Clinical experience with integrase inhibitors in HIV-2-infected individuals in Spain.

BACKGROUND: HIV-2 is a neglected virus despite estimates of 1-2 million people being infected worldwide. The virus is naturally resistant to some antiretrovirals used to treat HIV-1 and therapeutic options are limited for patients with HIV-2. METHODS: In this retrospective observational study, we analysed all HIV-2-infected individuals treated with integrase strand transfer inhibitors (INSTIs) recorded in the Spanish HIV-2 cohort. Demographics, treatment modalities, laboratory values, quantitative HIV-2 RNA and CD4 counts as well as drug resistance were analysed. RESULTS: From a total of 354 HIV-2-infected patients recruited by the Spanish HIV-2 cohort as of December 2017, INSTIs had been given to 44, in 18 as first-line therapy and in 26 after failing other antiretroviral regimens. After a median follow-up of 13 months of INSTI-based therapy, undetectable viraemia for HIV-2 was achieved in 89% of treatment-naive and in 65.4% of treatment-experienced patients. In parallel, CD4 gains were 82 and 126 cells/mm3, respectively. Treatment failure occurred in 15 patients, 2 being treatment-naive and 13 treatment-experienced. INSTI resistance changes were recognized in 12 patients: N155H (5), Q148H/R (3), Y143C/G (3) and R263K (1). CONCLUSIONS: Combinations based on INSTIs are effective and safe treatment options for HIV-2-infected individuals. However, resistance mutations to INSTIs are selected frequently in failing patients, reducing the already limited treatment options.

The hominid thumb and its influence on the employment during evolution.

Not available.

[Cerebral cryptococcosis and immune reconstitution inflammatory syndrome. Case report]. / Criptococosis cerebral, voriconazol, niveles plasmáticos y síndrome de reconstitución inmune. Reporte de un caso.

We report a 45-year-old male with AIDS who had a Cryptococcus neoformans central nervous system infection. He was treated with amphotericin B deoxycholate subsequently changed to voriconazole due to systemic toxicity of the former. Plasma levels of voriconazole were insufficient with a standard dose (0.7 µg/mL), therefore, the dose was increased thereafter to reach appropriate levels (4.5 µg/mL). Anti-retroviral therapy was started five weeks after voriconazole initiation with non-interacting drugs and he was discharged after a favorable evolution. He was re-admitted three months later due to seizures; a brain magnetic resonance showed new sub-cortical nodules. After excluding alternative causes and demonstrating fungal eradication, an immune reconstitution inflammatory syndrome (IRIS) event was suspected and treated with a short course of steroids. His evolution was satisfactory.

From art to science: the functional damage due to thumb osteoarthritis finely described by Velazquez 300 years before its clinical description.

Velazquez showed to know the entity of thumb osteoarthritis by finely describing it in one of his paintings. The concepts of anatomical damage, loss of strenght, and functional impairment are transmitted to the observer.

Analyzing the functional effects of dynamic and static splints after radial nerve injury.

The radial nerve is a commonly injured upper extremity peripheral nerve. The inability to extend the wrist results in a loss of hand function and dexterity that affects patients' ability to perform their activities of daily living. There is no strong evidence to support a particular splint design for improving dexterity. This cohort study compared whether a static or dynamic splint can improve hand dexterity when assessed with the 9-hole peg test (9-HPT) after radial nerve injury. Thirty-four subjects with radial nerve palsy participated in the study. The test was repeated three times for each subject, first without the splint, and then while wearing the control static wrist splint, and finally while wearing the dynamic splint. The 9-HPT was used as the outcome measure. The 9-HPT times were 36.4±4.8seconds without a wrist splint and improved when using the static and the dynamic splints to 33.5±4.5seconds (P<0.01) and 25.7±3.5seconds (P<0.01) respectively. The use of a dynamic splint after radial nerve palsy can provide the patient with greater manual dexterity when compared to using no splint or a static splint.

Intrahippocampal administration of 5-HT6 receptor drugs on memory consolidation and amnesia protocols.

