomers and recognized intracellular inclusions in human post-mortem brain tissue of Lewy body disease cases, but not aged controls. In vitro studies indicated scFvs inhibit the seeding of α-syn aggregation in a time-dependent manner, decreased α-syn seed-induced toxicity in a cell model of PD, and reduced the production of insoluble α-syn phosphorylated at Ser-129 (pS129-α-syn). These results suggest that our α-syn fibril-specific scFvs recognize α-syn pathology and can inhibit the aggregation of α-syn in vitro and prevent seeding-dependent toxicity. Therefore, the scFvs described here have considerable potential to be utilized towards immunotherapy in synucleinopathies and may also have applications in ante-mortem imaging modalities.Dr. El-Agnaf’s laboratory was funded by Qatar Biomedical Research Institute under the Start-up Fund SF 2017– 007. The Newcastle Brain Tissue Resource is funded in part by a grant from the UK Medical Research Council, by NIHR Newcastle Biomedical Research Centre awarded to the Newcastle upon Tyne NHS Foundation Trust and Newcastle University, and by a grant from the Alzheimer’s Society and Alzheimer’s Research UK as part of the Brains for Dementia Research Project

Effects of hospital facilities on patient outcomes after cancer surgery: an international, prospective, observational study

Background Early death after cancer surgery is higher in low-income and middle-income countries (LMICs) compared with in high-income countries, yet the impact of facility characteristics on early postoperative outcomes is unknown. The aim of this study was to examine the association between hospital infrastructure, resource availability, and processes on early outcomes after cancer surgery worldwide.Methods A multimethods analysis was performed as part of the GlobalSurg 3 study-a multicentre, international, prospective cohort study of patients who had surgery for breast, colorectal, or gastric cancer. The primary outcomes were 30-day mortality and 30-day major complication rates. Potentially beneficial hospital facilities were identified by variable selection to select those associated with 30-day mortality. Adjusted outcomes were determined using generalised estimating equations to account for patient characteristics and country-income group, with population stratification by hospital.Findings Between April 1, 2018, and April 23, 2019, facility-level data were collected for 9685 patients across 238 hospitals in 66 countries (91 hospitals in 20 high-income countries; 57 hospitals in 19 upper-middle-income countries; and 90 hospitals in 27 low-income to lower-middle-income countries). The availability of five hospital facilities was inversely associated with mortality: ultrasound, CT scanner, critical care unit, opioid analgesia, and oncologist. After adjustment for case-mix and country income group, hospitals with three or fewer of these facilities (62 hospitals, 1294 patients) had higher mortality compared with those with four or five (adjusted odds ratio [OR] 3.85 [95% CI 2.58-5.75]; p<0.0001), with excess mortality predominantly explained by a limited capacity to rescue following the development of major complications (63.0% vs 82.7%; OR 0.35 [0.23-0.53]; p<0.0001). Across LMICs, improvements in hospital facilities would prevent one to three deaths for every 100 patients undergoing surgery for cancer.Interpretation Hospitals with higher levels of infrastructure and resources have better outcomes after cancer surgery, independent of country income. Without urgent strengthening of hospital infrastructure and resources, the reductions in cancer-associated mortality associated with improved access will not be realised

Impact of opioid-free analgesia on pain severity and patient satisfaction after discharge from surgery: multispecialty, prospective cohort study in 25 countries

Background: Balancing opioid stewardship and the need for adequate analgesia following discharge after surgery is challenging. This study aimed to compare the outcomes for patients discharged with opioid versus opioid-free analgesia after common surgical procedures.Methods: This international, multicentre, prospective cohort study collected data from patients undergoing common acute and elective general surgical, urological, gynaecological, and orthopaedic procedures. The primary outcomes were patient-reported time in severe pain measured on a numerical analogue scale from 0 to 100% and patient-reported satisfaction with pain relief during the first week following discharge. Data were collected by in-hospital chart review and patient telephone interview 1 week after discharge.Results: The study recruited 4273 patients from 144 centres in 25 countries; 1311 patients (30.7%) were prescribed opioid analgesia at discharge. Patients reported being in severe pain for 10 (i.q.r. 1-30)% of the first week after discharge and rated satisfaction with analgesia as 90 (i.q.r. 80-100) of 100. After adjustment for confounders, opioid analgesia on discharge was independently associated with increased pain severity (risk ratio 1.52, 95% c.i. 1.31 to 1.76; P < 0.001) and re-presentation to healthcare providers owing to side-effects of medication (OR 2.38, 95% c.i. 1.36 to 4.17; P = 0.004), but not with satisfaction with analgesia (beta coefficient 0.92, 95% c.i. -1.52 to 3.36; P = 0.468) compared with opioid-free analgesia. Although opioid prescribing varied greatly between high-income and low- and middle-income countries, patient-reported outcomes did not.Conclusion: Opioid analgesia prescription on surgical discharge is associated with a higher risk of re-presentation owing to side-effects of medication and increased patient-reported pain, but not with changes in patient-reported satisfaction. Opioid-free discharge analgesia should be adopted routinely

