Association of polymorphisms rs2303729, rs10880, and rs1131620 of LTBP4 with sarcopenia in elderly patients with type 2 diabetes mellitus.

BACKGROUND: Latent TGFß binding protein 4 (LTBP4) modifies skeletal muscle function, and polymorphisms in this gene have been associated with a longer ambulation time in patients with Duchenne muscular dystrophy. However, no studies associate these polymorphisms with an acquired muscle condition. AIM: The study aims to determine whether three functional variants within the LTBP4 were associated with sarcopenia in patients with type 2 diabetes mellitus (T2DM). SUBJECTS AND METHODS: We performed an analysis with 144 elderly individuals with T2DM, including 101 without sarcopenia and 43 with sarcopenia. Polymorphism frequency was determined by real-time PCR allelic discrimination TaqMan assay. RESULTS: Under different genetic models, the univariant analysis did not show a significant association of any polymorphism with sarcopenia. But the multivariate model analysis showed that variant rs1131620 (OR 7.852, 95% CI 1.854-33.257, p = 0.005) was significantly associated with sarcopenia under a dominant model. Under the same analysis, the variants rs2303729 and rs10880 had a more discrete association (OR 3.537 95% CI 1.078-11.607, p = 0.037; OR 5.008, 95% CI 1.120-22.399, p = 0.035, respectively). CONCLUSIONS: Our study highlights the importance of studying LTBP4 polymorphisms associated with sarcopenia. These findings suggest that the rs1131620 polymorphism of the LTBP4 may be part of the observed sarcopenia process in patients with T2DM.

Serum concentrations of apelin-17 isoform vary in accordance to blood pressure categories in individuals with obesity class 3.

Background: The aim of this study was to investigate if serum concentrations of apelin-36, apelin-17, apelin-13 or apelin-12 were different in obesity class 3 individuals with hypertension, when compared to those without hypertension (normal or high-normal).Subjects and Methods: Twenty six individuals with obesity class 3-related hypertension and thirty three individuals without hypertension, who were divided in individuals with normal (n = 23) or with high-normal (n = 10) blood pressure (BP) were analyzed. All individuals presented obesity class 3, without diabetes mellitus. Measurements of all apelin isoforms were performed using enzyme-linked immunosorbent assay kits. Analysis of differences between groups of Apelin isoform concentrations was performed by a One-way ANOVA, with a Tukey test post hoc.Results: The individuals of the hypertensive group presented a slightly lower serum concentration of all apelin isoforms, but these differences were not statistically significant. These results were more evident when the group of patients without hypertension were divided based in normal and high-normal BP, observing that apelin-17 isoform were higher in individuals with high-normal BP in comparison to subjects with normal BP (P = 0.018); concentrations were also higher when compared to subjects with hypertension (P = 0.004).Conclusions: To our knowledge, this is the first study regarding the differences of apelin-17 isoform concentrations in individuals pertaining to different categories of BP, who presented obesity class 3. The group of patients that presented hypertension showed a lower concentration of all isoforms. This observation could be due to the fact that these patients were taking antihypertensive medication.

Analysis of the rs13306560 functional variant in the promoter region of the MTHFR gene in sporadic Parkinson´s disease.

OBJECTIVE: Among susceptibility genes for Sporadic Parkinson´s Disease (SPD), the MTHFR gene has been suggested as candidate. The A allele of the functional variant rs13306560 in its promoter region has been liked to decreased transactivation capacity. Therefore, we sought to determine a possible association of the rs13306560 and SPD. METHODS: In total, 237 individuals were genotyped, 113 patients with SPD diagnosed according to the Queen Square Brain Bank criteria and 124 neurologically healthy controls. Genotyping was performed using TaqMan probes for the rs13306560 and real-time PCR. RESULTS: The A allelle was associated to protection in SPD, under the dominant model, (OR=0.22, C.I.=[0.048-1.080], p=0.04), nevertheless, after logistic regression analysis with adjustment for gender, resulted only in a trend (Exp (ß)=0.211, [I.C. 95.0%, 0.042-1.057], p=0.058). CONCLUSION: Although further studies are needed, our data suggest an important role of the MTHFR gene variants in the fine-tuning regulation of one-carbon metabolism in the brain.