To our knowledge the intrahippocampal serotonergic 5-HT6 receptor tone on memory and amnesia models remains unexplored. Hence, in the present work we tested intrahippocampal administration of serotonin or 5-hydroxytryptamine (5-HT)6 receptor experimental molecules with differential intrinsic activity. Methods: In the present study, Automatized Autoshaping memory task was used, useful measuring memory, neural markers, and pharmacological effects. We are hypothesizing that experimental molecules with differential intrinsic activity might reveal serotonergic tone. Particularly, intrahippocampal administration of 5-HT6 receptor compounds with differential intrinsic activity (i.e., agonistic and antagonistic) might evidencing a serotonergic tone via this receptor. Bilateral intrahippocampal dose-response curves show that administration of EMD386088 (10 and 100 µg) had no effect or (50 µg) decreased conditioned responses (CR) in short- and long-term memory (STM and LTM, respectively); while SB-399885 (10 or 100 µg) significantly decreased CR in STM and LTM (24 and 48-h) or (50 µg) had no effect; thus suggesting that there is a 5-HT6 receptor tone regulating both STM and LTM. Moreover, intrahippocampal inactive doses of EMD386088 (5 µg) plus SB-399885 (0.5 µg) did not affect STM and LTM; however, partially or completely prevented the scopolamine or dizocilpine-induced amnesia. Thus confirming that both drugs exerted their effects through 5-HT6 receptor and that there is a hippocampal serotonergic tone under amnesic states, similar to that striatal.

TCNQ molecular semiconductor of the Cu(II)TAAB macrocycle: Optical and electrical properties.

The present study reports the doping of a semiconducting molecular material through the formation of hydrogen bonds between the macrocycle Cu(II)(TAAB) and the electronic acceptor TCNQ. According to density functional theory (DFT) calculations and electron paramagnetic resonance (EPR) analysis, the doped compound has the shape of a distorted square pyramid, with four nitrogen atoms in the equatorial position and the apical oxygen atom from the water ligands. These water molecules can generate strong hydrogen bonds with TCNQ and the TAAB metallic complex. Thin films of copper molecular material were obtained through high vacuum evaporation and were structurally characterized by IR spectroscopy, EPR and scanning electron microscopy (SEM). Additionally, the absorption coefficient (α) and photon energy (hν) were calculated from UV-vis spectroscopy and used to determine the optical activation energy in each film, from which its semiconducting behavior was established. An important aspect to consider is that the presence of hydrogen bonds is essential to establish the semiconducting nature of these species; this chemical behavior, as well as the resulting electronic mobility, have been studied by DFT theoretical calculations, which reinforce the experimental conclusion of a relationship between Cu(II)TAAB and TCNQ moieties generated by a weak bond. Finally, I-V characteristics have been obtained from a glass/ITO/doped molecular semiconductor/Ag device using Ag and ITO electrodes. Results for the copper-based device show that, at low voltages, the conduction process is of an ohmic nature while, at higher voltages, space-charge-limited current (SCLC) is found. It is highly probable that the doping effect in TCNQ favors electronic transport due to the formation of conduction channels caused by dopant-favored anisotropy.

O-CAS, a fast and universal method for siderophore detection.

In this work, the popular CAS assay for siderophore detection, based on the utilization of chrome azurol S, was redesigned and optimized to produce a new, fast, non-toxic, and easy method to determine a wide variety of microorganisms capable of siderophore production on a solid medium. Furthermore, this specific bioassay allows for the identification of more than one single siderophore-producing microorganism at the same time, using an overlay technique in which a modified CAS medium is cast upon culture agar plates (thus its name "O-CAS", for overlaid CAS). Detection was optimized through adjustments to the medium's composition and a quantifying strategy. Specificity of the bioassay was tested on microorganisms known for siderophore production. As a result, a total of 48 microorganisms were isolated from three different types of samples (fresh water, salt water, and alkaline soil), of which 36 were determined as siderophore producers. The compounds identified through this method belonged to both hydroxamate and catechol-types, previously reported to cause color change of the CAS medium from blue to orange and purple, respectively. Some isolated microorganisms, however, caused a color change that differed from previous descriptions.

A prepubertal surge of thyrotropin precedes an increase in thyroxine and 3,5,3'-triiodothyronine in normal children.

