Implications of cognitive and daily living capabilities on early type 2 diabetes management: a preliminary case-control study.

BACKGROUND: Adherence to the transition from oral agents to insulin injections in Type 2 Diabetes Mellitus therapy varies among patients and is not uniformly successful, leading to suboptimal glycemic control in certain cases. This study aims to investigate the potential correlation between cognitive and daily functional capabilities and glycemic control in middle-aged to older adults (40-74 years old) diagnosed with Type 2 Diabetes Mellitus for less than 10 years, specifically those who have recently transitioned to insulin injections and have lower education levels within the context of a developing country. METHODS: A case-control study was conducted with 30 poorly controlled diabetes mellitus (PCDM) patients recognized by HbA1c levels > 8% compared to 30 fairly controlled diabetes mellitus (FCDM) patients with HbA1c levels ≤ 8%. Basic Montreal Cognitive Assessment (MoCA-B) score of less than 27 was investigated as the exposure among two groups. Additionally, intra- and inter-battery correlations were assessed among MoCA-B and Instrumental Activities of Daily Living (IADL) domains using Pearson's r. RESULTS: The primary outcomes showed no crude difference between MoCA-B scores in the two diabetic groups (p-value = 0.82). However, after adjusting for age, education, and IADL scores, cognitive decline in the less-educated younger elderly with high IADL scores demonstrated an unexpected protective effect against PCDM (p-value < 0.0001, OR 95% CI = 0-0.26). In linear regression analysis among MoCA-B and IADL scores, "delayed recall" and "orientation" domains from MoCA-B, and "managing medications" and "using the phone" from IADL were negatively associated with HbA1c levels (p-values of < 0.01, 0.043, 0.015, and 0.023, respectively). Intra- and inter-battery correlations further illustrated a strong association between MoCA-B's "orientation" with IADL's "using the phone" and "managing medications" (p-values < 0.0001). CONCLUSION: Superior performance in certain cognitive domains is linked to better glycemic control. Still, since assessing cognitive domains may be timely in clinical routine, a potential rapid approach might be taken by assessing patients' instrumental abilities to use cell phone or manage medications. Future studies including a larger sample size and a broader spectrum of psychosocial factors are needed to elaborate on our findings.

Clinical performance of AI-integrated risk assessment pooling reveals cost savings even at high prevalence of COVID-19.

Individual testing of samples is time- and cost-intensive, particularly during an ongoing pandemic. Better practical alternatives to individual testing can significantly decrease the burden of disease on the healthcare system. Herein, we presented the clinical validation of Segtnan™ on 3929 patients. Segtnan™ is available as a mobile application entailing an AI-integrated personalized risk assessment approach with a novel data-driven equation for pooling of biological samples. The AI was selected from a comparison between 15 machine learning classifiers (highest accuracy = 80.14%) and a feed-forward neural network with an accuracy of 81.38% in predicting the rRT-PCR test results based on a designed survey with minimal clinical questions. Furthermore, we derived a novel pool-size equation from the pooling data of 54 published original studies. The results demonstrated testing capacity increase of 750%, 60%, and 5% at prevalence rates of 0.05%, 22%, and 50%, respectively. Compared to Dorfman's method, our novel equation saved more tests significantly at high prevalence, i.e., 28% (p = 0.006), 40% (p = 0.00001), and 66% (p = 0.02). Lastly, we illustrated the feasibility of the Segtnan™ usage in clinically complex settings like emergency and psychiatric departments.

Neuronal silence as a prosurvival factor for adult-born olfactory bulb interneurons.

Adult-born cells, arriving daily into the rodent olfactory bulb, either integrate into the neural circuitry or get eliminated. However, whether these two populations differ in their morphological or functional properties remains unclear. Using longitudinal in vivo two-photon imaging, we monitored dendritic morphogenesis, odor-evoked responsiveness, ongoing Ca2+ signaling, and survival/death of adult-born juxtaglomerular neurons (abJGNs). We found that the maturation of abJGNs is accompanied by a significant reduction in dendritic complexity, with surviving and subsequently eliminated cells showing similar degrees of dendritic remodeling. Surprisingly, ∼63% of eliminated abJGNs acquired odor responsiveness before death, with amplitudes and time courses of odor-evoked responses similar to those recorded in surviving cells. However, the subsequently eliminated cell population exhibited significantly higher ongoing Ca2+ signals, with a difference visible even 10 days before death. Quantitative supervised machine learning analysis revealed a relationship between the abJGNs' activity and survival probability, with low neuronal activity being supportive for survival.

