COL1A1, CCDC170, and ESR1 single nucleotide polymorphisms associated with distal radius fracture in postmenopausal Mexican women.

Objective: The aim of this study was to analyze the genetic association of five ESR1 single nucleotide polymorphisms (SNPs) (rs3020331, rs851982, rs1999805, rs2234693, rs3020404), four COL1A1 SNPs (rs1800012, rs2075555, rs2412298, rs1107946), and two SNPs on the CCDC170 gene (rs9479055, rs4870044) with distal radius fracture (DRF) in a group of postmenopausal Mexican women.Methods: A case-control study was conducted. Cases (n = 182) were women above the age of 38 years with low-energy DRF, and controls (n = 201) were women without. Analysis was done through real-time polymerase chain reaction. Frequencies and Hardy-Weinberg equilibrium were calculated. A multivariate analysis including bone mass index, age, menarche, and menopause as covariables was carried out. Finally, haplotype and linkage disequilibrium (LD) analyses were performed.Results:COL1A1 rs1107946 was strongly associated with DRF. Both CCDC170 SNPs showed strong association with DRF. For the ESR1 gene, four SNPs (rs2234693, 3020404, rs3020331, and rs851982) showed very strong association with DRF. Additionally, the region between the latter two showed strong LD.Conclusions: A strong association of DRF with variants in these genes was found, including haplotypes and a region with strong LD on ESR1. The results suggest that these SNPs could be useful to detect the population at risk of presenting DRF among Mexican perimenopausal women.

Mucocutaneous manifestations of cocaine abuse: a review.

Cocaine is an alkaloid extracted from the leaves of the Erythroxylum coca plant that emerged in the 1970s as a fashionable drug among members of certain social backgrounds. Cocaine abuse is a problem of current interest, which is mostly hidden and underdiagnosed, but dramatically widespread among all socio-economic strata, and with an incidence which is increasing at an alarming rate. There are 1.5 million cocaine consumers in the USA. In Spain, the prevalence of consumption among the population between 15 and 65 years old is higher, reaching 3.1%. Because of this, it seems important to understand and recognize all the mucocutaneous manifestations of cocaine abuse which have been reported in the literature to clarify and to help dermatologists in their daily practice. In this article, we describe the principal mucocutaneous manifestations of cocaine abuse and we review isolated case reports which have been published in the literature. Because the dermatologist may deal with an unknown problem as well as with an already well-known history of cocaine abuse, it seems logical to separate the mucocutaneous manifestations into those which are frequent and highly suggestive, such as those caused by vascular injury, damage to mucosal membranes, infectious diseases or neutrophilic dermatosis, especially when suffered by young people and in consonance with other systemic manifestations and, those which have been reported in the literature as isolated case reports. We also summarize the main aspects of its pathogeny, principal pharmacodynamic and pharmacokinetic characteristics, and diagnostic tools.

Guitar-String Suture to Facilitate Closure of a Finger-like Flap for Reconstruction of the Nose. / Suturas en «cuerda de guitarra¼ para facilitar el cierre del colgajo digitiforme en la reconstrucción nasal.

INTRODUCTION: The basic principle of a lobed or finger-like transposition flap is that, after covering the defect with the transposed tissue, the donor site is closed primarily. With large defects, a second lobe may be added to the flap if primary closure of the area left by the first lobe is not possible. The flap can often be made to adapt to the defect, but this maneuver, in combination with primary closure of the adjacent tissue, can sometimes produce excessive tension and compromise the blood supply. MATERIAL AND METHODS: We present a series of 4 patients with epithelial tumors of the lateral wall of the nose. The defects left by surgical excision were covered by finger-like transposition flaps. Subcutaneous sutures called guitar-string sutures were used to reduce the size of the defect and facilitate tension-free closure. CONCLUSIONS: We propose use of the guitar-string subcutaneous suture in those cases in which the defect is larger than the area that can be covered by the flap. This will make it easier to adapt the flap to the defect and will reduce the risk of excessive tension causing necrosis of the transposed tissue.

Advancing allele group-specific amplification of the complete HLA-C gene--isolation of novel alleles from three allele groups (C*04, C*07 and C*08).