Enhanced and selective optical trapping in a slot-graphite photonic crystal.

Applicability of optical trapping tools for nanomanipulation is limited by the available laser power and trap efficiency. We utilized the strong confinement of light in a slot-graphite photonic crystal to develop high-efficiency parallel trapping over a large area. The stiffness is 35 times higher than our previously demonstrated on-chip, near field traps. We demonstrate the ability to trap both dielectric and metallic particles of sub-micron size. We find that the growth kinetics of nanoparticle arrays on the slot-graphite template depends on particle size. This difference is exploited to selectively trap one type of particle out of a binary colloidal mixture, creating an efficient optical sieve. This technique has rich potential for analysis, diagnostics, and enrichment and sorting of microscopic entities.

Polymorphisms of APLN-APLNR system are associated with essential hypertension in Mexican-Mestizo individuals.

The aim of this study was to evaluate if polymorphisms of APLN and APLNR genes may play a role as susceptibility markers for hypertension in a group of Mexican-Mestizo patients. A case-control study was carried out including normotensive and hypertensive individuals. For these, two polymorphisms of APLN (rs3761581 and rs56204867) and two of APLNR () genes were genotyped by 5' exonuclease TaqMan assay in 400 normotensive individuals and 383 patients. The results showed that, under an additive model adjusted by BMI, HDL, triglycerides, glucose and family history of essential hypertension, the rs7119375 and rs10501367 polymorphisms of APLNR gene were associated significantly with a decreased risk of essential hypertension (P=0.039 and P=0.029, respectively). Besides, the haplotypes analysis of these polymorphisms showed that H1 haplotype was associated with an increased risk of essential hypertension (P=0.026), while the H2 haplotype was associated with a decreased risk (P=0.032). Contrary, the rs3761581 and rs56204867 polymorphisms of APLN gene were not associated with essential hypertension (P=0.1707 and P=0.0769, respectively). The data suggest that APLNR rs7119375 and rs10501367 are associated with a decreased risk of essential hypertension in our Mexican-Mestizo studied group, but further studies are warranted.

Optical Epitaxial Growth of Gold Nanoparticle Arrays.

We use an optical analogue of epitaxial growth to assemble gold nanoparticles into 2D arrays. Particles are attracted to a growth template via optical forces and interact through optical binding. Competition between effects determines the final particle arrangements. We use a Monte Carlo model to design a template that favors growth of hexagonal particle arrays. We experimentally demonstrate growth of a highly stable array of 50 gold particles with 200 nm diameter, spaced by 1.1 µm.

Light-assisted, templated self-assembly of gold nanoparticle chains.

We experimentally demonstrate the technique of light-assisted, templated self-assembly (LATS) to trap and assemble 200 nm diameter gold nanoparticles. We excite a guided-resonance mode of a photonic-crystal slab with 1.55 µm laser light to create an array of optical traps. Unlike our previous demonstration of LATS with polystyrene particles, we find that the interparticle interactions play a significant role in the resulting particle patterns. Despite a two-dimensionally periodic intensity profile in the slab, the particles form one-dimensional chains whose orientations can be controlled by the incident polarization of the light. The formation of chains can be understood in terms of a competition between the gradient force due to the excitation of the mode in the slab and optical binding between particles.

Light-assisted, templated self-assembly using a photonic-crystal slab.

We experimentally demonstrate the technique of light-assisted, templated self-assembly (LATS). We excite a guided-resonance mode of a photonic-crystal slab with 1.55 µm laser light to create an array of optical traps. We demonstrate assembly of a square lattice of 520 nm diameter polystyrene particles spaced by 860 nm. Our results demonstrate how LATS can be used to fabricate reconfigurable structures with symmetries different from traditional colloidal self-assembly, which is limited by free energetic constraints.

