An Explainable Artificial Intelligence Software Tool for Weight Management Experts (PRIMO): Mixed Methods Study.

BACKGROUND: Predicting the likelihood of success of weight loss interventions using machine learning (ML) models may enhance intervention effectiveness by enabling timely and dynamic modification of intervention components for nonresponders to treatment. However, a lack of understanding and trust in these ML models impacts adoption among weight management experts. Recent advances in the field of explainable artificial intelligence enable the interpretation of ML models, yet it is unknown whether they enhance model understanding, trust, and adoption among weight management experts. OBJECTIVE: This study aimed to build and evaluate an ML model that can predict 6-month weight loss success (ie, ≥7% weight loss) from 5 engagement and diet-related features collected over the initial 2 weeks of an intervention, to assess whether providing ML-based explanations increases weight management experts' agreement with ML model predictions, and to inform factors that influence the understanding and trust of ML models to advance explainability in early prediction of weight loss among weight management experts. METHODS: We trained an ML model using the random forest (RF) algorithm and data from a 6-month weight loss intervention (N=419). We leveraged findings from existing explainability metrics to develop Prime Implicant Maintenance of Outcome (PRIMO), an interactive tool to understand predictions made by the RF model. We asked 14 weight management experts to predict hypothetical participants' weight loss success before and after using PRIMO. We compared PRIMO with 2 other explainability methods, one based on feature ranking and the other based on conditional probability. We used generalized linear mixed-effects models to evaluate participants' agreement with ML predictions and conducted likelihood ratio tests to examine the relationship between explainability methods and outcomes for nested models. We conducted guided interviews and thematic analysis to study the impact of our tool on experts' understanding and trust in the model. RESULTS: Our RF model had 81% accuracy in the early prediction of weight loss success. Weight management experts were significantly more likely to agree with the model when using PRIMO (χ2=7.9; P=.02) compared with the other 2 methods with odds ratios of 2.52 (95% CI 0.91-7.69) and 3.95 (95% CI 1.50-11.76). From our study, we inferred that our software not only influenced experts' understanding and trust but also impacted decision-making. Several themes were identified through interviews: preference for multiple explanation types, need to visualize uncertainty in explanations provided by PRIMO, and need for model performance metrics on similar participant test instances. CONCLUSIONS: Our results show the potential for weight management experts to agree with the ML-based early prediction of success in weight loss treatment programs, enabling timely and dynamic modification of intervention components to enhance intervention effectiveness. Our findings provide methods for advancing the understandability and trust of ML models among weight management experts.

Early ß-hCG levels predict live birth after single embryo transfer.

PURPOSE: Specific serum beta human chorionic gonadotropin (ß-hCG) parameters that can predict live birth after an embryo transfer have yet to be defined. METHODS: We performed a retrospective cohort study of 1,028 patients with a detectable ß-hCG who underwent a single embryo transfer between 2002 and 2019 at a large academic center. Two ß-hCG parameters were examined in relation to live birth: 1) "doubling" defined as ß-hCG doubling over 48 h and 2) "reaching 100" defined as a ß-hCG ≥ 100 mIU/mL by 15 days after oocyte retrieval (AOR). RESULTS: One thousand three hundred forty cycles involving a single embryo were analyzed. Two thirds were frozen embryos and 86% were blastocyst transfers. Preimplantation genetic testing was performed in almost 30% of cycles. When ß-hCG levels "doubled," a live birth occurred in 80.7% of cycles and when ß-hCG levels "reached 100" by 15 days AOR, live birth occurred in 81.6% of cycles. When ß-hCG levels both doubled and reached 100 by 15 days, AOR 85.4% cycles resulted in live birth. A multiple logistic regression model to control for patient and cycle level factors revealed a live birth odds ratio (OR) of 8.0 (95% CI 5.7-11.1) when ß-hCG "doubled" and an OR of 21.2 (95% CI 14.3-31.5) when ß-hCG "reached 100." When both these latter parameters were met, the OR was 12.5 (95% CI 8.9-17.8). CONCLUSION: ß-hCG parameters of "doubling" and "reaching 100" by 15 days AOR are robust predictors of live birth and can aid in patient counseling regarding pregnancy outcomes soon after single embryo transfer.

Aperiodic measures of neural excitability are associated with anticorrelated hemodynamic networks at rest: A combined EEG-fMRI study.

