Clinical and mutational features of X-linked agammaglobulinemia in Mexico.

X-linked agammaglobulinemia (XLA) is caused by BTK mutations, patients typically show <2% of peripheral B cells and reduced levels of all immunoglobulins; they suffer from recurrent infections of bacterial origin; however, viral infections, autoimmune-like diseases, and an increased risk of developing gastric cancer are also reported. In this work, we report the BTK mutations and clinical features of 12 patients diagnosed with XLA. Furthermore, a clinical revision is also presented for an additional cohort of previously reported patients with XLA. Four novel mutations were identified, one of these located in the previously reported mutation refractory SH3 domain. Clinical data support previous reports accounting for frequent respiratory, gastrointestinal tract infections and other symptoms such as the occurrence of reactive arthritis in 19.2% of the patients. An equal proportion of patients developed septic arthritis; missense mutations and mutations in SH1, SH2 and PH domains predominated in patients who developed arthritis.

Evaluation of GenoFlow DR-MTB Array Test for Detection of Rifampin and Isoniazid Resistance in Mycobacterium tuberculosis.

The aim of this study was to evaluate the GenoFlow DR-MTB array test (DiagCor Bioscience, Hong Kong) on 70 cultured isolates and 50 sputum specimens. The GenoFlow array test showed good sensitivity and specificity compared to the phenotypic Bactec 460TB. This array accurately detected mutations inrpoB,katG, andinhAassociated with resistance to rifampin and isoniazid.

Characterization of the dengue outbreak in Nuevo Leon state, Mexico, 2010.

We studied serotypes circulating dengue virus (DENV) cases, entomological Breteau index, rain-fall index and epidemiology of groups affected during the 2010 outbreak in Nuevo Leon, Mexico. From 2,271 positive cases, 94% were dengue classic and 6% dengue hemorrhagic fever; DENV1 was mainly isolated (99%) (Central-American lineage of American-African-genotype). We found correlation between two environmental phenomena (Increment of rainfall and vector-indexes) (p ≤ 0.05) with epidemiological, clinical and risk of DENV-1 ongoing transmission.

Antimicrobial activity of Chlorhexidine, Peracetic acid and Sodium hypochlorite/etidronate irrigant solutions against Enterococcus faecalis biofilms.

AIM: To evaluate the antimicrobial effect of 2.5% sodium hypochlorite alone (NaOCl) and associated with 9% HEBP (NaOCl/HEBP), 2% peracetic acid (PAA) and 2% chlorhexidine (CHX), on the viability of Enterococcus faecalis biofilms attached to dentine. METHODOLOGY: Biofilms of E. faecalis were grown on the surface of dentine blocks for 5 days and then exposed to the irrigating solutions for 3 min. Distilled water was used as the control. The total biovolume and the percentage of dead cells of the infected dentine were measured by means of confocal microscopy and the live/dead technique. Nonparametric tests were used to determine statistical differences (P < 0.05). RESULTS: NaOCl and the NaOCl/HEBP mixture were associated with a significantly greater percentage of dead cells, followed by PAA (P < 0.05). No significant antimicrobial effect of CHX was observed in comparison with the control group. Total biovolume decreased significantly in NaOCl, NaOCl/HEBP and PAA solutions in comparison with the CHX and control groups. CONCLUSIONS: NaOCl alone or associated with HEBP were the most effective irrigant solutions in dissolving and killing E. faecalis biofilms.

A NEW OBSERVATION OF 13q DELETION SYNDROME: SEVERE UNDESCRIBED FEATURES.

