Pilot therapeutic education program in multiple system atrophy: Safety, quality of life and satisfaction from a national registry based longitudinal study.

BACKGROUND: Therapeutic education programs are effective in several chronic conditions. However, evidence is lacking in multiple system atrophy (MSA). We aimed to assess efficacy and safety of a comprehensive therapeutic education program in people with MSA (PwMSA) and their caregivers. METHODS: In this prospective longitudinal study we included 16 PwMSA and their main caregivers in 4 groups of 4 dyads each. The program consisted of eight 60-min interdisciplinary sessions: introduction, orthostatic hypotension, speech therapy, gait and respiratory physiotherapy, psychological support, urinary dysfunction, occupational therapy/social work. UMSARS, NMSS, PDQ39, EQ5 and Zarit scales were administered at baseline and 6 months later. After each session participants filled-out a modified EduPark satisfaction questionnaire and a Likert scale. Educational material was generated for each session after suggestions by participants. RESULTS: At baseline PwMSA and caregivers were comparable in age and sex, with significant correlation between UMSARS-IV (disability) and PDQ39 (quality of life). Adherence to sessions was of 94,92 %. Total modified EduPark scores and Likert scales did not differ in PwMSA vs. caregivers, mild-moderate vs. severe-advanced cases or between genders. The significant difference in satisfaction across sessions (p = 0.03) was driven by higher scores in speech, respiratory and occupational therapy sessions. Longitudinally there was no significant worsening in any scale, nor a significant increase post-vs. pre-program in the number of consultations. CONCLUSIONS: The healthcare education program in MSA was feasible, satisfactory, and safe for patients and caregivers. The educational material of the program is being forwarded to incident MSA cases attending our clinic.

Consensus on the management of complications of cirrhosis of the liver in pediatrics.

The Asociación Mexicana de Hepatología A.C. carried out the Consensus on the Management of Complications of Cirrhosis of the Liver in Pediatrics to provide physicians with useful information for treating said complications. A group of pediatric gastroenterologists and experts in nutrition, nephrology, and infectious diseases participated and reviewed the medical literature. The Delphi method was applied to obtain the level of agreement on the statements that were formulated. The statements were sent to the participants to be analyzed and voted upon, after which they were discussed in virtual sessions, and the final versions were produced. The aim of the consensus results was to issue indications for the management of pediatric patients with liver cirrhosis, to prevent or control complications.

Multidisciplinary consensus statement on the clinical management of patients with stage III non-small cell lung cancer.

Stage III non-small cell lung cancer (NSCLC) is a very heterogeneous disease that encompasses patients with resected, potentially resectable and unresectable tumours. To improve the prognostic capacity of the TNM classification, it has been agreed to divide stage III into sub-stages IIIA, IIIB and IIIC that have very different 5-year survival rates (36, 26 and 13%, respectively). Currently, it is considered that both staging and optimal treatment of stage III NSCLC requires the joint work of a multidisciplinary team of expert physicians within the tumour committee. To improve the care of patients with stage III NSCLC, different scientific societies involved in the diagnosis and treatment of this disease have agreed to issue a series of recommendations that can contribute to homogenise the management of this disease, and ultimately to improve patient care.

Sacral neuromodulation for fecal incontinence in Latin America: initial results of a multicenter study.

BACKGROUND: Sacral neuromodulation (SNM) is a widely used therapeutic option for fecal incontinence (FI). Larger series are mainly from Western countries, while few reports address the results of SNM in less developed or less wealthy countries. The aim of the present study was to evaluate the efficacy of SNM in patients with FI in Latin America. METHODS: A retrospective study was conducted on patients with FI who had SNM between 2009 and 2016 at 15 specialized colorectal surgery centers in Latin America. Main outcomes measures were functional outcomes, postoperative complications, requirement of revisional surgery, and requirement of device removal. All patients had failed conservative management and had clinical assessment including recording of the validated Cleveland Clinic Florida Fecal Incontinence Score (CCF-FIS) and, when available, anal manometry and endoanal ultrasound. Patients were followed up for a median of 36.7 (1-84) months. RESULTS: One hundred and thirty-one patients [119 females, median age of 62.2 (range 19-87) years] were included. The most common etiology of FI was obstetric injury (n = 60; 45.8%). After successful test lead implantation, the stimulator was permanently placed in 129 patients (98.5%). One patient failed to respond in the test phase and one patient did not proceed to permanent implantation for insurance reasons. Nineteen patients (14.7%) had 19 complications including infection (n = 5, 3.8%), persistent implant site pain (n = 5, 3.8%), generator/lead dislodgment (n = 5, 3.8%), malfunctioning device (n = 3, 2.3%), and hematoma (n = 1, 0.7%). Reimplantation after the first and second stages was necessary in 2 (1.5%) and 3 patients (2.3%), respectively. The device removal rate was 2.2%. At a median follow-up of 36.7 (range 1-84) months, the CCF-FIS significantly improved from a preoperative baseline of 15.9 ± 2.98 to 5.2 ± 3.92 (95%CI: 15.46 vs 4.43; p < 0.0001). Overall, 90% of patients rated their improvement as "significant". CONCLUSIONS: Sacral nerve stimulation for FI is safe and efficient, even in less wealthy or less developed countries.

