Pembrolizumab for locally advanced and recurrent/metastatic cutaneous squamous cell carcinoma (KEYNOTE-629 study): an open-label, nonrandomized, multicenter, phase II trial.

BACKGROUND: Pembrolizumab demonstrated clinically meaningful and durable antitumor activity with a manageable safety profile in recurrent/metastatic (R/M) cutaneous squamous cell carcinoma (cSCC). PATIENTS AND METHODS: KEYNOTE-629 was a global, open-label, nonrandomized, phase II trial of patients with locally advanced (LA) or R/M cSCC conducted at 59 centers. Eligible patients received intravenous pembrolizumab 200 mg every 3 weeks for up to 35 cycles. Primary endpoint was objective response rate (ORR), defined as the percentage of patients with a complete (CR) or partial response (PR), by blinded independent central review as per Response Evaluation Criteria in Solid Tumors 1.1. Secondary endpoints included duration of response (DOR), disease control rate, progression-free survival, overall survival, and safety and tolerability. Efficacy and safety were analyzed in patients who were treated with at least one dose of pembrolizumab. RESULTS: Between 29 November 2017 and 25 September 2019, 159 patients were enrolled and treated with pembrolizumab (LA cohort, n = 54; R/M cohort, n = 105). The median time from the first dose to data cut-off date (29 July 2020) was 14.9 [interquartile range (IQR), 12.6-17.2] months for the LA cohort and 27.2 (IQR, 25.6-29.2) months for the R/M cohort. In the LA cohort, ORR was 50.0% [95% confidence interval (CI), 36.1% to 63.9%], including 16.7% of patients with a CR and 33.3% with a PR. In the R/M cohort, ORR was 35.2% (95% CI, 26.2% to 45.2%), including 10.5% of patients with a CR and 24.8% with a PR. Median DOR was not reached in either cohort. Grade 3-5 treatment-related adverse events occurred in 11.9% of patients. CONCLUSIONS: The robust antitumor activity of pembrolizumab in both LA and R/M cSCC was confirmed and demonstrated to be durable without unexpected safety signals. Our findings establish pembrolizumab as a promising treatment option for cSCC.

Efficient solar removal of acetaminophen contaminant from water using flexible graphene composites functionalized with Ni@TiO2:W nanoparticles.

This work presents the morphological, structural and photocatalytic properties of flexible graphene composites decorated with Ni@TiO2:W nanoparticles (TiNiW NPs) with an average size of 27 ± 2 nm. The TiNiW NPs were immobilized on the surface of a flexible graphene composite using a PVA-based slurry-paste (FG/TiNiW composite). The SEM study showed that the TiNiW NPs remained exposed on the surface of the FG/TiNiW composite, which benefited its photocatalytic activity. The photocatalytic performance for the degradation of acetaminophen (ACT) was evaluated using both the TiNiW powders and the FG/TiNiW composite, obtaining maximum degradation efficiencies of 100 and 86%, respectively, after 3 h under natural solar irradiation. The degradation of ACT was caused mainly by the reactive oxygen species such as OH radicals and h+, which was confirmed by scavenger experiments. Photoluminescence, XPS and absorbance experiments revealed that oxygen vacancy defects were created by i) doping the TiNiW NPs with W and by ii) introducing graphene into the composites. These defects enhanced the absorbance of light in the range of 400-800 nm, which in turn, promoted the photocatalytic degradation of ACT. Moreover, the reuse experiments confirmed that both the TiNiW NPs and FG/TiNiW composite were very stable for the degradation of ACT, since degradation efficiencies >82% were obtained after 4 reuse cycles for both photocatalysts. The experimental findings of this work demonstrate that the flexible TiO2/graphene composites are a feasible option for the removal of pharmaceutical contaminants from water using natural solar irradiation.

Dysregulation of mitochondrial function and biogenesis modulators in adipose tissue of obese children.

