Miracle-dz/UniFAR-FTUs huggingface dataset:
Bioequivalence study between a fixed-dose single-pill formulation of nebivolol plus hydrochlorothiazide and separate formulations in healthy subjects using high-performance liquid chromatography coupled to tandem mass spectrometry.

Systemic arterial hypertension is a major risk factor for cerebrovascular disease. Therefore, adequate control of blood pressure is of enormous importance. One of the many fixed-dose single-pill antihypertensive formulations available on the market is the combination of nebivolol and hydrochlorothiazide. The objective of this study was to develop two distinct high-performance liquid chromatography coupled to tandem mass spectrometry methods to simultaneously quantify nebivolol and hydrochlorothiazide in human plasma. The methods were employed in a bioequivalence study, the first assay involving a nebivolol fixed-dose single-pill formulation based on healthy Brazilian volunteers. Nebilet HCT™ (nebivolol 5 mg + hydrochlorothiazide 12.5 mg tablet, manufactured by Menarini) was the test formulation. The reference formulations were Nebilet™ (nebivolol 5 mg tablet, manufactured by Menarini) and Clorana™ (hydrochlorothiazide 25 mg tablet, manufactured by Sanofi). For both analytes, liquid-liquid extraction was employed for sample preparation and the chromatographic run time was 3.5 min. The limits of quantification validated were 0.02 ng/mL for nebivolol and 1 ng/mL for hydrochlorothiazide. Since the 90% CI for Cmax , AUC(0-last) and AUC(0-inf) individual test/reference ratios were within the 80-125% interval indicative of bioequivalence, it was concluded that Nebilet HCT™ is bioequivalent to Nebilet™ and Clorana™.
Orthodontic Extrusion of the Upper Central Incisor: A Rare Case of Pulp Mummification

Debido a su localizacion anatomica, los incisivos centrales superiores son los dientes mas afectados cuando se refieren a las lesiones traumaticas de la region craneofacial, entre los traumas nasales. En la infancia, lesion traumatica suele ser ocasionado por accidentes de bicicleta, deportes, actividades recreativas o caidas. El objetivo de este articulo es describir un tratamiento para la intrusion del incisivo central superior izquierdo y las complicaciones posteriores en un nino de 8 anos de edad. Asimismo, el informe hace hincapie en la importancia de cuidado a largo plazo con un seguimiento intrusion dientes permanentes. Tejido de la pulpa, como otros tejidos en el cuerpo humano, tiende a cambiar con traumas. Algunos de estos cambios son naturales, mientras que otros se producen como consecuencia de las lesiones del complejo dentina-pulpa, como las lesiones de caries, enfermedad periodontal, calcificaciones, como en el presente informe, restauracion o intervencion dental. Tratamiento endodontico a cabo normalmente deben tener lugar para obtener los maximos resultados, pero solo despues de la re-estabilizacion del diente.
Family members’ experiences of driving disruption after acquired brain injury

ABSTRACT Primary objective: 1) To explore family members’ lived experiences of driving disruption at early and later stages of the recovery continuum following acquired brain injury (ABI). 2) To describe health-related quality of life of family members of individuals with ABI who are experiencing driving disruption. Research design: Mixed methods phenomenological research approach. Methods and procedures: Semi-structured interviews and health-related quality of life questionnaires were conducted with 15 family members of individuals with ABI (early group: 1–12 months post-injury, n = 6; later group: >1 year post-injury, n = 9). Results: Two main themes were identified: Different for everyone: how driving disruption affects families, and Making it harder: context of driving disruption. The challenges of driving disruption were reported more frequently and with a more intense focus by family members who were caring for their relative for more than 1 year post-injury. This group also reported higher caregiver strain and poorer health-related quality of life. Reduced satisfaction with life, poor mental health and affected family functioning were reported by both groups. Conclusions: Driving disruption impacts on family members and has long-lasting consequences. It is important for clinicians to work with family members to manage these challenges even years after ABI and consider individual contextual factors.
SUPERFICIAL BARRETT’S ESOPHAGEAL CANCER OBSERVED BY MAGNIFYING ENDOSCOPY

A 65‐year‐old man was referred for the precise examination of the distal esophagus. Endoscopy showed abnormality of the lower esophagus. Conventional and chromoendoscopy showed a salmon pink‐colored esophagus with partial irregular area. Magnifying endoscopy revealed villous epithelium and irregular minute surface. Barrett’s esophagus with dysplasia was diagnosed. Because the histological biopsy showed adenocarcinoma, esophagectomy was performed. Magnifying endoscopy is useful for the detection of malignancy in Barrett’s esophagus.
Cholera Acidosis and its Therapy.

Acidosis is now generally known to be present in various diseases, such as diabetes, nephritis, uremia, and when violent diarrhea and vomiting occur clinically, there is also a rapid decrease in the body fluids. In most cases of cholera, the victim falls into a state of temporary inanition, and in consequence of the action of the toxin on the kidneys, so-called cholera nephritis very often develops. The decrease of blood alkali and the accumulation of acid in the body, make the existence of acidosis a certainty. Sellards noted the remarkable tolerance of the urine to alkali, while Rogers observed a notable decrease of alkali in the blood. During the cholera epidemic of last year, 529 cases were treated in the Dairen Isolation Hospital. Owing to a lack of apparatus Van Slyke's method for the determination of acidosis could not be employed. Traube's quinin method was resorted to instead, and the
A novel dried blood spot LC-MS/MS method for the quantification of apalutamide in mouse whole blood: Application to pharmacokinetic study in mice.

