RNASEH1 gene variants are associated with autoimmune type 1 diabetes in Colombia.

BACKGROUND: In a previous work, we found linkage and association of type 1 diabetes (T1D) to a 12 known gene region at chromosome 2p25 in Colombian families. Here, we present further work on this candidate region. MATERIALS AND METHODS: Seventeen SNPs located on the 12 candidate genes, in 100 familial trios set, were tested by ARMS-tetraprimer-PCR or PCR-RFLP. Five extra SNPs in the vicinity of rs10186193 were typed. A replica phase included 97 novel familial trios, in whom diabetes-related auto-antibodies (AABs) were tested in sera of the patients. In addition to transmission disequilibrium tests, haplotype analyses were carried out using the unphased software. RESULTS: SNP rs10186193 (at RNASEH1 gene) showed association with T1D (P = 0.005). The additional five SNPs revealed that rs7607888 (P = 2.03 × 10-7), rs55981318 (P = 0.018), and rs1136545 (P = 1.93 × 10-9) were also associated with T1D. Haplotype analysis showed association for rs55981318-rs10186193 (P = 0.0005), rs7563960-rs7607888 (P = 0.0007), rs7607888-rs1136545 (P = 9.21 × 10-10), and rs1136545-rs11538545 (P = 6.67 × 10-8). In contrast, the new set of 97 familial trios tested for SNPs rs55981318, rs10186193, and rs7607888 did not support the previous finding; however, by combining the sample (197 trios), evidence of association of T1D with rs55981318 and rs7607888 was conclusive. In addition, a two-loci haplotype analysis of the combined sample showed significant association of RNASEH1 with T1D (P = 3.1 × 10-5). CONCLUSION: In conclusion, our analyses suggest that RNASEH1 gene variants associate with susceptibility/protection to T1D in Colombia.

Absorption of arsenic from soil and water by two chard (Beta vulgaris L.) varieties: A potential risk to human health.

The accumulation of arsenic (As) in vegetables poses a risk of contamination to humans via the food chain. Two chard (var. cicla and var. d'ampuis) crops were grown for 60 days in greenhouses on Aridisol soil, and irrigated with water from Pastos Chicos, Jujuy (Argentina). The soil and water used in the trial presented 49 and 1.44 mg/L As concentration levels, respectively. Total dry biomass (TDB) and total As were determined in soils, roots and leaves. The latter was quantified by atomic absorption spectrometry with hydride generation, and bioconcentration and translocation factors were determined. TDB in var. cicla showed statistically significant differences when the plant was cultivated in control soil and watered with the toxicant (2.04 g), as compared with the treatment without exposure (2.8 g). TDB in var. d'ampuis presented statistically significant differences with respect to that of the control when the plants were grown in soils with As and watered with the toxicant (3.3 g). This variety increased its biomass in the presence of As. In the two Swiss chard varieties evaluated, the largest As accumulation in root and leaves was found when they were cultivated in contaminated soil and watered with distilled water. The presence of the toxicant in the leaves exceeded the limits established by Código Alimentario Argentino, i.e. 0.30 mg/kg. Total target hazard quotient (THQ) values for As were higher than 1, suggesting that consumers would run significant risks when consuming these chard varieties. Furthermore, it was determined that the carcinogenic risk (CR) posed by this type of exposure to As exceeded the acceptable risk level of 1 × 10-6. Based on this evidence, we may conclude that consuming chard cultivated on the evaluated site brings about considerable risks to local residents' health.

Acclimation of nitrifying biomass and its effect on 2-chlorophenol removal.

The metabolic and kinetic behavior of a nitrifying sludge exposed to 2-chlorophenol (2-CP) was evaluated in batch cultures. Two kinds of nitrifying culture were used; one acclimated to 4-methylphenol (4-mp), and the other unacclimated to 4-mp. The unacclimated culture was affected adversely by the 2-CP's presence, since neither nitrification nor 2-CP oxidation was observed. Nonetheless, the acclimated culture showed metabolic capacity to nitrify and mineralize 2-CP. Ammonium removal was 100%, with a nitrifying yield of 0.92 ± 0.04 mg NO(3)(-)-N/mg NH(4)(+)-N consumed. The consumption efficiency for 2-CP was 100% and the halogenated compound was mineralized to CO2. Denaturing gradient gel electrophoresis (DGGE) patterns showed the shift in microbial community structure, indicating that microbial diversity was due to the acclimation process. This is the first evidence where nitrifying culture acclimated to 4-mp completely removed ammonium and 2-CP.

