Ethical and Social Considerations for Increasing Use of DTC Neurotechnologies.

AJOB Neurosci. 2019 Oct-Dec;10(4):183-185

Authors: Kostick KM, Sierra-Mercado D, Lázaro-Muñoz G

PMID: 31642754 [PubMed - in process]

Lessons Learned from a Medical Response Team 45 Days Post-Hurricane Maria in Puerto Rico.

Disaster Med Public Health Prep. 2019 Oct 23;:1-6

Authors: Gordon JM, Orriola D, Unangst M, Gordon F, Vellon YER

Abstract
INTRODUCTION: Describe the lived experience of a grassroots, nongovernmental disaster medical team (DMT) through a research lens and share practical lessons learned based on the DMT's experience to support and inform future response teams.
METHOD: Forty-five days after Hurricane Maria, a nongovernmental DMT provided primary medical care by means of community-based pop-up clinics and home visitations in 5 different areas of Puerto Rico. Observational data, photo images, and debriefing notes were collected and documented in the response team's daily activity log. Field notes were coded using a descriptive coding method and then categorized into 2 domains specific to public health and medical diagnosis.
RESULTS: Medical aid was provided to nearly 300 (N = 296) residents. Field note observations identified exhaustion related to living conditions and the exacerbation of underlying conditions, such as reactive airway diseases, diabetes, hypertension, and depression due to the compounding effects of multiple post-disaster triggers. During home visitations, feelings of sadness and helplessness were identified secondary to natural disaster trauma and current living conditions.
CONCLUSION: Our nongovernmental DMT displayed similar characteristics demonstrated by federal DMTs post-natural disaster. Several strategic lessons learned emerged from the public health intervention important to future nongovernmental DMTs.

PMID: 31642418 [PubMed - as supplied by publisher]

Colonization history and population differentiation of the Honey Bees (Apis mellifera L.) in Puerto Rico.

Ecol Evol. 2019 Oct;9(19):10895-10902

Authors: Acevedo-Gonzalez JP, Galindo-Cardona A, Avalos A, Whitfield CW, Rodriguez DM, Uribe-Rubio JL, Giray T

Abstract
Honey bees (Apis mellifera L.) are the primary commercial pollinators across the world. The subspecies A. m. scutellata originated in Africa and was introduced to the Americas in 1956. For the last 60 years, it hybridized successfully with European subspecies, previous residents in the area. The result of this hybridization was called Africanized honey bee (AHB). AHB has spread since then, arriving to Puerto Rico (PR) in 1994. The honey bee population on the island acquired a mosaic of features from AHB or the European honey bee (EHB). AHB in Puerto Rico shows a major distinctive characteristic, docile behavior, and is called gentle Africanized honey bees (gAHB). We used 917 SNPs to examine the population structure, genetic differentiation, origin, and history of range expansion and colonization of gAHB in PR. We compared gAHB to populations that span the current distribution of A. mellifera worldwide. The gAHB population is shown to be a single population that differs genetically from the examined populations of AHB. Texas and PR groups are the closest genetically. Our results support the hypothesis that the Texas AHB population is the source of gAHB in Puerto Rico.

PMID: 31641443 [PubMed]

Phenotypes of Hypertensive Ambulatory Blood Pressure Patterns: Design and Rationale of the ECHORN Hypertension Study.

Ethn Dis. 2019;29(4):535-544

Authors: Spatz ES, Martinez-Brockman JL, Tessier-Sherman B, Mortazavi B, Roy B, Schwartz JI, Nazario CM, Maharaj R, Nunez M, Adams OP, Burg M, Nunez-Smith M, ECHORN Writing Group