Effectiveness of decentralizing outpatient acute malnutrition treatment with community health workers and a simplified combined protocol: a cluster randomized controlled trial in emergency settings of Mali.

Background: Outpatient treatment of acute malnutrition is usually centralized in health centers and separated into different programs according to case severity. This complicates case detection, care delivery, and supply chain management, making it difficult for families to access treatment. This study assessed the impact of treating severe and moderate cases in the same program using a simplified protocol and decentralizing treatment outside health centers through community health workers (CHWs). Methods: A three-armed cluster randomized controlled trial under a non-inferiority hypothesis was conducted in the Gao region of Mali involving 2,038 children between 6 and 59 months of age with non-complicated acute malnutrition. The control arm consisted of 549 children receiving standard treatment in health centers from nursing staff. The first intervention arm consisted of 800 children treated using the standard protocol with CHWs added as treatment providers. The second intervention arm consisted of 689 children treated by nurses and CHWs under the ComPAS simplified protocol, considering mid-upper arm circumference as the sole anthropometric criterion for admission and discharge and providing a fixed dose of therapeutic food for severe and moderate cases. Coverage was assessed through cross-sectional surveys using the sampling evaluation of access and coverage (SLEAC) methodology for a wide area involving several service delivery units. Results: The recovery rates were 76.3% in the control group, 81.8% in the group that included CHWs with the standard protocol, and 92.9% in the group that applied the simplified protocol, confirming non-inferiority and revealing a significant risk difference among the groups. No significant differences were found in the time to recovery (6 weeks) or in anthropometric gain, whereas the therapeutic food expenditure was significantly lower with the simplified combined program in severe cases (43 sachets fewer than the control). In moderate cases, an average of 35 sachets of therapeutic food were used. With the simplified protocol, the CHWs had 6% discharge errors compared with 19% with the standard protocol. The treatment coverage increased significantly with the simplified combined program (SAM +42.5%, MAM +13.8%). Implications: Implementing a simplified combined treatment program and adding CHWs as treatment providers can improve coverage while maintaining non-inferior effectiveness, reducing the expenditure on nutritional intrants, and ensuring the continuum of care for the most vulnerable children.

Tuning the transmission lineshape of a photonic crystal slab guided-resonance mode by polarization control.

We demonstrate a system consisting of a two-dimensional photonic crystal slab and two polarizers which has a tunable transmission lineshape. The lineshape can be tuned from a symmetric Lorentzian to a highly asymmetric Fano lineshape by rotating the output polarizer. We use temporal coupled mode theory to explain the measurement results. The theory also predicts tunable phase shift and group delay.

Experimental broadband absorption enhancement in silicon nanohole structures with optimized complex unit cells.

We design silicon membranes with nanohole structures with optimized complex unit cells that maximize broadband absorption. We fabricate the optimized design and measure the optical absorption. We demonstrate an experimental broadband absorption about 3.5 times higher than an equally-thick thin film.

Tight-binding calculation of radiation loss in photonic crystal CROW.

The tight binding approximation (TBA) is used to relate the intrinsic, radiation loss of a coupled resonator optical waveguide (CROW) to that of a single constituent resonator within a light cone picture. We verify the validity of the TBA via direct, full-field simulation of CROWs based on the L2 photonic crystal cavity. The TBA predicts that the quality factor of the CROW increases with that of the isolated cavity. Moreover, our results provide a method to design CROWs with low intrinsic loss across the entire waveguide band.

Design and optical characterization of high-Q guided-resonance modes in the slot-graphite photonic crystal lattice.