Effects of endocrine disorders on maxillary and mandibular growth in Colombian children and adolescents: a cross-sectional study.

OBJECTIVE: To establish the influence of overweight/obesity, medicated hypothyroidism, and medicated non-syndromic hypogrowth on maxillary and mandibular growth. MATERIALS AND METHODS: The relation between 10 craniofacial anthropometric measurements and hypothyroidism (n = 216), overweight/obesity (n = 108), and non-syndromic hypogrowth (n = 250) were evaluated in patients aged 1-19 years and a control group of healthy patients (n = 587). A subgroup analysis was performed at the peak growth in all groups. RESULTS: Patients with overweight/obesity and hypothyroidism showed increased craniofacial growth, while hypogrowth patients showed differences in zygomatic width and nasal base growth. Females with hypothyroidism and non-syndromic hypogrowth showed decreased head circumference at peak growth. Several anthropometric measurements were increased in patients with overweight/obesity, including head circumference. When all age groups were analyzed, overweight/obese and hypothyroidism patients showed increased zygomatic width while decreased hypogrowth. Overall, most craniofacial anthropometric measurements in overweight/obese patients were increased. Finally, the peak growth in males with hypothyroidism and subjects with non-syndromic hypogrowth was delayed compared to the control group (p < 0.05). CONCLUSIONS: Children and adolescents with overweight/obesity and endocrine disorders showed alterations in craniofacial growth. Clinicians must be aware that the growth peak in these patients may be delayed when planning maxillary and mandibular orthopedic treatment.

Do habitat shifts drive diversification in teleost fishes? An example from the pufferfishes (Tetraodontidae).

Habitat shifts are implicated as the cause of many vertebrate radiations, yet relatively few empirical studies quantify patterns of diversification following colonization of new habitats in fishes. The pufferfishes (family Tetraodon-tidae) occur in several habitats, including coral reefs and freshwater, which are thought to provide ecological opportunity for adaptive radiation, and thus provide a unique system for testing the hypothesis that shifts to new habitats alter diversification rates. To test this hypothesis, we sequenced eight genes for 96 species of pufferfishes and closely related porcupine fishes, and added 19 species from sequences available in GenBank. We time-calibrated the molecular phylogeny using three fossils, and performed several comparative analyses to test whether colonization of novel habitats led to shifts in the rate of speciation and body size evolution, central predictions of clades experiencing ecological adaptive radiation. Colonization of freshwater is associated with lower rates of cladogenesis in pufferfishes, although these lineages also exhibit accelerated rates of body size evolution. Increased rates of cladogenesis are associated with transitions to coral reefs, but reef lineages surprisingly exhibit significantly lower rates of body size evolution. These results suggest that ecological opportunity afforded by novel habitats may be limited for pufferfishes due to competition with other species, constraints relating to pufferfish life history and trophic ecology, and other factors.

Mestizos with systemic lupus erythematosus develop renal disease early while antimalarials retard its appearance: data from a Latin American cohort.

OBJECTIVES: The objective of this paper is to assess the predictors of time-to-lupus renal disease in Latin American patients. METHODS: Systemic lupus erythematosus (SLE) patients (n = 1480) from Grupo Latino Americano De Estudio de Lupus (GLADEL's) longitudinal inception cohort were studied. Endpoint was ACR renal criterion development after SLE diagnosis (prevalent cases excluded). Renal disease predictors were examined by univariable and multivariable Cox proportional hazards regression analyses. Antimalarials were considered time dependent in alternative analyses. RESULTS: Of the entire cohort, 265 patients (17.9%) developed renal disease after entering the cohort. Of them, 88 (33.2%) developed persistent proteinuria, 44 (16.6%) cellular casts and 133 (50.2%) both; 233 patients (87.9%) were women; mean (± SD) age at diagnosis was 28.0 (11.9) years; 12.2% were African-Latin Americans, 42.5% Mestizos, and 45.3% Caucasians (p = 0.0016). Mestizo ethnicity (HR 1.61, 95% CI 1.19-2.17), hypertension (HR 3.99, 95% CI 3.02-5.26) and SLEDAI at diagnosis (HR 1.04, 95% CI 1.01-1.06) were associated with a shorter time-to-renal disease occurrence; antimalarial use (HR 0.57, 95% CI 0.43-0.77), older age at onset (HR 0.90, 95% CI 0.85-0.95, for every five years) and photosensitivity (HR 0.74, 95% CI 0.56-0.98) were associated with a longer time. Alternative model results were consistent with the antimalarial protective effect (HR 0.70, 95% CI 0.50-0.99). CONCLUSIONS: Our data strongly support the fact that Mestizo patients are at increased risk of developing renal disease early while antimalarials seem to delay the appearance of this SLE manifestation. These data have important implications for the treatment of these patients regardless of their geographic location.