The Cambridge Neuropsychological Test Automated Battery (CANTAB) Versus the Minimal Assessment of Cognitive Function in Multiple Sclerosis (MACFIMS) for the Assessment of Cognitive Function in Patients with Multiple Sclerosis.

BACKGROUND: We determined how the Cambridge Neuropsychological Test Automated Battery (CANTAB) compared to the Minimal Assessment of Cognitive Function in multiple sclerosis (MACFIMS) in terms of sensitivity, specificity, and predictive values in detecting cognitive impairment in multiple sclerosis (MS) patients. METHODS: Sixty MS patients were recruited, 2 of whom were lost to follow-up. On the first day of the neuropsychological examination, the standard MACFIMS battery and the day after, the CANTAB (paired-associate learning (PAL), reaction time (RTI), rapid visual information processing (RVP), and spatial working memory tasks (SWM)) were completed by the patients. The sensitivity, specificity, and predictive values of the CANTAB in the differentiation of cognitively impaired (CI) patients from not cognitively impaired (NCI) ones were compared with those of the MACFIMS battery using appropriate statistical tests. RESULTS: Fifty-eight patients were categorized into two groups of CI (n=16 (27.58%)) and NCI (n=42 (72.41%)) based on the MACFIMS battery standard criteria. The best reporter indices and their cut-off scores for differentiation of CI from NCI patients in each task of the CANTAB were "total errors=13" for PAL, "between errors=26" for SWM, "five-choice reaction time=368.57" for RTI, and "mean latency=522.14" for RVP. The optimal cut-off point for distinguishing CI from NCI in the CANTAB was found to be an impaired function in 3 or more tasks [(AUC (95% CI): 0.97 (0.94-1.00); p<0.001)]. Accordingly, 36.20% of the patients were CI based on the CANTAB criteria. The inter-test agreement (CANTAB and MACFIMS batteries) was found to be the highest (Cohen's κ (95% CI): 0.80 (0.64-0.96)). CONCLUSION: Results confirm that the CANTAB can discriminate CI from NCI MS patients with high accuracy, and its results are comparable to those of the MACFIMS battery; thus, they might be interchangeably used in the clinical practice.

Therapeutic potential of intranasal photobiomodulation therapy for neurological and neuropsychiatric disorders: a narrative review.

The application of photobiomodulation therapy (PBMT) for neuronal stimulation is studied in different animal models and in humans, and has shown to improve cerebral metabolic activity and blood flow, and provide neuroprotection via anti-inflammatory and antioxidant pathways. Recently, intranasal PBMT (i-PBMT) has become an attractive and potential method for the treatment of brain conditions. Herein, we provide a summary of different intranasal light delivery approaches including a nostril-based portable method and implanted deep-nasal methods for the effective systemic or direct irradiation of the brain. Nostril-based i-PBMT devices are available, using either lasers or light emitting diodes (LEDs), and can be applied either alone or in combination to transcranial devices (the latter applied directly to the scalp) to treat a wide range of brain conditions such as mild cognitive impairment, Alzheimer's disease, Parkinson's disease, cerebrovascular diseases, depression and anxiety as well as insomnia. Evidence shows that nostril-based i-PBMT improves blood rheology and cerebral blood flow, so that, without needing to puncture blood vessels, i-PBMT may have equivalent results to a peripheral intravenous laser irradiation procedure. Up to now, no studies were conducted to implant PBMT light sources deep within the nose in a clinical setting, but simulation studies suggest that deep-nasal PBMT via cribriform plate and sphenoid sinus might be an effective method to deliver light to the ventromedial part of the prefrontal and orbitofrontal cortex. Home-based i-PBMT, using inexpensive LED applicators, has potential as a novel approach for neurorehabilitation; comparative studies also testing sham, and transcranial PBMT are warranted.