A variety of strategies have been designed for sequence-based HLA typing (SBT) and for the isolation of new human leucocyte antigen (HLA) alleles, but unambiguous characterization of complete genomic sequences remains a challenge. We recently reported a simple method for the group-specific amplification (GSA) and sequencing of a full-length C*04 genomic sequence in isolation from the accompanying allele. Here we build on this strategy and present homologous methods that enable the isolation of HLA-C alleles belonging to another two allele groups. Using this approach, which can be applied to sequence-based typing in some clinical settings, we have successfully characterized three novel HLA-C alleles (C*04:128, C*07:01:01:02, and C*08:62).

Analysis of exosome release and its prognostic value in human colorectal cancer.

A significant proportion of extracellular nucleic acids in plasma circulate highly protected in tumor-specific exosomes, but it is unclear how the release of exosomes is modulated in carcinogenesis. We quantified by cytometry exosomes in plasma of 91 colorectal cancer patients to evaluate their potential as a tumor indicator and their repercussions on diagnosis and prognosis. We examined the involvement of TSAP6, a TP53-regulated gene involved in the regulation of vesicular secretion, in levels of circulating exosomes in plasma of colorectal patients and in HCT116 TP53-(wild-type and null) human colorectal cancer cell lines. The fraction of exosomes in cancer patients was statistically higher than in healthy controls (mean rank » 53.93 vs. 24.35). High levels of exosomes in plasma of patients correlated with high levels of carcino-embryonic antigen (P » 0.029) and with poorly differentiated tumors (P » 0.039) and tended to have shorter overall survival than patients with low levels (P » 0.056). Release of exosomes did not correlate with TSAP6 expression; and regulation of TSAP6 by TP53 was not shown either in tumor samples or in HCT116 cell lines. Although it was not suggested that the TP53/TSAP6 pathway regulates the release of exosomes into the plasma of colorectal cancer patients, the level of circulating exosomes may be used as a tumor indicator, because it correlates with poor prognosis parameters and shorter survival.

[On the Ten Commandments of the Finochietto Surgical School]. / Sobre los Diez Mandamientos de la Escuela Quirúrgica Finochietto.

No Abstract available.

The Mars 2020 Perseverance Rover Mast Camera Zoom (Mastcam-Z) Multispectral, Stereoscopic Imaging Investigation.

Mastcam-Z is a multispectral, stereoscopic imaging investigation on the Mars 2020 mission's Perseverance rover. Mastcam-Z consists of a pair of focusable, 4:1 zoomable cameras that provide broadband red/green/blue and narrowband 400-1000 nm color imaging with fields of view from 25.6° × 19.2° (26 mm focal length at 283 µrad/pixel) to 6.2° × 4.6° (110 mm focal length at 67.4 µrad/pixel). The cameras can resolve (≥ 5 pixels) ∼0.7 mm features at 2 m and ∼3.3 cm features at 100 m distance. Mastcam-Z shares significant heritage with the Mastcam instruments on the Mars Science Laboratory Curiosity rover. Each Mastcam-Z camera consists of zoom, focus, and filter wheel mechanisms and a 1648 × 1214 pixel charge-coupled device detector and electronics. The two Mastcam-Z cameras are mounted with a 24.4 cm stereo baseline and 2.3° total toe-in on a camera plate ∼2 m above the surface on the rover's Remote Sensing Mast, which provides azimuth and elevation actuation. A separate digital electronics assembly inside the rover provides power, data processing and storage, and the interface to the rover computer. Primary and secondary Mastcam-Z calibration targets mounted on the rover top deck enable tactical reflectance calibration. Mastcam-Z multispectral, stereo, and panoramic images will be used to provide detailed morphology, topography, and geologic context along the rover's traverse; constrain mineralogic, photometric, and physical properties of surface materials; monitor and characterize atmospheric and astronomical phenomena; and document the rover's sample extraction and caching locations. Mastcam-Z images will also provide key engineering information to support sample selection and other rover driving and tool/instrument operations decisions.

Pre-Flight Calibration of the Mars 2020 Rover Mastcam Zoom (Mastcam-Z) Multispectral, Stereoscopic Imager.