BACKGROUND/OBJECTIVES: We aimed to evaluate mitochondrial biogenesis (MB), structure, metabolism and dysfunction in abdominal adipose tissue from male pediatric patients with obesity. SUBJECTS/METHODS: Samples were collected from five children with obesity (percentile ⩾95) and five eutrophic boys (percentile ⩾5/⩽85) (8-12 years old) following parental informed consent. We analyzed the expression of key genes involved in MB (sirtuin-1 (SIRT1), peroxisome proliferator-activated receptor-γ (PPARγ), PPARγ coactivator-1α (PGC1α), nuclear respiratory factors 1 and 2 (NRF1, NRF2) and mitochondrial transcription factor A (TFAM) and surrogates for mitochondrial function/structure/metabolism (porin, TOMM20, complex I and V, UCP1, UCP2, SIRT3, SOD2) by western blot. Citrate synthase (CS), complex I (CI) activity, adenosine triphosphate (ATP) levels, mitochondrial DNA (mtDNA) content and oxidative stress end points were also determined. RESULTS: Most MB proteins were significantly decreased in samples from children with obesity except complex I, V and superoxide dismutase-2 (SOD2). Similarly, CS and CI activity showed a significant reduction, as well as ATP levels and mtDNA content. PPARγ, PGC1α, complex I and V and SOD2 were hyperacetylated compared with lean samples. Concurrently, in samples from children with obesity, we found decreased SOD2 activity and redox state imbalance highlighted by decreased reduced glutathione/oxidized glutathione (GSH/GSSG) ratio and significant increases in protein carbonylation. CONCLUSIONS: Adipose tissue from children with obesity demonstrates a dysregulation of key modulators of MB and organelle structure, and displays hyperacetylation of key proteins and altered expression of upstream regulators of cell metabolism.

[Endoscopic management of gastric volvulus in a 8-years old girl]. / Manejo endoscópico del vólvulo gástrico en una niña de 8 años.

INTRODUCTION: Gastric volvulus is a rare cause of acute abdomen in childhood, and it is usually a casual finding. We present the case of a girl with mesenteroaxial gastric volvulus, which was initially treated by endoscopic approach. CLINICAL CASE: 8 year-old patient, diagnosed of Down syndrome, who presented sudden and diffuse colic pain, associated with vomiting, sialorrhea and progressive compromise. She entered in bad general condition. At the physical examination it was highlighted a large abdominal mass. In the imaging study, a mesenteroaxial gastric volvulus and wandering spleen were confirmed. It was decided to perform an endoscopic gastric devolvulation under general anesthesia. Subsequently, gastropexy and splenopexy were performed by laparotomic approach. Evolution was uneventful, being discharged at the tenth postoperative day. COMMENTS: Endoscopic gastric devolvulation is an effective procedure in patients with gastric volvulus, especially in cases of great compromise of the general state, in which a prolonged surgery could suppose a greater risk.

INTRODUCCION: El vólvulo gástrico es una causa rara de abdomen agudo en la edad pediátrica, siendo generalmente un hallazgo. Se presenta el caso de una niña con vólvulo gástrico mesenteroaxial, que fue inicialmente tratado de forma endoscópica. CASO CLINICO: Paciente de 8 años, afecta de síndrome de Down, que acude por presentar un cuadro clínico de dolor abdominal cólico y súbito, asociado a vómitos, sialorrea y compromiso de estado general. La paciente ingresa en malas condiciones. Al examen físico, se constató una gran masa abdominal. Las exploraciones complementarias de imagen demuestran un vólvulo gástrico mesenteroaxial asociado a bazo errante. Se optó por efectuar desvolvulación gástrica endoscópica bajo anestesia general. Posteriormente a través de una laparotomía se realizó gastropexia y esplenopexia, evolucionando bien, siendo dada de alta al décimo día. COMENTARIOS: La desvolvulación endoscópica se presenta como una alternativa efectiva en pacientes afectos de vólvulo gástrico, en especial en casos de gran compromiso sistémico, en los que una cirugía prolongada pudiera suponer mayor riesgo.

[Antenatal ultrasound diagnosis and neonatal results of the congenital cystic adenomatoid malformation of the lung]. / Diagnóstico ecográfico prenatal y resultados neonatales de la malformación adenomatoidea quística pulmonar.