Abstract
Objective: To describe the rationale and design of a prospective study of ambulatory blood pressure measurement (ABPM) combined with measurement of contextual factors to identify hypertensive phenotypes in a Caribbean population with high rates of HTN and cardiovascular disease.
Design: Prospective, multi-center sub-study.
Setting: Eastern Caribbean Health Outcomes Research Network Cohort (ECHORN) Study, with study sites in Puerto Rico, the US Virgin Islands, Trinidad and Tobago, and Barbados.
Participants: Community-residing adults without a diagnosis of HTN and not taking antihypertensive medication.
Intervention: Ambulatory BP patterns are assessed using 24-hour ABPM. Contextual factors are assessed with: ecological momentary assessment (7-item survey of experiences, exposures and responses associated with daytime BP measurements); actigraphy (capturing physical activity and sleep quality); and self-report surveys (assessing physical and social health, environmental and social stressors and supports).
Main Outcome Measures: Phenotypes of contextual factors associated with hypertensive BP patterns (sustained HTN, masked HTN, and nocturnal non-dipping).
Methods and Results: This study will enroll 500 participants; assessments of blood pressure and contextual factors will be conducted during Waves 2 and 3 of the ECHORN parent study, occurring 2 years apart. In Wave 2, we will assess the association between contextual factors and ABPM patterns. Using advanced analytic clustering methods, we will identify phenotypes of contextual factors associated with hypertensive ABPM patterns. We will then test the stability of these phenotypes and their ability to predict change in ABPM patterns between Waves 2 and 3.
Conclusions: Assessment of ABPM, and the contextual factors influencing ABPM, can identify unique phenotypes of HTN, which can then be used to develop more precision-based approaches to the prevention, detection and treatment of HTN in high-risk populations.

PMID: 31641320 [PubMed - in process]

Non-Polar and Complementary Resistive Switching Characteristics in Graphene Oxide devices with Gold Nanoparticles: Diverse Approach for Device Fabrication.

Sci Rep. 2019 Oct 22;9(1):15103

Authors: Khurana G, Kumar N, Chhowalla M, Scott JF, Katiyar RS

Abstract
Downscaling limitations and limited write/erase cycles in conventional charge-storage based non-volatile memories stimulate the development of emerging memory devices having enhanced performance. Resistive random-access memory (RRAM) devices are recognized as the next-generation memory devices for employment in artificial intelligence and neuromorphic computing, due to their smallest cell size, high write/erase speed and endurance. Unipolar and bipolar resistive switching characteristics in graphene oxide (GO) have been extensively studied in recent years, whereas the study of non-polar and complementary switching is scarce. Here we fabricated GO-based RRAM devices with gold nanoparticles (Au Nps). Diverse types of switching behavior are observed by changing the processing methods and device geometry. Tri-layer GO-based devices illustrated non-polar resistive switching, which is a combination of unipolar and bipolar switching. Five-layer GO-based devices depicted complementary resistive switching having the lowest current values ~12 µA; and this structure is capable of resolving the sneak path issue. Both devices show good retention and endurance performance. Au Nps in tri-layer devices assisted the conducting path, whereas in five-layer devices, Au Nps layer worked as common electrodes between co-joined cells. These GO-based devices with Au Nps comprising different configuration are vital for practical applications of emerging non-volatile resistive memories.

PMID: 31641183 [PubMed - in process]

Caveolin-1 Regulates P2Y2 Receptor Signaling during Mechanical Injury in Human 1321N1 Astrocytoma.

Biomolecules. 2019 Oct 18;9(10):

