Mitochondrial dysfunction and immune activation are detectable in early Alzheimer's disease blood.

PublishedJournal ArticleResearch Support, Non-U.S. Gov'tAlzheimer's disease (AD), like other dementias, is characterized by progressive neuronal loss and neuroinflammation in the brain. The peripheral leukocyte response occurring alongside these brain changes has not been extensively studied, but might inform therapeutic approaches and provide relevant disease biomarkers. Using microarrays, we assessed blood gene expression alterations occurring in people with AD and those with mild cognitive changes at increased risk of developing AD. Of the 2,908 differentially expressed probes identified between the three groups (p < 0.01), a quarter were altered in blood from mild cognitive impairment (MCI) and AD subjects, relative to controls, suggesting a peripheral response to pathology may occur very early. There was strong evidence for mitochondrial dysfunction with decreased expression of many of the respiratory complex I-V genes and subunits of the core mitochondrial ribosome complex. This mirrors changes previously observed in AD brain. A number of genes encoding cell adhesion molecules were increased, along with other immune-related genes. These changes are consistent with leukocyte activation and their increased the transition from circulation into the brain. In addition to expression changes, we also found increased numbers of basophils in people with MCI and AD, and increased monocytes in people with an AD diagnosis. Taken together this study provides both an insight into the functional response of circulating leukocytes during neurodegeneration and also identifies potential targets such as the respiratory chain for designing and monitoring future therapeutic interventions using blood.InnoMed, European Union of the Sixth Framework programAlzheimer’s Research TrustJohn and Lucille van Geest FoundationNIHR Biomedical Research Centre for Mental Health at the South London and Maudsley NHS Foundation TrustInstitute of Psychiatry Kings College Londo

A Cross-sectional Study of Clinical Characteristics and Outcomes among Adults with Laboratory-confirmed SARS-CoV-2 Infection with Omicron Variant

The emergence of the SARS-CoV-2 Omicron variant has raised concerns due to its increased transmissibility and potential implications on clinical characteristics and outcomes in infected individuals. The aims of this report were to study the profile of SARS-CoV-2 infection with omicron variant, investigate the infection outcome, reinfection rates with associated factors, antibody levels, and explore the associations between biochemical markers and disease severity. This prospective cohort study was conducted in Duhok city in the Northern of Iraq. All volunteers with confirmed SARS-CoV-2 RT–PCR and confirmed Omicron infection who were older than 18 years old and agreed to participate were recruited for this study. The study was carried out from January to April 2022. There were 234 cases of confirmed SARS-CoV-2 RT–PCR Omicron infection. The mean age was 48.12±17.3 years, 43.2% were vaccinated, and 40.2% were male. Among the recruited patients, 99.1% recovered and did not need hospitalization. In this study, (38.9%) had a history of previously confirmed COVID-19 infection. Reinfection was significantly higher in females than males (p=0.04; OR= 0.56). It was found that the IgG antibody levels were higher in patients who received Pfizer-BioNTech than in those who received other vaccines (p=0.001). The levels of IgG were also significantly higher in patients with mild infection (p=0.046), whereas the levels of D-dimer were significantly higher in patients with severe cases of the infection compared to those with mild or moderate cases (p=0.001). Additionally, the levels of C-reactive protein (CRP) were observed to be higher in individuals with moderate cases of infection than in mild and severe cases (0.001). Individuals who contracted the Omicron strain generally had positive outcomes. Reinfection with the Omicron variant was relatively high. IgG levels were higher in patients with mild disease, implying that they were associated with decreased disease severity. We found significant associations between D-dimer levels and the severity of the disease. Additional research is required to investigate the long-term effects of Omicron infection

Clinical profile and treatment of infantile spasms using vigabatrin and ACTH - a developing country perspective

Background: Infantile spasms represent a serious epileptic syndrome that occurs in the early infantile age. ACTH and Vigabatrin are actively investigated drugs in its treatment. This study describes the comparison of their efficacy in a large series of Patients with infantile spasms from Pakistan. Methods: All Patients with infantile spasms who presented to Aga Khan University Hospital, Karachi, Pakistan from January, 2006 to April, 2008 were included in this study. Inclusion criteria were clinical symptoms of infantile spasms, hypsarrythmia or modified hyparrythmia on electroencephalography, at least six months of follow-up period and receipt of any of the two drugs mentioned above. The type of drug distribution was random according to the availability, cost and ease of administration. Results: Fifty six cases fulfilled the inclusion criteria. 62.5% were males. Mean age at onset of seizures was 5 +/- 1.4 months. Fifty two (92.8%) Patients demonstrated hypsarrythmia on electroencephalography. 64.3% cases were identified as symptomatic while 19.6% were cryptogenic and 16.1% were idiopathic. Eighteen Patients received ACTH while 38 Patients received Vigabatrin as first line therapy. Initial response to first line therapy was similar (50% for ACTH and 55.3% for Vigabatrin). Overall, the symptomatic and idiopathic groups responded better to Vigabatrin. The relapse rate was higher for ACTH as compared to Vigabatrin (55.5% vs. 33.3%) when considering the first line therapy. Four Patients evolved to Lennox-Gastaut variant, all of these Patients had initially received Vigabatrin and then ACTH. Conclusion: Vigabatrin and ACTH showed no significant difference in the initial treatment of infantile spasms. However, Patients receiving ACTH were 1.2 times more likely to relapse as compared to the Patients receiving Vigabatrin when considering monotherapy. We suggest that Vigabatrin should be the initial drug of choice in Patients presenting with infantile spasms. However, larger studies from developing countries are required to validate the therapeutic trends observed in this study