INTRODUCTION: Congenital cystic adenomatoid malformation (CCAM) is a rare congenital lung di sease, and in the most of cases, prenatal diagnosis is feasible. There are discrepancies regarding pre natal management and postpartum treatment. OBJECTIVE: To analyze prenatally diagnosed CCAM in our hospitals, in order to evaluate ultrasound findings with fetal and postnatal evolution. PATIENTS AND METHOD: Retrospective study of all cases diagnosed prenatally by ultrasound between 2005 and 2016 in two reference hospitals. The ultrasounds were performed using high-resolution ultrasound scanners, Toshiba Xario and Voluson 730 Expert Pro, with follow-up from diagnosis to delivery. The variables analyzed included gestational age at diagnosis, the characteristics of the lung lesion, associated malformations, cytogenetic study, the evolution of pregnancy, type of delivery, presence of respiratory distress, need for complementary imaging tests, pediatric clinical course, and necessary postnatal treatments. It was considered a resolution the total disappearance of the lesion in the pre natal ultrasound or that the postnatal chest X-ray showed no lesion. RESULTS: 17 cases were prenatally diagnosed. The evolution ranges from the prenatal resolution of the lesion to the persistence after bir th. Three patients voluntarily decided to have an abortion due to ultrasound findings of poor progno sis. Of the fourteen remaining cases there were no cases of fetal or neonatal deaths, one case required surgery after birth and four patients had mild symptoms during the first year of life. One case of false negative with neonatal death has been reported which necropsy reported as CCAM type 0. Conclu sions: This pulmonary malformation presents good prognosis, excluding cases with fetal hydrops. Two-dimensional ultrasound is usually enough for diagnosis and follow-up. Computed tomography is the technique of choice to confirm the resolution of lesions after birth. Surgical treatment is pre ferable over conservative management, although it is unknown if the potential complications of this disease, even when asymptomatic, justify surgical morbidity.

Crystal Structure Determination of the S/TiO2 System and the Correlation with Its Photocatalytic Properties.

A sulfur doped anatase photocatalyst was synthesized through a microwave-assisted sol-gel method and posteriorly, it was characterized using X-ray diffraction by powders (XRD) and High Resolution Electron Microscopy (HREM). Morphology and average size of the crystallite were determined for the sample, preferential crystal orientation was also analyzed and all these structural features were related to the photocatalytic properties. Moreover, a pure TiO2 sample was also obtained by the same synthesis method and it was used as a reference, and its structure and photocatalytic properties were compared to those observed for the sulfur doped anatase. The structural analysis showed similar results for both sample types but, photocatalytic properties are rather different. A small difference in chemical composition had an impact in the catalytic properties.

Multifactor-dimensionality reduction reveals interaction of important gene variants involved in allergy.

Elevated IgE levels in the atopic triad of asthma, allergic rhinitis and atopic dermatitis is a multifactorial condition whose genetic component involves interaction of several gene loci. One hundred and two matched pairs of allergic and nonallergic individuals were phenotyped for total serum IgE level using enzyme-linked immunosorbent assay (ELISA). Atopic status was defined by serum IgE concentration ≥100 IU mL(-1) . SNPs genotyped include the IL4 -590C>T (rs2243250), FCER1B E237G (rs569108), CD14 -159C>T (rs2569190), IL4RA Q551R (rs1801275) and ADRB2 R16G (rs1042713). Gene-gene interaction was analysed using multifactor-dimensionality reduction (MDR). Significant association between atopic allergy and the IL4 -590C>T polymorphism was confirmed in three genetic models. Interaction among the 5 gene variants was validated by MDR. The five-locus model was chosen as the best to describe the interaction of the SNPs within the context of atopy. The strongest interaction was between IL4 -590C>T and IL4RA Q551R and between FCER1B E237G and ADRB2 R16G. The IL4 variant also interacts synergistically with the FCER1B and ADRB2 coding variants. CD14 -159C>T, in general, interacts antagonistically with the rest of the SNPs. In conclusion, a five-locus interaction exists among IL4 -590C>T, FCER1B E237G, CD14 -159C>T, IL4RA Q551R and ADRB2 R16G in Filipino cases of atopic allergy.

Congenital malformations, chromosomal abnormalities and perinatal results in IVF/ICSI newborns resulting from very poor quality embryos: a case-control study.

AIMS: To explore whether the transfer of very poor quality (VPQ) embryos is associated with an increase in congenital malformations or perinatal problems. METHODS: In this retrospective case-control study, 74 children conceived by in vitro fertilization (IVF) and/or intracytoplasmic sperm injection (ICSI) resulting exclusively from the transfer of VPQ embryos were compared with 1,507 children born after the transfer of top morphological quality (TQ) embryos over the same period of time in the same centers. RESULTS: The prevalence of birth defects in children resulting from VPQ embryos was 1.35% (1/74), similar to the 1.72% (26/1,507) when only TQ embryos were transferred; the rate of chromosomal abnormalities detected was also similar (0.0 vs. 0.4%), as was perinatal mortality. After correcting for multiplicity (higher in the TQ group), the aforementioned parameters remained similar in the two groups. CONCLUSION: Congenital malformations and perinatal complications do not seem to be more common in children born after transfer of VPQ embryos in IVF/ICSI cycles. Given our preliminary data, which need to be confirmed in much larger studies, when only VPQ embryos are available for transfer in IVF/ICSI cycles, we do not believe that they should be discarded with the intention of avoiding birth defects or perinatal complications.