The NASA Perseverance rover Mast Camera Zoom (Mastcam-Z) system is a pair of zoomable, focusable, multi-spectral, and color charge-coupled device (CCD) cameras mounted on top of a 1.7 m Remote Sensing Mast, along with associated electronics and two calibration targets. The cameras contain identical optical assemblies that can range in focal length from 26 mm ( 25.5 ∘ × 19.1 ∘ FOV ) to 110 mm ( 6.2 ∘ × 4.2 ∘ FOV ) and will acquire data at pixel scales of 148-540 µm at a range of 2 m and 7.4-27 cm at 1 km. The cameras are mounted on the rover's mast with a stereo baseline of 24.3 ± 0.1  cm and a toe-in angle of 1.17 ± 0.03 ∘ (per camera). Each camera uses a Kodak KAI-2020 CCD with 1600 × 1200 active pixels and an 8 position filter wheel that contains an IR-cutoff filter for color imaging through the detectors' Bayer-pattern filters, a neutral density (ND) solar filter for imaging the sun, and 6 narrow-band geology filters (16 total filters). An associated Digital Electronics Assembly provides command data interfaces to the rover, 11-to-8 bit companding, and JPEG compression capabilities. Herein, we describe pre-flight calibration of the Mastcam-Z instrument and characterize its radiometric and geometric behavior. Between April 26 t h and May 9 t h , 2019, ∼45,000 images were acquired during stand-alone calibration at Malin Space Science Systems (MSSS) in San Diego, CA. Additional data were acquired during Assembly Test and Launch Operations (ATLO) at the Jet Propulsion Laboratory and Kennedy Space Center. Results of the radiometric calibration validate a 5% absolute radiometric accuracy when using camera state parameters investigated during testing. When observing using camera state parameters not interrogated during calibration (e.g., non-canonical zoom positions), we conservatively estimate the absolute uncertainty to be < 10 % . Image quality, measured via the amplitude of the Modulation Transfer Function (MTF) at Nyquist sampling (0.35 line pairs per pixel), shows MTF Nyquist = 0.26 - 0.50 across all zoom, focus, and filter positions, exceeding the > 0.2 design requirement. We discuss lessons learned from calibration and suggest tactical strategies that will optimize the quality of science data acquired during operation at Mars. While most results matched expectations, some surprises were discovered, such as a strong wavelength and temperature dependence on the radiometric coefficients and a scene-dependent dynamic component to the zero-exposure bias frames. Calibration results and derived accuracies were validated using a Geoboard target consisting of well-characterized geologic samples. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s11214-021-00795-x.

Multiple sclerosis associates with LILRA3 deletion in Spanish patients.

The genetic susceptibility to multiple sclerosis (MS) is only partially explained, and it shows geographic variations. We analyse here two series of Spanish patients and healthy controls and show that relapsing MS (R-MS) is associated with a gene deletion affecting the hypothetically soluble leukocyte immunoglobulin (Ig)-like receptor A3 (LILRA3, 19q13.4), in agreement with an earlier finding in German patients. Our study points to a gene-dose-dependent, protective role for LILRA3, the deletion of which synergizes with HLA-DRB1(*)1501 to increase the risk of R-MS. We also investigated whether the risk of suffering R-MS might be influenced by the genotypic diversity of killer-cell Ig-like receptors (KIRs), located only approximately 400 kb telomeric to LILRA3, and implicated in autoimmunity and defence against viruses. The relationship of LILRA3 deletion with R-MS is not secondary to linkage disequilibrium with a KIR gene, but we cannot exclude some contributions of KIR to the genetic susceptibility to R-MS.

Immunostaining in whole-mount lipid-cleared peripheral nerves and dorsal root ganglia after neuropathy in mice.

