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In low-resource settings like Nigeria, the rising prevalence of diabetes is accompanied by an excessive burden of microvascular complications from diabetes. This study aimed to determine the prevalence and predictors of microvascular complications among older patients with diabetes mellitus. Therefore, a 2-year retrospective cross-sectional study was carried out among elderly diabetes patients at the Chief Tony Anenih Geriatric Center outpatient diabetes clinic. A total of 148 diabetic patients were included in the study; the mean (± standard deviation) age was 70.89 (±6.99) years, with 71.6% of the studied population being female. Logistic regression analysis was employed to determine the prevalence and predictors of microvascular complications. Results show that the prevalence of microvascular complications in older diabetes patients was 73.9% [95% confidence interval (CI)=66.7-81.6] with peripheral neuropathy (77.1% prevalence, 95% CI=67.9-84.8) being the most common and retinopathy being the least prevalent (95% CI=4.7-16.8). The significant predictors of developing microvascular complications were intake of oral agents only [p=0.013, odds ratio (OR)=2.35, 95% CI=1.15-16.81], number of comorbidities (p=0.041, adjusted OR=5.28, 95% CI=1.09-27.93) and systolic blood pressure (p=0.042, OR=1.02, 95% CI=1.00-1.04). Considering the high prevalence of microvascular complications among aging patients with diabetes mellitus, older patients should comply with oral medications and undergo regular check-ups, and more advocacy should be undertaken to strengthen geriatric healthcare systems to mitigate comorbidities and reduce complications.

The nuclear-localized ethylene-insensitive3/ethylene-insensitive3-like (EIN3/EIL) proteins regulate the ethylene signaling pathway for growth and stress responses. This study presents a genome-wide analysis of nine Oryza sativa EIN3/EIL genes, exhibiting three clads in an ML phylogenetic tree. These proteins are conserved in both exon-intron organization and motif architecture aligned with their phylogenetic clustering. The EIN3/EIL proteins harbor the EIN3, EIN3 superfamily, and RDV-p3 conserved domains. OsEIN3/EIL expression profiling revealed consistently high transcript levels of LOC_Os03g20790 and LOC_Os02g36510 in leaf blades across vegetative and reproductive stages and in the endosperm, indicating a potential role in growth and yield enhancement. Additionally, LOC_Os03g20790, LOC_Os02g36510, LOC_Os07g48630, and LOC_Os09g31400 are highly expressed at later stages of root development, showing potential in nutrient signaling for seed-filling. Moreover, elevated expression of LOC_Os04g38400, LOC_Os09g31400, LOC_Os03g20790, LOC_Os08g39830, and LOC_Os07g48630 were detected under mannitol treatment, while LOC_Os04g38400 and LOC_Os08g39830 were highly upregulated in root and leaf tissues under drought stress exposure. The EIN3/EIL genes also intricately interacted with MPK1, MPK5, and MYC genes, underscoring their potential involvement in growth and stress tolerance. Altogether, our findings lay a foundation for improved rice growth and yield enhancement.

The need for food size reduction before consumption has led to the use of motorized grinding machine which operates on energized rubbing of two grooved cast-iron discs, and this unintentionally results in tribological degradation and corrosion of grinding discs into the ground food. The objective of this study was to carry out an assessment of corrosion susceptibility of grinding discs from different manufacturing methods in simulated gastro-intestinal environment. Six grinding discs from three states in Nigeria were selected for this study, based on manufacturing methods namely: rotary, cupola, and pit furnaces. Experimental techniques used for the study included: X-Ray Fluorescence spectroscope for determination of chemical composition and X-Ray Diffractometer was used for phase identification. Corrosion susceptibility of grinding discs on interaction with pseudo-body fluid was studied using potentiodynamic polarization scan and product analysis (gasometric) methods in simulated gastro-intestinal environment, typical of human stomach, as electrolyte. The electrolyte contained 2 g/L NaCl acidified to pH of 1.7 with HCl and regulated at 37 °C. Optical microscopy of the electrochemical samples was done for corrosion damage assessment. The key finding from the study was that all the grinding discs contain iron and silicon as dominant alloy elements, which existed predominantly as iron carbide and ferrosilicon phases. Corrosion of the discs in simulated gastric solution was well profound irrespective of the manufacturing method, though, with varying degree among the discs. The outcome of this study is applicable to food industries where cognitive measures may have to be taken on materials selection to minimise the risk of food contamination from materials corrosion.

Background: Dyslipidemia constitutes a serious public health concern globally. It has been established that excessive fructose intake results in dyslipidemia; however, whether dexamethasone aggravates or alleviates fructose-induced dyslipidemia is unknown. Thus, we examined the effects of dexamethasone on dyslipidemia and hyperuricemia in high fructose-taking Wister rats. Materials and Methods: Twenty male Wister rats were randomly grouped as control (distilled water), fructose (10% fructose w/v), dexamethasone (0.2 mg/kg, PO) and fructose+dexamethasone. After a 21-day exposure, the serum and heart samples were harvested, processed and analyzed for biochemical assays. Results: Our findings reveal that exposure of rats to high fructose significantly increased blood glucose, elevated serum triglycerides and uric acid, activity of xanthine oxidase, and lowered high density lipoprotein cholesterol (HDL) level. However, dexamethasone administration had no significant effect on the blood glucose and did not alter the serum levels of triglycerides, uric acid and xanthine oxidase. Meanwhile, both fructose and dexamethasone treatments independently elevated the serum levels of total cholesterol (TC), low density lipoprotein cholesterol (LDL) and malondialdehyde. Further, the fructose treatment elevated the TG/HDL ratio, while both fructose and dexamethasone treatments individually and synergistically elevated TC/HDL ratio. Our study also showed that co-administration of fructose and dexamethasone aggravated the elevated serum levels of TC and LDL, while it impaired the enzymatic antioxidant systems. Conclusion: Dexamethasone, though slightly reduced fructose-induced hyperglycemia, impaired the antioxidant enzymes and escalated dyslipidemia during fructose intake. Hence, our study suggests that dexamethasone administration may increase the risk of CVD in animals with excessive intake of fructose.

Background: Hypertension is the largest contributor to the global burden of disease. Emerging risk factors for cardiovascular disease include blood pressure variability (BPV), but evidence on BPV is lacking among older Nigerians. We reported BPV in a cohort of older persons at the University College Hospital (UCH), Ibadan. Methods: We conducted a retrospective cohort study of respondents aged >50 years within the Ibadan Ambulatory Blood Pressure Registry at the UCH, Ibadan, Nigeria. Socio-demographic characteristics, lifestyle habits and anthropometric measurements were obtained. Results: Among 639 respondents, 332 (52.0%) were female. The blood pressure (BP) variables were strongly associated with age. Compared with younger age groups, mean diastolic BP (DBP) was less at an older age, whereas mean pulse pressure was greater. During the wake-up and sleep periods, mean DBP and mean arterial BP were less with each increasing age category, whereas mean pulse pressure was larger with each increasing age category. BP dipping, systolic, diastolic and mean arterial BP decreased with age. Overall, timed BPV increased significantly with increasing age. The prevalence of white-coat hypertension was greater among older participants than younger participants. Most respondents in the 50–59 years' age group were non-dippers (55.8%), whereas 33.7% of older respondents were reverse-dippers. Conclusion: Older persons experienced a greater abnormal circadian blood variation and greater BPV than younger people. In Nigeria, follow-up data are needed to determine the prognostic significance of these data in this population.