Authors: Martínez M, Martínez NA, Miranda JD, Maldonado HM, Silva Ortiz WI

Abstract
Caveolae-associated protein caveolin-1 (Cav-1) plays key roles in cellular processes such as mechanosensing, receptor coupling to signaling pathways, cell growth, apoptosis, and cancer. In 1321N1 astrocytoma cells Cav-1 interacts with the P2Y2 receptor (P2Y2R) to modulate its downstream signaling. P2Y2R and its signaling machinery also mediate pro-survival actions after mechanical injury. This study determines if Cav-1 knockdown (KD) affects P2Y2R signaling and its pro-survival actions in the 1321N1 astrocytoma cells mechanical injury model system. KD of Cav-1 decreased its expression in 1321N1 cells devoid of or expressing hHAP2Y2R by ~88% and ~85%, respectively. Cav-1 KD had no significant impact on P2Y2R expression. Post-injury densitometric analysis of pERK1/2 and Akt activities in Cav-1-positive 1321N1 cells (devoid of or expressing a hHAP2Y2R) revealed a P2Y2R-dependent temporal increase in both kinases. These temporal increases in pERK1/2 and pAkt were significantly decreased in Cav-1 KD 1321N1 (devoid of or expressing a hHAP2Y2R). Cav-1 KD led to an ~2.0-fold and ~2.4-fold decrease in the magnitude of the hHAP2Y2R-mediated pERK1/2 and pAkt kinases' activity, respectively. These early-onset hHAP2Y2R-mediated signaling responses in Cav-1-expressing and Cav-1 KD 1321N1 correlated with changes in cell viability (via a resazurin-based method) and apoptosis (via caspase-9 expression). In Cav-1-positive 1321N1 cells, expression of hHAP2Y2R led to a significant increase in cell viability and decreased apoptotic (caspase-9) activity after mechanical injury. In contrast, hHAP2Y2R-elicited changes in viability and apoptotic (caspase-9) activity were decreased after mechanical injury in Cav-1 KD 1321N1 cells expressing hHAP2Y2R. These findings support the importance of Cav-1 in modulating P2Y2R signaling during mechanical injury and its protective actions in a human astrocytoma cell line, whilst shedding light on potential new venues for brain injury or trauma interventions.

PMID: 31635212 [PubMed - in process]

Microbiome Profiles of Ligature-Induced Periodontitis in Nonhuman Primates across the Life Span.

Infect Immun. 2019 06;87(6):

Authors: Kirakodu S, Chen J, Gonzalez Martinez J, Gonzalez OA, Ebersole J

Abstract
This investigation compared the microbiomes colonizing teeth during the initiation, progression, and resolution of periodontitis in nonhuman primates (Macaca mulatta) at different ages. Subgingival plaque samples were collected at baseline; 0.5, 1, and 3 months following ligature-induced periodontitis; and following naturally occurring disease resolution at 5 months. Samples were analyzed using 16S amplicon sequencing to identify bacterial profiles across age groups: young (<3 years of age), adolescent (3 to 7 years), adult (12 to 15 years), and aged (17 to 23 years). α-Diversity of the microbiomes was greater in the adult/aged samples than in the young/adolescent samples. β-Diversity of the samples demonstrated clear age group differences, albeit individual variation in microbiomes between animals within the age categories was noted. Phylum distributions differed between the young/adolescent animals and the adult/aged animals at each of the time points, showing an enrichment of the phyla Spirochetes, Fusobacteria, and Bacteroidetes associated with periodontitis. Major differences in the top 50 operational taxonomic units (OTUs) were noted in the young and adolescent microbiomes during initiation and progression postligation compared to the adult and aged animals. The proportions of a large number of species in the top 50 OTUs were lower at baseline and in resolved disease microbiomes in the young samples, while profiles in adolescent animals were more consistent with the disease microbiomes. Microbiome profiles for resolution for adults and aged animals appeared more resilient and generally maintained a pattern similar to that of disease. Use of the model can expand our understanding of the crucial interactions of the oral microbiome and host responses in periodontitis.

PMID: 30885927 [PubMed - indexed for MEDLINE]

Warming and pollutants interact to modulate octocoral immunity and shape disease outcomes.

Ecol Appl. 2019 Oct 19;:

Authors: Tracy AM, Weil E, Harvell CD

Abstract
Warming environments can alter the outcome of host-parasite relationships with important consequences for biodiversity. Warming often increases disease risk, and interactions with other environmental factors can intensify impacts by modifying the underlying mechanisms, such as host immunity. In coastal ecosystems, metal pollution is a pervasive stressor that influences disease and immunity in many organisms. Despite the crisis facing coral reefs, which stems in part from warming-associated disease outbreaks, the impacts of metal pollutants on scleractinian and octocoral disease are largely unknown. We investigated how warming oceans and copper pollution affect host immunity and disease risk for two diseases of the abundant Caribbean octocoral, the sea fan Gorgonia ventalina. Field surveys across a sediment copper concentration gradient in Puerto Rico revealed that cellular immunity of sea fans increased by 12.6% at higher sediment copper concentrations, while recovery from multifocal purple spots disease (MFPS) tended to decrease. MFPS severity in the field increased at warmer sites. In a controlled laboratory experiment, sea fans were inoculated with live cultures of a labyrinthulid parasite to test the interactive effects of temperature and copper on immune activation. As in the field, higher copper induced greater immunity, but the factorial design of the experiment revealed that copper and temperature interacted to modulate the immune response to the parasite: immune cell densities increased with elevated temperature at lower copper concentrations, but not with high copper concentrations. Tissue damage was also greater in treatments with higher copper and warmer temperatures. Field and lab evidence confirm that elevated copper hinders sea fan immune defenses against damaging parasites. Temperature and copper influenced host-pathogen interactions in octocorals by modulating immunity, disease severity and disease recovery. This is the first evidence that metal pollution affects processes influencing disease in octocorals and highlights the importance of immune mechanisms in environmentally-mediated disease outbreaks. Although coral conservation efforts must include a focus on global factors, such as rapid warming, reducing copper and other pollutants that compromise coral health on a local scale may help corals fight disease in a warming ocean.