The hallmark of resting EEG spectra are distinct rhythms emerging from a broadband, aperiodic background. This aperiodic neural signature accounts for most of total EEG power, although its significance and relation to functional neuroanatomy remains obscure. We hypothesized that aperiodic EEG reflects a significant metabolic expenditure and therefore might be associated with the default mode network while at rest. During eyes-open, resting-state recordings of simultaneous EEG-fMRI, we find that aperiodic and periodic components of EEG power are only minimally associated with activity in the default mode network. However, a whole-brain analysis identifies increases in aperiodic power correlated with hemodynamic activity in an auditory-salience-cerebellar network, and decreases in aperiodic power are correlated with hemodynamic activity in prefrontal regions. Desynchronization in residual alpha and beta power is associated with visual and sensorimotor hemodynamic activity, respectively. These findings suggest that resting-state EEG signals acquired in an fMRI scanner reflect a balance of top-down and bottom-up stimulus processing, even in the absence of an explicit task.

Painful gynecologic and obstetric complications of female genital mutilation/cutting: A systematic review and meta-analysis.

BACKGROUND: The health complications experienced by women having undergone female genital mutilation/cutting (FGM/C) are a source of growing concern to healthcare workers globally as forced displacement and migration from countries with high rates of this practice increases. In this systematic review and meta-analysis, we investigate the association between FGM/C and painful gynecologic and obstetric complications in women affected by the practice. METHODS AND FINDINGS: We performed a comprehensive literature search from inception to December 19, 2019 of Ovid MEDLINE, Ovid EMBASE, The Cochrane Library (Wiley), and POPLINE (prior to its retirement) for studies mentioning FGM/C. Two reviewers independently screened studies reporting prevalences of painful gynecologic and obstetric sequelae resulting from FGM/C. Random effects models were used to estimate pooled odds ratios (ORs) for outcomes obtained from cross-sectional, cohort, and case-control designs. Subgroup analysis was performed to assess and control for effect differences introduced by study design. Validated appraisal tools were utilized to assess quality and risk of bias. Our study was registered with PROSPERO. Two reviewers independently screened 6,666 abstracts. Of 559 full-text studies assessed for eligibility, 116 met eligibility criteria, which included studies describing the incidence or prevalence of painful sequelae associated with FGM/C. Pooled analyses after adjustment for study design found that FGM/C was associated with dyspareunia (6,283 FGM/C and 3,382 non-FGM/C participants; pooled OR: 2.47; 95% confidence interval [CI]: 1.45-4.21; I2: 79%; p-value < 0.01), perineal tears (4,898 FGM/C and 4,229 non-FGM/C participants; pooled OR: 2.63; 95% CI: 1.35-5.11; I2: 67%; p-value = 0.01), dysuria (3,686 FGM/C and 3,482 non-FGM/C participants; pooled OR: 1.43; 95% CI: 1.17-1.75; I2: 0%; p-value = 0.01), episiotomy (29,341 FGM/C and 39,260 non-FGM/C participants; pooled OR: 1.89; 95% CI: 1.26-2.82; I2: 96%; p-value < 0.01), and prolonged labor (7,516 FGM/C and 8,060 non-FGM/C participants; pooled OR: 2.04; 95% CI: 1.27-3.28; I2: 90%; p-value < 0.01). There was insufficient evidence to conclude that there was an association between FGM/C and dysmenorrhea (7,349 FGM/C and 4,411 non-FGM/C participants; pooled OR: 1.66; 95% CI: 0.97-2.84; I2: 86%; p-value = 0.06), urinary tract infection (4,493 FGM/C and 3,776 non-FGM/C participants; pooled OR: 2.11; 95% CI: 0.80-5.54; I2: 90%; p-value = 0.10), instrumental delivery (5,176 FGM/C and 31,923 non-FGM/C participants; pooled OR: 1.18; 95% CI: 0.78-1.79; I2: 63%; p-value = 0.40), or cesarean delivery (34,693 FGM/C and 46,013 non-FGM/C participants; pooled OR: 1.51; 95% CI: 0.99-2.30; I2: 96%; p-value = 0.05). Studies generally met quality assurance criteria. Limitations of this study include the largely suboptimal quality of studies. CONCLUSIONS: In this study, we observed that specific painful outcomes are significantly more common in participants with FGM/C. Women who underwent FGM/C were around twice as likely as non-FGM/C women to experience dyspareunia, perineal tears, prolonged labor, and episiotomy. These data indicate that providers must familiarize themselves with the unique health consequences of FGM/C, including accurate diagnosis, pain management, and obstetric planning. REVIEW PROTOCOL REGISTRATION: The review protocol registration in PROSPERO is CRD42018115848.