Self-diffusion in two-dimensional quasimagnetized rotating dusty plasmas.

The self-diffusion phenomenon in a two-dimensional dusty plasma at extremely strong (effective) magnetic fields is studied experimentally and by means of molecular dynamics simulations. In the experiment the high magnetic field is introduced by rotating the particle cloud and observing the particle trajectories in a corotating frame, which allows reaching effective magnetic fields up to 3000 T. The experimental results confirm the predictions of the simulations: (i) superdiffusive behavior is found at intermediate timescales and (ii) the dependence of the self-diffusion coefficient on the magnetic field is well reproduced.

Dendritic Immunotherapy Improvement for an Optimal Control Murine Model.

Therapeutic protocols in immunotherapy are usually proposed following the intuition and experience of the therapist. In order to deduce such protocols mathematical modeling, optimal control and simulations are used instead of the therapist's experience. Clinical efficacy of dendritic cell (DC) vaccines to cancer treatment is still unclear, since dendritic cells face several obstacles in the host environment, such as immunosuppression and poor transference to the lymph nodes reducing the vaccine effect. In view of that, we have created a mathematical murine model to measure the effects of dendritic cell injections admitting such obstacles. In addition, the model considers a therapy given by bolus injections of small duration as opposed to a continual dose. Doses timing defines the therapeutic protocols, which in turn are improved to minimize the tumor mass by an optimal control algorithm. We intend to supplement therapist's experience and intuition in the protocol's implementation. Experimental results made on mice infected with melanoma with and without therapy agree with the model. It is shown that the dendritic cells' percentage that manages to reach the lymph nodes has a crucial impact on the therapy outcome. This suggests that efforts in finding better methods to deliver DC vaccines should be pursued.

Bilevel Parameter Learning for Higher-Order Total Variation Regularisation Models.

We consider a bilevel optimisation approach for parameter learning in higher-order total variation image reconstruction models. Apart from the least squares cost functional, naturally used in bilevel learning, we propose and analyse an alternative cost based on a Huber-regularised TV seminorm. Differentiability properties of the solution operator are verified and a first-order optimality system is derived. Based on the adjoint information, a combined quasi-Newton/semismooth Newton algorithm is proposed for the numerical solution of the bilevel problems. Numerical experiments are carried out to show the suitability of our approach and the improved performance of the new cost functional. Thanks to the bilevel optimisation framework, also a detailed comparison between TGV 2 and ICTV is carried out, showing the advantages and shortcomings of both regularisers, depending on the structure of the processed images and their noise level.

Feeding habits of the speckled guitarfish Rhinobatos glaucostigma (Elasmobranchii: Rhinobatidae).

The stomachs of 464 speckled guitarfish Rhinobatos glaucostigma were sampled from the south-eastern Gulf of California (GC) to determine diet composition. Numerical indices and prey-specific index of relative importance ((%I)PSIR ) were used to determine the feeding strategy of the species. An analysis of similarity (ANOSIM) was used to determine differences in diet with respect to sex, season (dry or rainy) and maturity stages (immature or mature). The diversity and niche breadth (by sex, season and maturity) and a general trophic level were determined. The overall diet was dominated by shrimps ((%I)PSIR = 43.47), amphipods ((%I)PSIR = 18.89) and crabs ((%I)PSIR = 18.07). ANOSIM demonstrated differences in the diet by maturity and season, but not by sex. Rainy and dry season diets were dominated by shrimps and amphipods, respectively. Immature specimens fed mainly on amphipods, whereas mature fish preferred shrimps and crabs. Rhinobatos glaucostigma showed a narrow niche breadth with an intermediary trophic level (TL = 3.72) and can be considered as a secondary consumer in the soft-bottom demersal community of the south-east GC. Understanding the feeding habits and trophic level of R. glaucostigma is vital to help identify the segments of the population vulnerable to overfishing by artisanal and industrial fisheries, and to aid in conservation and management of this elasmobranch.