BackgroundAgeing in Place is the emerging social policy drive for long-term care coordination of older persons globally. This decision may be the only viable option in many low- and middle-income countries like Nigeria. Nevertheless, the risk of older persons being 'stuck in place' is high if their preferences are not considered or other alternatives are neither acceptable nor available. This study determined factors associated with the preferred care setting among community-dwelling older persons and explored their views about their choices.MethodsThe study utilised a mixed-methods approach. Participants were older persons (≥ 60 years) in a selected rural and urban community in Oyo State, south-western Nigeria. Quantitative data were collected using an interviewer-administered, semi-structured questionnaire and analysed using Stata version 14 at pResults1,180 participants (588 rural vs 592 urban) were interviewed with a mean age of 73.2 ±9.3 years. More rural participants preferred to AIP (61.6%) compared to urban participants (39.2%), p = 0.001. Factors associated with the decision for rural participants were older age [OR:2.07 (95%CI:1.37-3.14)], being male [OR:2.41(95%CI:1.53-3.81)] and having assistance at home [OR:1.79 (95%CI:1.15-2.79)]. In comparison, significant factors for urban participants were older age (≥70years) [OR:1.54(95%CI:1.03-2.31)] and home-ownership [OR:5.83 (95%CI:3.82-8.91)]. The FGD revealed that the traditional expectation of reciprocity of care mostly influenced the desire to AIP. Advantages include improved social connectedness, quality of care, community participation and reduced isolation. Interestingly, participants were not opposed to the option of institutional care.ConclusionAgeing in place is preferred and influenced by advanced age and home ownership in our setting. Information provided could guide age-friendly housing policies and community-based programmes for the care of older persons.

Breast cancer is a deadly disease affecting women around the world. It can spread rapidly into other parts of the body, causing untimely death when undetected due to rapid growth and division of cells in the breast. Early diagnosis of this disease tends to increase the survival rate of women suffering from the disease. The use of technology to detect breast cancer in women has been explored over the years. A major drawback of most research in this area is low accuracy in the detection rate of breast cancer in women. This is partly due to the availability of few data sets to train classifiers and the lack of efficient algorithms that achieve optimal results. This research aimed to develop a model that uses a machine learning approach (convolution neural network) to detect breast cancer in women with significantly high accuracy. In this paper, a model was developed using 569 mammograms of various breasts diagnosed with benign and maligned cancers. The model achieved an accuracy of 98.25% and sensitivity of 99.5% after 80 iterations.

Summary: 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

Objectives- Traditional medicines have been widely used to prevent and treat diseases for thousands of years. This study was designed to evaluate the effect of ginger feed on cardiac biomarker in isoproterenol induced myocardial toxicity. Materials and Methods- Thirty male wistar rats were grouped into six groups of 5 rats each: Control; ISO- induced toxicity; ginger fed ; ginger fed before; ginger fed+ isoproterenol simultaneously and ginger fed after. Freshly prepared solution of isoproterenol was injected subcutaneously at a dosage of 20mg/kg, while the control recieved distilled water. Blood was collected via cardiac puncture after two weeks of administration, the serum was used to evaluate biomarkers. Results- The CK-MB of ginger fed groups was significantly lower (p < 0.05) compared to ISO group(8.2 ± 0.5µ/L). The CK of the ginger fed groups showed significant decrease (p>0.05) compared to isoproterenol group (39.36±5.28 µ/L), there was no significant difference in the CK-MB and CK levels of all the groups fed with ginger compared to the control(2.2± 0.3µ/L; 17. 07 ± 3.4.90 µ/L) except the group that was fed with ginger after isoproterenol induction, which was significantly higher compared to the control(p>0.05). The mean value of LDH were lower in all ginger treated groups compared to the ISO group (67.17± 0.88; p≤ 0.05), but significantly higher (p < 0.05) compared to the control(26.45 ± 2.52). The mean value of ALT were lower in all ginger fed groups compared to the ISO group (83.11± 4.88; p ≤ 0.05). Conclusion- Ginger feed hindered toxic effects of isoproterenol.

Purpose: The aim of this paper focuses on advancing the entrepreneurial literature by enhancing the understanding of the connections between personal behavior and cognitive skills in decision making under uncertainty. Methodology: The method of this research has been adapted the framework used by Garrett and Holland (2015), who developed propositions from the conceptual narratives of how environmental uncertainty and complexity differentially affect the motivations and cognition of independent entrepreneurs and corporate entrepreneurs to engage in entrepreneurial action. Findings: The findings of this research provide a conceptual basis for a broader perspective on behaviors and cognitions that motivate or hinder entrepreneurial actions while at the same time, positioning the entrepreneur’s decision at the core of decision theory. Implications for theory and practice: Theoretically, this research contributes to a holistic view of opportunity decisions. It redirects the traditional analyses path of entrepreneurial decisions discussed distinctively from the personal behavior or cognition paradigm, which does not provide a complete view into the larger entrepreneurial decisions under uncertainty. Practically, our argument provides further insight into the black box of entrepreneurial opportunity decisions under uncertainty and thus highlights the need for a broader perspective for the entrepreneur, especially in the early stage of venture formation, where some cognitions and required personal attributes are needed in consonance for entrepreneurial action. Originality and value: Entrepreneurship research on decision making under uncertainty has mainly focused on the effect of uncertainty on entrepreneurial actions, while an attempt at the individual level, particularly, from the cognitive framework seeks to explain why actions differ. Scholarly efforts have also been made on what informs entrepreneurial actions from the perspective of the entrepreneur’s personal attributes. However, no integrated approach is offered in the literature to study how cognitive skills and personality traits complement each other.

Testosterone induces intra-uterine growth restriction (IUGR) with maternal glucose dysregulation and oxidant release in various tissues. Adiponectin, which modulates the antioxidant nuclear factor erythroid 2-related factor 2 (Nrf2) signaling is expressed in the placenta and affects fetal growth. Sildenafil, a phosphodiesterase type 5 inhibitor (PDE5i), used mainly in erectile dysfunction has been widely studied as a plausible pharmacologic candidate in IUGR. Therefore, the present study sought to determine the effect of PDE5i on placental adiponectin/Nrf2 pathway in gestational testosterone-induced impaired glucose tolerance and fetal growth. Fifteen pregnant Wistar rats were allotted into three groups (n = 5/group) receiving vehicles (Ctr; distilled water and olive oil), testosterone propionate (Tes; 3.0 mg/kg; sc) or combination of testosterone propionate (3.0 mg/kg; sc) and sildenafil (50.0 mg/kg; po) from gestational day 14–19. On gestational day 20, plasma and placenta homogenates were obtained for biochemical analysis as well as fetal biometry. Pregnant rats exposed to testosterone had 4-fold increase in circulating testosterone compared with control (20.9 ± 2.8 vs 5.1 ± 1.7 ng/mL; p < 0.05) whereas placenta testosterone levels were similar in testosterone- and vehicle-treated rats. Exposure to gestational testosterone caused reduction in fetal and placental weights, placental Nrf2 and adiponectin. Moreover, impaired glucose tolerance, elevated plasma triglyceride-glucose (TyG) index, placental triglyceride, total cholesterol, lactate, malondialdehyde and alanine aminotransferase were observed in testosterone-exposed rats. Treatment with sildenafil improved glucose tolerance, plasma TyG index, fetal and placental weights and reversed placental adiponectin in testosterone-exposed pregnant rats without any effect on placental Nrf2. Therefore, in testosterone-exposed rats, sildenafil improves impaired glucose tolerance, poor fetal outcome which is accompanied by augmented placental adiponectin regardless of depressed Nrf2.