Wildlife reservoirs of brucellosis: Brucella in aquatic environments.

Neurobrucellosis and osteomyelitis are common pathologies of humans and cetaceans infected with Brucella ceti or B. pinnipedialis. Currently, 53 species of marine mammal are known to show seropositivity for brucellae, and B. ceti or B. pinnipedialis have been isolated or identified in polymerase chain reaction assays in 18 of these species. Brucellae have also been isolated from fish and identified in lungworm parasites of pinnipeds and cetaceans. Despite these circumstances, there are no local or global requirements for monitoring brucellosis in marine mammals handled for multiple purposes such as capture, therapy, rehabilitation, investigation, slaughter or consumption. Since brucellosis is a zoonosis and may be a source of infection to other animals, international standards for Brucella in potentially infected marine mammals are necessary.

Nitrification activity in the presence of 2-chlorophenol using whole nitrifying cells and cell-free extracts: batch and SBR assays.

Kinetic assays with a nitrifying consortium with whole nitrifying cells amended with 5 mg 2-CP-C/L and 100, 200, 300, or 500 mg NH4+-N/L were carried out in batch and nitrifying sequencing batch reactor (SBR) cultures. No nitrification activity was observed in batch assays with 100 mg NH4+-N/L and 5 mg 2-CP-C/L. Nevertheless, increasing the ammonium concentration from 200 to 500 mg NH4+-N/L allowed simultaneous ammonium and nitrite oxidation even in the presence of 5 mg 2-CP-C/L plus the halogenated compound consumption. Under these conditions, the ammonium monooxygenase enzyme participated in 2-CP consumption. Complete nitrification and simultaneous elimination of 5 mg 2-CP-C/L were achieved in the SBR amended with 200-500 mg NH4+-N/L. The inhibitory effect of 2-CP on the nitrite oxidation process completely disappeared under these conditions. Assays with nitrifying cell-free extracts, ammonium (100 mg NH4+-N/L), and 2-CP (5 mg 2-CP-C/L) were also conducted. In the absence of 2-CP, the nitrifying cell-free extracts maintained up to 60% of the nitrifying activity compared to whole-cells. Contrary to whole-cell assays, cell-free extracts were capable of simultaneously oxidizing ammonium and consuming 2-CP. However, the inhibitory effect of 2-CP on nitrification was still present as lower specific rates of ammonium consumption and nitrate production were obtained. Thus, these assays indicate that the presence of 2-CP affects both, the ammonium transport mechanism and the activity of nitrifying enzymes. Supplementary Information: The online version contains supplementary material available at 10.1007/s13205-023-03764-z.

Identifying Interaction Forces Via EMG Under Changing Motion Dynamics.

Musculoskeletal injuries can severely inhibit performance of activities of daily living. In order to regain function, rehabilitation is often required. Assistive rehabilitation devices can be used to increase arm mobility by guiding therapeutic exercises or assisting with motion. Electromyography (EMG) may be able to provide an intuitive interface between the patient and the device if appropriate classification models allow smart systems to relate these signals to the desired device motion. Unfortunately, the accuracy of pattern recognition models classifying motion in constrained laboratory environments significantly drops when used for detecting dynamic unconstrained movements. The objectives of this study were to quantity how various motion factors affect arm muscle activations during dynamic motion, and to use these motion factors and EMG signals for detecting interaction forces between the person and the environment during motion. The results quantity how EMG features change significantly with variations in arm positions, interaction forces, and motion velocities. The results also show that pattern recognition models were able to detect intended characteristics of motion based solely on EMG signals. Prediction of force was improved from 73.77% correct to 79.17% accuracy during elbow flexion-extension by properly selecting the features, and providing measurable arm position and velocity information as additional inputs to a linear discriminant analysis model.

