Medication Development For Aud: A Systematic Review Of Clinical Trial Methodology.

Refining clinical trial methodology has become increasingly important as study design is shown to influence treatment efficacy. To maximize the efficiency of randomized clinical trials (RCTs), researchers aim to establish standardized practices. The goal of this systematic review is to describe methodological practices of clinical trials for alcohol use disorder (AUD) over the past 40 years. To achieve this goal, a PubMed search was conducted in April 2023 for RCTs on AUD medications published between July 2018 through April 2023. Resulting studies were combined with a previous search from 1985 through 2018. Inclusion criteria for the RCT studies were: (1) a randomized controlled trial, (2) double or single blinded, (3) placebo or active control condition, (4) alcohol use as the primary endpoint, (5) 4 or more weeks of treatment, and (6) 12 or more weeks of follow-up. In total, methodological data from 139 RCTs representing 19 medications and spanning the past four decades were summarized. Results indicated that the most common medications tested were naltrexone (k=42), acamprosate (k=24), and baclofen (k=11). On average, participants were 74% male and consumed 226 drinks per month pre-randomization. The median length of treatment was 12 weeks (IQR= 12-16; min=4 max=52) and the median follow-up duration was 12.5 weeks (IQR: 12-26; min=7 max= 104). There were two broad domains of outcomes (i.e., abstinence and heavy drinking), with most studies featuring outcomes from both domains (k=87; 63%). Reporting practices were summarized by decade, revealing an increased enrollment of females, better reporting of race and ethnicity data, and less studies requiring pre-trial abstinence. This review summarizes the current state of the literature on randomized clinical trials for AUD including effect sizes for individual studies and summaries of key methodological features across this representative set of clinical trials.

[Medical-surgical complications and their impact on patients' return to work whilst follow-up major lower-limb amputations in Hospital del Trabajador in Santiago (HTS)]. / Complicaciones médico-quirúrgicas y su impacto en el retorno laboral durante el seguimiento de pacientes con amputación mayor de extremidades inferiores en el Hospital del Trabajador de Santiago (HTS).

INTRODUCTION: The presence of different complications whilst follow-up amputee patients reaches 10-80%. The main objective of this research is to assess the impact of these in the return-to-work of lower-limb traumatic amputation cases. MATERIALS AND METHODS: A retrospective cohort research was carried out. Clinic-demographic variables information was recollected in order to assess its linkage to different medical-surgical complications and functional outcomes. Survival curves were created to evaluate the return-to-work of patients with and without complications. RESULTS: A total of 46 patients, on average aged 45.7 years old (91.3% men, 71.7% without comorbidities), were included on this research. The most frequent level of amputation was transtibial (65.2%). Residual limb pain, phantom pain, dermatological-infectious complications and painful neuroma were registered in 80.4%, 58.7%, 50% y 30.4% of the cases respectively. Half of the patients had returned to their workplace after 2years of post-surgical follow-up. The return-to-work rates were significantly lower in patients suffering from residual limb pain (p=0.0083) and from painful neuroma (p=0.0051). CONCLUSION: Complications are frequent during traumatic-amputee patients' follow-up and, some of them, may impact on the return-to-work rate.

Eight-and-a-half syndrome as manifestation of acute disseminated adenovirus encephalomyelitis.

Acute disseminated encephalomyelitis is an immune mediated inflammatory-demyelinizing disease that usually manifests after infection or vaccination in school-age children. It typically presents a prodromal phase with flu-like symptoms, followed by a phase with varied clinical symptoms, neuro-ophthalmological alterations such as ophthalmoplegia or optic neuritis may occur. The differential diagnosis includes tumor, vascular, infectious, inflammatory and demyelinating diseases. Diagnosis is based on the clinical history and the characteristics of brain magnetic resonance imaging, the gold standard test. The study of the cerebrospinal fluid can help to guide the clinical picture. The prognosis is favorable, with an excellent response to corticosteroids and immunoglobulins, with minimal long-term sequelae in most cases. We report the case of an 8-year-old male with acute demyelinating disease due to adenovirus whose manifestation was an eight-and-a-half syndrome.