Background: The excessive intake of fructose (FRD) induces insulin resistance (IR)-associated renal impairment. Similarly, the use of estrogen-progestin oral contraceptive therapy (EEL) has been associated with cardiometabolic syndrome, and its non-contraceptive benefits particularly in metabolic pathologies remain inconclusive. Therefore, the present study investigated the effects of EEL on renal metabolic function in rats exposed to FRD.Methods: Female rats received vehicle (po), EEL (1.0 µg ethinylestradiol+5.0 µg levonorgestrel.), fructose (10%; w/v) and EEL+FRD respectively for 8 weeks. All data were expressed as means ± SEM and significance were accepted at p

Leptin and hypothalamic-adipose lipid handling are relevant in determining the shift of metabolic activities. There are scanty findings connecting glucose dysregulation as a result of hyperandrogenism during gestation to hypothalamic-adipose axis and leptin resistance. Sildenafil has recently gained attention in the prevention of intra-uterine growth restriction. The present study aimed at demonstrating the effect of sildenafil on leptin resistance and hypothalamic-adipose lipid handling in testosterone-exposed pregnant rats. Three groups of pregnant Wistar rats (n = 5/group) received olive oil (Ctr, S.C.) or testosterone propionate (Tes, 3.0 mg/kg; sc)or testosterone propionate (3.0 mg/kg; sc) and sildenafil (Tes + PDE5, 50 mg/kg; po)from gestational day 14–19. Blood samples, hypothalamus and adipose tissue were excised for biochemical analysis on day 20. Adipose and body weights, plasma leptin and adiponectin, adipose and hypothalamic leptin and triglyceride, adipose uric acid, hypothalamic Nrf2, catalase and nitric oxide were reduced following gestational testosterone exposure. Also, fasting insulin, plasma triglyceride, uric acid, leptin-adiponectin ratio, hypothalamic free fatty acid, total cholesterol, uric acid, aspartate transaminase and cyclic guanine monophosphate were elevated by testosterone exposure to pregnant animals. Sildenafil ameliorated leptin resistance and normalized hypothalamic-adipose lipid handling. Therefore, sildenafil protects against testosterone-induced leptin resistance and adverse hypothalamic-adipose lipid handling in pregnant rats.

Objective: Accumulation of lipids in non-adipose tissues particularly the liver is a feature of tissue insulin resistance. Hepatic glycogen depletion reflects counter glucoregulation in an insulin-resistant state and/or obesity. The effect of l-glutamine on fructose-induced increased hepatic lipid accumulation and depleted glycogen content, particularly in pregnancy, is not known. We therefore aimed at investigating the effect of glutamine on fructose-induced weight gain, hepatic lipids and glycogen contents in pregnant rats and also tested the hypothesis that hepatoprotective role of l-glutamine is through suppression of PDK-4. Methods: Eleven-week-old pregnant Wistar rats were allotted into the Control, Glutamine, Fructose and Fructose plus Glutamine groups (6 rats/group). The groups received distilled water (vehicle, p.o.), 1 g/kg bw l-glutamine (p.o.), 10% Fructose (w/v) and 10% Fructose (w/v) plus 1 g/kg bw l-glutamine (p.o.) respectively, daily for 19 days. Biochemical analysis and histology of the liver were performed. Results: Data showed that fructose intake caused insulin resistance, hyperglycemia, hyperlipidemia, increased body weight gain, visceral fat mass, hepatic mass, lactate production, uric acid production, lipid peroxidation and decreased pancreatic β-cell function and hepatic glycogen synthesis. These alterations were accompanied by elevated pyruvate dehydrogenase kinase-4 (PDK-4). However, the fructose-induced dysmetabolism were improved by l-glutamine. Conclusion: Our results demonstrate that obesity and hepatic lipid accumulation induced by fructose in pregnant rats is accompanied by increased PDK-4. The findings also suggest that l-glutamine would protect against obesity and hepatic lipid accumulation by suppression of PDK-4.

Dipeptidyl peptidase-4 (DPP-4) inhibition has been shown to exert beneficial effects against insulin resistance (IR) and type 2 diabetes. Combined oral contraceptive (COC) treatment is associated with impaired glucose and lipid metabolism but the mechanisms are elusive. We therefore, hypothesized that DPP-4 inhibition ameliorates COC-induced glucose dysregulation and hepatic triglyceride (TG) accumulation through adenosine deaminase (ADA) /xanthine oxidase (XO) /uric acid-dependent pathway. Female Wistar rats received (po) vehicle and COC (1.0 μg ethinylestradiol plus 5.0 μg levonorgestrel; po) with or without DPP-4 inhibitor (sitagliptin; 100 mg/kg; po) for 8 weeks (n = 6/group). Glucose dysmetabolism was assessed by elevated fasting blood glucose, impaired oral glucose tolerance test and homeostatic model assessment of IR. Treatment with COC led to increased plasma fasting glucose, triglyceride-glucose index, 1-h postload glucose response, insulin, free fatty acid, IR and impaired glucose tolerance. COC treatment also resulted in increased plasma and hepatic TG, TG/HDL-cholesterol ratio, malondialdehyde, uric acid (plasma; 25.2 ± 0.6 mg/dl; hepatic 128.9 ± 8.0 mg/100 mg tissue), lactate dehydrogenase, DPP-4, ADA and XO (plasma;10.5 ± 1.1 U/L; hepatic 21.2 ± 1.4 U/g protein) activities. Likewise, COC led to reduction in nitric oxide level. However, DPP-4 inhibition significantly ameliorated these alterations induced by COC treatment through suppression of uric acid (plasma; 15.1 ± 1.0 mg/dl, hepatic; 75.6 ± 5.0 mg/100 mg tissue), XO (plasma; 4.1 ± 0.9 U/L, hepatic; 8.7 ± 0.4 U/g protein), ADA and DPP-4 activities suggesting their involvement in glucose dysregulation and hepatic TG accumulation induced by COC treatment. Therefore, DPP-4 inhibition would impact positively on cardiometabolic disorders, at least in part, through XO, ADA and uric acid suppression.

Background: Metabolic adaptation of pregnant mothers is crucial for placental development and fetal growth/survival. However, evidence exists that indiscriminate consumption of fructose-enriched drink (FED) during pregnancy disrupts maternal-fetal metabolic tolerance with attendant adverse fetal outcomes. Glutamine supplementation (GLN) has been shown to exert a modulatory effect in metabolic disorders. Nevertheless, the effects of GLN on FED-induced poor fetal outcome, and in particular the impacts on placental uric acid/lipid accumulation are unknown. The present study was conducted to test the hypothesis that oral GLN improves fetal outcome by attenuating placental lipid accumulation and uric acid synthesis in pregnant rats exposed to FED. Materials and methods: Pregnant Wistar rats (160–180 g) were randomly allotted to control, GLN, FED and FED + GLN groups (6 rats/group). The groups received vehicle by oral gavage, glutamine (1 g/kg) by oral gavage, fructose (10%; w/v) and fructose + glutamine, respectively, through gestation. Results: Data showed that FED during pregnancy caused placental inefficiency, reduced fetal growth, and caused insulin resistance with correspondent increase in fasting blood glucose and plasma insulin. FED also resulted in an increased placental triglyceride, total cholesterol and de novo uric acid synthesis by activating adenosine deaminase and xanthine oxidase activities. Moreover, FED during pregnancy led to increased lipid peroxidation, lactate production with correspondent decreased adenosine and glucose-6-phosphate dehydrogenase-dependent antioxidant defense. These alterations were abrogated by GLN supplementation. Conclusion: These findings implicate that high FED intake during pregnancy causes poor fetal outcome via defective placental uric acid/triglyceride-dependent mechanism. The findings also suggest that oral GLN improves fetal outcome by ameliorating placental defects through suppression of uric acid/triglyceride accumulation.

Background: Sustained drug therapy in Parkinson's disease may alter the psychomotor responses to acute challenges with dopaminergic drugs, L-dopa and methylphenidate, and cause cross sensitisation.Methods: The mood, psychomotor and reward potentiating effects of an acute challenge with L-dopa and methylphenidate on separate occasions were assessed under double blind (medication naïve) conditions after a placebo and then the testing sessions were repeated in the same (medication experienced) patients following a median period of 16.7 months of continuous dopaminergic drug therapy.Results: In the medication naïve condition, affect was not changed by L-dopa or methylphenidate and only L-dopa improved motor function. In the medication experienced condition, active drugs improved positive affect compared with the medication naïve condition and there was an enhanced effect of L-dopa on motor function. Reward responsivity was enhanced by both L-dopa and methylphenidate in medication naïve and experienced conditions.Conclusion: Sustained dopaminergic drug therapy augments the motor effects of an acute challenge with L-dopa and induces euphoriant effects to L-dopa and methylphenidate challenges. [ABSTRACT FROM AUTHOR]