Immunohistochemical characterization of primary afferent fibers (intact or after nerve damage) is traditionally performed in thin sections from dorsal root ganglia (DRGs) or in teased fibers, as light scattering in whole-mounts compromises visualization. These procedures are time-consuming, require specific equipment and advanced experimental skills. Lipid-clearing techniques are increasing in popularity, but they have never been used for the peripheral nervous system. We established a modified, inexpensive clearing method based on lipid-removal protocols to make transparent peripheral nerve tissue (inCLARITY). We compared retrograde-labeling and free-floating immunostaining with cryo-sections. Confocal microscopy on whole-mount transparent DRGs showed neurons marked with retrograde tracers applied to experimental neuromas (Retrobeads, Fluoro-ruby, Fluoro-emerald, DiI, and Fluoro-gold). After immunostaining with calcitonin gene-related peptide (peptidergic) or isolectin IB4 (non-peptidergic), nociceptors were visualized. Immunostaining in transparent whole-mount nerves allows simultaneous evaluation of the axotomized branches containing the neuroma and neighboring intact branches as they can be mounted preserving their anatomical disposition and fiber integrity. The goal of our study was to optimize CLARITY for its application in peripheral nerve tissues. The protocol is compatible with the use of retrograde tracers and improves immunostaining outcomes when compared to classical cryo-sectioning, as lack of lipids maximizes antibody penetration within the tissue.

Ulnar shortening: results for treatment of distal radioulnar joint pathology and conversion to DRUJ replacement arthroplasty.

BACKGROUND: Ulnar shortening (US) is used for treatment of ulnar abutment, early osteoarthrosis (OA) and distal radioulnar joint (DRUJ) instability. However, it has never been strongly advocated as a mid-stage procedure to slow OA progression and reduce requirement of secondary DRUJ procedures. The study aim was to determine if a specific sigmoid notch type is likely to lead to DRUJ replacement after US. METHODS: A retrospective study of 119 patients (124 wrists) with DRUJ painful early osteoarthritis, ulnar abutment and DRUJ instability that underwent US was performed. The goals of osteotomy were to decrease pain and slow the initiation or progression of OA. Sigmoid notch type, previous trauma, bone healing time, pain relief, ulnar variance and conversion to DRUJ arthroplasty were analyzed. RESULTS: Of the 124 wrists studied, bone healing took 3.33 months of average (union rate 98.3%). Sigmoid notch type distribution was 55.6% for type 1, 25.8% for type 2, and 18.5% for type 3. Of the patients with pain after US, 37 had hardware removal and 13 required a DRUJ semi-constrained arthroplasty. Even though analysis did not show any statistically significant correlation, a slight trend towards association of sigmoid notch type 3 with conversion to DRUJ arthroplasty was found. CONCLUSION: US has a role in treatment of DRUJ pathology, and its use may delay the need for DRUJ secondary procedures, protecting the native joint. A specific sigmoid notch type does not present risk for OA and does not appear to be related to conversion to DRUJ arthroplasty. Type of study: Therapeutic.

ANTECEDENTES: El acortamiento cubital es utilizado para el tratamiento del síndrome de impactación, osteoartrosis (OA) temprana y la inestabilidad de la articulación radiocubital distal (ARCD). Sin embargo, no se ha recomendado como procedimiento intermedio para detener la progresión de la OA y reducir la necesidad de procedimientos secundarios. El objetivo es determinar si un tipo específico de la escotadura sigmoidea predispone a una artroplastia de la ARCD después del acortamiento cubital. MÉTODOS: Estudio retrospectivo de 119 pacientes (124 muñecas) a las que se les realizó acortamiento cubital. El objetivo de la osteotomía fue disminuir el dolor y retardar el progreso de la OA. Se analizó el tipo de escotadura sigmoidea, trauma previo, tiempo de consolidación ósea, alivio del dolor, varianza cubital y conversión a artroplastia. RESULTADOS: De las 124 muñecas estudiadas, la consolidación ocurrió en 3.33 meses en promedio (98.3% de consolidación). El tipo de escotadura sigmoidea fue 55.6% tipo 1; 25.8% tipo 2 y 18.5% tipo 3, 37 pacientes ameritaron retiro de material y 13 una artroplastia de la ARCD semiconstriñida. Aunque el análisis no mostró ninguna correlación estadísticamente significativa, una tendencia leve hacia la Asociación del tipo 3 de la escotadura sigmoidea con la conversión a la artroplastia de ARCD fue encontrada. CONCLUSIONES: El acortamiento cubital juega un papel en el tratamiento de la patología de la ARCD, su uso puede retrasar la necesidad de procedimientos secundarios. Un tipo de escotadura sigmoidea específica no presenta riesgo para la OA y no parece estar relacionado con la conversión a la artroplastia de la ARCD.