RUNX3 gene polymorphisms and haplotypes in Mexican patients with colorectal cancer.

We analyzed a possible association between RUNX3 gene polymorphisms and haplotypes in Mexican patients with colorectal cancer (CRC). Genomic DNA samples were obtained from the peripheral blood of 176 Mexican patients with CRC at diagnosis and from 195 individuals that formed the control group. The polymorphisms were detected by polymerase chain reaction-restriction fragment length polymorphism. Association was estimated by odds ratio (OR). The haplotypes and linkage disequilibrium were established using the Arlequin v3.5 software. We found that the RUNX3 polymorphisms analyzed were in Hardy-Weinberg equilibrium. The RUNX3 rs2236852 AA genotype and A allele showed association with CRC (OR = 0.39, 95%CI = 0.21-0.73, P < 0.01; OR = 0.65, 95%CI = 0.49-0.87, P < 0.01, respectively), while the rs6672420, rs11249206, and rs760805 polymorphisms did not show significant association with CRC. The TA haplotype (SNPs rs760805 and rs2236852) showed an increased risk for CRC (OR = 2.52, 95%CI = 1.47-4.30, P < 0.001). In conclusion, we found that the AA genotype and A allele of rs2236852 polymorphism confer a decreased CRC risk, while the TA haplotype appears to increase the risk of CRC development in Mexican patients.

Effect of ZNF217 gene polymorphisms on colorectal cancer development in a Mexican population.

The ZNF217 gene, a potential oncogene amplified and overexpressed in several cancers including colorectal cancer (CRC), acts as a transcription factor that activates or represses target genes. The polymorphisms rs16998248 (T>A) and rs35720349 (C>T) in coronary artery disease have been associated with reduced expression of ZNF217. In this study, we analyzed the 2 polymorphisms in Mexican patients with CRC. Genotyping of rs16998248 and rs35720349 sites was performed by polymerase chain reaction-restriction fragment length polymorphism in 203 Mexican Mestizos, 101 CRC patients, and 102 healthy blood donors. Although no statistical differences regarding genotype and allele frequencies of ZNF217 polymorphisms were observed (P > 0.05), linkage disequilibrium was significant in CRC patients (r(2) = 0.39, P < 0.0001), as a result of reduced AC haplotype frequency. Thus, the AC haplotype may protect against CRC.

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.

Association of MMP7-181A/G and MMP13-77A/G polymorphisms with colorectal cancer in a Mexican population.

Colorectal cancer (CRC) is characterized by enhanced expression and activity of several metalloproteinases (MMPs), including MMP13 and MMP7, which play an important role in tumor invasion and metastasis. The objective of this study was to analyze the association of functional MMP7-181A/G and MMP13-77A/G promoter polymorphisms with susceptibility to CRC in a Mexican population. Genomic DNA samples were obtained from peripheral blood of 102 CRC patients and 125 blood donors who were included as the control group. Identification of polymorphisms was based on polymerase chain reaction-restriction fragment length polymorphism methodology. The association was estimated by the odds ratio (OR) test. The results showed that MMP7-181A/G and MMP13-77A/G variants were associated with CRC. For MMP7-181A/G, the AA (P=0.02, OR=3.38, 95% confidence interval (CI)=1.16-9.84) and AG (P=0.01, OR=3.4, 95%CI=1.17-9.83) genotypes were associated with an increased risk of CRC. For MMP13-77A/G, the AA and AG genotypes were associated with CRC (AA genotype: P=0.04, OR=3.2, 95%CI=1.004-10.2; AG genotype: P=0.01, OR=4.08, 95%CI=1.3-13.07). In conclusion, AA and AG genotype carriers for both polymorphisms are at a higher risk of developing CRC in this Mexican population.

Impact of obesity severity and duration on pancreatic ß- and α-cell dynamics in normoglycemic non-human primates.