Corrigendum to "Structural determinants of peptide-dependent TAP1-TAP2 transit passage targeted by viral proteins and altered by cancer-associated mutations" [Comput. Struct. Biotechnol. J. 19 (2021) 5072-5091].

[This corrects the article DOI: 10.1016/j.csbj.2021.09.006.].

Phase II clinical trial of liposomal-encapsulated doxorubicin citrate and docetaxel, associated with trastuzumab, as neoadjuvant treatment in stages II and IIIA HER2-overexpressing breast cancer patients. GEICAM 2003-03 study.

BACKGROUND: we previously reported a phase I trial of liposome-encapsulated doxorubicin citrate (LD), docetaxel and trastuzumab as neoadjuvant in stages II and IIIA human epidermal growth factor receptor 2-overexpressing breast cancer patients. This study evaluates the efficacy of this regimen in a phase II trial. PATIENTS AND METHODS: patients were treated with LD 50 mg/m(2) and docetaxel 60 mg/m(2) every 21days associated with standard trastuzumab dose and pegfilgrastim support. RESULTS: fifty-nine patients were enrolled; median age: 48 years (range 24-71 years); premenopausal patients: 36 (61%); 19 patients (32%) presented stage IIIA disease and 40 patients (67%) stage II; histological grades 2-3 tumors: 50 patients (84%) and estrogen receptor-progesterone receptor negative: 28 patients (47%). In all, 27% achieved a pathological complete response in breast and axilla (grade 5-Miller and Payne classification); 15% of patients achieved grade 4. Clinical and radiological response rates were 86% and 81%, respectively. Forty-two patients (71%) underwent breast-conserving surgery. The main grades 3-4 toxic effects were non-febrile neutropenia (29%) and fatigue (8%). Grade 2 left ventricular ejection fraction decline was observed in nine patients. No congestive heart failure was observed. CONCLUSIONS: LD plus docetaxel combination associated with trastuzumab as neoadjuvant is active in breast cancer and entails a favorable cardiotoxicity profile. This regimen is a new treatment option in these patients.

Exercise and cancer: a position statement from the Spanish Society of Medical Oncology.

Due to improvements in the number of cancer survivors and survival time, there is a growing interest in healthy behaviors, such as physical activity (PA), and their potential impact on cancer- and non-cancer-related morbidity in individuals with cancer. Commissioned by the Spanish Society of Medical Oncology (SEOM), in this review, we sought to distill the most recent evidence on this topic, focusing on the mechanisms that underpin the effects of PA on cancer, the role of PA in cancer prevention and in the prognosis of cancer and practical recommendations for clinicians regarding PA counseling. Despite the available information, the introduction of exercise programs into the global management of cancer patients remains a challenge with several areas of uncertainty. Among others, the most effective behavioral interventions to achieve long-term changes in a patient's lifestyle and the optimal intensity and duration of PA should be defined with more precision in future studies.

Randomized, double-blind, controlled trial, phase III, to evaluate the use of platelet-rich plasma versus hyaluronic acid in hip coxarthrosis. / Ensayo clínico fase III para evaluar la eficacia y seguridad del uso de plasma rico en plaquetas frente a ácido hialurónico en coxartrosis.