The variations in plasma levels of TSH, T4, T3, and rT3, during the pubertal period, were studied in 647 school students from the urban area of Santiago in Chile (47% males and 53% females) with ages ranging between 7.5 and 15 yr. The subjects were grouped by age in consecutive intervals of 6 months each, and pubertal development was determined in every subject. TSH showed a significant increase, reaching a peak in the 9- to 9.5-yr interval. The same was found for T3 and T4, which reached a peak by 10 and 11 yr. The T4/T3 ratio did not show any significant variation with age. After 9.5 yr, a decrease in rT3 and increase in the T4/rT3 ratio was found. The TSH peak preceded the onset of clinical pubertal development, while the T3 and T4 peaks coincided with this onset. The variations in rT3 suggest an increase of peripheral conversion of T4 to T3. These transient events, not described until now, could be termed thyroidarche and could have a significant effect on pubertal growth and development.

Folylpolyglutamate analogs can inhibit casein kinase II from Xenopus laevis.

Polyglutamate analogs of folate and related compounds were tested as inhibitors of casein kinase II (CK II) obtained from Xenopus laevis. The inhibitory capacity of the pteroyl, 4-amino-10-methyl pteroyl (the methotrexate aromatic moiety), and p-aminobenzoil derivatives increased as the number of gamma-glutamates attached went from 2 to 7. The nature of the aromatic head, group was also important since hexa-gamma-glutamatic acid had no inhibitory activity while the folylhexaglutamate derivatives were strong inhibitors with relative potency of methotrexate greater than pteroyl greater than p-aminobenzoic acid. The inhibition of CK II by methotrexate gamma-pentaglutamate was competitive with casein and showed an apparent K(i) of 90 microM.

Copolymers of glutamic acid and tyrosine are potent inhibitors of oocyte casein kinase II.

Polypeptides rich in glutamic acid are strong inhibitors purified from isolated nuclei of Xenopus laevis oocytes of casein kinase II. The presence of tyrosine in these peptides greatly enhances their inhibitory capacity. Using casein as a substrate, copolyglu:tyr (4:1) has an I50 value of 20 nM, 250 fold lower than that of polyglutamic acid which is 5 microM. A similar large difference is observed when a synthetic peptide is used as substrate. The inhibition of copolyglu:tyr is competitive with casein and can be completely reversed by high ionic strength. The relative inhibitory capacity of the polypeptides tested, in descending order, is copolyglu:tyr (4:1) greater than copolyglu:tyr (1:1) greater than polyglu greater than copolyglu:phe (4:1) greater than copolyglu:ala (6:4) greater than copolyglu:leu (4:1). The high affinity for tyrosine-containing acid peptides is shared by rat liver and yeast casein kinase II so that it seems to be a general property of these enzymes.

Effect of ethionine on the in vitro synthesis and degradation of mitochondrial translation products in yeast.

The effect of ethionine, an amino acid analog of methionine, has been studied in Saccharomyces cerevisiae in relation to cell growth, oxygen consumption, in vitro protein synthesis of mitochondrial translation products (MTPs) and the degradation of those mitoribosomally made proteins by an ATP-dependent process present within the organelle. Ethionine was found to increase the generation time of those cells already committed to cell division and to abolish the initiation of new cell cycles. Oxygen consumption of cultures grown in the presence of the analog was drastically reduced. Ethionine was also found to impair the incorporation of methionine and leucine into mitochondrial translation products, however the synthesis of proteins was not totally blocked and, apparently, mitochondria utilized ethionine as a precursor amino acid. MTPs synthesized by isolated mitochondria in the presence of ethionine were rapidly degraded inside the organelle at a faster rate compared with the normal proteins synthesized under identical conditions in the mitochondria. It is also shown that these in vitro synthesized proteins are degraded by an ATP-stimulated proteolytic system, as has been previously established.

Does perchlorate in drinking water affect thyroid function in newborns or school-age children?

