Uncovering the Role of Natural and Synthetic Small Molecules in Counteracting the Burden of α-Synuclein Aggregates and Related Toxicity in Different Models of Parkinson's Disease.

A proteostasis network represents a sophisticated cellular system that controls the whole process which leads to properly folded functional proteins. The imbalance of proteostasis determines a quantitative increase in misfolded proteins prone to aggregation and elicits the onset of different diseases. Among these, Parkinson's Disease (PD) is a progressive brain disorder characterized by motor and non-motor signs. In PD pathogenesis, alpha-Synuclein (α-Syn) loses its native structure, triggering a polymerization cascade that leads to the formation of toxic inclusions, the PD hallmark. Because molecular chaperones represent a "cellular arsenal" to counteract protein misfolding and aggregation, the modulation of their expression represents a compelling PD therapeutic strategy. This review will discuss evidence concerning the effects of natural and synthetic small molecules in counteracting α-Syn aggregation process and related toxicity, in different in vitro and in vivo PD models. Firstly, the role of small molecules that modulate the function(s) of chaperones will be highlighted. Then, attention will be paid to small molecules that interfere with different steps of the protein-aggregation process. This overview would stimulate in-depth research on already-known small molecules or the development of new ones, with the aim of developing drugs that are able to modify the progression of the disease.

Willingness of Mothers to Receive Reminders for Routine Vaccination Appointments in Northern Nigeria: A Multi-Centre Cross-Sectional Study.

BACKGROUND: Routine vaccination, a cost-effective means of preventing deadly childhood disease, has a low coverage in Nigeria. The study assessed the willingness of mothers to receive reminder messages for routine vaccination appointments in Northern Nigeria. METHODS: A multi-centre cross-sectional study involving at least 363 mother-infant pairs per centre from five states in Northern Nigeria. Data collected include the socio-demographic details, responses on parental phone ownership, mothers' willingness to receive reminders for immunization appointments and the reminder type characteristics. Data analysis was done with SPSS. RESULTS: Of the 1952 mother-infant pairs, ownership of at least one household phone was 97.7%. In total, 1613 (82.6%) mothers were willing to receive reminders. A majority (62.2%) of mothers preferred phone calls. A day before the vaccination appointment was the preferred timing (78.1%), and the predominant communication language was the local language for each region.The odds of being willing to receive reminders were 3.1 times, 2.6 times and 1.8 times higher in those with no formal education, primary education and secondary education, respectively, compared with mothers with tertiary education, each p < 0.05. Mothers who delivered at home were significantly less likely to want reminder messages (p = 0.03). CONCLUSION: Eight of 10 women in Northern Nigeria are willing to receive a reminder for their child. The predominant mode of reminder preferred is phone calls using the local language. Deployment of mobile phone reminders strategy in Northern Nigeria as a means to improve vaccination uptake is feasible. The institution of this strategy can be in collaboration with service providers.

A Comparative Study of Serum Lipid Levels in Pregnant Normotensive and Pre-eclamptic Women in Dalhatu Araf Specialist Hospital Lafia, Nigeria.

Background: Pre-eclampsia is associated with significant maternal and perinatal mortality and morbidity. Increased oxidative stress due to endothelial dysfunction in pre-eclampsia has been linked with lipid abnormality. This study compared the fasting serum lipid levels in pre-eclamptic and normotensive pregnant women. Methodology: A case-control study in which venous blood samples (5mls) were collected from 50 consenting pregnant healthy normotensive women and 50 women with pre-eclampsia accessing care at the hospital. Study participants were matched for maternal age, parity, and gestational age after 8-12 hours of fasting. The fasting serum levels of total cholesterol (TC), low-density lipoprotein (LDL-C), very low-density lipoprotein (VLDL-C), high-density lipoprotein (HDL-C) and triglycerides (TGs) of the participants were evaluated using standard enzymatic methods. Result: Of the 50 pre-eclamptic and 50 pregnant normotensive women who participated in the study, the mean maternal age was 24.92±4.38 and 24.90±4.27 years respectively (p=0.98).There were statistically significant higher mean levels of TC, triglycerides, and VLDL-C among women with pre-eclampsia compared to normotensive pregnant women (p<0.001, p<0.001, p=0.007 respectively). The mean HDL-C level was significantly reduced among women with pre-eclampsia compared to controls (p<0.001). However, there was no statistically significant difference in the mean serum level of LDL-C in both groups (p=0.068). The serum lipid profile did not significantly change with the severity of pre-eclampsia. Conclusion: Women with pre-eclampsia have increased serum levels of TC, triglycerides, and VLDL-C and decreased levels of HDL-C compared to normotensive pregnant women. However, the lipid profile of women with severe pre-eclampsia did not differ significantly from those with mild pre-eclampsia.

