Effects of sleep deprivation on brain atrophy in individuals with mild cognitive impairment and Alzheimer's disease.

Dementia, a prevalent condition in the United States, affecting millions of individuals and their families, underscores the importance of healthy cognitive ageing, which involves maintaining cognitive function and mental wellness as individuals grow older, promoting overall well-being and quality of life. Our original research study investigates the correlation between lifestyle factors and brain atrophy in individuals with mild cognitive impairment (MCI) or Alzheimer's disease (AD), as well as healthy older adults. Conducted over six months in West Texas, the research involved 20 participants aged 62-87. Findings reveal that sleep deprivation in MCI subjects and AD patients correlate with posterior cingulate cortex, hippocampal atrophy and total brain volume, while both groups exhibit age-related hippocampal volume reduction. Notably, fruit/vegetable intake negatively correlates with certain brain regions' volume, emphasizing the importance of diet. Lack of exercise is associated with reduced brain volume and hippocampal atrophy, underlining the cognitive benefits of physical activity. The study underscores lifestyle's significant impact on cognitive health, advocating interventions to promote brain health and disease prevention, particularly in MCI/AD cases. While blood profile data showed no significant results regarding cognitive decline, the study underscores the importance of lifestyle modifications in preserving cognitive function.

Creating Cultural and Lifestyle Awareness About Dementia and Co-morbidities.

Dementia is a major health concern in society, particularly in the aging population. It is alarmingly increasing in ethnic minorities such as Native Americans, African Americans, Hispanics/Latinos, and to some extent Asians. With increasing comorbidities of dementia such as diabetes, obesity, and hypertension, dementia rates are expected to increase in the next decade and beyond. Understanding and treating dementia, as well as determining how to prevent it, has become a healthcare priority across the globe for all races and genders. Awareness about dementia and its consequences such as healthcare costs, and caregiver burden are immediate needs to be addressed. Therefore, it is high time for all of us to create awareness about dementia in society, particularly among Hispanics/Latinos, Native Americans, and African Americans. In the current article, we discuss the status of dementia, cultural, and racial impacts on dementia diagnosis and care, particularly in Hispanic populations, and possible steps to increase dementia awareness. We also discussed factors that need to be paid attention to, including, cultural & language barriers, low socioeconomic status, limited knowledge/education, religious/spiritual beliefs and not accepting modern medicine/healthcare facilities. Our article also covers both mental & physical health issues of caregivers who are living with patients with dementia, Alzheimer's disease, and Alzheimer's disease-related dementias. Most importantly, we discussed possible measures to create awareness about dementia, including empowering community advocacy, promoting healthy lifestyle choices, education on the impact of nutrition, encouraging community participation, and continued collaboration and evaluation of the success of dementia awareness.

SuperAgers and centenarians, dynamics of healthy ageing with cognitive resilience.

Graceful healthy ageing and extended longevity is the most desired goal for human race. The process of ageing is inevitable and has a profound impact on the gradual deterioration of our physiology and health since it triggers the onset of many chronic conditions like dementia, osteoporosis, diabetes, arthritis, cancer, and cardiovascular disease. However, some people who lived/live more than 100 years called 'Centenarians" and how do they achieve their extended lifespans are not completely understood. Studying these unknown factors of longevity is important not only to establish a longer human lifespan but also to manage and treat people with shortened lifespans suffering from age-related morbidities. Furthermore, older adults who maintain strong cognitive function are referred to as "SuperAgers" and may be resistant to risk factors linked to cognitive decline. Investigating the mechanisms underlying their cognitive resilience may contribute to the development of therapeutic strategies that support the preservation of cognitive function as people age. The key to a long, physically, and cognitively healthy life has been a mystery to scientists for ages. Developments in the medical sciences helps us to a better understanding of human physiological function and greater access to medical care has led us to an increase in life expectancy. Moreover, inheriting favorable genetic traits and adopting a healthy lifestyle play pivotal roles in promoting longer and healthier lives. Engaging in regular physical activity, maintaining a balanced diet, and avoiding harmful habits such as smoking contribute to overall well-being. The synergy between positive lifestyle choices, access to education, socio-economic factors, environmental determinants and genetic supremacy enhances the potential for a longer and healthier life. Our article aims to examine the factors associated with healthy ageing, particularly focusing on cognitive health in centenarians. We will also be discussing different aspects of ageing including genomic instability, metabolic burden, oxidative stress and inflammation, mitochondrial dysfunction, cellular senescence, immunosenescence, and sarcopenia.