A new observation of 13q deletion syndrome: severe undescribed features: 13q deletion syndrome is characterized by a wide phenotypic spectrum resulting from a partial deletion-of the long arm of chromosome 13. It consists predominantly of mental and motor retardation, craniofacial dysmorphia, growth retardation, and several congenital malformations. We present a new case with 13q deletion syndrome phenotypically characterized by severe major malformations, some of them still undescribed, consisting of left diaphragmatic hernia, right pulmonary sequestration, hypoplastic left heart syndrome, pancreatic agenesis, polysplenia, and catastrophic central nervous system malformations: semilobar holoprosencephaly, occipital myelomeningocele, partial agenesis of the corpus callosum and agenesis of olfactory bulbs. Fluorescence in situ hybridization technique using the probe LSI D13S319 (13q1l4) SO/ LSI 13q34 SG determined partial monosomy of chromosome 13 in 39/100 cells (mosaicism).

Stromal disrupting effects of nab-paclitaxel in pancreatic cancer.

BACKGROUND: Nab-paclitaxel and gemcitabine have demonstrated a survival benefit over gemcitabine alone in advanced pancreatic cancer (PDA). This study aimed to investigate the clinical, biological, and imaging effects of the regimen in patients with operable PDA. METHODS: Patients with operable PDA received two cycles of nab-paclitaxel and gemcitabine before surgical resection. FDG-PET and CA19.9 tumour marker levels were used to measure clinical activity. Effects on tumour stroma were determined by endoscopic ultrasound (EUS) elastography. The collagen content and architecture as well as density of cancer-associated fibroblasts (CAFs) were determined in the resected surgical specimen and compared with a group of untreated and treated with conventional chemoradiation therapy controls. A co-clinical study in a mouse model of PDA was conducted to differentiate between the effects of nab-paclitaxel and gemcitabine. RESULTS: A total of 16 patients were enrolled. Treatment resulted in significant antitumour effects with 50% of patients achieving a >75% decrease in circulating CA19.9 tumour marker and a response by FDG-PET. There was also a significant decrement in tumour stiffness as measured by EUS elastography. Seven of 12 patients who completed treatment and were operated had major pathological regressions. Analysis of residual tumours showed a marked disorganised collagen with a very low density of CAF, which was not observed in the untreated or conventionally treated control groups. The preclinical co-clinical study showed that these effects were specific of nab-paclitaxel and not gemcitabine. CONCLUSION: These data suggest that nab-paclitaxel and gemcitabine decreases CAF content inducing a marked alteration in cancer stroma that results in tumour softening. This regimen should be studied in patients with operable PDA.

A preclinical and clinical study of mycophenolate mofetil in pancreatic cancer.

A high throughput screening for anticancer activity of FDA approved drugs identified mycophenolic acid (MPA), an inhibitor of inositol monophosphate dehydrogenase (IMPDH) as an active agent with an antiangiogenesis mode of action. Exposure of pancreatic cancer cell lines to MPA resulted in growth inhibition and reduced the expression of VEGF that was reversed by supplementing the media with guanosine supporting and IMPDH-dependant mechanism. In preclinical in vivo study, MPA showed a moderate inhibition of tumor growth in a panel of 6 human derived pancreatic cancer xenografts but reduced the expression of VEGF. To investigate the effects of MPA in human pancreatic cancer, a total of 12 patients with resectable pancreatic cancer (PDA) received increasing doses of mycophenolate mofetil (MMF) in cohorts of 6 patients each from 5-15 days prior to surgical resection. Treatment was well tolerated with one episode of grade 1 muscle pain, one episode of grade 2 lymphopenia (2 gr/day dose) and one episode of grade 2 elevantion in LFT (all in the 2 gr./day dose). Patients recovered from surgery uneventfully with no increased post-operative complications. Assessment of CD31, VEGF, and TUNEL in resected specimens compared to a non treated control of 6 patients showed no significant variations in any of the study endpoints. In conclusion, this study shows the feasibility of translating a preclinical observation to the clinical setting and to explore a drug mechanism of action in patients. MPA, however, did not show any hints of antiangiogenesis of anticancer clinical activity questioning if this agent should be further developed in PDA.

Effect of omega-3 dietary supplements with different oxidation levels in the lipidic profile of women: a randomized controlled trial.