PMID: 31628889 [PubMed - as supplied by publisher]

Passive Sampling of Persistent Organic Pollutants in Four Coastal Aquatic Systems of Puerto Rico: A Pilot Study.

Bull Environ Contam Toxicol. 2019 Oct 16;:

Authors: Rodríguez-Sierra CJ, Adelman D, Vojta Š, Mansilla-Rivera I, Lohmann R

Abstract
Little is known about the presence and effects of polychlorinated biphenyls (PCBs) and organochlorine pesticides (OCPs) in Puerto Rico's waters. Four coastal aquatic systems were investigated using low-density polyethylene passive sampling for PCBs and OCPs in water and its overlying air. The highest total freely dissolved and gaseous concentrations of PCBs were found in Guánica Bay, with 4000 pg/L and 270 pg/m3, respectively. Five OCPs were detected, mainly in water, with greatest concentrations (pg/L) in Guánica Bay: α-HCH (7400), p,p'-DDE (390), aldrin (2000), dieldrin (420), and endrin (77). The compound α-HCH was also measured at elevated water concentrations in Condado Lagoon (5700 pg/L) and Laguna Grande (2900 pg/L). Jobos Bay did not show values of concern for these persistence organic pollutants. Levels of PCBs and OCPs in water, particularly in Guánica Bay, exceeded USEPA ambient water quality criteria values representing a human health risk regarding consumption of aquatic organisms.

PMID: 31620816 [PubMed - as supplied by publisher]

Kounis Syndrome: A More Commonly Encountered Cause of Acute Coronary Syndrome.

Heart Views. 2019 Jul-Sep;20(3):122-125

Authors: Rodríguez-Ruiz C, Puig-Carrión G, Delgado-Nieves A, López-Candales A

Abstract
Kounis syndrome (KS) has been defined as cardiovascular symptoms that occur secondary to allergic or hypersensitivity insults. It was thought to be a rare condition but is now being more commonly identified as the cause of acute coronary events in patients without previous history of coronary artery disease (CAD). The most identified KS cases have been provoked by medications on elderly male patients. The purpose of this case report is to describe an unusual case of KS, triggered by a food allergen in a young female patient. This case reminds us that it is important to have a high index of suspicion, particularly in MI patients presenting without previous history of CAD. In this manner, an appropriate management, considering both cardiac and allergic components of KS, can be given without further delay and progression of symptoms.

PMID: 31620259 [PubMed]

The Storytelling Brain: How Neuroscience Stories Help Bridge the Gap between Research and Society.

J Neurosci. 2019 Oct 16;39(42):8285-8290

Authors: Martinez-Conde S, Alexander RG, Blum D, Britton N, Lipska BK, Quirk GJ, Swiss JI, Willems RM, Macknik SL

Abstract
Active communication between researchers and society is necessary for the scientific community's involvement in developing science-based policies. This need is recognized by governmental and funding agencies that compel scientists to increase their public engagement and disseminate research findings in an accessible fashion. Storytelling techniques can help convey science by engaging people's imagination and emotions. Yet, many researchers are uncertain about how to approach scientific storytelling, or feel they lack the tools to undertake it. Here we explore some of the techniques intrinsic to crafting scientific narratives, as well as the reasons why scientific storytelling may be an optimal way of communicating research to nonspecialists. We also point out current communication gaps between science and society, particularly in the context of neurodiverse audiences and those that include neurological and psychiatric patients. Present shortcomings may turn into areas of synergy with the potential to link neuroscience education, research, and advocacy.