A new photonic crystal structure is generated by using a regular graphite lattice as the base and adding a slot in the center of each unit cell to enhance field confinement. The theoretical Q factor in an ideal structure is over 4 × 10(5). The structure was fabricated on a silicon-on-insulator wafer and optically characterized by transmission spectroscopy. The resonance wavelength and quality factor were measured as a function of slot height. The measured trends show good agreement with simulation.

RS3480 Polymorphism of FNDC5/Irisin Is Associated with Type 2 Diabetes Mellitus in Maya-Mestizo Women.

Objective: To investigate the possible association between rs3480 and rs16835198 of the fibronectin type III domain containing 5 (FNDC5)/Irisin and their haplotypes with the presence of type 2 diabetes mellitus (T2DM) in Maya-Mestizo women. Methods: We studied 547 postmenopausal women of Maya-Mestizo origin. The diagnosis of T2DM was based on the criteria of the American Diabetes Association. DNA was obtained from blood leukocytes. rs3480 and rs16835198 of FNDC5/Irisin were studied using real-time polymerase chain reaction allelic discrimination. Deviations from Hardy-Weinberg equilibrium and alleles differences, as well as genotype frequencies between groups, were assessed by χ2 tests. Using logistic regression analysis, the odds ratio and 95% confidence intervals were calculated to estimate the association between both polymorphisms of FNDC5/Irisin and the presence of T2DM. Pairwise linkage disequilibrium between polymorphisms was calculated by direct correlation r2, and haplotype analysis was conducted. Results: We found that the G-allele of rs3480, as well as under a dominant model, this polymorphism was significantly associated with T2DM (P = 0.028 and P = 0.003, respectively). Besides, one haplotype was associated with T2DM (P = 0.035). Conclusions: Our results suggest that the FNDC5/Irisin rs3480, and one haplotype formed by rs3480 and rs16835198 were associated with the risk of presenting T2DM in Maya-Mestizo women.

(-)-Epicatechin modulates the expression of myomiRs implicated in exercise response in mouse skeletal muscle.

The flavanol (-)-epicatechin has exercise-mimetic properties. Besides, several miRNAs play a role in modulating the adaptation of the muscle to different training protocols. However, notwithstanding all information, few studies aimed to determine if (-)-epicatechin can modify the expression of miRNAs related to skeletal muscle development and regeneration. Mice were treated for fifteen days by oral gavage with the flavanol (-)-epicatechin. After treatment, the quadriceps of the mice was dissected, and total RNA was extracted. The expression level of miR-133, -204, -206, -223, -486, and -491 was analyzed by qRT-PCR. We also used bioinformatic analysis to predict the participation of these miRNAs in different skeletal muscle signal transduction pathways. Additionally, we analyzed the level of the myogenic proteins MyoD and myogenin by Western blot and measured the cross-sectional area of muscle fibers stained with E&H. (-)-Epicatechin upregulated the expression of miR-133, -204, -206, -223, and -491 significantly, which was associated with an increase in the level of the myogenic proteins MyoD and Myogenin and an augment in the fiber size. The bioinformatics analysis showed that the studied miRNAs might participate in different signal transduction pathways related to muscle development and adaptation. Our results showed that (-)-epicatechin upregulated miRNAs that participate in skeletal exercise muscle adaptation, induced muscle hypertrophy, and increased the level of myogenic proteins MyoD and MyoG.

Effectiveness and Coverage of Severe Acute Malnutrition Treatment with a Simplified Protocol in a Humanitarian Context in Diffa, Niger.