Merging Excited-State Copper Catalysis and Triplet Nitro(hetero)arenes for Direct Synthesis of 2-Aminophenol Derivatives.

Nitro(hetero)arene derivatives are essential commodity chemicals used in various products, such as drugs, polymers, and agrochemicals. In this study, we leverage the excited-state reactivities of copper catalysts and nitro(hetero)arenes, and the Umpolung reactivity of acyl radicals to convert readily available nitro(hetero)arenes directly to valuable 2-aminophenol derivatives, which are important scaffolds in many top-selling pharmaceuticals. This reaction is applicable to a variety of nitro(hetero)arenes, acyl chlorides, and late-stage modifications of complex molecules, making it a useful tool for the discovery of new functional molecules. Mechanistic studies, including radical trapping experiments, Stern Volmer quenching studies, light ON/OFF experiments, and 18O-labeling studies, suggest a reaction mechanism involving photoexcitation of a copper complex, diradical couplings, and an in-cage contact ion pair (CIP) migration. Our findings offer a streamlined protocol for synthesizing essential pharmacophores from nitro(hetero)arenes while simultaneously advancing knowledge in excited-state and radical chemistry and stimulating new reaction design and development.

Excited-State Palladium-Catalyzed α-Selective C1-Ketonylation.

C-Glycosides are important carbohydrate mimetics found in natural products, bioactive compounds, and marketed drugs. However, stereoselective preparation of this class of glycomimetics remains a significant challenge in organic synthesis. Herein, we report an excited-state palladium-catalyzed α-selective C-ketonylation strategy using readily available 1-bromosugars to access a range of C-glycosides. The reaction features excellent α-selectivity and mild conditions that tolerate a wide range of functional groups and complex molecular architectures. The resulting α-ketonylsugars can serve as versatile precursors for their ß-isomers and other C-glycosides. Preliminary experimental and computational studies of the mechanism suggest a radical pathway involving the formation of palladoradical and glycosyl radical that undergoes polarity-mismatched coupling with silyl enol ether, affording the desired α-ketonylsugars. Insight into the reactivity and mechanism will inspire new reaction development and provide straightforward access to both α- and ß-C-glycosides, greatly expanding the chemical and patent spaces of glycomimetics.

Excited-State Copper-Catalyzed [4 + 1] Annulation Reaction Enables Modular Synthesis of α,ß-Unsaturated-γ-Lactams.

Synthesis of α,ß-unsaturated-γ-lactams continue to attract attention due to the importance of this structural motif in organic chemistry. Herein, we report the development of a visible-light-induced excited-state copper-catalyzed [4 + 1] annulation reaction for the preparation of a wide range of γ-H, -OH, and -OR-substituted α,ß-unsaturated-γ-lactams using acrylamides as the 4-atom unit and aroyl chlorides as the 1-atom unit. This modular synthetic protocol features mild reaction conditions, broad substrate scope, and high functional group tolerance. The reaction is amenable to late-stage diversification of complex molecular architectures, including derivatives of marketed drugs. The products of the reaction can serve as versatile building blocks for further derivatization. Preliminary mechanistic studies suggest an inner-sphere catalytic cycle involving photoexcitation of the Cu(BINAP) catalyst, single-electron transfer, and capture of radical intermediates by copper species, followed by reductive elimination or protonation to give the desired γ-functionalized α,ß-unsaturated-γ-lactams.

C2-ketonylation of carbohydrates via excited-state palladium-catalyzed 1,2-spin-center shift.