HMG20A is required for SNAI1-mediated epithelial to mesenchymal transition.

HMG20A is a high mobility group (HMG) domain containing protein homologous to HMG20B, a core subunit of the Lys-specific demethylase 1/REST co-repressor 1 (LSD1-CoREST) histone demethylase complex. Here, we show that HMG20A can replace HMG20B and, therefore, they are mutually exclusive subunits of the complex. Both proteins interact through a coiled-coil domain with BHC80, another subunit of the LSD1-CoREST complex. To investigate the functional differences between the two proteins, we performed transcriptomic analysis of HMG20A- and HMG20B-depleted cells. Analysis of the misregulated genes in HMG20A-knockdown cells evidenced a high proportion of genes related to the epithelial-to-mesenchymal transition (EMT) process. EMT occurs during embryonic development or during the course of malignant cancer progression and consists in the dynamic and reversible transitions between epithelial and mesenchymal phenotypes. We show that HMG20A together with LSD1 are required for SNAI1-dependent repression of epithelial genes and for (transforming growth factor ß) TGF-ß-triggered EMT. Importantly, HMG20A-depleted cells displayed reduced binding of LSD1 to epithelial gene promoters and increased methylation of lysine 4 of histone H3, suggesting a role of HMG20A in recruiting or in stabilizing the complex at the chromatin. SNAI1 and the TGF-ß-related transcription factor SMAD4 were found to be associated with the LSD1-CoREST complex containing HMG20A. Furthermore, we show that HMG20A-depleted cells displayed reduced motility and invasion activity. Finally, we show that expression of HMG20A correlates positively with mesenchymal markers and negatively with epithelial markers in human tumor samples. Taken together, our data demonstrate that HMG20A is essential for the mesenchymal phenotype.

Cytoplasmic interaction of the tumour suppressor protein hSNF5 with dynamin-2 controls endocytosis.

Human SNF5 (hSNF5; INI1, SMARCB1 or BAF47) is a component of the human SWI/SNF chromatin remodelling complex and a tumour suppressor mutated in rhabdoid tumours. It also associates with the integrase of the human immunodeficiency virus (HIV)-1. We show by fluorescence loss in photobleaching that hSNF5 is constantly shuttling between the nucleus and the cytoplasm, raising the question of what the role of hSNF5 is in the cytoplasm. Here, we demonstrate that hSNF5 directly interacts with the GTPase dynamin-2 (DNM2) in the cytoplasm. DNM2 is a large GTPase involved in endocytosis and vesicle dynamics, which has been related to HIV-1 internalization. We show that hSNF5 colocalizes with DNM2 in endocytic vesicles. Depletion of hSNF5, but not of other components of the SWI/SNF complex, destabilizes DNM2 and impairs DNM2-dependent endocytosis. Furthermore, we show that hSNF5 inhibits assembly-stimulated DNM2 GTPase activity but not basal GTPase activity in vitro. Altogether, these results indicate that hSNF5 affects both the stability and the activity of DNM2, uncovering an unexpected role of hSNF5 in modulating endocytosis, and open new perspectives in understanding the role of hSNF5 in tumour genesis.

The emerging of xylazine as a new drug of abuse and its health consequences among drug users in Puerto Rico.

During the last decade, the veterinary anesthetics have gained popularity as recreational drugs. The aim of this study was to document the use of "anestecia de caballo" (xylazine) and its consequences among drug users in Puerto Rico. The study combined a cross-sectional survey with 89 drug users and two focus groups conducted in Mayagüez with frontline drug treatment providers. Drug users were recruited from communities of the San Juan metropolitan area using a variety of ethnographic and outreach strategies. A short questionnaire developed for the study collected information on sociodemographics, xylazine use, and its consequences. The two focus groups were conducted to discuss the details related to xylazine use, its consequences, and utilization awareness. The sample comprised 63 males (70.8%) and 26 females with a mean age of 37.2 years. The mean number of years of drug use was 14.3, with a mean frequency of drug use of 5.9 times daily. More than 65% reported speedball as the principal drug of use. The prevalence of xylazine use was 80.7%. More than 42% of the sample used xylazine in a mixture with speedball. The main route of administration of xylazine was injection but 14% reported the use of xylazine by inhalation. More than 35% of the sample reported skin lesions and 21.1% reported at least one overdose episode. Multiple logistic regression analysis revealed that males (OR = 3.47, CI = 1.10-12.00) and those who reported speedball as their main drug of use (OR = 9.34, CI = 2.51-34.70) were significantly more likely to be xylazine users. Focus groups revealed that drug users claimed to recognize the presence of xylaxine in a mixture of speedball based on its effects, taste, the color of the drug (dark brown), and its odor. In conclusion, the use of xylazine among drug users in Puerto Rico seems to be an emerging trend with potentially serious health consequences.