BACKGROUND: the aim of this study is to evaluate the effectiveness and coverage of a simplified protocol that is implemented in health centers (HCs) and health posts (HPs) for children who are suffering from severe acute malnutrition (SAM) in the humanitarian context of Diffa. METHODS: We conducted a non-randomized community-controlled trial. The control group received outpatient treatment for SAM, without medical complications, at HCs and HPs with the standard protocol of community management of acute malnutrition (CMAM). Meanwhile, with respect to the intervention group, the children with SAM received treatment at the HCs and HPs through a simplified protocol wherein the mid-upper arm circumference (MUAC) and the presence of edema were used as the admission criteria, and the children with SAM were administered doses of fixed ready-to-use therapeutic food (RUTF). RESULTS: A total of 508 children, who were all under 5 years and had SAM, were admitted into the study. The cured proportion was 87.4% in the control group versus 96.6% in the intervention group (p value = 0.001). There was no difference between the groups in the length of stay, which was 35 days, but the intervention group used a lower quantity of RUTF-70 sachets versus 90 sachets, per child cured. Coverage increases were observed in both groups. DISCUSSION: the simplified protocol used at the HCs and HPs did not result in worse recovery and resulted in fewer discharge errors compared to the standard protocol.

Differential histological features and myogenic protein levels in distinct muscles of d-sarcoglycan null muscular dystrophy mouse model.

Skeletal muscle (SkM) comprises slow and fast-twitch fibers, which differ in molecular composition, function, and systemic energy consumption. In addition, muscular dystrophies (DM), a group of diverse hereditary diseases, present different patterns of muscle involvement, progression, and severity, suggesting that the regeneration-degeneration process may differ depending on the muscle type. Therefore, the study aimed to explore the expression of proteins involved in the repair process in different muscles at an early stage of muscular dystrophy in the δ-sarcoglycan null mice (Sgcd-null), a limb-girdle muscular dystrophy 2 F model. Hematoxylin & Eosin (H&E) Staining showed a high number of central nuclei in soleus (Sol), tibialis (Ta), gastrocnemius (Gas), and extensor digitorum longus (Edl) from four months Sgcd-null mice. However, fibrosis, determined by trichrome of Gomori modified staining, was only observed in Sgcd-null Sol. In addition, the number of Type I and II fibers variated differentially in the Sgcd-null muscles vs. wild-type muscles. Besides, the protein expression level of ß-catenin, myomaker, MyoD, and myogenin also presented different expression levels in all the Sgcd-null muscles studied. In summary, our study reveals that muscles with different metabolic characteristics showed distinct expression patterns of proteins involved in the muscle regeneration process. These results could be relevant in designing therapies for genetic and acquired myopathy.

Impact of a simplified treatment protocol for moderate acute malnutrition with a decentralized treatment approach in emergency settings of Niger.

Introduction: Of the 45.4 million children under five affected by acute malnutrition in the world, the majority (31.8 million) are affected by moderate acute malnutrition (MAM). Its treatment is particularly complex in emergency settings such as the Diffa region in Niger. This study aims to evaluate the effectiveness and coverage of a simplified treatment protocol with Community Health Workers (CHWs) as treatment providers. Methods: This study is a non-randomized controlled trial. The control group (n = 181) received the standard protocol currently used in country, delivered by nursing staff only in health centres and health posts, while the intervention group (n = 483) received the simplified protocol which included nursing at health centres and CHWs at health post as treatment providers. Results: The recovery rate was higher in the simplified protocol group (99.6% vs. 79.56%, p < 0.001) recording lower time to recover and higher anthropometric gain. Treatment coverage in the intervention group increased from 28.8% to 84.9% and reduced in the control group (25.3% to 13.6%). No differences were found in the recovery rate of children treated by CHWs and nursing staff. Conclusion: The outcomes using the simplified protocol exceeded humanitarian requirements and demonstrated improvements compared to the standard protocol showing that the simplified protocol could be safely provided by CHWs in an emergency context. Further research in other contexts is needed to scale up this intervention.

Optical trapping via guided resonance modes in a Slot-Suzuki-phase photonic crystal lattice.

A novel photonic crystal lattice is proposed for trapping a two-dimensional array of particles. The lattice is created by introducing a rectangular slot in each unit cell of the Suzuki-Phase lattice to enhance the light confinement of guided resonance modes. Large quality factors on the order of 105 are predicted in the lattice. A significant decrease of the optical power required for optical trapping can be achieved compared to our previous design.