Background: An inverse relation exists between smoking and coffee intake and Parkinson's disease (PD). The present study explored whether this is explained by low sensation seeking, a personality trait believed to characterise PD.Methods: A total of 106 non-demented patients with PD and 106 age and sex matched healthy controls completed a short version of Zuckerman's Sensation Seeking Scale (SSS), the Geriatric Depression Scale, and the Trait Anxiety Inventory. Data were collected on past and current cigarette smoking, and participants also completed food frequency questionnaires to estimate current caffeine and alcohol intake.Results: Patients with PD had lower sensation seeking and higher depression and anxiety scores. They were also less likely to have ever smoked, and had lower caffeine and alcohol intakes. Analysis of the data using conditional logistic regression suggested that the inverse association of PD risk with sensation seeking was independent of smoking, and caffeine and alcohol intake. Moreover, low sensation seeking explained some of the apparent effect of caffeine and alcohol intake on PD. However, the effect of smoking was weakened only slightly when SSS was included in the regression model.Conclusion: This study raises the possibility that there is a neurobiological link between low sensation seeking traits--which might underlie the parkinsonian personality--and the hypothetical protective effect of cigarette smoking and caffeine consumption on PD. [ABSTRACT FROM AUTHOR]

INTRODUCTION: Advanced directives enable the planning of care and support services independent of the older person's ability to make the decision. There is a paucity of information regarding the views and preferences regarding advanced directives and other end of life issues among older persons in low and middle-income countries such as Nigeria. The study aimed to explore the knowledge, attitude and belief of older persons regarding decision making surrounding end of life and advance directives. METHODS: data were collected through focus group discussions at a monthly social gathering of outpatients in a geriatric center in Oyo State, Nigeria. Discussions were audiotaped, transcribed and analyzed manually using a thematic approach. RESULTS: respondents' knowledge about the end of life care and advanced directives as prescribed in high income settings were sparse and did not include choices about treatment options or any medical directives. The predominant perceptions among the participants bordered mainly on the arrangements for place of death, burial and property sharing. Participants listed in order of preference the major decision makers in the advanced directive process mainly, the oldest male child, religious leaders and legal practitioners. CONCLUSION: our findings imply the need for improving knowledge and awareness about the benefits of advanced directives among older persons with a focus on opportunities for their active participation.

Background: Osteoporosis is a silent disabling clinical condition often attributed to ageing. It is of public health importance because of its complications and attendant morbidity and mortality. Methods: A cross-sectional study was undertaken of 2401 older patients (60 years and above) at the Geriatric Centre, University College Hospital, Ibadan. Candidate variables such as socio-demographic characteristics, anthropometric indices, physical and lifestyle habits were assessed. Bivariate and multivariate analyses were carried out using SPSS 17®. Results: The point prevalence of osteoporosis was 56.9% (males = 43.7% and females = 65.8%). The most significant factors associated with osteoporosis on logistics regression analyses were increasing age, female sex, lack of formal education, lack of engagement in occupational activities and living with relatives/friends. Receiving social support from relatives/friends, nonparticipation in sporting activities at younger ages, prolonged use of medications for peptic ulcer disease, hospitalisation on or after the age of 60 years and asthenic build were also found to be significant. Yearly increase in age shows a 6.9% (95% CI 5.4–8.4%) increase in the odds of having osteoporosis. Conclusion: The high prevalence of osteoporosis among older persons in this study calls for concerted efforts by the healthcare workers to prevent osteoporosis among older patients. (Full text of the research articles are available online at www.medpharm.tandfonline.com/ojfp) S Afr Fam Pract 2017; DOI: 10.1080/20786190.2016.1272248

The Volta-Comoe languages1 belonging to Greenberg's (1963) Niger-Congo undergo a historical change in which underlying labial /b/ is reflexed as velar [g] and labio-palatal [Ɉɥ] in their Central members and as [b] in their Eastern and Western subgroups. We maintain that this process can be accounted for naturally by positing the feature Grave proposed by Jakobson, Fant and Halle (1956) in their early work on distinctive-feature phonology. This permits one to say that a non-back grave segment changed to a back one in specified linguistic contexts. Other processes which help explain the change are palatalisation, vowel- labialisation, consonant-labialisation and velar fronting. .

IINTRODUCTION: snoring is the major symptom of sleep disordered breathing (SDB) which is of immense public health importance. It is associated with some morbidities and mortality in the elderly. Few studies have addressed this problem in the elderly Nigerians.Methods: cross-sectional study of 843 elderly patients at the Geriatric Centre, University College Hospital, Ibadan, Nigeria. Data were collected on the following candidate variables which may be associated with snoring such as socio-demographic characteristics, morbidities, lifestyle habits and functional disability using Katz index. Anthropometric measurements such as body mass index and neck, waist and hip circumferences were taken. Statistical analysis was done with SPSS 17.Results: the point prevalence of reported snoring was 31.2%. Habitual snoring was reported by 24.8%. Snoring was significantly associated with obesity, moderate to severe oropharyngeal crowding, wide neck and waist circumferences in both sexes. Logistic regression analysis showed wide neck circumference (OR=6.005; 95%CI= 2.150-16.770) among the males and obesity (OR=2.028; 95%CI= 1.344-3.061) and moderate to severe oropharyngeal crowding (OR=1.639; 95%CI= 1.057-2.543) in the females to be the most significant factors associated with snoring.Conclusion: the high prevalence of snoring among elderly patients in Nigeria calls for concerted effort by healthcare workers to educate the elderly.

Prior univariate functional magnetic resonance imaging (fMRI) studies in humans suggest that the anteromedial subicular complex of the hippocampus is a hub for scene-based cognition. However, it is possible that univariate approaches were not sufficiently sensitive to detect scene-related activity in other subfields that have been implicated in spatial processing (e.g., CA1). Further, as connectivity-based functional gradients in the hippocampus do not respect classical subfield boundary definitions, category selectivity may be distributed across anatomical subfields. Region-of-interest approaches, therefore, may limit our ability to observe category selectivity across discrete subfield boundaries. To address these issues, we applied searchlight multivariate pattern analysis to 7T fMRI data of healthy adults who undertook a simultaneous visual odd-one-out discrimination task for scene and non-scene (including face) visual stimuli, hypothesising that scene classification would be possible in multiple hippocampal regions within, but not constrained to, anteromedial subicular complex and CA1. Indeed, we found that the scene-selective searchlight map overlapped not only with anteromedial subicular complex (distal subiculum, pre/para subiculum), but also inferior CA1, alongside posteromedial (including retrosplenial) and parahippocampal cortices. Probabilistic overlap maps revealed gradients of scene category selectivity, with the strongest overlap located in the medial hippocampus, converging with searchlight findings. This was contrasted with gradients of face category selectivity, which had stronger overlap in more lateral hippocampus, supporting ideas of parallel processing streams for these two categories. Our work helps to map the scene, in contrast to, face processing networks within, and connected to, the human hippocampus., Competing Interests: Declaration of competing interest None., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Microalgae play an essential role in global net primary productivity and global biogeochemical cycling. Despite their phototrophic lifestyle, over half of algal species depend for growth on acquiring an external supply of the corrinoid vitamin B12 (cobalamin), a micronutrient produced only by a subset of prokaryotic organisms. Previous studies have identified protein components involved in vitamin B12 uptake in bacterial species and humans. However, little is known about its uptake in algae. Here, we demonstrate the essential role of a protein, cobalamin acquisition protein 1 (CBA1), in B12 uptake in Phaeodactylum tricornutum using CRISPR-Cas9 to generate targeted knockouts and in Chlamydomonas reinhardtii by insertional mutagenesis. In both cases, CBA1 knockout lines could not take up exogenous vitamin B12. Complementation of the C. reinhardtii mutants with the wild-type CBA1 gene restored B12 uptake, and regulation of CBA1 expression via a riboswitch element enabled control of the phenotype. When visualized by confocal microscopy, a YFP-fusion with C. reinhardtii CBA1 showed association with membranes. Bioinformatics analysis found that CBA1-like sequences are present in all major eukaryotic phyla. In algal taxa, the majority that encoded CBA1 also had genes for B12-dependent enzymes, suggesting CBA1 plays a conserved role. Our results thus provide insight into the molecular basis of algal B12 acquisition, a process that likely underpins many interactions in aquatic microbial communities., Competing Interests: Conflict of interest statement. None declared., (© The Author(s) 2023. Published by Oxford University Press on behalf of American Society of Plant Biologists.)