Obstetric anal sphicnter injury in a Spanish hospital.

OBJECTIVE: Estimation of the prevalence of obstetric anal sphincter injury (OASIS) in our environment and study of the associated risk factors. STUDY DESING: A retrospective observational study of cases and controls of assisted deliveries at the Severo Ochoa University Hospital of Leganés during the period from January 1, 2012, to December 31, 2017. A total of 88 OASIS diagnosed in the study period is compared with a randomly selected group of 181 controls of similar characteristics, vaginal births of cephalic of 36 weeks gestation or more, occurring during the same period. RESULTS: During the study period, a total of 8160 deliveries were attended in our hospital, of which 6187 were vaginal and we diagnosed a total of 88 OASIS at the time of delivery. The prevalence of OASIS is 1.07 % for total births and 1.42 % for total vaginal deliveries. In the case-control study, the univariate analysis shows statistical significance for nulliparity (OR 3.84; 95 % CI 2.155-6.834; p < 0.001), instrumental delivery (OR 8.73; 95 % CI 4.706-16.2016; p < 0.001), occipital posterior position (OR 7.23; 95 % CI 2.535-20.633; p < 0.001), long duration of the second stage of labor (OR 1.99; IC95 % 1,159-3,438; p 0.01), episiotomy (OR 3.51; 95 % CI 1,956-6,309; p < 0.001) and OBGYN labor assistant (<0.001). When performing the multivariate analysis, forceps delivery (OR19.68), Thierry spatulas delivery (OR 8.15), vacuum delivery (OR 2.74), nulliparity (OR 2.56) and fetal weight in grams (OR 1.12) remain significant in the final model. CONCLUSION: The main risk factors for the onset of OASIS are instrumental delivery, nulliparity and fetal birth weight.

Trichoderma asperellum Induces Maize Seedling Growth by Activating the Plasma Membrane H+-ATPase.

Although Trichoderma spp. have beneficial effects on numerous plants, there is not enough knowledge about the mechanism by which they improves plant growth. In this study, we evaluated the participation of plasma membrane (PM) H+-ATPase, a key enzyme involved in promoting cell growth, in the elongation induced by T. asperellum and compared it with the effect of 10 µM indol acetic acid (IAA) because IAA promotes elongation and PM H+-ATPase activation. Two seed treatments were tested: biopriming and noncontact. In neither were the tissues colonized by T. asperellum; however, the seedlings were longer than the control seedlings, which also accumulated IAA and increased root acidification. An auxin transport inhibitor (2,3,5 triiodobenzoic acid) reduced the plant elongation induced by Trichoderma spp. T. asperellum seed treatment increased the PM H+-ATPase activity in plant roots and shoots. Additionally, the T. asperellum extracellular extract (TE) activated the PM H+-ATPase activity of microsomal fractions of control plants, although it contained 0.3 µM IAA. Furthermore, the mechanism of activation of PM H+-ATPase was different for IAA and TE; in the latter, the activation depends on the phosphorylation state of the enzyme, suggesting that, in addition to IAA, T. asperellum excretes other molecules that stimulate PM H+-ATPase to induce plant growth.

In vivo postprandial bioavailability of interesterified-lipids in sodium-caseinate or chitosan based O/W emulsions.

Recent studies have shown that it should be possible to control lipid bioavailability through food structural approaches. Nevertheless, the gastrointestinal-tract physiological conditions must also be considered. To get a better understanding of this phenomenon, we evaluated the effect of emulsification, as well as the use of sodium caseinate or chitosan, on the postprandial bioavailability of interesterified-lipids in O/W emulsions after oral gastric feeding Sprague-Dawley rats. We verified that emulsification may increase lipid absorption, as determined after feeding sodium-caseinate emulsions. However, this result could not be generalised. Interesterified-lipids that were emulsified with chitosan were equally absorbed as those contained in non-emulsified interesterified-lipids/distilled-water blends.