PMID: 31619498 [PubMed - in process]

The impact of polar fraction of the fine particulate matter on redox responses in different rat tissues.

Environ Sci Pollut Res Int. 2019 Oct 15;:

Authors: de Paula Ribeiro J, Kalb AC, de Bastos Maya S, Gioda A, Martinez PE, Monserrat JM, Jiménez-Vélez BD, Gioda CR

Abstract
Particulate matter (PM) contains different chemical substances that have been associated with health effects and an increased risk of mortality due to their toxicity. In this study, fine particulate matter (PM2.5) samples were collected in a region with rural characteristics (Seropédica (Se)) and another with some industries (Duque de Caxias (DC)) (Brazil, RJ). Rats were exposed to PM2.5 extracts daily for 25 days at different dilutions: 10×, 5×, and a concentrated solution (CS). Biochemical analyses were investigated for total antioxidant capacity (ACAP), lipid peroxidation (LPO) levels, reduced glutathione (GSH) concentration, activity of glutamate cysteine ligase (GCL), and activity of glutathione S-transferase (GST). The liver showed a significant increase in GCL (DC-5×, DC-CS and Se-CS) and GST activities (DC-CS and Se-CS) in both regions when compared to the control group. In the renal cortex, GCL activity decreased in most of the tested groups while GST activity increased only in the 5× groups of both regions (DC and Se). In the renal medulla, GCL activity decreased for Se-10× and DC-CS but increased for Se-5×, and GST activity increased in the Se-10×, DC-5×, and DC-CS groups. Lung GCL increased in all groups for both regions. Moreover, this organ also showed an increase in GST activity when higher metal concentrations were present (5× and CS). TBARS levels were increased for all tissues in most tested concentrations. These data indicate that soluble compounds (e.g., metals) from PM2.5 sampled in areas with different pollution indexes can change the redox status and cause damage to different tissues.

PMID: 31617135 [PubMed - as supplied by publisher]

Multi-cohort modeling strategies for scalable globally accessible prostate cancer risk tools.

BMC Med Res Methodol. 2019 Oct 15;19(1):191

Authors: Tolksdorf J, Kattan MW, Boorjian SA, Freedland SJ, Saba K, Poyet C, Guerrios L, De Hoedt A, Liss MA, Leach RJ, Hernandez J, Vertosick E, Vickers AJ, Ankerst DP

Abstract
BACKGROUND: Online clinical risk prediction tools built on data from multiple cohorts are increasingly being utilized for contemporary doctor-patient decision-making and validation. This report outlines a comprehensive data science strategy for building such tools with application to the Prostate Biopsy Collaborative Group prostate cancer risk prediction tool.
METHODS: We created models for high-grade prostate cancer risk using six established risk factors. The data comprised 8492 prostate biopsies collected from ten institutions, 2 in Europe and 8 across North America. We calculated area under the receiver operating characteristic curve (AUC) for discrimination, the Hosmer-Lemeshow test statistic (HLS) for calibration and the clinical net benefit at risk threshold 15%. We implemented several internal cross-validation schemes to assess the influence of modeling method and individual cohort on validation performance.
RESULTS: High-grade disease prevalence ranged from 18% in Zurich (1863 biopsies) to 39% in UT Health San Antonio (899 biopsies). Visualization revealed outliers in terms of risk factors, including San Juan VA (51% abnormal digital rectal exam), Durham VA (63% African American), and Zurich (2.8% family history). Exclusion of any cohort did not significantly affect the AUC or HLS, nor did the choice of prediction model (pooled, random-effects, meta-analysis). Excluding the lowest-prevalence Zurich cohort from training sets did not statistically significantly change the validation metrics for any of the individual cohorts, except for Sunnybrook, where the effect on the AUC was minimal. Therefore the final multivariable logistic model was built by pooling the data from all cohorts using logistic regression. Higher prostate-specific antigen and age, abnormal digital rectal exam, African ancestry and a family history of prostate cancer increased risk of high-grade prostate cancer, while a history of a prior negative prostate biopsy decreased risk (all p-values < 0.004).
CONCLUSIONS: We have outlined a multi-cohort model-building internal validation strategy for developing globally accessible and scalable risk prediction tools.