Knockout of mouse receptor accessory protein 6 leads to sperm function and morphology defects†.

Receptor accessory protein 6 (REEP6) is a member of the REEP/Ypt-interacting protein family that we recently identified as essential for normal endoplasmic reticulum homeostasis and protein trafficking in the retina of mice and humans. Interestingly, in addition to the loss of REEP6 in our knockout (KO) mouse model recapitulating the retinal degeneration of humans with REEP6 mutations causing retinitis pigmentosa (RP), we also found that male mice are sterile. Herein, we characterize the infertility caused by loss of Reep6. Expression of both Reep6 mRNA transcripts is present in the testis; however, isoform 1 becomes overexpressed during spermiogenesis. In vitro fertilization assays reveal that Reep6 KO spermatozoa are able to bind the zona pellucida but are only able to fertilize oocytes lacking the zona pellucida. Although spermatogenesis appears normal in KO mice, cauda epididymal spermatozoa have severe motility defects and variable morphological abnormalities, including bent or absent tails. Immunofluorescent staining reveals that REEP6 expression first appears in stage IV tubules within step 15 spermatids, and REEP6 localizes to the connecting piece, midpiece, and annulus of mature spermatozoa. These data reveal an important role for REEP6 in sperm motility and morphology and is the first reported function for a REEP protein in reproductive processes. Additionally, this work identifies a new gene potentially responsible for human infertility and has implications for patients with RP harboring mutations in REEP6.

Iliac Vein Stenting for Chronic Proximal Venous Outflow Obstruction in a Predominantly Asian-American Cohort.

BACKGROUND: We investigated the outcome of vein stenting placement for chronic proximal venous outflow obstruction (PVOO) in a predominantly Asian-American cohort to improve patient selection, enhance technical approach, and better define quality measurements of this emerging vascular intervention. METHODS: A total of 462 consecutive patients, 73% Asian American (n = 336), who underwent iliac vein stenting for chronic PVOO from October 2013 to July 2016 were reviewed. Postoperative outcomes at five follow-up visits were assessed. Wilcoxon-Mann-Whitney and Kruskal-Wallis tests were run for demographic and operative variables. Ordered logistic regressions were run for the outcome at each time point, and Chi-squared tests as well as Fisher's exact tests were used for categorical variables. RESULTS: Follow-up was maintained in 90% of patients, with a mean follow-up time of 695 days. Asian-American patients were more likely to present with varicose veins (77.4% vs. 54.8%, P < 0.001), and non-Asian patients were more likely to present with active ulceration (26.2% vs. 5.1%, P < 0.001). Asian-American patients were more likely to have bilateral stents placed (61.6% vs. 50%, P = 0.026) and were less likely to have reinterventions (11.3% vs. 27.8%, P < 0.001), a history of deep vein thrombosis (8.3% vs. 29.4%, P < 0.001), or intraoperative findings of chronic postphlebitic changes (17.6% vs. 33.3%, P < 0.001). Kruskal-Wallis tests were significant for improvement in patients of all the Clinical, Etiology, Anatomy, Pathophysiology classes at 30 days (P = 0.041), 90 days (P = 0.045), 6 months (P = 0.041), and 1 year (P < 0.01). The Asian-American population had improved but comparatively lower follow-up scores at the 30-day mark (48% significantly improved or better vs. 63%, P = 0.008) but higher follow-up scores at the >1 year mark (80% significantly improved or better vs. 59%, P < 0.001). CONCLUSIONS: Asian-American patients undergoing vein stent placement for chronic PVOO had comparatively worse outcomes than non-Asian patients at 30 days and better outcomes after one year. These patient groups had different outcomes postoperatively and outcomes which evolve differently over time.

Instilling Hope and Resiliency: A Narrative Photo-Taking Intervention During an Intercultural Exchange Involving 9/11 Survivors in Post 3/11 Japan.