Phototoxicity of environmental radiations in human lens: revisiting the pathogenesis of UV-induced cataract.

The magnitude of cataract pathology is indeed significant as it is the principal cause of blindness worldwide. Also, the prominence of this concept escalates with the current aging population. The burden of the disease is more tangible in developing countries than developed ones. Regarding this concern, there is a gap in classifying the pathogenesis of the ultraviolet (UV) radiation-induced cataracts and explaining the possible cellular and subcellular pathways. In this review, we aim to revisit the effect of UV radiation on cataracts categorizing the cellular pathways involved. This may help for better pharmaceutical treatment alternatives and their wide-reaching availability. Also, in the last section, we provide an overview of the protecting agents utilized as UV shields. Further studies are required to enlighten new treatment modalities for UV radiation-induced pathologies in human lens.

Photodynamic therapy for cancer: Role of natural products.

Photodynamic therapy (PDT) is a promising modality for the treatment of cancer. PDT involves administering a photosensitizing dye, i.e. photosensitizer, that selectively accumulates in tumors, and shining a light source on the lesion with a wavelength matching the absorption spectrum of the photosensitizer, that exerts a cytotoxic effect after excitation. The reactive oxygen species produced during PDT are responsible for the oxidation of biomolecules, which in turn cause cell death and the necrosis of malignant tissue. PDT is a multi-factorial process that generally involves apoptotic death of the tumor cells, degeneration of the tumor vasculature, stimulation of anti-tumor immune response, and induction of inflammatory reactions in the illuminated lesion. Numerous compounds with photosensitizing activity have been introduced commercially. Although many papers have been published with regard to PDT in the last decade, there has been relatively little focus on natural medicinal plant extracts and compounds derived therefrom. Herbal plants and their extracts are natural substances, and in comparison with synthetic chemicals are considered "green". This review focuses on the different mechanisms of PDT and discusses the role of various plant extracts and natural compounds either alone or in combination for carrying out PDT on different types of cancers.

A Protocol for Transcranial Photobiomodulation Therapy in Mice.

Transcranial photobiomodulation is a potential innovative noninvasive therapeutic approach for improving brain bioenergetics, brain function in a wide range of neurological and psychiatric disorders, and memory enhancement in age-related cognitive decline and neurodegenerative diseases. We describe a laboratory protocol for transcranial photobiomodulation therapy (PBMT) in mice. Aged BALB/c mice (18 months old) are treated with a 660 nm laser transcranially, once daily for 2 weeks. Laser transmittance data shows that approximately 1% of the incident red light on the scalp reaches a 1 mm depth from the cortical surface, penetrating the dorsal hippocampus. Treatment outcomes are assessed by two methods: a Barnes maze test, which is a hippocampus-dependent spatial learning and memory task evaluation, and measuring hippocampal ATP levels, which is used as a bioenergetics index. The results from the Barnes task show an enhancement of the spatial memory in laser-treated aged mice when compared with age-matched controls. Biochemical analysis after laser treatment indicates increased hippocampal ATP levels. We postulate that the enhancement of memory performance is potentially due to an improvement in hippocampal energy metabolism induced by the red laser treatment. The observations in mice could be extended to other animal models since this protocol could potentially be adapted to other species frequently used in translational neuroscience, such as rabbit, cat, dog, or monkey. Transcranial photobiomodulation is a safe and cost-effective modality which may be a promising therapeutic approach in age-related cognitive impairment.

Solubility Prediction of Drugs in Binary Solvent Mixtures at Various Temperatures Using a Minimum Number of Experimental Data Points.