PMID: 31615451 [PubMed - in process]

The Role of Adenine Nucleotide Translocase in the Assembly of Respiratory Supercomplexes in Cardiac Cells.

Cells. 2019 Oct 13;8(10):

Authors: M Parodi-Rullán R, Chapa-Dubocq X, Guzmán-Hernández R, Jang S, A Torres-Ramos C, Ayala-Peña S, Javadov S

Abstract
Individual electron transport chain complexes have been shown to assemble into the supramolecular structures known as the respiratory chain supercomplexes (RCS). Several studies reported an associative link between RCS disintegration and human diseases, although the physiological role, structural integrity, and mechanisms of RCS formation remain unknown. Our previous studies suggested that the adenine nucleotide translocase (ANT), the most abundant protein of the inner mitochondrial membrane, can be involved in RCS assembly. In this study, we sought to elucidate whether ANT knockdown (KD) affects RCS formation in H9c2 cardiomyoblasts. Results showed that genetic silencing of ANT1, the main ANT isoform in cardiac cells, stimulated proliferation of H9c2 cardiomyoblasts with no effect on cell viability. ANT1 KD reduced the ΔΨm but increased total cellular ATP levels and stimulated the production of total, but not mitochondrial, reactive oxygen species. Importantly, downregulation of ANT1 had no significant effects on the enzymatic activity of individual ETC complexes I-IV; however, RCS disintegration was stimulated in ANT1 KD cells as evidenced by reduced levels of respirasome, the main RCS. The effects of ANT1 KD to induce RCS disassembly was not associated with acetylation of the exchanger. In conclusion, our study demonstrates that ANT is involved in RCS assembly.

PMID: 31614941 [PubMed - in process]

The longitudinal effect of early-life sensation seeking on gambling and gambling problems among Puerto Rican young adults.

Psychol Addict Behav. 2019 Oct 14;:

Authors: Levy NS, Duarte CS, Segura LE, Santaella-Tenorio J, Okuda M, Wall M, Chen C, Ramos-Olazagasti MA, Canino G, Bird H, Martins SS

Abstract
Sensation seeking has been proposed as a risk factor for gambling and gambling problems; however, existing evidence for a relationship between sensation seeking and gambling behaviors is inconclusive and data are lacking for emerging adults and racial and ethnic minorities. In this longitudinal study, we explored the association between developmental trajectories of sensation seeking in childhood and adolescence and gambling and gambling problems in early adulthood in individuals of Puerto Rican origin. Gambling data were collected during 2014-2018 from a subsample of participants in the Boricua Youth Study who were recruited in the South Bronx of New York City and in San Juan and Caguas, Puerto Rico. Sensation seeking was measured using a 10-item instrument modified from the scale created by Russo et al. for use in children as young as 5 years old. Developmental trajectories of age-adjusted sensation seeking were created using growth mixture models. Gambling and gambling problems were assessed based on the Canadian Adolescent Gambling Inventory (CAGI) Version 1.09. Data were analyzed using descriptive methods and multivariable logistic regression. Individuals in the high sensation-seeking class had lower adjusted odds of past-year gambling (OR = .36; 95% confidence interval [.14, .92]) than did those in the normative sensation-seeking class, whereas no differences were observed for individuals in the low and accelerated classes. No relationship was found between sensation seeking and past-year gambling problems. Given the severe consequences of early initiation of gambling and gambling problems, other early life risk factors and alternative hypotheses for the elevated prevalence of gambling problems in young adults and racial and ethnic minority populations should be explored. (PsycINFO Database Record (c) 2019 APA, all rights reserved).

PMID: 31613115 [PubMed - as supplied by publisher]

Biological therapy for pustular psoriasis: a systematic review.