Perchlorate is known to suppress thyroid function by inhibiting uptake of iodide by the human thyroid at doses of 200 mg/day or greater. A study was conducted to investigate the potential effects of perchlorate in drinking water on thyroid function in newborns and school-age children. A total of 162 school-age children and 9784 newborns were studied in three proximate cities in northern Chile that have different concentrations of perchlorate in drinking water: Taltal (100 to 120 micrograms/L), Chañaral (5 to 7 micrograms/L), and Antofagasta (non-detectable: < 4 micrograms/L). Among schoolchildren, no difference was found in thyroid-stimulating hormone levels or goiter prevalence among lifelong residents of Taltal or Chañaral compared with those of Antofagasta, after adjusting for age, sex, and urinary iodine. No presumptive cases of congenital hypothyroidism were detected in Taltal or Chañaral; seven cases were detected in Antofagasta. Neonatal thyroid-stimulating hormone levels were significantly lower in Taltal compared with Antofagasta; this is opposite to the known pharmacological effect of perchlorate, and the magnitude of difference did not seem to be clinically significant. These findings do not support the hypothesis that perchlorate in drinking water at concentrations as high as 100 to 120 micrograms/L suppresses thyroid function in newborns or school-age children.

Criptococosis cerebral, voriconazol, niveles plasmáticos y síndrome de reconstitución inmune: reporte de un caso / Cerebral cryptococcosis and immune reconstitution inflammatory syndrome: case report

We report a 45-year-old male with AIDS who had a Cryptococcus neoformans central nervous system infection. He was treated with amphotericin B deoxycholate subsequently changed to voriconazole due to systemic toxicity of the former. Plasma levels of voriconazole were insufficient with a standard dose (0.7 μg/mL), therefore, the dose was increased thereafter to reach appropriate levels (4.5 μg/mL). Anti-retroviral therapy was started five weeks after voriconazole initiation with non-interacting drugs and he was discharged after a favorable evolution. He was re-admitted three months later due to seizures; a brain magnetic resonance showed new sub-cortical nodules. After excluding alternative causes and demonstrating fungal eradication, an immune reconstitution inflammatory syndrome (IRIS) event was suspected and treated with a short course of steroids. His evolution was satisfactory.

[Analysis of the Structure of Acute Psychotic Disorder]. / Análisis de la estructura del síndrome psicótico agudo.

INTRODUCTION: Schizophrenia is a clinically heterogeneous disorder. A multifactorial structure of this syndrome has been described in previous reports. The aim of this study was to evaluate what are the possible diagnostic categories in patients having acute psychotic symptoms, studying their clinical characteristics in a cross-sectional study. METHODS: An instrument for measuring psychotic symptoms was created using previous scales (SANS, SAPS, BPRS, EMUN, Zung depression scale). Using as criteria statistical indexes and redundance of items, the initial instrument having 101 items has been reduced to 57 items. 232 patients with acute psychotic symptoms, in most cases schizophrenia, attending Clínica Nuestra Señora de la Paz in Bogotá and Hospital San Juan de Dios in Chía have been evaluated from April, 2008 to December, 2009. Multivariate statistical methods have been used for analyzing data. RESULTS: A six-factor structure has been found (Deficit, paranoid-aggressive, disorganized, depressive, bizarre delusions, hallucinations). Cluster analysis showed eight subtypes that can be described as: 1) bizarre delusions-hallucinations; 2) deterioration and disorganized behavior; 3) deterioration; 4) deterioration and paranoid-aggressive behavior; 5) bizarre delusions; 6) paranoia-anxiety- aggressiveness; 7) depressive symptoms and bizarre delusions; 8) paranoia and aggressiveness with depressive symptoms CONCLUSION: These subtypes allow a more exhaustive characterization that those included in standard classification schemes and should be validated in longitudinal studies.

Effects of d-amphetamine on short- and long-term memory in spontaneously hypertensive, Wistar-Kyoto and Sprague-Dawley rats.

Diverse studies indicate that the attention deficit hyperactivity disorder (ADHD) is associated with alterations in encoding processes, including working or short-term memory. Some ADHD dysfunctional domains are reflected in the spontaneously hypertensive rat (SHR). Here SHR-saline group showed significantly poor STM and LTM relative to SD and WKY saline rats. SD and WKY rats treated with d-amphetamine displayed better STM and LTM, compared to SD-vehicle, WKY-vehicle or SHR-d-amphetamine groups.