This study aimed to provide a rational experimental design to collect a minimum number of experimental data points for a drug dissolved in a given binary solvent mixture at various temperatures, and to describe a computational procedure to predict the solubility of the drugs in any solvent composition and temperature of interest. We gathered available solubility data sets from papers published from 2012 to 2016 (56 data sets, 3488 data points totally). The mean percentage deviations (MPD) used to check the accuracy of predictions was calculated by Eq. 10. Fifty-six datasets were analyzed using 8 training data points which the overall MPD was calculated to be 15.5% ± 15.1%, and for 52 datasets after excluding 5 outlier sets was 12.1% ± 8.9%. The paired t test was conducted to compare the MPD values obtained from the models trained by 7 and 8 training data points and the reduction in prediction overall MPD (from 17.7% to 15.5%) was statistically significant (p < 0.04). To further reduction in MPD values, the computations were also conducted using 9 training data points, which did not reveal any significant difference comparing to the predictions using 8 training data points (p > 0.88). This observation revealed that the model adequately trained using 8 data points and could be used as a practical strategy for predicting the solubility of drugs in binary solvent mixtures at various temperatures with acceptable prediction error and using minimum experimental efforts. These sorts of predictions are highly in demand in the pharmaceutical industry.

Brain Photobiomodulation Therapy: a Narrative Review.

Brain photobiomodulation (PBM) therapy using red to near-infrared (NIR) light is an innovative treatment for a wide range of neurological and psychological conditions. Red/NIR light is able to stimulate complex IV of the mitochondrial respiratory chain (cytochrome c oxidase) and increase ATP synthesis. Moreover, light absorption by ion channels results in release of Ca2+ and leads to activation of transcription factors and gene expression. Brain PBM therapy enhances the metabolic capacity of neurons and stimulates anti-inflammatory, anti-apoptotic, and antioxidant responses, as well as neurogenesis and synaptogenesis. Its therapeutic role in disorders such as dementia and Parkinson's disease, as well as to treat stroke, brain trauma, and depression has gained increasing interest. In the transcranial PBM approach, delivering a sufficient dose to achieve optimal stimulation is challenging due to exponential attenuation of light penetration in tissue. Alternative approaches such as intracranial and intranasal light delivery methods have been suggested to overcome this limitation. This article reviews the state-of-the-art preclinical and clinical evidence regarding the efficacy of brain PBM therapy.

Molecular Insights Into Memory-Enhancing Metabolites of Nicotine in Brain: A Systematic Review.

Background: The alleged procognitive effects of nicotine and its metabolites in brain are controversial. Objective: Here, we review the pharmacologically active metabolites of nicotine in brain and their effects on neuronal mechanisms involving two main cognitive domains, i.e., learning and memory. Methods: We searched Embase, Medline via PubMed, Scopus, and Web of Science databases for entries no later than May 2018, and restricted the search to articles about nicotine metabolites and cognitive behavior or cognitive mechanisms. Results: The initial search yielded 425 articles, of which 17 were eligible for inclusion after application of exclusion criteria. Of these, 13 were experimental, two were clinical, and two were conference papers. Conclusions: The results revealed three pharmacologically active biotransformations of nicotine in the brain, including cotinine, norcotinine, and nornicotine, among which cotinine and nornicotine both had a procognitive impact without adverse effects. The observed effect was significant only for cotinine.

Revisiting nicotine's role in the ageing brain and cognitive impairment.

Brain ageing is a complex process which in its pathologic form is associated with learning and memory dysfunction or cognitive impairment. During ageing, changes in cholinergic innervations and reduced acetylcholinergic tonus may trigger a series of molecular pathways participating in oxidative stress, excitotoxicity, amyloid-ß toxicity, apoptosis, neuroinflammation, and perturb neurotrophic factors in the brain. Nicotine is an exogenous agonist of nicotinic acetylcholine receptors (nAChRs) and acts as a pharmacological chaperone in the regulation of nAChR expression, potentially intervening in age-related changes in diverse molecular pathways leading to pathology. Although nicotine has therapeutic potential, paradoxical effects have been reported, possibly due to its inverted U-shape dose-response effects or pharmacokinetic factors. Additionally, nicotine administration should result in optimum therapeutic effects without imparting abuse potential or toxicity. Overall, this review aims to compile the previous and most recent data on nicotine and its effects on cognition-related mechanisms and age-related cognitive impairment.