On March 11, 2011 ("3/11"), a magnitude 9.0 earthquake in Northeastern Japan triggered a tsunami and nuclear power plant meltdown that killed 16,000 people and displaced more than 470,000 people. Since 2012, a group of volunteer docents from the September 11th Families Association in New York City has traveled throughout Northeastern Japan and held organized meetings where 9/11 and 3/11 survivors share their experiences and stories of trauma as part of an intercultural exchange to promote posttraumatic recovery. We sought to elucidate whether participating 9/11 docents developed a sense of increased resiliency by participating in this international outreach. This study employed photo-taking as well as framing questions, which were developed by 9/11 docents from the August 2016 trip. These questions guided photo-taking and resulting photographs informed discussion in individual and group sharing sessions. This process helped identify codes that guided analysis. Participants acquired a deeper appreciation of their own ability to overcome adversity and experienced a gratifying desire to help 3/11 survivors better cope with their experiences. This narrative photo-taking and group sharing experience demonstrates that a cross-cultural exchange between survivors of different disasters can instill feelings of resilience among participants. It additionally provides early evidence of the efficacy of such an exchange in benefitting disaster survivors in the long term.

Steering Transforms the Cortical Representation of Self-Movement from Direction to Destination.

Steering demands rapid responses to heading deviations and uses optic flow to redirect self-movement toward the intended destination. We trained monkeys in a naturalistic steering paradigm and recorded dorsal medial superior temporal area (MSTd) cortical neuronal responses to the visual motion and spatial location cues in optic flow. We found that neuronal responses to the initial heading direction are dominated by the optic flow's global radial pattern cue. Responses to subsequently imposed heading deviations are dominated by the local direction of motion cue. Finally, as the monkey steers its heading back to the goal location, responses are dominated by the spatial location cue, the screen location of the flow field's center of motion. We conclude that MSTd responses are not rigidly linked to specific stimuli, but rather are transformed by the task relevance of cues that guide performance in learned, naturalistic behaviors. SIGNIFICANCE STATEMENT: Unplanned heading changes trigger lifesaving steering back to a goal. Conventionally, such behaviors are thought of as cortical sensory-motor reflex arcs. We find that a more reciprocal process underlies such cycles of perception and action, rapidly transforming visual processing to suit each stage of the task. When monkeys monitor their simulated self-movement, dorsal medial superior temporal area (MSTd) neurons represent their current heading direction. When monkeys steer to recover from an unplanned change in heading direction, MSTd shifts toward representing the goal location. We hypothesize that this transformation reflects the reweighting of bottom-up visual motion signals and top-down spatial location signals, reshaping MSTd's response properties through task-dependent interactions with adjacent cortical areas.

A comparative examination of cortisol effects on muscle myostatin and HSP90 gene expression in salmonids.

Cortisol, the primary corticosteroid in teleost fishes, is released in response to stressors to elicit local functions, however little is understood regarding muscle-specific responses to cortisol in these fishes. In mammals, glucocorticoids strongly regulate the muscle growth inhibitor, myostatin, via glucocorticoid response elements (GREs) leading to muscle atrophy. Bioinformatics methods suggest that this regulatory mechanism is conserved among vertebrates, however recent evidence suggests some fishes exhibit divergent regulation. Therefore, the aim of this study was to evaluate the conserved actions of cortisol on myostatin and hsp90 expression to determine if variations in cortisol interactions have emerged in salmonid species. Representative salmonids; Chinook salmon (Oncorhynchus tshawytscha), cutthroat trout (Oncorhynchus clarki), brook trout (Salvelinus fontinalis), and Atlantic salmon (Salmo salar); were injected intraperitoneally with a cortisol implant (50µg/g body weight) and muscle gene expression was quantified after 48h. Plasma glucose and cortisol levels were significantly elevated by cortisol in all species, demonstrating physiological effectiveness of the treatment. HSP90 mRNA levels were elevated by cortisol in brook trout, Chinook salmon, and Atlantic salmon, but were decreased in cutthroat trout. Myostatin mRNA levels were affected in a species, tissue (muscle type), and paralog specific manner. Cortisol treatment increased myostatin expression in brook trout (Salvelinus) and Atlantic salmon (Salmo), but not in Chinook salmon (Oncorhynchus) or cutthroat trout (Oncorhynchus). Interestingly, the VC alone increased myostatin mRNA expression in Chinook and Atlantic salmon, while the addition of cortisol blocked the response. Taken together, these results suggest that cortisol affects muscle-specific gene expression in species-specific manners, with unique Oncorhynchus-specific divergence observed, that are not predictive solely based upon mammalian stress responses.