Converging evidence from studies of human and nonhuman animals suggests that the hippocampus contributes to sequence learning by using temporal context to bind sequentially occurring items. The fornix is a white matter pathway containing the major input and output pathways of the hippocampus, including projections from medial septum and to diencephalon, striatum, lateral septum and prefrontal cortex. If the fornix meaningfully contributes to hippocampal function, then individual differences in fornix microstructure might predict sequence memory. Here, we tested this prediction by performing tractography in 51 healthy adults who had undertaken a sequence memory task. Microstructure properties of the fornix were compared with those of tracts connecting medial temporal lobe regions but not predominantly the hippocampus: the Parahippocampal Cingulum bundle (PHC) (conveying retrosplenial projections to parahippocampal cortex) and the Inferior Longitudinal Fasciculus (ILF) (conveying occipital projections to perirhinal cortex). Using principal components analysis, we combined Free-Water Elimination Diffusion Tensor Imaging and Neurite Orientation Dispersion and Density Imaging measures obtained from multi-shell diffusion MRI into two informative indices: the first (PC1) capturing axonal packing/myelin and the second (PC2) capturing microstructural complexity. We found a significant correlation between fornix PC2 and implicit reaction-time indices of sequence memory, indicating that greater fornix microstructural complexity is associated with better sequence memory. No such relationship was found with measures from the PHC and ILF. This study highlights the importance of the fornix in aiding memory for objects within a temporal context, potentially reflecting a role in mediating inter-regional communication within an extended hippocampal system., (© 2023 The Authors. European Journal of Neuroscience published by Federation of European Neuroscience Societies and John Wiley & Sons Ltd.)

The parahippocampal cingulum bundle (PHCB) interconnects regions known to be vulnerable to early Alzheimer's disease (AD) pathology, including posteromedial cortex and medial temporal lobe. While AD-related pathology has been robustly associated with alterations in PHCB microstructure, specifically lower fractional anisotropy (FA) and higher mean diffusivity (MD), emerging evidence indicates that the reverse pattern is evident in younger adults at increased risk of AD. In one such study, Hodgetts et al. (2019) reported that healthy young adult carriers of the apolipoprotein-E ( APOE ) ε4 allele - the strongest common genetic risk factor for AD - showed higher FA and lower MD in the PHCB but not the inferior longitudinal fasciculus (ILF). These results are consistent with proposals claiming that heightened neural activity and intrinsic connectivity play a significant role in increasing posteromedial cortex vulnerability to amyloid-β and tau spread beyond the medial temporal lobe. Given the implications for understanding AD risk, here we sought to replicate Hodgetts et al.'s finding in a larger sample ( N  = 128; 40 APOE ε4 carriers, 88 APOE ε4 non-carriers) of young adults (age range = 19-33). Extending this work, we also conducted an exploratory analysis using a more advanced measure of white matter microstructure: hindrance modulated orientational anisotropy (HMOA). Contrary to the original study, we did not observe higher FA or lower MD in the PHCB of APOE ε4 carriers relative to non-carriers. Bayes factors (BFs) further revealed moderate-to-strong evidence in support of these null findings. In addition, we observed no APOE ε4-related differences in PHCB HMOA. Our findings indicate that young adult APOE ε4 carriers and non-carriers do not differ in PHCB microstructure, casting some doubt on the notion that early-life variation in PHCB tract microstructure might enhance vulnerability to amyloid-β accumulation and/or tau spread., Competing Interests: The authors declare no competing financial or non-financial interests., (© 2022 The Author(s).)

Humans differ from each other in a wide range of biometrics, but to what extent brain connectivity varies between individuals remains largely unknown. By combining diffusion-weighted imaging (DWI) and magnetoencephalography (MEG), this study characterizes the inter-subject variability (ISV) of multimodal brain connectivity. Structural connectivity is characterized by higher ISV in association cortices including the core multiple-demand network and lower ISV in the sensorimotor cortex. MEG ISV exhibits frequency-dependent signatures, and the extent of MEG ISV is consistent with that of structural connectivity ISV in selective macroscopic cortical clusters. Across the cortex, the ISVs of structural connectivity and beta-band MEG functional connectivity are negatively associated with cortical myelin content indexed by the quantitative T1 relaxation rate measured by high-resolution 7 T MRI. Furthermore, MEG ISV from alpha to gamma bands relates to the hindrance and restriction of the white-matter tissue estimated by DWI microstructural models. Our findings depict the inter-relationship between the ISV of brain connectivity from multiple modalities, and highlight the role of tissue microstructure underpinning the ISV., (© 2022. The Author(s).)

Background: Social cognitive impairments, specifically in facial emotion processing and mental state attribution, are common in post-traumatic stress disorder. However few studies so far have examined whether social cognitive ability impacts on PTSD recovery. Objective: To examine whether baseline social cognitive abilities are associated with treatment outcomes following trauma-focused therapy for PTSD. Method: This is a cohort study that will relate treatment outcomes post-discharge to baseline measures of social cognition (five tasks: Emotion Odd-One-Out Task (Oddity), Reading the Mind in the Eyes Task (RMET), Social Shapes Test (SST), Spontaneous Theory of Mind Protocol (STOMP), and Reflective Functioning Questionnaire (RFQ-8)) in people starting a course of psychological therapy for PTSD (target N  = 60). The primary outcome will be pre- to post-treatment change in PTSD symptom severity (assessed using the PTSD Checklist for DSM-5). Secondary outcomes include functional impairment (assessed using the Work and Social Adjustment Scale), drop-out rate, and analyses differentiating participants with DSM-5 PTSD and ICD-11 PTSD and CPTSD. Regression models will be used to examine associations between baseline social cognitive performance and outcome measures while adjusting for potential confounders. Two pilot studies informed the development of our study protocol. The first involved qualitative analysis of interviews with nine participants with lived experience of mental health problems to inform our research questions and study protocol. The second involved trialling social cognitive tasks on 20 non-clinical participants to refine our test battery. Discussion: This study will address a gap in the literature about whether abilities in social cognition in people living with PTSD are associated with treatment-related recovery., Highlights: Impairments in social cognition are recognised in people with PTSD.Few studies have examined whether social cognitive ability is associated with recovery from PTSD.We present a study protocol, developed after pilot testing, to address this question., Competing Interests: No potential conflict of interest was reported by the author(s)., (© 2022 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group.)

Invasive tract-tracing studies in rodents implicate a direct connection between the subiculum and bed nucleus of the stria terminalis (BNST) as a key component of neural pathways mediating hippocampal regulation of the Hypothalamic-Pituitary-Adrenal (HPA) axis. A clear characterisation of the connections linking the subiculum and BNST in humans and non-human primates is lacking. To address this, we first delineated the projections from the subiculum to the BNST using anterograde tracers injected into macaque monkeys, revealing evidence for a monosynaptic subiculum-BNST projection involving the fornix. Second, we used in vivo diffusion MRI tractography in macaques and humans to demonstrate substantial subiculum complex connectivity to the BNST in both species. This connection was primarily carried by the fornix, with additional connectivity via the amygdala, consistent with rodent anatomy. Third, utilising the twin-based nature of our human sample, we found that microstructural properties of these tracts were moderately heritable (h 2 ∼ 0.5). In a final analysis, we found no evidence of any significant association between subiculum complex-BNST tract microstructure and indices of perceived stress/dispositional negativity and alcohol use, derived from principal component analysis decomposition of self-report data. Our findings address a key translational gap in our knowledge of the neurocircuitry regulating stress., (Copyright © 2022. Published by Elsevier Inc.)