Expresión inmunohistoquímica de p53 en individuos con liquen / Immunohistochemical expression of p53 in individuals with lichen planus

Objetivo: Estimar el riesgo del potencial de malignización del liquen plano bucal analizando la expresión de la proteína p53. Materiales y metodos: Se realizó un diseño de cohorte de sujetos con diagnostico histopatológico de liquen. El desenlace fue el desarrollo de cáncer si/no. El total de individuos que cumplió con los criterios de inclusión/exclusión fue de 58. A los 58 sujetos se les realizó la determinación de p53. Resultados: Cuarenta y nueve individuos mostraron una expresión de p53 menor al 5% con una P>0,05% intrasujeto no transformado. En los 9 individuos transformados se observaron diferencias significativas entre la determinación pre y post de la proteína p53. El Riesgo Relativo fue de 188 con una significación estadística de P< 0,01. Conclusion: La expresión de la proteína p53 en los individuos con liquen apoya la hipótesis que niveles superiores al 5%constituye un factor de incremento del riesgo en la transformación maligna de esta patología. Nuestros hallazgos deberían ser corroborados en el futuro con mayor número de individuos. La determinación de la p53 mediante IHQ en individuos con liquen plano bucal podría modificar el seguimiento clínico de estos individuos. Esto permitiría un diagnóstico precoz de cualquier alteración que pueda indicar un posible cambio hacia la malignización.

Objective: To determine the risk for potential malignant transformation of oral lichen planus by analyzing protein p53 expression. Materials and methods: Cohort study of subjects with a histopathologic diagnosis of lichen. The study analyzed whether or not subjects developed cancer. A total of 58 subjects fulfilled the inclusion/exclusion criteria, and were analyzed for p53. Results: Fortynine(49) subjects showed a p53 expression <5%, with a p>0.05 among subjects undergoing no transformation. In the 9 subjects undergoing malignant transformation, significant differences were observed between pre and post p53 expression. The relative risk was 188, with a statistical significance of p< 0.01. Conclusions: Protein p53 expression in subjects with lichen supports the hypothesis that levels >5% are associated with an increased risk of malignant transformation of this condition. Should our findings be proved in a larger series in the future, the clinical follow-up of these subjects could be modified. This would allow an early diagnosis of any disorder indicative of a potential malignant transformation.

The effect of interesterification on the bioavailability of fatty acids in structured lipids.

Fatty acid (FA) profile is a critical factor in the nutritional properties of fats, but, stereochemistry may also play a fundamental role in the rate and extent to which FAs are absorbed and become available. To better understand this phenomenon, we evaluated the bioavailability of FAs in linseed-oil and palm-stearin blends compared to their interesterified mix, using a sn-1,3 stereospecific lipase, to determine if there was any difference in terms of FA availability when using this technology. Test meals were fed through an intragastric feeding tube on Sprague-Dawley male rats after 18 h fasting. Postprandial blood samples were collected after meal or physiological serum (control) administration and the FA profile of plasma lipids was determined. Results showed that modification of the melting profile through interesterification, without altering the bioavailability determined by sn-2 stereochemistry, could delay lipid absorption at the beginning, but had no effect on total lipid absorption.

Inhibition of Ephrin B3-mediated survival signaling contributes to increased cell death response of non-small cell lung carcinoma cells after combined treatment with ionizing radiation and PKC 412.

Radiation therapy is frequently used to treat non-small cell lung cancers (NSCLCs). We have previously shown that a combination of ionizing radiation (IR) and the staurosporine analog PKC 412, but not Ro 31-8220, increases cell death in NSCLC cells. To identify genes involved in the enhancement of cell death, a total gene profiling in response to co-administration of (i) PKC 412 with IR, or (ii) Ro 31-8220 with IR was implemented. These combined treatments caused upregulation of 140 and 179 genes and downregulation of 253 and 425 genes, respectively. Certain genes were selected and verified by real-time quantitative PCR and, of these genes, robust suppression of Ephrin B3 expression was suggested as a possible cell death-inducing mechanism of combined treatment with IR and PKC 412. Indeed, silencing of Ephrin B3 using siRNA in NSCLC cells resulted in a major alteration of their morphology with an elongated phenotype, decreased proliferation and increased cell death signaling. Moreover, silencing of Ephrin B3 in combination with IR caused a decrease in IR-mediated G(2)-arrest, induced cellular senescence, inhibited MAPK ERK and p38 phosphorylation, and caused an upregulation of p27(kip1) expression. Finally, silencing of Ephrin B3 in combination with IR sensitized U-1810 cells to IR-induced apoptosis. In conclusion, we identify and describe Ephrin B3 as a putative signaling molecule involved in the response of NSCLC cells to combined treatment with PKC 412 and ionizing radiation.