OBJECTIVE: Obesity is associated with high insulin and glucagon plasma levels. Enhanced ß-cell function and ß-cell expansion are responsible for insulin hypersecretion. It is unknown whether hyperglucagonemia is due to α-cell hypersecretion or to an increase in α-cell mass. In this study, we investigated the dynamics of the ß-cell and α-cell function and mass in pancreas of obese normoglycemic baboons. METHODS: Pancreatic ß- and α-cell volumes were measured in 51 normoglycemic baboons divided into six groups according to overweight severity or duration. Islets morphometric parameters were correlated to overweight and to diverse metabolic and laboratory parameters. RESULTS: Relative α-cell volume (RαV) and relative islet α-cell volume (RIαV) increased significantly with both overweight duration and severity. Conversely, in spite of the induction of insulin resistance, overweight produced only modest effects on relative ß-cell volume (RßV) and relative islet ß-cell volume (RIßV). Of note, RIßV did not increase neither with overweight duration nor with overweight severity, supposedly because of the concomitant, greater increase in RIαV. Baboons' body weights correlated with serum levels of interleukin-6 and tumor necrosis factor-α soluble receptors, demonstrating that overweight induces abnormal activation of the signaling of two cytokines known to impact differently ß- and α-cell viability and replication. CONCLUSION: In conclusion, overweight and insulin resistance induce in baboons a significant increase in α-cell volumes (RαV, RIαV), whereas have minimal effects on the ß cells. This study suggests that an increase in the α-cell mass may precede the loss of ß cells and the transition to overt hyperglycemia and diabetes.

Bariatric surgery and bone disease: from clinical perspective to molecular insights.

The use of bariatric surgery for the treatment of morbid obesity has increased annually for the last decade. Although many studies have demonstrated the efficacy and durability of bariatric surgery for weight loss, there are limited data regarding long-term side effects of these procedures. Recently, there has been an increased focus on the impact of bariatric surgery on bone metabolism. Bariatric surgery utilizes one or more of three mechanisms of action resulting in sustained weight loss. These include restriction (gastric banding, vertical banded gastroplasty and sleeve gastrectomy), malabsorption surgery with or without associated restriction (Roux en Y gastric bypass, duodenal switch, biliopancreatic diversion and jejunoileal bypass) and changes in gut-derived hormones that control energy metabolism also referred to as neuro-hormonal control of energy metabolism (Roux en Y gastric bypass, duodenal switch, biliopancreatic diversion, jejunoileal bypass, surgical procedures as above and gastric sleeve). Weight reduction has been associated with increased bone resorption but the mechanisms behind this have not yet been fully elucidated. Each of the mechanisms of action of bariatric surgery (restriction, malabsorption, neuro-hormonal control of energy metabolism) may uniquely affect bone resorption. In this paper we will review the current state of knowledge regarding the relationship between bariatric surgery and bone metabolism with emphasis on possible mechanisms of action such as malnutrition, hormonal interactions and mechanical unloading of the skeleton. Further, we suggest a future research agenda.

Field reversed configuration confinement enhancement through edge biasing and neutral beam injection.

Field reversed configurations (FRCs) with high confinement are obtained in the C-2 device by combining plasma gun edge biasing and neutral beam injection. The plasma gun creates an inward radial electric field that counters the usual FRC spin-up. The n = 2 rotational instability is stabilized without applying quadrupole magnetic fields. The FRCs are nearly axisymmetric, which enables fast ion confinement. The plasma gun also produces E × B shear in the FRC edge layer, which may explain the observed improved particle transport. The FRC confinement times are improved by factors 2 to 4, and the plasma lifetimes are extended from 1 to up to 4 ms.

Human chorionic gonadotropin (hCG) plasma levels at oocyte retrieval and IVF outcomes.

PURPOSE: The aim of our study was to ascertain the influence of hCG levels at oocyte pick-up on IVF outcomes, and their relationship with clinical parameters. METHODS: A prospective study was performed including 473 women undergoing IVF, aged under 40 years. Blood samples to analyze hCG levels were obtained at the time of follicular aspiration, 36 h after the administration of 250 µg of recombinant hCG. RESULTS: Neither the numbers of oocytes obtained or fertilized, nor the pregnancy rate, were correlated with hCG levels. Moreover, hCG values were very similar in women who did and did not become pregnant (123.3 ± 48.7 and 117.5 ± 44.7 mUI/mL). Cases in which no oocytes were recovered after follicular aspiration had similar hCG levels to those in which more than 1 oocyte was obtained. On the other hand, hCG levels were negatively related to body mass index, weight, and age. CONCLUSIONS: These data indicate that after the administration of 250 µg of recombinant hCG, hCG levels are not responsible for failure to recover oocytes. Specifically, there was no correlation between plasma hCG levels and the number of oocytes obtained or other markers of IVF outcome. There was, however, an inverse relationship with BMI, body weight and age.