Int J Dermatol. 2019 Oct 15;:

Authors: Falto-Aizpurua LA, Martin-Garcia RF, Carrasquillo OY, Nevares-Pomales OW, Sánchez-Flores X, Lorenzo-Rios D

Abstract
BACKGROUND: The anecdotic evidence of the benefits from biologic agents for psoriasis is extensive. However, data on the efficacy of biologic agents for pustular psoriasis are limited.
METHODS: To update the data on the efficacy and safety of biologic agents for the management of pustular psoriasis. A systematic review of published data regarding biologic therapies on PubMED database, used in the management of pustular psoriasis from 2012 was undertaken.
RESULTS: A total of 209 articles were identified, and 43 articles were selected for inclusion. TNF-α inhibitors were used in 205 patients, and 86 patients received ustekinumab, secukinumab, brodalumab, ixekizumab and IL-1 inhibitors. Overall response was favorable for most modalities. No serious adverse events were reported. Inconsistent measures of treatment response and study variability limited the overall evaluation of data.
CONCLUSIONS: Infliximab and ustekinumab have the most evidence of efficacy and safety for the treatment of pustular psoriasis. Recent evidence supports the use of IL-17 antagonists. Prospective controlled and comparative trials are needed to further explore the efficacy and safety of biologic agents in order to establish objective recommendations for the management of this challenging condition.

PMID: 31612467 [PubMed - as supplied by publisher]

The Vital Role of Professionalism in Physical Medicine and Rehabilitation.

Am J Phys Med Rehabil. 2019 Oct 11;:

Authors: Silver JK, Cuccurullo S, Weiss LD, Visco C, Oh-Park M, Karimi DP, Frontera WR, Fleming TK, Bosques G, Bhatnagar S, Ambrose AF, Nguyen VQ

Abstract
Professionalism in medicine is universally embraced, and it is the foundation for core competencies in medical education, clinical practice, and research. Physical Medicine and Rehabilitation physicians must master a complex body of knowledge and use this to responsibly care for patients. Rehabilitation professionals work in various settings; however, each one must establish and maintain ethical standards consistent with the specialty and national standards. For example, the Accreditation Council for Graduate Medical Education lists professionalism as 1 of its 6 core competencies which trainees must master. There is a growing interest in professionalism and some of the ethical issues that it encompasses. This report provides a general overview of professionalism. Future reports are needed, and there is an opportunity to consider many facets of professionalism in greater detail.

PMID: 31609732 [PubMed - as supplied by publisher]

The association between, depression, anxiety and mortality in older people across eight low- and middle-income countries: results from the 10/66 cohort study.

Int J Geriatr Psychiatry. 2019 Oct 13;:

Authors: Wu YT, Kralj C, Acosta D, Guerra M, Huang Y, Jotheeswaran AT, Jimenez-Velazquez IZ, Liu Z, Llibre Rodriguez JJ, Salas A, Sosa AL, Alkholy R, Prince M, Prina AM

Abstract
OBJECTIVES: Depression and anxiety are common mental disorders in later life. Few population-based studies have investigated their potential impacts on mortality in low- and middle-income countries (LMICs). The aim of this study is to examine the associations between depression, anxiety, their comorbidity and mortality in later life using a population-based cohort study across eight LMICs.
METHODS: This analysis was based on the 10/66 cohort study including 15991 people aged 65 or above in Cuba, Dominican Republic, Venezuela, Mexico, Peru, Puerto Rico, China and India, with an average follow-up time of 3.9 years. Sub-threshold and clinical levels of depression were determined using EURO-D and ICD-10 criteria and anxiety was based on GMS-AGECAT. Cox proportional hazard modelling was used to estimate how having depression, anxiety or both was associated with mortality adjusting for sociodemographic and health factors.
RESULTS: Participants with clinical depression (Hazard Ratio (HR): 1.45; 95%CI:1.24-1.70) and sub-threshold anxiety (HR: 1.26; 95%CI:1.15-1.38) had higher risk of mortality than those without the conditions after adjusting for sociodemographic factors and health conditions. Co-morbidity of depression and anxiety was associated with a 30% increased risk of mortality but the effect sizes varied across countries (Higgins I2 =58.8%), with the strongest association in India (HR: 1.99; 95%CI:1.21-3.27).
CONCLUSIONS: Depression and anxiety appear to be associated with mortality in older people living in LMICs. Variation in effect sizes may indicate different barriers to health service access across countries. Future studies may investigate underlying mechanisms and identify potential interventions to reduce the impact of common mental disorders.