The oxidation level of omega-3 fatty acid supplements commercialized in capsules may be a risk to consumers' health. For this purpose, we have designed a single-blind, parallel-group, randomized controlled trial in which 52 women participated. Volunteers were randomly distributed into three groups consuming: (1) less oxidized oil pills, (2) highly oxidized oil pills and (3) no capsules. All groups consumed a fish-rich diet. Circulating glucose, total cholesterol, triglycerides and glutamic pyruvic transaminase were determined at the beginning and end (30 days) of the study. As a result, the ingestion of less oxidized ω-3 supplements reduced circulating triglyceride and cholesterol levels, as opposed to the highly oxidized omega-3 capsules, which had a negative effect on cholesterol levels. In conclusion, the level of oxidation of the supplements is a key factor in controlling circulating lipid profile. Therefore, manufacturers must pay attention to the quality of the prime product prior to encapsulation.

Diagnostic benefits of adding EspC, EspF and Rv2348-B to the QuantiFERON Gold In-tube antigen combination.

Interferon (IFN)-γ release assays (IGRAs) are used to diagnose latent tuberculosis (TB) infection (LTBI). To improve the accuracy of these tests, different approaches, such as alternative cytokine detection and using different antigens, are considered. Following this purpose, this study aims to evaluate the addition of EspC, EspF and Rv2348-B to those present in the QuantiFERON-TB Gold In-Tube (QFN-G-IT). We included 115 subjects: 74 active TB patients, 17 LTBI individuals and 24 healthy controls. Whole blood samples were collected in QFN-G-IT and in-house tubes containing different combinations of EspC, EspF and Rv2348-B, together with ESAT-6, CFP-10, and TB7.7. After overnight incubation at 37 ºC, plasma was harvested and IFN-γ quantified. IFN-γ levels in the QFN-G-IT and in-house tubes correlated very good (Spearman Rho(r) > 0.86). In-house antigen combinations distinguished healthy individuals from those with active TB and LTBI (specificities and sensitivities higher than 87.5% and 96.3%, respectively [AUC > 0.938]). Adding EspC, EspF and Rv2348-B, increased the sensitivity of the test, being the addition of EspC and Rv2348-B the combination that yielded a higher sensitivity with no specificity loss. Addition of these antigens could improve diagnosis in patients with impaired or immature immune response who are at high risk of developing TB.

[Final size attained in type 1 diabetes children]. / Talla final en diabéticos tipo 1 diagnosticados en la edad pediátrica.

OBJECTIVE: To describe the final height and height-gain in relation to target height, in children with type 1 diabetes mellitus, and analyse their relationship to different variables. PATIENTS AND METHODS: Retrospective analysis of the growth data of 52 children (27 girls) diagnosed with type 1 diabetes mellitus before 14 years old, and followed up until their final height was attained. MAIN VARIABLES: final height, target height, illness duration, glycated haemoglobin (HbA1c), insulin dose, BMI, and other autoimmune diseases. RESULTS: The height SDS (standard deviation scale) at diagnosis was slightly higher (0.734 in boys and 0.563 in girls). During the development of the disease, a growth reduction was seen, which was significantly higher in boys of prepubertal age (p = 0.016). The mean final height attained was 173.14 +/- 5.28 cm in boys and 161.9 +/- 6.97 cm in girls. Height gain was 1.56 +/- 3.66 in boys (SDS = -0.034) and 2.26 +/- 6.13 in girls (SDS = 0.385). The only variable significantly related to height gain was mean glycated-haemoglobin (growth reduction of 2 cm for every increment of 1% in mean glycated-haemoglobin). CONCLUSIONS: At onset, diabetic children were slightly taller than the general population. A growth reduction was shown as the disease developed, significantly higher in boys of prepubertal age. The final height in boys was slightly lower than the mean, but in girls was similar to the general population. Both sexes attained their target height, although the height gain was less in boys. Poorer metabolic control was associated with reduced height gain.