Demulsification of crude oil emulsion via electrocoagulation method

During oil production and processing emulsions were formed and seriously cause problem, both in terms of chemicals used and production losses. The traditional methods of breaking crude oil emulsions are disadvantageous from both economic and environmental perspectives. In this paper, the potentials of electrocoagulation technology in demulsification of crude oil emulsion were investigated. The crude oil obtained from Petronas Ponapean Melaka, Malaysia. For stability performance test, Span 80 was used as emulsifier, while for chemical demulsification performance test, Hexylamine was used. The electrocoagulation method was used for demulsification of W/O emulsion. For electrocoagulation demulsification, three factors namely; voltages 15-50 V, current density 1.04-3.94 mAcm-2, and concentration of NaCl 0.5-2.5 g/L. The electrocoagulation demulsification showed that the best water separation efficiency was achieved at voltage 50 V, current density 3.94 mAcm-2, and NaCl concentration 2.5 g/L, whereas the separation efficiency reached at 98%. Results have shown the potential of electrocoagulation method in separation of water-in-crude oil emulsions, W/O

Significance of growth differentiation factor 15 in chronic HCV patients

Background and objective: Hepatitis C virus is the most common cause of chronic liver disease in Egypt. This work aims to assess the use of the simple and noninvasive biomarker Serum Growth differentiation Factor 15 (GDF-15), along with Alpha Fetoprotein (AFP) and Ferritin for the diagnosis of advanced liver disease in chronic hepatitis C patients. Subjects and methods: This study was conducted on 60 patients, who were recruited from the National Liver and Tropical Diseases Institute, Cairo, Egypt, who were suffering from early & advanced liver cirrhosis and chronic active hepatitis. Twenty cases of healthy subjects served as controls. Serum (GDF-15), (AFP), Ferritin and Hepatitis markers were measured by ELISA method. Measurement of different liver enzyme activity was done by the kinetic methods. Results: Data analysis revealed significant increase in serum levels of GDF15 in patients with Hepatocellular carcinoma (HCC) and Liver Cirrhosis (LC) compared to the healthy subjects. These results were parallel to those of serum levels of AFP, which also demonstrated significant increase in all patients groups as compared to normal control. A moderate increase in the GDF15 level was detected in the patients with chronic hepatitis C (CHC) compared to normal healthy subjects. Conclusion: This study demonstrated that GDF15 and AFP detection can help in the diagnosis and prediction of complications associated with CHC including liver cirrhosis and HCC. Also GDF15 can be used as a satisfactory serum marker of HCC and LC

The challenges of managing glioblastoma multiforme in developing countries: a trade-off between cost and quality of care