Surgical Approaches to Congenital Anomalies of Esophagus

With prevalence of about 1 in 3000 live births, pediatric surgeons commonly deal with esophageal abnormalities, which may provide substantial clinical complications. Surprisingly, the embryologic processes underlying esophageal atresia (EA) with or without tracheoesophageal fistula (TEF), one of the hallmark disease entities of pediatric surgery, have only lately been largely uncovered. When it comes to the treatment of congenital esophageal abnormalities, notably esophageal atresia and tracheoesophageal fistula, surgical methods are essential. In order to address the anatomical abnormalities and restore normal function, surgical correction is often necessary in the care of congenital esophageal anomalies, including esophageal atresia and tracheoesophageal fistula. In this review we are going to cover surgical approaches to repair those malformations, long-term outcomes, and latest developments in esophageal surgical approaches

Quality of life among people living with hypertension in a rural Vietnam community

Background - To respond to growing prevalence of hypertension in Vietnam, it is critical to have an in-depth understanding about quality of life (QOL) among people living with hypertension and related factors. This study aimed to measure QOL among hypertensive people in a rural community in Vietnam, and its association with socio-demographic characteristics and factors related to treatment. Methods - This study was conducted in a rural community located 60 km from Ho Chi Minh City. Face-to-face interviews were conducted among 275 hypertensive people aged 50 years and above using WHOQOL-BREF questionnaire. Descriptive statistics were used to examine mean scores of quality of life. Cronbach’s alpha coefficient and Pearson’s correlation coefficient were applied to estimate the internal consistency, and the level of agreement between different domains of WHOQOL-BREF, respectively. Independent T-test and ANOVA test followed by multiple linear regression analyses were used to measure the association between QOL domains and independent variables. Results - Both overall WHOQOL-BREF and each domain had a good internal consistency, ranging from 0.65 to 0.88. The QOL among hypertensive patients was found moderate in all domains, except for psychological domain that was fairly low (mean = 49.4). Backward multiple linear regressions revealed that being men, married, attainment of higher education, having physical activities at moderate level, and adherence to treatment were positively associated with QOL. However, older age and presence of co-morbidity were negatively associated with QOL. Conclusion - WHOQOL-BREF is a reliable instrument to measure QOL among hypertensive patients. The results revealed low QOL in psychological domain and inequality in QOL across socio-demographic characteristics. Given the results, encouraging physical activities and strengthening treatment adherence should be considered to improve QOL of hypertensive people, especially for psychological aspect. Actions to improve QOL among hypertensive patients targeted towards women, lower educated and unmarried patients are needed in the setting

Ecological–Health Risk of Antimony and Arsenic in Centella asiatica, Topsoils, and Mangrove Sediments: A Case Study of Peninsular Malaysia

The current study assessed the ecological–health risks of potentially toxic arsenic (As) and antimony (Sb) in the vegetable Centella asiatica, topsoils, and mangrove sediments sampled from Peninsular Malaysia. The As concentrations ranged from 0.21 to 4.33, 0.18 to 1.83, and 1.32 to 20.8 mg/kg dry weight, for the leaves, stems, and roots of the vegetable, respectively. The ranges of Sb concentrations were 0.31–0.62, 0.12–0.35, and 0.64–1.61 mg/kg dry weight, for leaves, stems, and roots of the vegetable, respectively. The children’s target hazard quotient (THQ) values indicated no non-carcinogenic risks of As and Sb in both leaves and stems, although children’s THQ values were higher than those in adults. The calculated values of estimated weekly intake were lower than established provisional tolerable weekly intake of As and Sb for both children and adult consumers. The carcinogenic risk (CR) values of As for children’s intake of leaves and stems of vegetables showed more public concern than those of adults. The levels of Sb and As in the topsoils were generally higher (although not significantly) than those in the mangrove sediments, resulting in a higher geoaccumulation index, contamination factor and ecological risk, hazard index, THQ, and CR values. This indicated that the anthropogenic sources of Sb and As originated from the land-based activities before reaching the mangrove near the coast. The CR of As signifies a dire need for comprehensive ecological–health risks exposure studies, as dietary intake involves more than just vegetable consumption. Therefore, risk management for As and Sb in Malaysia is highly recommended. The present findings of the ecological–health risks of As and Sb based on 2010–2012 samples can be used as an important baseline for future reference and comparison. Copyright © 2022 Yap, Tan, Cheng, Syazwan, Azrizal-Wahid, Krishnan, Go, Nulit, Ibrahim, Mustafa, Omar, Chew, Edward, Okamura, Al-Mutairi, Al-Shami, Sharifinia, Keshavarzifard, You, Bakhtiari, Bintal, Zakaly, Arai, Naji, Saleem, Abd Rahman, Ong, Subramaniam and Wong.Ministry of Higher Education, Malaysia, MOHEThe present study was supported financially by the Fundamental Research Grant Scheme (FRGS), (Vote No.: 5524953) and by the Ministry of Higher Education, Malaysia