The chromatin remodeling factor CHD8 interacts with elongating RNA polymerase II and controls expression of the cyclin E2 gene.

CHD8 is a chromatin remodeling ATPase of the SNF2 family. We found that depletion of CHD8 impairs cell proliferation. In order to identify CHD8 target genes, we performed a transcriptomic analysis of CHD8-depleted cells, finding out that CHD8 controls the expression of cyclin E2 (CCNE2) and thymidylate synthetase (TYMS), two genes expressed in the G1/S transition of the cell cycle. CHD8 was also able to co-activate the CCNE2 promoter in transient transfection experiments. Chromatin immunoprecipitation experiments demonstrated that CHD8 binds directly to the 5' region of both CCNE2 and TYMS genes. Interestingly, both RNA polymerase II (RNAPII) and CHD8 bind constitutively to the 5' promoter-proximal region of CCNE2, regardless of the cell-cycle phase and, therefore, of the expression of CCNE2. The tandem chromodomains of CHD8 bind in vitro specifically to histone H3 di-methylated at lysine 4. However, CHD8 depletion does not affect the methylation levels of this residue. We also show that CHD8 associates with the elongating form of RNAPII, which is phosphorylated in its carboxy-terminal domain (CTD). Furthermore, CHD8-depleted cells are hypersensitive to drugs that inhibit RNAPII phosphorylation at serine 2, suggesting that CHD8 is required for an early step of the RNAPII transcription cycle.

Kinematic study of refraction properties of a ZnSe-ZnTe dielectric grating.

The plane wave expansion method is applied to determine the thickness of the ZnSe-ZnTe slabs in a semi-infinite dielectric grating in such a way that the maximum reflectivity of the system is obtained. In this way the potential of the ZnSe-ZnTe system for applications in CdSe ultra thin quantum well based monolithic II-VI Vertical Cavity Surface Emitting Laser for the green spectral region is demonstrated. A kinematic analysis of the thickness-dependent refraction at the boundary between a ZnSe-ZnTe semi-infinite one dimensional photonic crystal and a homogeneous material in transverse magnetic polarization and oblique incidence case is presented.

Hepatitis C in Puerto Rico: a time for public health action

Studies investigating the seroprevalence of HCV infection have been carried out in diverse populations, showing an estimated worldwide prevalence of 3%. A seroprevalence survey conducted among randomly selected non-institutionalized adults aged 21-64 years in San Juan, Puerto Rico in 2001-2002 revealed that 6.3% were positive for HCV antibodies. These data suggest that Puerto Ricans are burdened with a significantly greater prevalence of HCV infection compared to the general United States population aged 20-69 years (0.9%-4.3%). This article illustrates data from different sources that taken together establish the need to start addressing HCV infection in Puerto Rico with prompt and decisive public health actions. Some of these include (1) establish hepatitis C prevention as a priority for state and municipal public health authorities, (2) raise awareness and educate target populations about HCV transmission and prevention, (3) increase clinician awareness of the HCV reporting system and the epidemiology and management of hepatitis C, (4) increase availability of diagnosis and treatment facilities, (5) increase access to effective drug treatment services, and (6) develop appropriate control measures to help reduce continued transmission in correctional settings.

A nucleosome interaction module is required for normal function of Arabidopsis thaliana BRAHMA.

The BRAHMA (BRM) gene encodes the SNF2-type ATPase of the putative Arabidopsis thaliana SWI/SNF chromatin remodelling complex. This family of ATPases is characterized by the presence of a conserved catalytic domain and an arrangement of auxiliary domains, whose functions in the remodelling activity remains unclear. Here, we characterize, at the molecular and functional level, the carboxy-terminal part of Arabidopsis BRM. We have found three DNA-binding regions that bind various free DNA and nucleosomal probes with different specificity. One of these regions contains an AT-hook motif. The carboxy terminus also contains a bromodomain able to bind histones H3 and H4. We propose that this array of domains constitute a nucleosome interaction module that helps BRM to interact with its substrate. We also characterize an Arabidopsis mutant that expresses a BRM protein lacking the last 454 amino acid residues (BRM-DeltaC), encompassing the bromodomain and two of the three DNA-binding activities identified. This mutant displays an intermediate phenotype between those of the wild-type and a null allele mutant, suggesting that the nucleosome interaction module is required for the normal function of BRM but it is not essential for the remodelling activity of BRM-containing SWI/SNF complexes.