PMID: 31608478 [PubMed - as supplied by publisher]

Insights into intestinal regeneration signaling mechanisms.

Dev Biol. 2019 Oct 09;:

Authors: Bello SA, Torres-Gutiérrez V, Rodríguez-Flores EJ, Toledo-Román EJ, Rodríguez N, Díaz-Díaz LM, Vázquez-Figueroa LD, Cuesta JM, Grillo-Alvarado V, Amador A, Reyes J, García-Arrarás JE

Abstract
The cellular mechanisms underlying the amazing ability of sea cucumbers to regenerate their autotomized intestines have been widely described by us and others. However, the signaling pathways that control these mechanisms are unknown. Previous studies have shown that Wnt homologs are upregulated during early intestinal regenerative stages, suggesting that the Wnt/β-catenin pathway is active during this process. Here, we used small molecules, putative disruptors of the Wnt pathway, to determine the potential role of the canonical Wnt pathway on intestine regeneration in the sea cucumber Holothuria glaberrima. We evaluated their effects in vivo by using histological analyses for cell dedifferentiation, cell proliferation and apoptosis. We found that iCRT14, an alleged Wnt pathway inhibitor, decreased the size of the regenerating intestine, while LiCl, a presumed Wnt pathway activator, increased its size. The possible cellular mechanisms by which signaling pathway disruptors affect the gut rudiment size were further studied in vitro, using cultures of tissue explants and additional pharmacological agents. Among the tested signaling modulators that act through GSK-3 inhibition, LiCl, 1-Azakenpaullone, and CHIR99021 were found to increase muscle cell dedifferentiation, while iCRT14 blocked cell dedifferentiation. Differently, cell proliferation was reduced by all GSK-3 inhibitors, as well as by iCRT14 and C59, which interferes with Wnt ligand secretion. The in vivo temporal and spatial pattern of β-catenin activity was determined using an antibody against phosphorylated β-catenin and shown to correlate with cell proliferative activity. In vitro treatment using C59 decreased the number of cells immunostained for nuclear phosphorylated β-catenin. Our results showed that the cell dedifferentiation observed during intestinal regeneration can be decoupled from the cell proliferation event and that these cellular events can be modulated by particular signaling pathway inhibitors and activators. These results open the door for future studies where the cellular signaling pathways involved at each regeneration stage can be determined.

PMID: 31605680 [PubMed - as supplied by publisher]

Increased interactions and engulfment of dendrites by microglia precede Purkinje cell degeneration in a mouse model of Niemann Pick Type-C.

Sci Rep. 2019 Oct 11;9(1):14722

Authors: Kavetsky L, Green KK, Boyle BR, Yousufzai FAK, Padron ZM, Melli SE, Kuhnel VL, Jackson HM, Blanco RE, Howell GR, Soto I

Abstract
Niemann Pick Type-C disease (NPC) is an inherited lysosomal storage disease (LSD) caused by pathogenic variants in the Npc1 or Npc2 genes that lead to the accumulation of cholesterol and lipids in lysosomes. NPC1 deficiency causes neurodegeneration, dementia and early death. Cerebellar Purkinje cells (PCs) are particularly hypersensitive to NPC1 deficiency and degenerate earlier than other neurons in the brain. Activation of microglia is an important contributor to PCs degeneration in NPC. However, the mechanisms by which activated microglia promote PCs degeneration in NPC are not completely understood. Here, we are demonstrating that in the Npc1nmf164 mouse cerebellum, microglia in the molecular layer (ML) are activated and contacting dendrites at early stages of NPC, when no loss of PCs is detected. During the progression of PCs degeneration in Npc1nmf164 mice, accumulation of phagosomes and autofluorescent material in microglia at the ML coincided with the degeneration of dendrites and PCs. Feeding Npc1nmf164 mice a western diet (WD) increased microglia activation and corresponded with a more extensive degeneration of dendrites but not PC somata. Together our data suggest that microglia contribute to the degeneration of PCs by interacting, engulfing and phagocytosing their dendrites while the cell somata are still present.

PMID: 31605022 [PubMed - in process]