C2-ketonyl-2-deoxysugars, sugars with the C2-hydroxyl group replaced by a ketone side chain, are important carbohydrate mimetics in glycobiology and drug discovery studies; however, their preparation remains a vital challenge in organic synthesis. Here we report the first direct strategy to synthesize this class of glycomimetics from readily available 1-bromosugars and silyl enol ethers via an excited-state palladium-catalyzed 1,2-spin-center shift (SCS) process. This step-economic reaction features broad substrate scope, has a high functional group tolerance, and can be used in late-stage functionalization of natural product- and drug-glycoconjugates. Preliminary experimental and computational mechanistic studies suggested a non-chain radical mechanism involving photoexcited palladium species, a 1,2-SCS process, and a radical Mizoroki-Heck reaction.

Excited-State Palladium-Catalyzed Radical Migratory Mizoroki-Heck Reaction Enables C2-Alkenylation of Carbohydrates.

Excited-state palladium catalysis has emerged as a promising strategy for developing novel and valuable reactions. Herein, we report the first excited-state Pd-catalyzed 1,2-radical migratory Mizoroki-Heck reaction that enables C2-alkenylation of carbohydrates using readily available 1-bromosugars and alkenes. The reaction tolerates a wide variety of functional groups and complex molecular architectures, including derivatives of natural products and marketed drugs. Preliminary mechanistic studies and DFT calculations suggest the involvement of visible-light-induced photoexcitation of Pd species, 1,2-spin-centered-shift (SCS) process, and Heck-type cross-coupling reaction. The reaction expands the reactivity profile of excited-state Pd catalysis and provides a streamlined protocol for the preparation of a wide variety of C2-alkenylated carbohydrate mimetics to aid the discovery and development of new therapeutics, agrochemicals, and materials.

Association between hypertension, obesity and dietary intake in post-menopausal women from rural Zambian communities.

BACKGROUND: Amongst the cardiovascular risk (CVR) factors, hypertension (HT) and obesity appear to be prominent in post-menopausal women. The underlying mechanisms of HT development in menopause are not fully understood. AIM: To determine the association between HT, obesity and dietary intakes in post-menopausal women from rural Zambia. SETTING: This study was conducted in Twatasha Compound of Kitwe and Ndeke Community of Ndola. METHODS: Blood pressure (BP), weight, height and dietary intakes (24-h recall) were measured in 153 women (> 50 years) from households. The South African Hypertension Society (SAHS), the World Health Organization (WHO) and estimated average requirements (EARs) guidelines were followed for HT, obesity and dietary intake definitions, respectively. Statistical Package for the Social Sciences (SPSS) version 26 was used for descriptive and inferential statistical analyses. RESULTS: Prevalence of HT was 70%, whilst 37.25% and 28.10% of the participants were overweight and obese, respectively. The median interquartile range (IQR) dietary intakes showed inadequate intakes for most nutrients, except for carbohydrates (170 g [133; 225]). The total fat intake represented 14% of total energy intake. All median fatty acid intakes and sodium intakes (409 mg [169; 662]) were below the recommended levels. Only body mass index (BMI) correlated with HT (r = 0.268; p = 0.001). CONCLUSIONS: Despite low dietary intakes, an alarming prevalence of HT and obesity was found in our population. Hormonal changes, a high energy-dense diet and poor treatment adherence, may be possible underlying factors. We recommend measures to better manage HT as a CVR factor. CONTRIBUTION: This article supplements evidence on the prevalence of obesity-related hypertension in post-menopausal women and the link to dietary intake.

Diastereoselective Spirocyclization of Cyclic N-Sulfonyl Ketimines with Nitroalkenes via Iridium-Catalyzed Redox-Neutral Cascade Reaction.

An Ir(III)-catalyzed [3 + 2] annulation of weakly coordinating N-sulfonyl ketimines with challenging α, ß-unsaturated nitro olefins has been achieved via redox-neutral C-H functionalization in the presence of a catalytic amount of silver hexafluoroantimonate. The generation of three consecutive stereogenic centers in a single step via direct C-H functionalization is the prime feature of this methodology. A wide array of pharmaceutically relevant nitro-substituted spirocyclic benzosultams was synthesized with good to excellent diastereoselectivity as well as in high yield starting from easily accessible substrates.

Is iodine deficiency still a problem in sub-Saharan Africa?: a review.