MLH1 and XRCC1 polymorphisms in Mexican patients with colorectal cancer.

DNA repair proteins maintain DNA integrity; polymorphisms in genes coding for these proteins can increase susceptibility to colorectal cancer (CRC) development. We analyzed a possible association of MLH1 -93G>A and 655A>G and XRCC1 Arg194Trp and Arg399Gln polymorphisms with CRC in Mexican patients. Genomic DNA samples were obtained from peripheral blood of 108 individuals with CRC (study group) at diagnosis and 120 blood donors (control group) from Western Mexico; both groups were mestizos. The polymorphisms were detected by PCR-RFLP. Association was estimated by calculating the odds ratio (OR). We found that the MLH1 and XRCC1 polymorphisms were in Hardy- Weinberg equilibrium. The MLH1 655A>G polymorphism in the 655G allele was associated with a 2-fold increase risk for CRC (OR = 2.04 and 95% confidence interval (95%CI) = 1.12-3.69; P < 0.01), while the MLH1 -93G>A polymorphism allele was associated with a protective effect (OR = 0.60, 95%CI = 0.40-0.89; P = 0.01 in the -93A allele and OR = 0.32, 95%CI = 0.13-0.79; P = 0.01 in the AA genotype). The XRCC1 Arg194Trp and Arg399Gln polymorphisms did not show any significant associations. In conclusion, we found that MLH1 -93G>A and 655A>G polymorphisms are associated with CRC in Mexican patients.

Tomographic and centroid reconstructions of plasma emission on C-2W via enhanced 300-channel bolometry system.

The C-2W experimental device at TAE Technologies utilizes neutral beam injection and edge biasing to sustain long-lived, stable field reversed configuration (FRC) plasma. An ongoing effort is under way to optimize the electrode biasing system, which provides boundary control to stabilize the FRC. To this end, tomography offers a powerful and non-invasive technique as tomographic reconstruction of the FRC emission profile provides an important assessment of global stability. Recently, a new signal acquisition system was implemented on a bolometer array dedicated to tomography on C-2W, significantly enhancing the signal-to-noise of the collected data. The array consists of 300 simultaneously digitized photodiode channels that respond to a broad range of wavelengths, from soft x-ray to near-infrared, as well as energetic particles, yielding 180 unique lines of sight that intersect a toroidal plane of the FRC near the mid-plane. Utilizing the collected photo-signals from a set of plasma discharges in which the electrode biasing was intentionally terminated mid-shot, time-resolved reconstruction of the plasma emissivity is achieved via pixel-based 1D and 2D tomographic algorithms, revealing sharply annular profiles with a clear magnetohydrodynamic (MHD) mode structure. In addition, reconstruction of the plasma center-of-emission trajectories via a centroid algorithm applied to the same set of discharges demonstrates a cyclical plasma wobble. Crucially, both the tomography reconstruction and centroid reconstruction indicate an n = 1 toroidal mode that reverses from the electron diamagnetic direction to the ion diamagnetic direction and grows in amplitude after bias termination, qualitatively consistent with the expected stabilizing effect of electrodes.

Diabetic neuropathy: Molecular approach a treatment opportunity.

Diabetic neuropathy (DN) encompasses a group of clinical or subclinical manifestations involving a dysfunction in the peripheral nervous system. The cause of the dysfunction is the development of microvascular complications related to diabetes, a disease that affects about 381 million people worldwide. Approximately 50% of patients currently diagnosed with diabetes are expected to manifest DN in the next 10 years. The diagnosis can be made clinically by establishing a good patient history and delving into the symptoms to rule out other etiologies. Treatment of DN focuses on glycemic control and the use of medications to reduce pain, including NSAIDs, antidepressants and antiepileptic drugs. The pathogenesis is of multifactorial origin, associated with various metabolic, vascular, inflammatory and neurodegenerative disorders. The three fundamental cellular alterations participating in the development of DN are chronic inflammation, endothelial dysfunction and oxidative stress. Since the combination of all three is capable of giving rise to nerve ischemia and direct axonal injury, these factors play a key role in the development of polyneuropathy. However, neuronal and microvascular changes do not occur in the same way in all patients with DN, some of whom have no detectable blood abnormalities.