AIMS OF THE STUDY: To compare efficacy and safety of a home-made platelet-rich plasma (PRP) solution versus hyaluronic acid in patients with hip osteoarthritis not responding to conservative treatment and to correlate cellular composition of PRP to clinical outcomes. MATERIAL AND METHODS: This is a phase III clinical trial, double-blinded, controlled and randomised into two treatment groups (PRP and hyaluronic acid). Patients received one hip ultrasound-guided injection. Follow up was 12 months. Pain was assessed using VAS score, HHS and WOMAC were used as functional scores, analgesia, adverse events, cellular components (PRP group) in peripheral blood and in PRP were recorded. Clinical response was assessed using OARSI criteria. RESULTS: Seventy-four patients were included. Both groups improved in VAS, WOMAC and HHS score and reduced the amount of analgesia (p<.05). Significant differences were seen at 1 year post-treatment in HHS score (PRP 70.9 [3.7-58], hyaluronic acid 60.2[43-74.2] p<.05). No adverse events were observed in none of the groups. Platelet concentration was different between responders and non-responders (at 1 month, non-responders 449[438-578] x103 platelets/µl versus responders 565 [481-666] x103 platelets/µl, p<.044). There was a correlation between leukocytes concentration and clinical scores (VAS at six months, r=0.748, p<.013, WOMAC at 6 months r=0.748, p <.013). Patients with early stage hip OA showed higher response rate to PRP compared with late stage (11.51 OR, 95%CI 2.34-50.65, p<.03). CONCLUSIONS: Platelet-rich plasma injection improved hip function, reduced pain and the use of analgesia. It is important to bear in mind the cellular composition in order to achieve a better clinical response.

Arsenic accumulation in lettuce (Lactuca sativa L.) and broad bean (Vicia faba L.) crops and its potential risk for human consumption.

Exposure to arsenic (As) is considered one of the primary health risks humans face worldwide. This study was conducted to determine As absorption by broad beans and lettuce crops grown in soil with As contents and irrigated with water contaminated with this toxic element, in Pastos Chicos, Jujuy (Argentina). Total dry biomass (TDB) and total As were determined in soils, roots, leaves, pods and seeds. These data were used to determine several parameters, such as translocation (TF) and bioconcentration (BCF) factors, target hazard quotient (THQ), and carcinogenic risk (CR). Broad bean plants had the lowest biomass production when exposed to As in irrigation water and soil. Lettuce plants presented TDB reductions of 33.3 and 42.8% when grown in soil polluted with As, and in control soil under irrigation with contaminated water, respectively. The presence of this toxicant in broad bean seeds and lettuce leaves (edible parts) exceeded the limits established by Código Alimentario Argentino, i.e. 0.10 and 0.30 mg/kg, respectively. THQ values for lettuce leaves were higher than 1, the same as those for broad bean seeds when grown in soil with As contents and irrigated with arsenic-contaminated water, thus suggesting that consumers would run significant risks when consuming these vegetables. Furthermore, this type of exposure to As implied a CR that exceeded the acceptable 1 × 10-4 risk level. Hence, we may conclude that consuming lettuce and broad beans grown at the evaluated site brings about considerable health risks for local residents.

Design of User-Independent Hand Gesture Recognition Using Multilayer Perceptron Networks and Sensor Fusion Techniques.

According to the World Health Organization, stroke is the third leading cause of disability. A common consequence of stroke is hemiparesis, which leads to the impairment of one side of the body and affects the performance of activities of daily living. It has been proven that targeting the motor impairments as early as possible while using wearable mechatronic devices as a robot assisted therapy, and letting the patient be in control of the robotic system, can improve the rehabilitation outcomes. However, despite the increased progress on control methods for wearable mechatronic devices, a need for a more natural interface that allows for better control remains. In this work, a user-independent gesture classification method based on a sensor fusion technique using surface electromyography (EMG) and an inertial measurement unit (IMU) is presented. The Myo Armband was used to extract EMG and IMU data from healthy subjects. Participants were asked to perform 10 types of gestures in 4 different arm positions while using the Myo on their dominant limb. Data obtained from 14 participants were used to classify the gestures using a Multilayer Perceptron Network. Finally, the classification algorithm was tested on 5 novel users, obtaining an average accuracy of 78.94%. These results demonstrate that by using the proposed approach, it is possible to achieve a more natural human machine interface that allows better control of wearable mechatronic devices during robot assisted therapies.

Functional and histologic effects after implanting pluripotent stem cells in a murine model with sphincterotomy. / Efectos funcionales e histológicos posteriores al implante de células madre pluripotentes en un modelo murino con esfinterotomía.