[Effectiveness of the virtual reality in the rehabilitation of the upper limb in the spinal cord injury. A systematic review]. / Efectividad de la realidad virtual en la rehabilitacion del miembro superior en la lesion de la medula espinal. Revision sistematica.

INTRODUCTION: Spinal cord injury is a complex and life-disrupting condition. The functional recovery of the upper limb has been considered as an important objective in tetraplegia because it improves significantly the quality of living in these patients. Virtual reality is a new emerging tool of rehabilitation in spinal cord injured patients. AIM: To carry out a systematic review about the information about the application of these systems in spinal cord injury in the rehabilitation of the upper limb. PATIENTS AND METHODS: This review includes clinical trials dated until April 2018, which investigate the functional recovery of the upper limb through virtual reality systems in patients with complete or incomplete tetraplegia. The following databases were used to search for those clinical trials: Scopus, Web of Science, PubMed, Medline Complete, Science Direct, CINHAL and Brain. RESULTS: Five articles were selected for this review, including randomized clinical trials and clinical trials. The main results show a good tendency on the functional recovery with the combination of virtual reality systems and conventional therapy. CONCLUSIONS: The main limitations and the low quality of the studies show the necessity of further investigations with this new tool of rehabilitation. However, the incorporation of virtual reality systems as a rehabilitation supplement might be a beneficial tool on the functional recovery in spinal cord injury.

TITLE: Efectividad de la realidad virtual en la rehabilitacion del miembro superior en la lesion de la medula espinal. Revision sistematica.Introduccion. La lesion de la medula espinal es un estado funcional complejo que limita gravemente la vida de la persona. Por ello, la recuperacion de la funcionalidad del miembro superior en la tetraplejia se considera un objetivo primordial, ya que mejora significativamente la calidad de vida de estas personas. Ademas de las terapias convencionales, la realidad virtual supone un nuevo enfoque terapeutico en la rehabilitacion del lesionado medular. Objetivo. Realizar una revision sistematica sobre la efectividad de la rehabilitacion del miembro superior en pacientes con lesion medular a traves de la realidad virtual. Pacientes y metodos. Se recopilaron datos de ensayos clinicos hasta abril de 2018 que investigaran la rehabilitacion con sistemas de realidad virtual en los miembros superiores de pacientes con lesion medular completa e incompleta. Las bases de datos consultadas en esta revision incluyeron: Scopus, Web of Science, PubMed, Medline Complete, Science Direct, CINHAL y Brain. Resultados. Se analizaron cinco articulos, los cuales incluyeron ensayos controlados aleatorizados y ensayos clinicos. Los principales resultados de los estudios muestran buena tendencia de la rehabilitacion a traves de la realidad virtual en combinacion con terapia convencional. Conclusiones. Las limitaciones encontradas en los estudios, asi como su baja calidad metodologica, suponen la necesidad de mayores investigaciones acerca de la efectividad de esta nueva herramienta. Aun asi, la buena tendencia de los estudios se considera de interes para futuras investigaciones.

Sociodemographic factors affecting the comprehension of clinical information by inpatients undergoing trauma surgery. / Determinantes sociodemográficos de la comprensión de la información clínica en pacientes hospitalizados intervenidos de cirugía traumatológica.

INTRODUCTION: The clinical information process is the basis of the doctor-patient relationship. It starts with the information provided before signing informed consent and ends on the termination of the doctor-patient relationship. The influence of demographic variables in the information process has not been thoroughly studied for inpatients undergoing surgery. In this study we aim to answer two questions: 1) Does gender have an influence on the information process for these patients? 2) Are there other factors that affect the process? METHOD: A prospective study carried out using an 'ad hoc' designed survey on a 200-inpatient sample after undergoing surgery in the trauma and orthopaedics department of our hospital. Sampling was simple random. RESULTS: We found differences in the consistency of the answers by gender in the question regarding surgical priority, with the women having a better understanding of it (p=.04). The rest of the questions show no differences by gender. However, in the population analyzed, age and educational level are the main modifiers of understanding, and they are both related to gender (p<.0001; p=.003, respectively). CONCLUSIONS: In clinical practice, it is fundamental to keep in mind the factors that affect the information process. According to our results, the factors that define greater vulnerability in relation to the information process are age and low educational level.