Brain MRI findings in children and adolescents with Fabry disease.

OBJECTIVE: To evaluate the presence of white matter and hemorrhagic lesions in brain MRI of children and adolescents with Fabry disease (FD). METHODS: Brain MRI studies in 44 consecutive children and teenagers (20 boys, mean age 14.6 years, range 7-21 years) were evaluated using classic sequences as well as, GRE-weighted images, for white matter lesions (WML) and chronic microbleed detection. All patients lacked history of stroke or TIA. Brain MRI findings in 46 consecutive children and adolescents without FD, referred for the evaluation of headaches (36 females, mean age 14.1 years, range 7-21 years) were evaluated as a control group. Additionally, we assessed the clinical manifestations of FD. RESULTS: Seven children (15.9%) with FD had brain MRI evidence of asymptomatic WML (5 girls, mean age 14.8 years, range: 13-20 years) compared with 3 children (6.5%) in the control group (p = 0.01). Brain abnormalities in patients with FD revealed WML, deep gray matter and infratentorial involvement. Three patients presented two lesions each. None of the children showed microbleeds. Regarding clinical manifestations, 90.9% of the patients had signs or symptoms of FD. CONCLUSION: We identified asymptomatic white matter brain lesions in 15.9% of children with FD without clinical history of stroke. FD is a treatable disorder that should be routinely included in the differential diagnosis of both symptomatic and asymptomatic brain lesions in children and adolescents. The detection of brain lesions may foster earlier treatment.

Report From the First and Second Spanish Killer Immunoglobulin-Like Receptor Genotyping Workshops: External Quality Control for Natural Killer Alloreactive Donor Selection in Haploidentical Stem Cell Transplantation.

An important factor affecting the success in the setting of related haploidentical hematopoietic stem cell transplantation (HSCT) is the graft-versus-leukemia effect mediated by natural killer (NK) cells when the donor displays NK alloreactivity versus the recipient. NK cell function is regulated by killer immunoglobulin-like receptors (KIR) and it has been described that donor KIR genotype influences transplantation outcome. This has led to a requirement of laboratories to have a quality assurance program for validation and control of their KIR genotyping methods. The goal of the 1st and 2nd Spanish KIR Genotyping Workshops was to provide an external proficiency testing program in KIR genotyping for Spanish immunology and transplant laboratories. These workshops were conducted during the years 2014-2016 and consisted of 17 participating laboratories typing a set of 20 samples. The presence/absence of 16 mandatory KIR loci (2DL1, 2DL2, 2DL3, 2DL4, 2DL5, 2DS1, 2DS2, 2DS3, 2DS4, 2DS5, 2DP1, 3DL1, 3DL2, 3DL3, 3DS1, and 3DP1) was evaluated per sample. Methods for KIR genotyping included polymerase chain reaction with the use of sequence-specific primers and sequence-specific oligoprobes. Consensus typing was reached in all samples, and the performance of laboratories in external proficiency testing was satisfactory in all cases. The polymorphism detected in the small sample studied in both workshops is indicative of an ample variety of KIR gene profiles in the Spanish population.

Restriction end-converting vectors with tandem repeated multiple cloning sites.

The construction, characterization and uses of four vectors with novel multiple cloning sites (MCS) are described. The MCS consist of a central zone with unique restriction sites, flanked by two zones in which four sites are repeated in a direct sense. These vectors allow the insertion of fragments with the same or different restriction ends and their rescue with a multiple combination of ends, identical or different. This system conserves the XGal blue-white selection characteristics of the pUC plasmids, as well as their use as sequencing vehicles.

Distribution of insertion sequence IS1 in multiple-antibiotic resistant clinical Enterobacteriaceae strains.