Evolutionary history and epigenetic regulation of the three paralogous pax7 genes in rainbow trout.

The extraordinary muscle growth potential of teleost fish, particular those of the Salmoninae clade, elicits questions about the regulation of the relatively highly conserved transcription factors of the myogenic program. The pseudotetraploid nature of the salmonid genome adds another layer of regulatory complexity that must be reconciled with epigenetic data to improve our understanding of the achievement of lifelong muscle growth in these fish. We identify three paralogous pax7 genes (pax7a1, pax7a2 and pax7b) in the rainbow trout genome. During in vitro myogenesis, pax7a1 transcripts remain stable, whereas pax7a2 and pax7b mRNAs increase in abundance, similarly to myogenin mRNAs but in contrast to the expression pattern of the mammalian ortholog. We also profile the distribution of repressive H3K27me3 and H3K9me3 and permissive H3K4me3 marks during in vitro myogenesis across these loci and find that pax7a2 expression is associated with decreased H3K27 trimethylation, whereas pax7b expression is correlated with decreased H3K9me3 and H3K27me3. These data link the unique differential expression of pax7 paralogs with epigenetic histone modifications in a vertebrate species displaying growth divergent from that of mammals and highlight an important divergence in the regulatory mechanisms of pax7 expression among vertebrates. The system described here provides a more comprehensive picture of the combinatorial control mechanisms orchestrating skeletal muscle growth in a salmonid, leading to a better understanding of myogenesis in this species and across Vertebrata more generally.

The effects of exogenous cortisol on myostatin transcription in rainbow trout, Oncorhynchus mykiss.

Glucocorticoids (GCs) strongly regulate myostatin expression in mammals via glucocorticoid response elements (GREs), and bioinformatics methods suggest that this regulatory mechanism is conserved among many vertebrates. However, the multiple myostatin genes found in some fishes may be an exception. In silico promoter analyses of the three putative rainbow trout (Oncorhynchus mykiss) myostatin promoters have failed to identify putative GREs, suggesting a divergence in myostatin function. Therefore, we hypothesized that myostatin mRNA expression is not regulated by glucocorticoids in rainbow trout. In this study, both juvenile rainbow trout and primary trout myoblasts were treated with cortisol to examine the effects on myostatin mRNA expression. Results suggest that exogenous cortisol does not regulate myostatin-1a and -1b expression in vivo, as myostatin mRNA levels were not significantly affected by cortisol treatment in either red or white muscle tissue. In red muscle, myostatin-2a levels were significantly elevated in the cortisol treatment group relative to the control, but not the vehicle control, at both 12 h and 24 h post-injection. As such, it is unclear if cortisol was acting alone or in combination with the vehicle. Cortisol increased myostatin-1b expression in a dose-dependent manner in vitro. Further work is needed to determine if this response is the direct result of cortisol acting on the myostatin-1b promoter or through an alternative mechanism. These results suggest that regulation of myostatin by cortisol may not be as highly conserved as previously thought and support previous work that describes potential functional divergence of the multiple myostatin genes in fishes.

High-fat diet reduces local myostatin-1 paralog expression and alters skeletal muscle lipid content in rainbow trout, Oncorhynchus mykiss.

Muscle growth is an energetically demanding process that is reliant on intramuscular fatty acid depots in most fishes. The complex mechanisms regulating this growth and lipid metabolism are of great interest for human health and aquaculture applications. It is well established that the skeletal muscle chalone, myostatin, plays a role in lipid metabolism and adipogenesis in mammals; however, this function has not been fully assessed in fishes. We therefore examined the interaction between dietary lipid levels and myostatin expression in rainbow trout (Oncorhynchus mykiss). Five weeks of high-fat diet (HFD; 25 % lipid) intake increased white muscle lipid content and decreased circulating glucose levels and hepatosomatic index when compared to low-fat diet (LFD; 10 % lipid) intake. In addition, HFD intake reduced myostatin-1a and myostatin-1b expression in white muscle and myostatin-1b expression in brain tissue. Characterization of the myostatin-1a, myostatin-1b, and myostatin-2a promoters revealed putative binding sites for a subset of transcription factors associated with lipid metabolism. Taken together, these data suggest that HFD may regulate myostatin expression through cis-regulatory elements sensitive to increased lipid intake. Further, these findings provide a framework for future investigations of mechanisms describing the relationships between myostatin and lipid metabolism in fish.