Correlates of early sexual activity among Hispanic children in middle adolescence

OBJECTIVE: We analyzed early sexual activity among Hispanic 14 to 15-year-old adolescents residing in a poor neighborhood in Puerto Rico. METHODS: Information from a sample of 325 adolescents was collected from a randomized sample of community households. Logistic regression analysis was used to identify the variables that help explained adolescents' sexual behavior. RESULTS: Adolescents whose parents reported poor communication and poor parent control were more likely to engage in early sexual activity that those peers that did not report this type of family relationship. Adolescents who reported poor parent bonding and lack of discipline were more likely to engage in early sexual relationships. CONCLUSIONS: Intervention and prevention programs need to be aware and address the role of the Hispanic culture in gender differences in early sexual activity in adolescence. If sexual norms related to gender role are changing in Puerto Rico, is a question that needs to be answered in future research.

Alcohol use among adolescents in Puerto Rico: the influence of physical and social neighborhood disorder.

INTRODUCTION: The characteristics of social settings are increasingly being recognized as important factors influencing the health of individuals. This study examines the association of neighborhood physical and social disorganization with alcohol consumption in a sample of adolescents 12- to 15-years-old residing in communities of the San Juan metropolitan area with high availability of illicit drugs. METHODS: The sampling frame was developed encompassing all census sectors in three municipalities of the San Juan metropolitan area with outdoor illegal drug-selling areas operating within them. Consent from parents and their adolescent offspring was obtained from 691 of these households for a response rate of 96%. Alcohol use was measured by asking adolescents if they had consumed alcohol during the last 12 months. Neighborhood social disorganization included hearing gunfire in the neighborhood, seeing neighbors selling stolen merchandise and drugs, vandalism, neighbors using alcohol and drugs, and seeing persons carrying weapons. Neighborhood physical disorganization included the presence of abandoned vehicles and buildings in the neighborhood, graffiti, and places where people go to inject drugs. RESULTS: Multiple logistic regression analysis revealed that older participants were more likely to use alcohol. Neighborhood social disorder was significantly associated with alcohol use. The strong positive gradient between neighborhood social disorder and alcohol use remained highly significant after controlling by sociodemographic characteristics. In contrast, neighborhood physical disorder was not significantly associated with alcohol use. CONCLUSION: These findings suggest that social signs of neighborhood disorganization have a more direct influence over adolescents' behaviors than the physical signs. Health professionals need to be cognizant of the strong effects that social environments have on adolescents and develop strategies to address these when intervening with adolescents.

Risk and protective factors associated with youth violence among secondary school students in a nationally representative sample in Puerto Rico

During the past decade, youth violence has received increasing attention as a major public health issue in Puerto Rico as well as in the United States. This study sought to identify risk and protective factors of youth violence in a representative sample of school adolescents in Puerto Rico. Risk and protective factors were grouped into five domains: individual, family, peer group, school and community. From a total of 2,385 participants, 10.7 reported at least one violent behavior and 3.4 reported two or more violent behaviors. In multiple regression analysis the risk factors identified were male gender, junior grade students, having a favorable attitude towards antisocial behavior, use of ecstasy, involvement with antisocial peers and reporting antisocial parents. Participation in family decisions was the only protective factor associated with violence. Findings from this study could have important implications for the development of preventive programs for the adolescent population in Puerto Rico

Risk and protective factors associated with youth violence among secondary school students in a nationally representative sample in Puerto Rico.

During the past decade, youth violence has received increasing attention as a major public health issue in Puerto Rico as well as in the United States. This study sought to identify risk and protective factors of youth violence in a representative sample of school adolescents in Puerto Rico. Risk and protective factors were grouped into five domains: individual, family, peer group, school and community. From a total of 2,385 participants, 10.7% reported at least one violent behavior and 3.4% reported two or more violent behaviors. In multiple regression analysis the risk factors identified were male gender, junior grade students, having a favorable attitude towards antisocial behavior, use of ecstasy, involvement with antisocial peers and reporting antisocial parents. Participation in family decisions was the only protective factor associated with violence. Findings from this study could have important implications for the development of preventive programs for the adolescent population in Puerto Rico.