The presence of insertion sequence IS1 in 70 multiple-antibiotic resistant clinical strains was determined. This 70-strain collection comprised 46 Escherichia coli, 18 Salmonella and 6 Shigella strains. The presence of IS1 was detected in the chromosome and plasmids of 73% and 63% of the strains, respectively, and 51% of the strains carried IS1 in both. The frequency of IS1 was higher in Salmonella than in E. coli and Shigella strains. A total of 31 strains carried large plasmids with IS1; 10 of these strains (32.3%) were able to transfer all or some of the antibiotic resistance markers to E. coli K12 or S. typhimurium recipient strains. Resistance markers of all clinical strains were maintained stably after several generations of growth. The presence of IS1 in a relatively high percentage of plasmids of multiple-antibiotic resistant clinical isolates, suggests a role for this sequence in the dissemination of genes which code for antibiotic resistance.

Neurotransmitter amino acids in cerebrospinal fluid of patients with Parkinson's disease.

We measured the CSF and plasma levels of glutamate, glutamine, aspartate (only in plasma), asparagine, glutamine, glycine and GABA in 31 patients with Parkinson's disease and in 45 matched controls. We used an ion-exchange chromatography method. When compared to controls, PD patients had similar CSF levels of glutamate, glutamine, asparagine, and glycine higher CSF GABA levels higher plasma levels of glutamine, asparagine, and glycine, and lower plasma levels of aspartate. The CSF levels of the amino acids measured were not correlated with the clinical features of PD. Our results that CSF GABA levels are not decreased in PD as previously suggested.

Cerebrospinal fluid cyclic guanosine 3'5' monophosphate levels in Parkinson's disease.

We measured CSF and plasma levels of cGMP in 22 patients with Parkinson's disease (PD) and in 28 age and sex-matched controls. PD patients had similar plasma cGMP levels than those of controls, although they showed a non-significant trend towards higher CSF cGMP levels (P=0.07). PD patients treated with levodopa showed significantly higher CSF cGMP levels than those not treated with this drug (P<0.01), and controls (P<0.01). However, treatment with dopamine agonists did not influence CSF cGMP levels. Plasma and CSF levels of cGMP did not correlate with age at onset, duration, and severity of PD. These results suggest that changes in the concentration of cGMP in CSF of patients with PD are not related with the disease, but rather with levodopa therapy.

Use and acceptance of the "paper pill". A novel approach to oral contraception.

A randomized, crossover study comparing the acceptance of and attitudes towards two dosage forms of the same oral contraceptive product - a paper presentation and the conventional tablet, was carried out in a network of rural and suburban research centers in the State of Durango, México. The results failed to show any significant advantage (in terms of acceptability or continuation) of the paper formulation. Although two-thirds of the participants indicated a preference for the conventional tablet, there was a high degree of acceptance of the paper formulation among new oral contraceptive acceptors.

PIP: A randomized, crossover study comparing the acceptance of and attitude towards 2 dosage forms of the same oral contraceptive product -- a paper presentation and the conventional tablet -- was carried out in a network of rural and suburban research centers in the State of Durango, Mexico. 68 women used the paper pill for 3 months and then switched to the tablet for another 3, while 70 women took the tablet 1st and switched to the paper pill. The results failed to show any significant advantage in terms of acceptability or continuation for the paper formulation. Both formulations were perceived as effective and easy to use. 2/3 of the participants indicated a preference for the tablets at the end of the study, but there was a high degree of acceptance of the paper formulation among new oral contraceptive acceptors. The authors believe that an improved paper formulation could be successfully introduced into a national program, if there were substantial savings in cost associated with the "paper pill."

[Vocal and respiratory diadochokinesia in Friedreich's ataxia. Neuropathological correlations]. / Diadococinésies vocales et respiratoires dans l'ataxie de Friedreich. Corrélations neuropathologiques.

Acoustic analysis of unvoiced diadochokinetic respiratory cycles helped identify two kinds of impairments in ten Friedreich's ataxia patients. Four patients manifested moderate problems maintaining regularity in the repetition of unvoiced respiratory cycles, and also showed moderate articulatory dysarthric problems in a syllabic repetition task. Six patients had severe respiratory insufficiency in the inspiration/expiration repetition task, and exhibited very important amplitude and fundamental frequency disturbances and a much slower rate of syllabic utterances. This respiratory insufficiency and aggravated speech disorders were linked to presence of pontine and medullary atrophy, sites comprising the respiratory centers of the brain stem.