Vitamin B 12 , cobalamin, belongs to the broader cobamide family whose members are characterized by the presence of a cobalt-containing corrinoid ring. The ability to detect, isolate and characterize cobamides and their biosynthetic intermediates is an important prerequisite when attempting to study the synthesis of this remarkable group of compounds that play diverse roles across the three kingdoms of life. The synthesis of cobamides is restricted to only certain prokaryotes and their structural complexity entails an equally complex synthesis orchestrated through a multi-step biochemical pathway. In this chapter, we have outlined methods that we have found extremely helpful in the characterization of the biochemical pathway, including a plate microbiological assay, a corrinoid affinity extraction method, LCMS characterization and a multigene cloning strategy., (Copyright © 2022 Elsevier Inc. All rights reserved.)

This study tested the hypothesis that early life adversity (ELA) heightens psychopathology risk by concurrently altering pubertal and neurodevelopmental timing, and associated gene transcription signatures. Analyses focused on threat- (family conflict/neighbourhood crime) and deprivation-related ELAs (parental inattentiveness/unmet material needs), using longitudinal data from 1514 biologically unrelated youths in the Adolescent Brain and Cognitive Development (ABCD) study. Typical developmental changes in white matter microstructure corresponded to widespread BOLD signal variability (BOLD sv) increases (linked to cell communication and biosynthesis genes) and region-specific task-related BOLD sv increases/decreases (linked to signal transduction, immune and external environmental response genes). Increasing resting-state (RS), but decreasing task-related BOLD sv predicted normative functional network segregation. Family conflict was the strongest concurrent and prospective contributor to psychopathology, while material deprivation constituted an additive risk factor. ELA-linked psychopathology was predicted by higher Time 1 threat-evoked BOLD SV (associated with axonal development, myelination, cell differentiation and signal transduction genes), reduced Time 2 RS BOLD sv (associated with cell metabolism and attention genes) and greater Time 1 to Time 2 control/attention network segregation. Earlier pubertal timing and neurodevelopmental alterations independently mediated ELA effects on psychopathology. Our results underscore the differential roles of the immediate and wider external environment(s) in concurrent and longer-term ELA consequences., (Copyright © 2021 The Authors. Published by Elsevier Ltd.. All rights reserved.)

A strategy to gain insight into early changes that may predispose people to Alzheimer's disease (AD) is to study the brains of younger cognitively healthy people that are at increased genetic risk of AD. The Apolipoprotein (APOE) E4 allele is the strongest genetic risk factor for AD, and several neuroimaging studies comparing APOE E4 carriers with non-carriers at age ∼20-30 years have detected hyperactivity (or reduced deactivation) in posteromedial cortex (PMC), a key hub of the default network (DN), which has a high susceptibility to early amyloid deposition in AD. Transgenic mouse models suggest such early network activity alterations may result from altered excitatory/inhibitory (E/I) balance, but this is yet to be examined in humans. Here we test the hypothesis that PMC fMRI hyperactivity could be underpinned by altered levels of excitatory (glutamate) and/or inhibitory (GABA) neurotransmitters in this brain region. Forty-seven participants (20 APOE E4 carriers and 27 non-carriers) aged 18-25 years underwent resting-state proton magnetic resonance spectroscopy ( 1 H-MRS), a non-invasive neuroimaging technique to measure glutamate and GABA in vivo . Metabolites were measured in a PMC voxel of interest and in a comparison voxel in the occipital cortex (OCC). There was no difference in either glutamate or GABA between the E4 carriers and non-carriers in either MRS voxel, or in the ratio of glutamate to GABA, a measure of E/I balance. Default Bayesian t-tests revealed evidence in support of this null finding. Our findings suggest that PMC hyperactivity in APOE E4 carriers is unlikely to be associated with, or possibly may precede, alterations in local resting-state PMC neurotransmitters, thus informing our understanding of the spatio-temporal sequence of early network alterations underlying APOE E4 related AD risk., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Crown Copyright © 2021 Published by Elsevier Inc.)

Uroporphyrinogen III, the universal progenitor of macrocyclic, modified tetrapyrroles, is produced from aminolaevulinic acid (ALA) by a conserved pathway involving three enzymes: porphobilinogen synthase (PBGS), hydroxymethylbilane synthase (HmbS) and uroporphyrinogen III synthase (UroS). The gene encoding uroporphyrinogen III synthase has not yet been identified in Plasmodium falciparum , but it has been suggested that this activity is housed inside a bifunctional hybroxymethylbilane synthase (HmbS). Additionally, an unknown protein encoded by PF3D7&#95;1247600 has also been predicted to possess UroS activity. In this study it is demonstrated that neither of these proteins possess UroS activity and the real UroS remains to be identified. This was demonstrated by the failure of codon-optimized genes to complement a defined Escherichia coli hemD - mutant (SASZ31) deficient in UroS activity. Furthermore, HPLC analysis of the oxidized reaction product from recombinant, purified P. falciparum HmbS showed that only uroporphyrin I could be detected (corresponding to hydroxymethylbilane production). No uroporphyrin III was detected, showing that P. falciparum HmbS does not have UroS activity and can only catalyze the formation of hydroxymethylbilane from porphobilinogen.

BOLD fMRI studies have provided compelling evidence that the human brain demonstrates substantial moment-to-moment fluctuations in both activity and functional connectivity (FC) patterns. While the role of brain signal variability in fostering cognitive adaptation to ongoing environmental demands is well-documented, the relevance of moment-to-moment changes in FC patterns is still debated. Here, we adopt a graph theoretical approach in order to shed light on the cognitive-affective implications of FC variability and associated profiles of functional network communication in adulthood. Our goal is to identify brain communication pathways underlying FC reconfiguration at multiple timescales, thereby improving understanding of how faster perceptually bound versus slower conceptual processes shape neural tuning to the dynamics of the external world and, thus, indirectly, mold affective and cognitive responding to the environment. To this end, we used neuroimaging and behavioural data collected during movie watching by the Cambridge Center for Ageing and Neuroscience (N = 642, 326 women) and the Human Connectome Project (N = 176, 106 women). FC variability evoked by changes to both the concrete perceptual and the more abstract conceptual representation of an ongoing situation increased from young to older adulthood. However, coupling between variability in FC patterns and concrete environmental features was stronger at younger ages. FC variability (both moment-to-moment/concrete featural and abstract conceptual boundary-evoked) was associated with age-distinct profiles of network communication, specifically, greater functional integration of the default mode network in older adulthood, but greater informational flow across neural networks implicated in environmentally driven attention and control (cingulo-opercular, salience, ventral attention) in younger adulthood. Whole-brain communication pathways anchored in default mode regions relevant to episodic and semantic context creation (i.e., angular and middle temporal gyri) supported FC reconfiguration in response to changes in the conceptual representation of an ongoing situation (i.e., narrative event boundaries), as well as stronger coupling between moment-to-moment fluctuations in FC and concrete environmental features. Fluid intelligence/abstract reasoning was directly linked to levels of brain-environment alignment, but only indirectly associated with levels of FC variability. Specifically, stronger coupling between moment-to-moment FC variability and concrete environmental features predicted poorer fluid intelligence and greater affectively driven environmental vigilance. Complementarily, across the adult lifespan, higher fluid (but not crystallised) intelligence was related to stronger expression of the network communication profile underlying momentary and event boundary-based FC variability during youth. Our results indicate that the adaptiveness of dynamic FC reconfiguration during naturalistic information processing changes across the lifespan due to the associated network communication profiles. Moreover, our findings on brain-environment alignment complement the existing literature on the beneficial consequences of modulating brain signal variability in response to environmental complexity. Specifically, they imply that coupling between moment-to-moment FC variability and concrete environmental features may index a bias towards perceptually-bound, rather than conceptual processing, which hinders affective functioning and strategic cognitive engagement with the external environment., Competing Interests: Declaration of Competing Interest The authors declare no competing interests., (Copyright © 2021 The Author(s). Published by Elsevier Inc. All rights reserved.)