Iodine is an essential trace mineral, vital for its functions in many physiological processes in the human body. Both iodine deficiency (ID) and excess are associated with adverse health effects; ID and excess iodine intake have both been identified in sub-Saharan Africa (SSA). The review aims to (1) review the iodine status among populations in SSA until October 2018, and (2) identify populations at risk of excess or inadequate iodine intakes. A systematic search of relevant articles was carried out by a seven-member research team using PubMed, Science Direct and Scopus. A total of twenty-two articles was included for data extraction. Of the articles reviewed, the majority sought to determine the prevalence of iodine status of the study populations; others measured the impact of uncontrolled and unmonitored salt iodisation on iodine excess and tested the effectiveness of water iodisation. Although iodine status varied largely in study populations, ID and excessive iodine intake often coexisted within populations. The implementation of nutrition interventions and other strategies across SSA has resulted in the reduction of goitre prevalence. Even so, goitre prevalence remains high in many populations. Improvements in access to iodised salt and awareness of its importance are needed. The emerging problem of excess iodine intakes, however, should be taken into consideration by policy makers and programme implementers. As excessive iodine intakes may have adverse health effects greater than those induced by iodine deficient diets, more population-based studies are needed to investigate iodine intakes of the different population groups.

Ir(III)/MPAA-Catalyzed Mild and Selective C-H Amidation of N-Sulfonyl Ketimines: Access To Benzosultam-Fused Quinazolines/Quinazolinones.

Ir(III)-catalyzed unprecedented mild C-H amidation for weakly coordinating cyclic N-sulfonyl ketimines, accelerated by a mono protected l-amino acid, has been developed. The method uses 1,4,2-dioxazol-5-ones as the robust amidating reagent in conjunction with a catalytic amount of silver triflate. It is highly selective and does not require a stoichiometric amount of oxidants or additives. A series of mechanistic experiments was performed to gain some insights into the reaction mechanism. The strategy provides easy access to novel benzosultam-quinazoline and benzosultam-quinazolinone hybrid scaffolds endowed with pharmaceutically relevant features.

Pattern of Failure with Locally Advanced Cervical Cancer­ A Retrospective Audit and Analysis of Contributory Factors

Background: The majority of the global burden of cervical cancer is affecting developing countries. Despite improvement in treatment of patients presenting at a locally advanced stage, approximately 50% experience recurrence within the 1st two years. This study was conducted to analyse contributory factors for recurrence within 24 months. Methods: The present retrospective study was undertaken to analyse factors affecting recurrence, type of failure and the follow up pattern of patients who completed treatment with a minimum follow-up period of 6 months during the study period of 5 years. Results: Out of 323 patients included in the study, 112 (34.7%) presented with recurrence within the follow-up period. The stage and histology had a significant impact on disease free survival (DFS). Of those who were followed-up regularly, recurrence was observed in 28.7% with a DFS of 81.3 months, in contrast to the 48. 5% patients with a DFS of 45.0 months for whom follow-up was irregular. The failure pattern was mostly in the form of nodal recurrence (61%). On univariate analysis, treatment time, EBRT and ICBT gap and mean EQD2 point A were found to associated with a better outcome in terms of 2yr DFS. On Cox regression analysis, stage, histology, treatment gap (HR-0.48) and follow up pattern (HR-0.24) retained their effects on survival. Point A dose was higher in patients without recurrence (P value 0.000) unlike other assymmetric parameters. Conclusion: Apart from point A cumulative dose (mean EQD2), stage, histology and treatment gap were the factors that affected early local failure. An interesting result was that follow-up pattern had a significant impact on DFS period.

A Cross-Dehydrogenative Annulation Strategy towards Synthesis of Polyfluorinated Phenanthridinones with Copper.

The first cross-dehydrogenative annulation of (hetero)aromatic amides with polyfluoro(hetero)arenes is presented. This operationally simple oxidative annulation process is mediated by inexpensive copper salt, accommodates a wide range of substrates with exquisite chemo- and regioselectivity profile, and produces demanding polyfluorinated phenanthridinones in high yields (up to 92 %). Using alkenyl amides under identical conditions, the synthesis of polyfluorinated 2-quinolones has also been accomplished. Given the importance of fluorinated heterocycles in the pharmaceutical industry and drug discovery, this work is highly significant.