BACKGROUND AND OBJECTIVES: The management of glioblastoma multiforme (GBM) in developing countries is hindered by the paucity of clear protocols due in part to growing economic constraints and the lack of availability of expensive chemotherapeutic agents. We evaluated the deliverable treatment protocols and achievable outcomes for patients with GBM in a low-income country prior and subsequent to the worldwide adoption of temozolomide. DESIGN AND SETTING: Retrospective case series. PATIENTS AND METHODS: Charts of consecutive patients with a pathologic diagnosis of high-grade glioma diagnosed between January 2003 and December 2008 were retrospectively reviewed. RESULTS: We identified 146 adult patients, including 105 males and 41 females between 19 and 81 years of age (median age, 51 years), with histologically confirmed high-grade glioma. All patients underwent craniotomy. Eighty-two patients were treated with radiotherapy and temozolomide, of whom 42 patients received temozolomide concurrent with radiation followed by adjuvant temozolomide; 40 patients received irradiation followed sequentially by 6 cycles of temozolomide. In 40 patients irradiation was utilized as a single modality treatment adjuvant to surgery. The follow-up ranged from 1 to 56 months (median, 9.4 months). The median survival for the whole cohort was 10.2 months. The median survival for the radiotherapy-alone group was 5.3 months and for combined radiotherapy/temozolomide was 14.8 months. Survival was similar in both concurrent and sequential groups. Temozolomide conferred a statistically significant survival benefit of 9 months compared with standard therapeutic modalities. CONCLUSIONS: The results compare favorably to those reported in developed nations. Current management of GBM in developing countries should include maximal surgical resection followed by radiotherapy/temozolomide whenever medically and/or financially feasible. Outcomes comparable to those obtained within the context of randomized trials can be expected in low-income settings if healthcare delivery is carefully planned. Our results indicate that concurrent and sequential regimens are equally effective in these patients

Fibrillar form of α-synuclein-specific scFv antibody inhibits α-synuclein seeds induced aggregation and toxicity

Synucleinopathies including Parkinson’s disease (PD), dementia with Lewy bodies (DLB), and multiple system atrophy (MSA) are characterized by pathological accumulation of α-synuclein (α-syn). Amongst the various approaches attempting to tackle the pathological features of synucleinopathies, antibody-based immunotherapy holds much promise. However, the large size of antibodies and corresponding difficulty in crossing the blood-brain barrier has limited development in this area. To overcome this issue, we engineered single-chain variable fragments (scFvs) against fibrillar α-syn, a putative disease-relevant form of α-syn. The purified scFvs showed specific activity towards α-syn fibrils and oligomers in comparison to monomers and recognized intracellular inclusions in human post-mortem brain tissue of Lewy body disease cases, but not aged controls. In vitro studies indicated scFvs inhibit the seeding of α-syn aggregation in a time-dependent manner, decreased α-syn seed-induced toxicity in a cell model of PD, and reduced the production of insoluble α-syn phosphorylated at Ser-129 (pS129-α-syn). These results suggest that our α-syn fibril-specific scFvs recognize α-syn pathology and can inhibit the aggregation of α-syn in vitro and prevent seeding-dependent toxicity. Therefore, the scFvs described here have considerable potential to be utilized towards immunotherapy in synucleinopathies and may also have applications in ante-mortem imaging modalities.Other Information Published in: Scientific Reports License: https://creativecommons.org/licenses/by/4.0See article on publisher's website: http://dx.doi.org/10.1038/s41598-020-65035-8</p

A new One Health Framework in Qatar for future emerging and re-emerging zoonotic diseases preparedness and response

One Health is increasingly recognized as an optimal approach to address the global risk of health threats originating at the human, animal, and ecosystem interface, and their impact. Qatar has successfully practiced One Health approach for investigation and surveillance of zoonotic diseases such as MERS-CoV, and other health threats. However, the current gaps at institution and policy level hinder the sustainment of One Health. In this paper, we have assessed the potential for implementation of One Health Framework to reinforce and sustain One Health capacities in Qatar for 2022–2027. To implement One Health Framework in the country, Qatar Joint External Evaluation (JEE) report, lessons learnt during One Health experiences on zoonotic, vector-borne, and food borne diseases were used to present an outline for multisectoral coordination. In addition, technical capacities of One Health and factors that are required to operationalize it in the country were also assessed in series of meetings and workshops held at Ministry of Public Health on March 2022. Present health care infrastructure and resources were found to be conducive for effective management and response to shared health threats as evident during MERS-CoV, despite being more event based. Regardless, the need for more sustainable capacity development was unanimously emphasized. The consensus between all relevant stakeholders and partners was that there is a need for better communication channels, policies and protocols for data sharing, and the need to invest more resources for better sustainability. The proposed framework is expected to strengthen and facilitate multilateral coordination, enhanced laboratory capacity and network, improve active surveillance and response, risk communication, community engagement, maximize applied research, and build One Health technical work force. This would enable advancement and sustainment of One Health activities to prevent and control health threats shared between humans-animals-ecosystem interface