Pre-clinical and human neuroimaging research implicates the extended-amygdala (ExtA) (including the bed nucleus of the stria terminalis [BST] and central nucleus of the amygdala [CeA]) in networks mediating negative emotional states associated with stress and substance-use behaviours. The extent to which individual ExtA structures form a functionally integrated unit is controversial. We utilised a large sample (n > 1,000 healthy young adult humans) to compare the intrinsic functional connectivity networks (ICNs) of the BST and CeA using task-free functional magnetic resonance imaging (fMRI) data from the Human Connectome Project. We assessed whether inter-individual differences within these ICNs were related to two principal components representing negative disposition and alcohol use. Building on recent primate evidence, we tested whether within BST-CeA intrinsic functional connectivity (iFC) was heritable and further examined co-heritability with our principal components. We demonstrate the BST and CeA to have discrete, but largely overlapping ICNs similar to previous findings. We found no evidence that within BST-CeA iFC was heritable; however, post hoc analyses found significant BST iFC heritability with the broader superficial and centromedial amygdala regions. There were no significant correlations or co-heritability associations with our principal components either across the ICNs or for specific BST-Amygdala iFC. Possible differences in phenotype associations across task-free, task-based, and clinical fMRI are discussed, along with suggestions for more causal investigative paradigms that make use of the now well-established ExtA ICNs., (© 2020 The Authors. Human Brain Mapping published by Wiley Periodicals LLC.)

In this Registered Report, we assessed the utility of the affective priming paradigm (APP) as an indirect measure of food attitudes and related choice behaviour in two separate cohorts. Participants undertook a speeded evaluative categorization task in which target words were preceded by food primes that differed in terms of affective congruence with the target, explicit liking (most liked or least liked), and healthiness (healthy or unhealthy). Non-food priming effects were tested as a manipulation check, and the relationship between food priming effects and impulsive choice behaviour was also investigated using a binary food choice task. As predicted, priming effects were observed for both healthy and unhealthy foods, but there was no difference in the magnitude of these effects. This may suggest that the paradigm is most sensitive to affective, but not cognitive, components of attitudes (i.e., healthiness), but alternative theoretical explanations and implications of this finding are discussed. Food and non-food priming effects were observed in both reaction time (RT) and error rate (ER) data, but contrary to expectations, we found no association between food RT priming effects and choice behaviour. All findings from confirmatory analyses regarding RT and ER priming effects, and the absence of the expected correlations between priming effects and impulsive food choices, were successfully replicated in the online cohort of participants. Overall, this study confirms the robustness of the APP as an indirect measure of food liking and raises questions about its applied value for research of eating behaviours.

The (formal) replacement of Co in cobalamin (Cbl) by Ni II generates nibalamin (Nibl), a new transition-metal analogue of vitamin B 12 . Described here is Nibl, synthesized by incorporation of a Ni II ion into the metal-free B 12  ligand hydrogenobalamin (Hbl), itself prepared from hydrogenobyric acid (Hby). The related Ni II  corrin nibyric acid (Niby) was similarly synthesized from Hby, the metal-free cobyric acid ligand. The solution structures of Hbl, and Niby and Nibl, were characterized by spectroscopic studies. Hbl features two inner protons bound at N2 and N4 of the corrin ligand, as discovered in Hby. X-ray analysis of Niby shows the structural adaptation of the corrin ligand to Ni II ions and the coordination behavior of Ni II . The diamagnetic Niby and Nibl, and corresponding isoelectronic Co I corrins, were deduced to be isostructural. Nibl is a structural mimic of four-coordinate base-off Cbls, as verified by its ability to act as a strong inhibitor of bacterial adenosyltransferase., (© 2020 The Authors. Published by Wiley-VCH GmbH.)

Prospection (mentally simulating future events) generates emotionally-charged mental images that guide social decision-making. Positive and negative social expectancies-imagining new social interactions to be rewarding versus threatening-are core components of social approach and avoidance motivation, respectively. Interindividual differences in such positive and negative future-related cognitions may be underpinned by distinct neuroanatomical substrates. Here, we asked 100 healthy adults to vividly imagine themselves in a novel self-relevant event that was ambiguous with regards to possible social acceptance or rejection. During this task we measured participants' expectancies for social reward (anticipated feelings of social connection) or threat (anticipated feelings of rejection). On a separate day they underwent structural MRI; voxel-based morphometry was used to explore the relation between social reward and threat expectancies and regional grey matter volumes (rGMV). Increased rGMV in key default-network regions involved in prospection, socio-emotional cognition, and subjective valuation, including ventromedial prefrontal cortex, correlated with both higher social reward and lower social threat expectancies. In contrast, social threat expectancies uniquely correlated with rGMV of regions involved in social attention (posterior superior temporal sulcus, pSTS) and interoception (somatosensory cortex). These findings provide novel insight into the neurobiology of future-oriented cognitive-affective processes critical to adaptive social functioning.

The Uncinate Fasciculus (UF) is an association fibre tract connecting regions in the frontal and anterior temporal lobes. UF disruption is seen in several disorders associated with impaired social behaviour, but its functional role is unclear. Here we set out to test the hypothesis that the UF is important for facial expression processing, an ability fundamental to adaptive social behaviour. In two separate experiments in healthy adults, we used high-angular resolution diffusion-weighted imaging (HARDI) and constrained spherical deconvolution (CSD) tractography to virtually dissect the UF, plus a control tract (the corticospinal tract (CST)), and quantify, via fractional anisotropy (FA), individual differences in tract microstructure. In Experiment 1, participants completed the Reading the Mind in the Eyes Task (RMET), a well-validated assay of facial expression decoding. In Experiment 2, a different set of participants completed the RMET, plus an odd-emotion-out task of facial emotion discrimination. In both experiments, participants also completed a control odd-identity-out facial identity discrimination task. In Experiment 1, FA of the right-, but not the left-hemisphere, UF was significantly correlated with performance on the RMET task, specifically for emotional, but not neutral expressions. UF FA was not significantly correlated with facial identity discrimination performance. In Experiment 2, FA of the right-, but not left-hemisphere, UF was again significantly correlated with performance on emotional items from the RMET, together with performance on the facial emotion discrimination task. Again, no significant association was found between UF FA and facial identity discrimination performance. Our findings highlight the contribution of right-hemisphere UF microstructure to inter-individual variability in the ability to decode facial emotion expressions, and may explain why disruption of this pathway affects social behaviour., (Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Neuropsychological and functional magnetic resonance imaging evidence suggests that the ability to vividly remember our personal past, and imagine future scenarios, involves two closely connected regions: the hippocampus and ventromedial prefrontal cortex (vmPFC). Despite evidence of a direct anatomical connection from hippocampus to vmPFC, it is unknown whether hippocampal-vmPFC structural connectivity supports both past- and future-oriented episodic thinking. To address this, we applied a novel deterministic tractography protocol to diffusion-weighted magnetic resonance imaging (dMRI) data from a group of healthy young adult humans who undertook an adapted past-future autobiographical interview (portions of this data were published in Hodgetts et al., 2017a). This tractography protocol enabled distinct subdivisions of the fornix, detected previously in axonal tracer studies, to be reconstructed in vivo, namely the pre-commissural (connecting the hippocampus to vmPFC) and post-commissural (linking the hippocampus and medial diencephalon) fornix. As predicted, we found that inter-individual differences in pre-commissural - but not post-commissural - fornix microstructure (fractional anisotropy) were significantly correlated with the episodic richness of both past and future autobiographical narratives. Notably, these results held when controlling for non-episodic narrative content, verbal fluency, and grey matter volumes of the hippocampus and vmPFC. This study provides novel evidence that reconstructing events from one's personal past, and constructing possible future events, involves a distinct, structurally-instantiated hippocampal-vmPFC pathway., Competing Interests: Declaration of competing interest The authors declare no competing financial and non-financial interests., (Copyright © 2020 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Experiments on rodents have demonstrated that transecting the white matter fibre pathway linking the hippocampus with an array of cortical and subcortical structures - the fornix - impairs flexible navigational learning in the Morris Water Maze (MWM), as well as similar spatial learning tasks. While diffusion magnetic resonance imaging (dMRI) studies in humans have linked inter-individual differences in fornix microstructure to episodic memory abilities, its role in human spatial learning is currently unknown. We used high-angular resolution diffusion MRI combined with constrained spherical deconvolution-based tractography, to ask whether inter-individual differences in fornix microstructure in healthy young adults would be associated with spatial learning in a virtual reality navigation task. To efficiently capture individual learning across trials, we adopted a novel curve fitting approach to estimate a single index of learning rate. We found a statistically significant correlation between learning rate and the microstructure (mean diffusivity) of the fornix, but not that of a comparison tract linking occipital and anterior temporal cortices (the inferior longitudinal fasciculus, ILF). Further, this correlation remained significant when controlling for both hippocampal volume and participant gender. These findings extend previous animal studies by demonstrating the functional relevance of the fornix for human spatial learning in a virtual reality environment, and highlight the importance of a distributed neuroanatomical network, underpinned by key white matter pathways, such as the fornix, in complex spatial behaviour., Competing Interests: Declaration of Competing Interest None., (Copyright © 2019 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Freezing of gait (FOG) is a common symptom of Parkinson's disease (PD) which can result in falls and fall related injuries, poor quality of life and reduced functional independence. It is a heterogeneous phenomenon that is difficult to quantify and eludes a unified pathophysiological framework., Objective: Our aim was to document the occurrence and nature of freezing, cognitive stops and stumbles in people with PD during walks with varying cognitive loads and conditions designed to elicit FOG., Methods: 130 people with PD walked under four conditions (normal walking, walking plus easy and hard dual-tasks, and a FOG elicitation condition. Video and accelerometry recordings were examined to document freezes and other gait disruptions., Results: Participants experienced 391 freezes, 97 cognitive stops and 73 stumbles in the trial walks; with total gait disruptions increasing with task complexity. Most freezes in the FOG elicitation condition occurred during turning and approach destination. People who experienced freezing during the walks were more likely to have Postural Instability and Gait Difficulty (PIGD) subtype, longer disease duration and more severe UPDRS part II and part III sub-scores than people who did not freeze. They also took higher doses of levodopa, reported freezing in the past month, more prior falls, had poorer executive function, poorer proprioception, slower reaction time, poorer standing and leaning balance, more depressive symptoms, lower quality of life and greater fear of falling. PD disease duration, reduced controlled leaning balance and poor proprioception were identified as independent and significant determinants of freezing in logistic regression analysis., Conclusion: The multiple motor and cognitive factors identified as being associated with freezing, including poor proprioception and impaired controlled leaning balance provide new insights into this debilitating PD symptom and may contribute to potential new targets for rehabilitation.