Assessment of the Timely Administration of Birth Dose Vaccines in Northern Nigeria and Associated Factors.

Background: Lack of a timely receipt of vaccines can cause uncertain immune response and under-vaccination. Hence, timely vaccination is crucial to ensure an infant's early protection. Objectives: To identify the age of presentation for the birth dose vaccines, vaccine antigens received and factors associated with vaccination presentation by day one in Northern Nigeria. Method: A descriptive cross-sectional study involving 1 952 mother-infant pairs enrolled from 5 different states in Northern Nigeria. Data was collected using a questionnaire including the socio-demographic, antenatal care (ANC), delivery details, birth dates, vaccination presentation and birth vaccine antigens received. Data analysis was done with the SPSS-21 software. Findings: The median age of the infants at presentation for birth vaccines was six (interquartile range 2-16) days. A total of 413 (21.2%) infants were brought by the day of birth (day 0) or the next day (Day one), while one-fifth (20.6%) presented after Day 28. The most frequently received antigen was the Bacille-Calmette-Guerin by 1 781 infants (91.2%), oral polio vaccine 1 703 (87.2%), and hepatitis B vaccine birth dose the lowest at 75.1% (1 565). The commonest reasons for delayed presentations were an ill baby (24.7%) and an ill mother (21.9%).Factors associated with presentation within Day one post-birth were hospital delivery (OR-1.67, 95% CI; 1.28-2.19), firstborn (OR-1.40; 95%CI; 1.02-1.93), Christianity (OR-2.14 95% CI; 1.63-2.81), and mother with tertiary education (OR-1.62, 95% CI; 1.05-2.48). Conclusion: Timely administration of the birth dose vaccines is low in Northern Nigeria. Furthermore, some babies do not get the required vaccines despite presenting for vaccination due to stockout. Strategies for early neonatal vaccination such as vaccination in hospital suites post-delivery and utilizing relatives/fathers to take the baby for vaccination when a mother is indisposed are imperative.

The efficacy of two doses versus 7 days' course of prophylactic antibiotics following cesarean section: An experience from Aminu Kano Teaching Hospital.

Background: Postcesarean wound infection is a leading cause of prolonged hospital stay. Considerable debates still exist regarding choice of antibiotics, dose, and duration of use. Objectives: The objective is to compare the efficacy of 2 doses of amoxicillin-clavulanic acid versus a 7 days combination of amoxicillin-clavulanic acid and metronidazole as prophylactic antibiotics following cesarean section (CS). Methodology: It was a randomized controlled trial that was conducted among 160 women undergoing CS at Aminu Kano Teaching Hospital. Women were randomized into two groups. Group I (study group) received 2 doses of 1.2 g amoxicillin-clavulanic acid. Group II (control group) received a 7 days course of amoxicillin-clavulanic acid and metronidazole. The data obtained were analyzed using SPSS version 17. Categorical (qualitative) variables were analyzed using Chi-square test and Fisher's exact test as appropriate while continuous (quantitative) variables were analyzed using independent sample t-test. P < 0.05 was considered statistically significant. Results: There was no statistically significant association in the occurrence of fever (12.8% vs. 15.8%, P = 0.6), wound infection (6.4% vs. 10.5%, P = 0.36), endometritis (7.7% vs. 11.8%, P = 0.38), UTI (6.4% vs. 5.3%, P = 1.00), mean duration of hospital stay (129.7 vs. 134.2 h, P = 0.48), and neonatal outcomes between the two groups. There was statistically significant difference in the mean cost of antibiotics (₦2883/US$9.5 vs. ₦7040/US$23.1, P < 0.001) and maternal side effects (10.3% vs. 26.3%, P < 0.001) between the study and the control groups, respectively. Conclusion: This study found no statistically significant difference in infectious morbidity, duration of hospital stay, and neonatal outcomes when two doses of amoxicillin-clavulanic acid was compared with a 7 days course of prophylactic antibiotic following CS. The use of two doses of amoxicillin-clavulanic acid has the advantages of reduced cost and some maternal side effects. The two doses were cheaper with minimal side effects.