Inorganic arsenic content in Ecuadorian rice-based products.

Arsenic intake in the world is linked with drinking water and food; the main sources of inorganic As (i-As) exposure in food are rice and rice-based products. The consumption of rice in Ecuador is 53.2 kg year-1 and it is the most commonly used cereal for the preparation of many popular dishes especially for subjects with celiac disease. Objectives of this research were: (i) to determine the content of i-As in foods widely consumed by Ecuadorians with celiac disease, (ii) to calculate the i-As dietary intake, and (iii) to model and predict the health risks of the population under study as a result of their exposure to i-As from rice-based food. The estimated daily intakes of Ecuadorian children (below 3 years of age) and adults were established at 0.52 and 0.55 µg kg-1 body weight d-1, respectively. These values were above the lower BMDL01 value established for i-As established by the EFSA; consequently, it can be concluded that health risk cannot be excluded for the Ecuadorian population with celiac disease.

Use of IP-10 detection in dried plasma spots for latent tuberculosis infection diagnosis in contacts via mail.

The aim of this study was to test the use of IP-10 detection in dried plasma from contact studies individuals (contacts of smear positive patients), by comparing it with IP-10 and IFN-γ detection in direct plasma, to establish IP-10 detection in DPS as a useful assay for LTBI diagnosis. Whole blood samples were collected from 80 subjects: 12 with active tuberculosis (TB), and 68 from contact studies. The amount of IFN-γ produced by sensitized T cells was determined in direct plasma by QuantiFERON Gold In-Tube test. IP-10 levels were determined in direct and dried plasma by an in-house ELISA. For dried plasma IP-10 determination, two 25 µl plasma drops were dried in Whatman903 filter paper and sent by mail to the laboratory. Regarding TB patients, 100.0%, 91.7% and 75.0% were positive for IFN-γ detection and IP-10 detection in direct and dried plasma, respectively. In contacts, 69.1%, 60.3% and 48.5% had positive results after IFN-γ and IP-10 in direct and dried plasma, respectively. The agreement among in vitro tests was substantial and IP-10 levels in direct and dried plasma were strongly correlated (r = 0.897). In conclusion, IP-10 detection in dried plasma is a simple and safe method that would help improve LTBI management.

Bcl-XL modulates the differentiation of immortalized human neural stem cells.

Understanding basic processes of human neural stem cell (hNSC) biology and differentiation is crucial for the development of cell replacement therapies. Bcl-X(L) has been reported to enhance dopaminergic neuron generation from hNSCs and mouse embryonic stem cells. In this work, we wanted to study, at the cellular level, the effects that Bcl-X(L) may exert on cell death during differentiation of hNSCs, and also on cell fate decisions and differentiation. To this end, we have used both v-myc immortalized (hNS1 cell line) and non-immortalized neurosphere cultures of hNSCs. In culture, using different experimental settings, we have consistently found that Bcl-X(L) enhances neuron generation while precluding glia generation. These effects do not arise from a glia-to-neuron shift (changes in fate decisions taken by precursors) or by only cell death counteraction, but, rather, data point to Bcl-X(L) increasing proliferation of neuronal progenitors, and inhibiting the differentiation of glial precursors. In vivo, after transplantation into the aged rat striatum, Bcl-X(L) overexpressing hNS1 cells generated more neurons and less glia than the control ones, confirming the results obtained in vitro. These results indicate an action of Bcl-X(L) modulating hNSCs differentiation, and may be thus important for the future development of cell therapy strategies for the diseased mammalian brain.