INTRODUCTION AND AIMS: Fecal incontinence is a disabling condition with devastating consequences for the patients. Medical and surgical options are not very satisfactory, reason by which regenerative medicine has been considered in this field. In the present research, we analyzed functional and histologic effects after implanting pluripotent stem cells (PSCs) in a murine model with sphincterotomy. MATERIALS AND METHODS: Female Wistar rats were subjected to sphincterotomy and divided into three groups. Group 1 (control group) was treated with 300µL of balanced saline solution and group 2 (late treatment) and group 3 (early treatment) received 50,000 PSCs resuspended in 300µL of balanced saline solution. All animals were evaluated through high-resolution anorectal manometry 24hours before and after sphincterotomy and every month for three months. Finally, the rats were euthanized and histopathologic sections from the anal canal were obtained. RESULTS: All groups showed a decrease in resting anal pressure and squeeze anal pressure 24hours after sphincterotomy. At the third month, higher anal pressures in the groups treated with PSCs were detected. Regarding the histologic effects, the microscopic architecture was restored and there was a significant decrease in the inflammatory response in the groups treated with PSCs. CONCLUSION: PSCs implantation improves anal tone, as well as histologic structure, presenting better regenerative results when implanted as early treatment.

Jumping performance differences among elite professional handball players with or without previous ACL reconstruction.

AIM: Handball is one of the most challenging sports for the knee joint. Persistent strength and jumping capacity alterations may be observed among athletes who have suffered anterior cruciate ligament (ACL) injury. The aim of this study was to examine unilateral and bilateral jumping ability differences between previously ACL-reconstructed rehabilitated elite handball athletes and sex, age and uninjured sport activity level-pairs of control players. METHODS: It was a Cross-sectional study with one factor: previous ACL injury. We recruited 22 male (6 ACL-reconstructed and 16 uninjured control players) and 21 female (6 ACL-reconstructed and 15 uninjured control players) elite handball players who were evaluated 6.2±3.4 years after surgical ACL reconstruction. A battery of jump tests, including both bilateral and unilateral maneuvers, was performed. Two-tailed unpaired (intergroup comparison) and paired (intragroup comparison) t-tests were performed for mean comparisons. The P-value cut-off for significance was set at <0.05. RESULTS: The previously ACL-reconstructed female athletes showed a lower bilateral drop jump contact time (0.429±179.9 vs. 0.349±151 s, P<0.05) and less distance reached (3.820±0.54 vs. 4.428±0.44 m, P<0.05) in the unilateral triple hop for distance (UTHD) on their reconstructed leg compared with the dominant legs of the uninjured control athletes. No significant differences were observed for any other recorded variable. Among the male athletes, no significant differences between groups were found for the studied jumping variables. CONCLUSION: Previously ACL-reconstructed elite female handball athletes demonstrated both lower vertical bilateral drop jump (VBDJ) contact times and lower UTHD scores for the injured leg several years after injury. These deficits could contribute to an increase in ACL re-injury risk.

The complete normalization of the adrenocortical function as the criterion of cure after transsphenoidal surgery for Cushing's disease.

Transsphenoidal microsurgery is the standard treatment for patients with Cushing's disease. However, there is general lack of agreement regarding the definition of cure. We studied 58 patients with corrected hypercortisolism after transsphenoidal surgery for Cushing's disease. Plasma and urinary cortisol levels were measured after surgery. After the postsurgical hypocortisolism stage (or periodically in patients without hypocortisolism), urinary free cortisol, plasma cortisol at 0800 h and 2300 h, morning cortisol after 1 mg dexamethasone, and cortisol response to insulin-induced hypoglycemia were performed. Patients were classified in 3 groups: group I, patients with transient hypocortisolism and normal hypothalamus-pituitary-adrenal axis afterwards; group II, patients with transient hypocortisolism and abnormalities in the circadian rhythm or the stress response afterwards; and group III, patients without postoperative hypocortisolism. Thirty-three patients were included in group I, 8 in group II, and 17 in group III. Groups I and II were similar in postsurgical plasma cortisol (46.9 +/- 30.3 vs. 60.7 +/- 38.6 nM) and mean follow-up (69.8 vs. 68.8 months) but were significantly different in their recurrence rate (3.4% vs. 50%, P < 0.001). Patients in group III had normal postsurgical plasma and urinary cortisol but persistent abnormalities in circadian rhythm and stress response. After a mean follow-up of 39.1 months, their recurrence rate was similar to that of group II (64.7% vs. 50%). The complete normalization of the adrenocortical function, which is always preceded by postsurgical hypocortisolism, is associated with a very low recurrence risk and should be considered, in our opinion, the main criterion of surgical cure in Cushing's disease.