RésuméContexte: L'infection des plaies post-césariennes est l'une des principales causes d'hospitalisation prolongée. Des débats considérables existent toujours concernant le choix antibiotiques, dose et durée d'utilisation. Objectifs: L'objectif est de comparer l'efficacité de 2 doses d'acide amoxicilline-clavulanique par rapport à 7 jours association d'acide amoxicilline-clavulanique et de métronidazole comme antibiotiques prophylactiques après une césarienne (CS). Méthodologie: c'était un essai contrôlé randomisé mené auprès de 160 femmes subissant une CS à l'hôpital universitaire Aminu Kano. Les femmes ont été randomisées en deux groupes. Le groupe I (groupe d'étude) a reçu 2 doses d'acide amoxicilline-clavulanique de 1,2 g. Le groupe II (groupe témoin) a reçu 7 jours de l'acide amoxicilline-clavulanique et du métronidazole. Les données obtenues ont été analysées à l'aide de SPSS version 17. Catégorie (qualitative) les variables ont été analysées à l'aide du test du chi carré et du test exact de Fisher, selon le cas, tandis que les variables continues (quantitatives) ont été analysées en utilisant un test t pour échantillon indépendant. P <0,05 était considéré comme statistiquement significatif. Résultats: Il n'y avait pas d'association statistiquement significative en cas de fièvre (12,8% vs 15,8%, P = 0,6), infection des plaies (6,4% vs 10,5%, P = 0,36), endométrite (7,7% vs 11,8%, P = 0,38), IVU (6,4% contre 5,3%, P = 1,00), durée moyenne de séjour à l'hôpital (129,7 contre 134,2 h, P = 0,48) et résultats néonatals entre les deux groupes. Il y avait une différence statistiquement significative dans le coût moyen des antibiotiques (83 2883 / US $ 9,5 contre ₦ 7040 / US $ 23,1, P <0,001) et côté maternel effets (10,3% contre 26,3%, P <0,001) entre l'étude et les groupes témoins, respectivement. Conclusion: Cette étude n'a trouvé aucune statistique différence significative dans la morbidité infectieuse, la durée du séjour à l'hôpital et les résultats néonatals lorsque deux doses d'amoxicilline-clavulanique l'acide a été comparé à un traitement antibiotique prophylactique de 7 jours après la CS. L'utilisation de deux doses d'acide amoxicilline-clavulanique a avantages du coût réduit et de certains effets secondaires maternels. Les deux doses étaient moins chères avec des effets secondaires minimes.

Early result of hemiarthroplasty in elderly patients with fracture neck of femur.

BACKGROUND: Fractured neck of femur is a frequent and severe injury in elderly patients with consequent high morbidity and mortality. Hemiarthroplasty is an established treatment modality for displaced intracapsular femoral neck fractures in elderly patients above 60 years. This study analysed the early functional outcome and complications of Austin Moore endoprosthesis in elderly patients above 60 years with fractured neck of femur. MATERIALS AND METHODS: Retrospective data were obtained over a 5 year period from January 2007 to December 2012. Thirty-five elderly patients of 60 years and above with displaced intracapsular fracture neck of femur treated with hemiarthroplasty using Austin Moore endoprosthesis were included. Data were analysed using SPSS version 21. RESULTS: A total of 35 patients were involved. The age-range was 60-90 years with mean age of 69.7 ± 7 years. The predominant mechanism of injury was trivial falls in 18 (66.7%) patients. The commonest complication was pressure sore in 2 (5.7%) patients, followed by surgical site infection in 1 (2.9%) patient and periprosthetic fracture in 1 (2.9%) patients. Early post-operative mortality was 2.9%. Post-operative hip functional status according to Postel and Merle d Aubigne revealed that majority (66.6%) of patients had satisfactory hip function. CONCLUSION: Functional outcome of Austin Moore in elderly patients above 60 years with fracture neck of femur was satisfactory in most of the cases with minimal morbidity. Careful patient selection for hemiarthroplasty is vital and may decrease the incidence of complications and ameliorate the outcomes in the treatment of intracapsular femoral neck fractures.