Degradation of phenol by mechanical activation of a rutile catalyst.

In the present paper a novel mechanochemical process for the elimination of organic pollutants dissolved in water is proposed. In this regard, phenol aqueous solutions (100mgL(-1)) were ball-milled for 0, 12, 18, 24, 36, 48, and 72h with and without a well-characterized (XRD, SEM, and N(2) Adsorption), rutile powder catalyst and the reaction products analyzed with UV and GC/MS. It was found that when the catalyst was not included in the process, phenol was not affected, but when it was included, phenol was decomposed. The catalyst itself did not change and the reaction follows a pseudo-first-order kinetics. Besides, intermediates which are characteristic of the ()OH radical mechanism were found in the reaction products. Then, a mechanism similar to those accepted for other advanced oxidation processes was proposed. The value measured for the pseudo-first-order reaction constant was very low, indicating that the reported process is inefficient. Nevertheless, this problem could be solved by applying catalysts consisting of particles with smaller diameters.

Hole distribution in phononic crystals: design and optimization.

An exhaustive study has been made into the potential improvement in attenuation and focusing of phononic crystal arrays resulting from the deliberate creation of vacancies. Use is made of a stochastic search algorithm based on evolutionary algorithms called the epsilon variable multi-objective genetic algorithm which, in conjunction with the application of multiple scattering theory, enables the design of devices for effectively controlling sound waves. Several parameters are analyzed, including the symmetries used in the distribution of holes and the optimum number of holes. The validity and utility of the general rules obtained have been confirmed experimentally.

Intracerebral Hodgkin's lymphoma in a patient with human immunodeficiency virus.

Central nervous system (CNS) involvement by Hodgkin Lymphoma (HL) is rarely reported. Retrospective and prospective cohort studies suggest an incidence of 0.2-0.5%, mostly in relapsed disease. In spite of a 3 to 18-fold increased risk of HL in patients with human immunodeficiency virus (HIV), only two cases have been reported so far. In this paper, we now report a third case of HIV patient with HL who progressed with isolated CNS infiltration after a standard chemotherapy induced clinical remission. In 1991, when the first case of intracerebral involvement in HIV+ HL was reported an increase of this type of cases would have been expected, but only one more case has been reported since then.

Primary malignant schwannoma of the cervical plexus with melanocytic differentiation.

Primary malignant schwannomas are rare neoplasms of nerve sheath origin, especially in the location of the head and neck where few cases are described in the literature. These tumours may pose a diagnostic dilemma in the work-up of a neck mass. The case presented here is of a malignant schwannoma that originated in the cervical plexus with the rare histological feature of melanocytic differentiation. Histopathological examination with immunostaining techniques is essential for the diagnosis of these tumours. The management of these neoplasms is still controversial, although the treatment of choice is radical surgical excision of the lesion. The role of postoperative radiotherapy or chemotherapy is not clear, although some authors recommend its use to prevent local recurrence, for unresectable recurrent tumours or in cases of distant metastases.

Rapidly-progressive liver failure secondary to melanoma infiltration.

We describe the case of a 51-year-old man with a history of intraocular melanoma treated with radiotherapy 2 years previously. The patient was diagnosed with mild hypertransaminasemia that progressed to acute liver failure and death in a period of one month. Radiological investigations such as spiral computed tomography and abdominal ultrasonography failed to give an etiologic diagnosis. Autopsy revealed melanoma with diffuse infiltration of the hepatic parenchyma. Because diagnosis is usually delayed, the prognosis of intraocular melanoma is poor. In 40% of cases metastases are present at diagnosis, and the most frequently affected organ is the liver (93-95%). Presentation as acute liver failure can appear after a long disease-free period. For this reason, periodic laboratory tests and hepatic ultrasound examination are recommended in patients diagnosed with this malignancy.