Patterns of Passage into protected areas: drivers and outcomes of Fulani immigration, settlement and integration into the Kachia Grazing Reserve, Northwest Nigeria

Abstract Increasing land use and associated competition for natural resources in the wake of high human and livestock population pressures have been major challenges confronting pastoralists of West Africa. This is especially true in Nigeria where Fulani make up 4% of the national population and prevailing national insecurity issues are impacting on pastoral livelihoods, including violent conflicts over land and ethnic, religious and political disparities. This study examined the dynamics of immigration within the Kachia Grazing Reserve (KGR), an exclusively Fulani pastoralist community in Kaduna State, northwest Nigeria, prompted by concerns from both the farming communities and the authorities about mounting pressure on existing limited resources, particularly in regard to availability of cattle grazing resources. Drawing from a household census conducted in 2011 and employing a range of qualitative methods (focus group discussions and key informant interviews), this study explored the drivers and consequences of immigration and subsequent integration within the KGR community. The study revealed two types of immigration: a steady trickle of pastoralists migrating to the reserve to settle and acquire land, secure from the stresses of competition from cultivators, and the sudden influx of internally displaced persons fleeing violent clashes in their areas of origin. Population pressure within the reserve has risen steadily over the past three decades, such that it is severely overgrazed (as evidenced by reports from the KGR community that the animals run short of pasture even during the wet season due to desertification and the spread of non-edible weeds). The newer immigrants, fleeing conflict, tended to arrive in the reserve with significantly larger herds than those kept by established residents. Pastoralists in the reserve have been forced back into the practice of seasonal transhumance in both wet and dry seasons to support their herds, with all the attendant risks of theft, clashes with cultivators and increased disease transmission

Careers work in higher education in Pakistan: current practice and options for the future

In this article we examine the development of career guidance in Pakistani higher education. The article is primarily based on a review of the existing literature on career guidance in Pakistan, but also includes the consideration of some new data gathered from a review of higher education institutions websites and five case study interviews. It considers both local and global influences as relevant contexts for understanding how the development of career guidance in Pakistani higher education is taking place. Concerns about alignment between skills supply and demand provide key drivers both for the development of career guidance and for wider higher education reform. However the practice of career guidance in Pakistani higher education is shown to be lagging behind the policy aspirations, both due to limited investment and due to more fundamental cultural challenges that have yet to be fully addressed. If career guidance is going to continue to develop within Pakistan it will need to be strengthened by new policy and resources but also through the development of indigenous theories.N/

Global overview of the management of acute cholecystitis during the COVID-19 pandemic (CHOLECOVID study)

Background: This study provides a global overview of the management of patients with acute cholecystitis during the initial phase of the COVID-19 pandemic. Methods: CHOLECOVID is an international, multicentre, observational comparative study of patients admitted to hospital with acute cholecystitis during the COVID-19 pandemic. Data on management were collected for a 2-month study interval coincident with the WHO declaration of the SARS-CoV-2 pandemic and compared with an equivalent pre-pandemic time interval. Mediation analysis examined the influence of SARS-COV-2 infection on 30-day mortality. Results: This study collected data on 9783 patients with acute cholecystitis admitted to 247 hospitals across the world. The pandemic was associated with reduced availability of surgical workforce and operating facilities globally, a significant shift to worse severity of disease, and increased use of conservative management. There was a reduction (both absolute and proportionate) in the number of patients undergoing cholecystectomy from 3095 patients (56.2 per cent) pre-pandemic to 1998 patients (46.2 per cent) during the pandemic but there was no difference in 30-day all-cause mortality after cholecystectomy comparing the pre-pandemic interval with the pandemic (13 patients (0.4 per cent) pre-pandemic to 13 patients (0.6 per cent) pandemic; P = 0.355). In mediation analysis, an admission with acute cholecystitis during the pandemic was associated with a non-significant increased risk of death (OR 1.29, 95 per cent c.i. 0.93 to 1.79, P = 0.121). Conclusion: CHOLECOVID provides a unique overview of the treatment of patients with cholecystitis across the globe during the first months of the SARS-CoV-2 pandemic. The study highlights the need for system resilience in retention of elective surgical activity. Cholecystectomy was associated with a low risk of mortality and deferral of treatment results in an increase in avoidable morbidity that represents the non-COVID cost of this pandemic

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&lt;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&lt;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