Languaging psychopathology: neurobiology and metaphor.

Explanatory models of the mind inform our working assumptions about mental illness with direct implications for clinical practice. Neurobiological models assert that the mind can be understood in terms of genetics, chemistry, and neuronal circuits. Growing evidence suggests that clinical deployment of neurobiological models of illness may have unintended adverse effects on patient attitudes, public perception, provider empathy, and the effectiveness of psychiatric treatment. New approaches are needed to find a better language for describing (let alone explaining) the experience of mental illness. To address this gap, we draw upon interdisciplinary sources and semiotic theory to characterize the role of metaphor in the conceptualization and communication of psychopathology. We examine the metaphors recruited by contemporary neurobiological models and metaphor's role in facilitating descriptive clarity or evocative creativity, depending on intention and context. These multiple roles reveal the implications of metaphorical reasoning in clinical practice, including cognitive flexibility, personalized communication, and uncertainty tolerance. With this analysis, we propose a clinical approach that embraces the meta-process of ongoing novel metaphor generation and co-elaboration, or languaging metaphors of psychopathology. Our goal is to bring attention to the value of employing ever-evolving, shapeable metaphorical depictions of psychiatric illness: metaphors that enable a capacity for change in individuals and society, reduce stigma, and nurture recovery.

Artificial intelligence in Parkinson's disease: Early detection and diagnostic advancements.

Parkinson's disease (PD) is the second most common neurodegenerative disorder, globally affecting men and women at an exponentially growing rate, with currently no cure. Disease progression starts when dopaminergic neurons begin to die. In PD, the loss of neurotransmitter, dopamine is responsible for the overall communication of neural cells throughout the body. Clinical symptoms of PD are slowness of movement, involuntary muscular contractions, speech & writing changes, lessened automatic movement, and chronic tremors in the body. PD occurs in both familial and sporadic forms and modifiable and non-modifiable risk factors and socioeconomic conditions cause PD. Early detectable diagnostics and treatments have been developed in the last several decades. However, we still do not have precise early detectable biomarkers and therapeutic agents/drugs that prevent and/or delay the disease process. Recently, artificial intelligence (AI) science and machine learning tools have been promising in identifying early detectable markers with a greater rate of accuracy compared to past forms of treatment and diagnostic processes. Artificial intelligence refers to the intelligence exhibited by machines or software, distinct from the intelligence observed in humans that is based on neural networks in a form and can be used to diagnose the longevity and disease severity of disease. The term Machine Learning or Neural Networks is a blanket term used to identify an emerging technology that is created to work in the way of a "human brain" using many intertwined neurons to achieve the same level of raw intelligence as that of a brain. These processes have been used for neurodegenerative diseases such as Parkinson's disease and Alzheimer's disease, to assess the severity of the patient's condition. In the current article, we discuss the prevalence and incidence of PD, and currently available diagnostic biomarkers and therapeutic strategies. We also highlighted currently available artificial intelligence science and machine learning tools and their applications to detect disease and develop therapeutic interventions.

Treating Alzheimer's disease using nanoparticle-mediated drug delivery strategies/systems.

The administration of promising medications for the treatment of neurodegenerative disorders (NDDs), such as Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease (HD), and amyotrophic lateral sclerosis (ALS) is significantly hampered by the blood-brain barrier (BBB). Nanotechnology has recently come to light as a viable strategy for overcoming this obstacle and improving drug delivery to the brain. With a focus on current developments and prospects, this review article examines the use of nanoparticles to overcome the BBB constraints to improve drug therapy for AD The potential for several nanoparticle-based approaches, such as those utilizing lipid-based, polymeric, and inorganic nanoparticles, to enhance drug transport across the BBB are highlighted. To shed insight on their involvement in aiding effective drug transport to the brain, methods of nanoparticle-mediated drug delivery, such as surface modifications, functionalization, and particular targeting ligands, are also investigated. The article also discusses the most recent findings on innovative medication formulations encapsulated within nanoparticles and the therapeutic effects they have shown in both preclinical and clinical testing. This sector has difficulties and restrictions, such as the need for increased safety, scalability, and translation to clinical applications. However, the major emphasis of this review aims to provide insight and contribute to the knowledge of how nanotechnology can potentially revolutionize the worldwide treatment of NDDs, particularly AD, to enhance clinical outcomes.