[Functional disorders of FOF1-ATPase in submitochondrial particles obtained from platelets of patients with a diagnosis of probable Alzheimer's disease]. / Alteración funcional de la F0F1-ATPasa en partículas submitocondriales obtenidas de plaquetas de pacientes con diagnóstico de enfermedad de Alzheimer probable.

INTRODUCTION: Recent studies indicate that decreased energy generation by mitochondria is a feature that is common across neurodegenerative diseases. PATIENTS AND METHODS: In order to obtain direct evidence that mitochondrial functioning is altered, we measured the hydrolytic activity of F0F1-ATPase and its capacity to generate a stable proton gradient in submitochondrial particles in 29 patients diagnosed with probable Alzheimer's disease (AD). Submitochondrial particles were obtained from platelets of patients with a diagnosis of probable AD and from clinically healthy controls. RESULTS: Data revealed that the hydrolytic activity of F0F1-ATPase increases significantly in patients with probable AD (41.7+/-4.3 nmol PO4 min-1[mg protein]-1, n=29) as compared to the control subjects (29.1+/-1.9 nmol PO4 min-1 [mg protein]-1, n=29). It is important to note that, in the male population with probable AD, we found that hydrolytic activity of F0F1-ATPase increased as cerebral deterioration progressed. We also detected a lower pH gradient in the submitochondrial particles of patients with probable AD (0.28+/-0.08 pH units, n=25) as compared to the controls (0.5+/-0.1 pH units, n=20). CONCLUSIONS: Overall, these data point to an alteration in the functioning of the enzyme.

Development of mammalian embryos exposed to mixed-size nanoparticles.

Inhaled or ingested ultrafine nanoparticles and their effects on early pregnancy remain polemic. The objectives of the study were: (a) to determine the embryotoxic effects of nanoparticles at the 2-cell stage and (b) to localize the internalized nanoparticles in the blastocyst. Thawed mouse 2-cell embryos (no. = 128) were exposed to either mixed-size polystyrene-based nanoparticles (11 million/ml) or control G1.3 medium and assessed after 72 hours. Additionally, blastocysts (no. = 146) were exposed to nanoparticles and analyzed. The results showed that the nanoparticles did not inhibit 2-cell embryo development to the blastocyst stage (89.4 vs 96.8%; treated vs control). There were no differences in hatching (34.8 vs 43.5%), implantation (13.6 vs 24.2%) and degeneration (10.6 vs 3.2%). Delayed exposure to nanoparticles showed similar percent hatching (40.7 vs 47.3%) and implantation (17.6 vs 20.0%). Although nanoparticles were internalized, embryo development was not inhibited suggesting a lack of embryotoxicity. During hatching, the larger nanoparticles adhered to the extruding blastocyst, preferentially on trophoblasts, but interference was insignificant. Exposure to polystyrene-based nanoparticles at the concentration tested are not associated with embryonic loss.

Progressive multifocal leukoencephalopathy after stem cell transplantation, unsuccessfully treated with cidofovir.

We report a patient with progressive multifocal leukoencephalopathy (PML) after autologous stem cell transplantation (SCT) for non-Hodgkin's lymphoma (NHL). This is an unusual association, and to date only seven cases have been reported. This is the first case of PML after SCT treated with cidofovir, and the fifth case treated with this drug in a patient without human immunodeficiency virus (HIV) infection. In the previous four patients treated with cidofovir the outcome was discouraging, as was the case in this patient.

[Hookwire localization of pulmonary nodules for video-thorascopic surgical resection]. / Localización mediante arpón de nódulos pulmonares para su resección por cirugía videotoracoscópica.

OBJECTIVES: To assess the usefulness of a technique for inserting hookwires guided by computed tomography to locate and resect pulmonary nodules by video-assisted thoracoscopy. To describe the procedure and its complications. PATIENTS AND METHODS: Nine pulmonary nodules were located in nine patients. All were