Replacing the central cobalt ion of vitamin B 12 by other metals has been a long-held aspiration within the B 12 -field. Herein, we describe the synthesis from hydrogenobyric acid of zincobyric acid (Znby) and zincobalamin (Znbl), the Zn-analogues of the natural cobalt-corrins cobyric acid and vitamin B 12 , respectively. The solution structures of Znby and Znbl were studied by NMR-spectroscopy. Single crystals of Znby were produced, providing the first X-ray crystallographic structure of a zinc corrin. The structures of Znby and of computationally generated Znbl were found to resemble the corresponding Co II -corrins, making such Zn-corrins potentially useful for investigations of B 12 -dependent processes. The singlet excited state of Znby had a short life-time, limited by rapid intersystem crossing to the triplet state. Znby allowed the unprecedented observation of a corrin triplet (E T =190 kJ mol -1 ) and was found to be an excellent photo-sensitizer for 1 O 2 (Φ Δ =0.70)., (© 2019 The Authors. Published by Wiley-VCH Verlag GmbH & Co. KGaA.)

The B 12 cofactors instill a natural curiosity regarding the primordial selection and evolution of their corrin ligand. Surprisingly, this important natural macrocycle has evaded molecular scrutiny, and its specific role in predisposing the incarcerated cobalt ion for organometallic catalysis has remained obscure. Herein, we report the biosynthesis of the cobalt-free B 12 corrin moiety, hydrogenobyric acid (Hby), a compound crafted through pathway redesign. Detailed insights from single-crystal X-ray and solution structures of Hby have revealed a distorted helical cavity, redefining the pattern for binding cobalt ions. Consequently, the corrin ligand coordinates cobalt ions in desymmetrized "entatic" states, thereby promoting the activation of B 12 -cofactors for their challenging chemical transitions. The availability of Hby also provides a route to the synthesis of transition metal analogues of B 12 ., (© 2019 The Authors. Published by Wiley-VCH Verlag GmbH & Co. KGaA.)

The speed of motor reaction to an external stimulus varies substantially between individuals and is slowed in aging. However, the neuroanatomical origins of interindividual variability in reaction time (RT) remain unclear. Here, we combined a cognitive model of RT and a biophysical compartment model of diffusion-weighted MRI (DWI) to characterize the relationship between RT and microstructure of the corticospinal tract (CST) and the optic radiation (OR), the primary motor output and visual input pathways associated with visual-motor responses. We fitted an accumulator model of RT to 46 female human participants' behavioral performance in a simple reaction time task. The non-decision time parameter ( T er ) derived from the model was used to account for the latencies of stimulus encoding and action initiation. From multi-shell DWI data, we quantified tissue microstructure of the CST and OR with the neurite orientation dispersion and density imaging (NODDI) model as well as the conventional diffusion tensor imaging model. Using novel skeletonization and segmentation approaches, we showed that DWI-based microstructure metrics varied substantially along CST and OR. The T er of individual participants was negatively correlated with the NODDI measure of the neurite density in the bilateral superior CST. Further, we found no significant correlation between the microstructural measures and mean RT. Thus, our findings suggest a link between interindividual differences in sensorimotor speed and selective microstructural properties in white-matter tracts. SIGNIFICANCE STATEMENT How does our brain structure contribute to our speed to react? Here, we provided anatomically specific evidence that interindividual differences in response speed is associated with white-matter microstructure. Using a cognitive model of reaction time (RT), we estimated the non-decision time, as an index of the latencies of stimulus encoding and action initiation, during a simple reaction time task. Using an advanced microstructural model for diffusion MRI, we estimated the tissue properties and their variations along the corticospinal tract and optic radiation. We found significant location-specific correlations between the microstructural measures and the model-derived parameter of non-decision time but not mean RT. These results highlight the neuroanatomical signature of interindividual variability in response speed along the sensorimotor pathways., (Copyright © 2019 Karahan et al.)

Precuneus/posterior cingulate cortex (PCu/PCC) are key components of a midline network, activated during rest but also in tasks that involve construction of scene or situation models. Despite growing interest in PCu/PCC functional alterations in disease and disease risk, the underlying neurochemical modulators of PCu/PCC's task-evoked activity are largely unstudied. Here, a multimodal imaging approach was applied to investigate whether interindividual differences in PCu/PCC fMRI activity, elicited during perceptual discrimination of scene stimuli, were correlated with local brain metabolite levels, measured during resting-state 1 H-MRS. Forty healthy young adult participants completed an fMRI perceptual odd-one-out task for scenes, objects and faces. 1 H-MRS metabolites N-acetyl-aspartate (tNAA), glutamate (Glx) and γ-amino-butyric acid (GABA+) were quantified via PRESS and MEGA-PRESS scans in a PCu/PCC voxel and an occipital (OCC) control voxel. Whole brain fMRI revealed a cluster in right dorsal PCu/PCC that showed a greater BOLD response to scenes versus faces and objects. When extracted from an independently defined PCu/PCC region of interest, scene activity (vs. faces and objects and also vs. baseline) was positively correlated with PCu/PCC, but not OCC, tNAA. A voxel-wise regression analysis restricted to the PCu/PCC 1 H-MRS voxel area identified a significant PCu/PCC cluster, confirming the positive correlation between scene-related BOLD activity and PCu/PCC tNAA. There were no correlations between PCu/PCC activity and Glx or GABA+ levels. These results demonstrate, for the first time, that scene activity in PCu/PCC is linked to local tNAA levels, identifying a neurochemical influence on interindividual differences in the task-driven activity of a key brain hub., (© 2019 The Authors. Human Brain Mapping published by Wiley Periodicals, Inc.)