Caring for Individuals with Alzheimer's Disease: A Spotlight on Hispanic Caregivers.

 A caregiver is a constantly evolving role that an individual most likely undertakes at some point in their lifetime. With discoveries and research in increasing life expectancy, the prevalence of neurological-related diseases, such as Alzheimer's disease (AD) and dementia, is certainly likely to require more caregivers. The demand for AD caregivers is escalating as the prevalence of the disease continues to rise. The projected rise in AD within the Hispanic population in the United States over the next few decades is expected to be the most significant among all ethnic groups. The Hispanic population faces unique dementia risks due to cultural factors like language barriers, lower education, and limited healthcare access. Higher rates of conditions such as diabetes and cardiovascular disease further elevate dementia risk. Family dynamics and caregiving responsibilities also differ, affecting dementia management within Hispanic households. Addressing these distinct challenges requires culturally sensitive approaches to diagnosis, treatment, and support for Hispanic individuals and their family's facing dementia. With AD and other dementia becoming more prevalent, this article will attempt to expand upon the status of caregivers concerning their economic, health, and cultural statuses. We will attempt to focus on the Hispanic caregivers that live in Texas and more specifically, West Texas due to the lack of current literature that applies to this area of Texas. Lastly, we discuss the ramifications of a multitude of factors that affect caregivers in Texas and attempt to provide tools that can be readily available for Hispanics and others alike.

Serotonin acts through multiple cellular targets during an olfactory critical period.

Serotonin (5-HT) is known to modulate early development during critical periods when experience drives heightened levels of plasticity in neurons. Here, we take advantage of the genetically tractable olfactory system of Drosophila to investigate how 5-HT modulates critical period plasticity in the CO2 sensing circuit of fruit flies. Our study reveals that 5HT modulation of multiple neuronal targets is necessary for experience-dependent structural changes in an odor processing circuit. The olfactory CPP is known to involve local inhibitory networks and consistent with this we found that knocking down 5-HT7 receptors in a subset of GABAergic local interneurons was sufficient to block CPP, as was knocking down GABA receptors expressed by olfactory sensory neurons (OSNs). Additionally, direct modulation of OSNs via 5-HT2B expression in the cognate OSNs sensing CO2 is also essential for CPP. Furthermore, 5-HT1B expression by serotonergic neurons in the olfactory system is also required during the critical period. Our study reveals that 5-HT modulation of multiple neuronal targets is necessary for experience-dependent structural changes in an odor processing circuit.

Toward a Bio-Organon: A model of interdependence between energy, information and knowledge in living systems.

What is an organism? In the absence of a fundamental biological definition, what constitutes a living organism, whether it is a unicellular microbe, a multicellular being or a multi-organismal society, remains an open question. New models of living systems are needed to address the scale of this question, with implications for the relationship between humanity and planetary ecology. Here we develop a generic model of an organism that can be applied across multiple scales and through major evolutionary transitions to form a toolkit, or bio-organon, for theoretical studies of planetary-wide physiology. The tool identifies the following core organismic principles that cut across spatial scale: (1) evolvability through self-knowledge, (2) entanglement between energy and information, and (3) extrasomatic "technology" to scaffold increases in spatial scale. Living systems are generally defined by their ability to self-sustain against entropic forces of degradation. Life "knows" how to survive from the inside, not from its genetic code alone, but by utilizing this code through dynamically embodied and functionally specialized flows of information and energy. That is, entangled metabolic and communication networks bring encoded knowledge to life in order to sustain life. However, knowledge is itself evolved and is evolving. The functional coupling between knowledge, energy and information has ancient origins, enabling the original, cellular "biotechnology," and cumulative evolutionary creativity in biochemical products and forms. Cellular biotechnology also enabled the nesting of specialized cells into multicellular organisms. This nested organismal hierarchy can be extended further, suggesting that an organism of organisms, or a human "superorganism," is not only possible, but in keeping with evolutionary trends.