A simple, sensitive and rapid assay method has been developed and validated for the estimation of apalutamide on mouse dried blood spots (DBS) using liquid chromatography coupled to tandem mass spectrometry with electrospray ionization in the positive-ion mode. The method utilizes liquid extraction of apalutamide from 3 mm punched disks from DBS cards (spiked or study samples). The extracted sample was chromatographed on an Atlantis dC18 column using gradient elution with 0.2% formic acid and acetonitrile at a flow rate of 1.00 mL/min. The total run time was 3.0 min. The MS/MS ion transitions monitored were m/z 478 → 450 for apalutamide and m/z 481 → 453 for the IS (apalutamide-d3 ). Method validation was performed as per regulatory guidelines. The assay was linear in the range of 0.95-2030 ng/mL. The intra- and inter-day precisions were in the ranges of 2.37-8.53 and 6.76-11.5%, respectively. Stability studies showed that apalutamide was stable on DBS cards for one month. This novel method has been applied to analyze the DBS samples of apalutamide obtained from a pharmacokinetic study in mice.
Stability, degradation impurities and decomposition kinetics for paliperidone from osmotic tablets.

The antipsychotic paliperidone was investigated with a focus on stability, degradation impurities and kinetics reaction profile. Osmotic tablets 3 mg (OROS® ) were subjected to extraction in an ultrasonic bath and the resulting acidic solution was stressed by forced conditions. Degraded samples were monitored by HPLC-DAD in different storage times for acidic and alkaline hydrolysis, oxidation, heat and photolysis. Photolysis was shown to be a strong degradation factor, with a drug content of 24.64% remaining after 24 h. Oxidation (H2 O2 18%) caused a slow decomposition, with a drug content of 83.49% remaining after 72 h. Through kinetics graphics, first-order reactions were found for oxidation, heat and photolysis. By UPLC-MS analysis, the degraded matrix could be investigated for identification of impurities with m/z 445.3128, m/z 380.8906, m/z 364.9391, m/z 232.9832 and m/z 217.0076, allowing the identification of derivatives N-oxide and with modifications in the lactam, benzisoxazole and pyrimidine rings. Paliperidone in liquid state, like analytical solutions or formulation, must be carefully handled to avoid drug exposure, specially in storage conditions.
Diffusion imaging of mild traumatic brain injury in the impact accelerated rodent model: A pilot study

ABSTRACT Primary Objective: There is a need to understand pathologic processes of the brain following mild traumatic brain injury (mTBI). Previous studies report axonal injury and oedema in the first week after injury in a rodent model. This study aims to investigate the processes occurring 1 week after injury at the time of regeneration and degeneration using diffusion tensor imaging (DTI) in the impact acceleration rat mTBI model. Research Design: Eighteen rats were subjected to impact acceleration injury, and three rats served as sham controls. Seven days post injury, DTI was acquired from fixed rat brains using a 7T scanner. Group comparison of Fractional Anisotropy (FA) values between traumatized and sham animals was performed using Tract-Based Spatial Statistics (TBSS), a method that we adapted for rats. Main Outcomes and Results: TBSS revealed white matter regions of the brain with increased FA values in the traumatized versus sham rats, localized mainly to the contrecoup region. Regions of increased FA included the pyramidal tract, the cerebral peduncle, the superior cerebellar peduncle and to a lesser extent the fibre tracts of the corpus callosum, the anterior commissure, the fimbria of the hippocampus, the fornix, the medial forebrain bundle and the optic chiasm. Conclusion: Seven days post injury, during the period of tissue reparation in the impact acceleration rat model of mTBI, microstructural changes to white matter can be detected using DTI.
Neuroimaging of deployment-associated traumatic brain injury (TBI) with a focus on mild TBI (mTBI) since 2009

ABSTRACT Objectives: A substantial body of recent research has aimed to better understand the clinical sequelae of military trauma through the application of advanced brain imaging procedures in Veteran populations. The primary objective of this review was to highlight a portion of these recent studies to demonstrate how imaging tools can be used to understand military-associated brain injury. Methods: We focus here on the phenomenon of mild traumatic brain injury (mTBI) given its high prevalence in the Veteran population and current recognition of the need to better understand the clinical implications of this trauma. This is intended to provide readers with an initial exposure to the field of neuroimaging of mTBI with a brief introduction to the concept of traumatic brain injury, followed by a summary of the major imaging techniques that have been applied to the study of mTBI. Results: Taken together, the collection of studies reviewed demonstrates a clear role for neuroimaging towards understanding the various neural consequences of mTBI as well as the clinical complications of such brain changes. Conclusions: This information must be considered in the larger context of research into mTBI, including the potentially unique nature of blast exposure and the long-term consequences of mTBI.
A comparison of insufficient effort rates, neuropsychological functioning, and neuropsychiatric symptom reporting in military veterans and civilians with chronic traumatic brain injury.

Neuropsychological evaluation of persons with chronic traumatic brain injury (TBI) symptoms is complicated by multiple factors. The authors explored the impact of mechanism of injury, effort testing performance, and neuropsychiatric status in a sample of military veterans (V-TBI) and civilians (C-TBI) with chronic TBI. V-TBI (n = 74), C-TBI (n = 67), and healthy civilian control (C-HC) participants (n = 66), completed a battery of neuropsychological, effort, and self-report neuropsychiatric measures. Results indicated that C-HC and C-TBI participants exhibited comparably low failure rates on effort tests (6% and 3%, respectively). V-TBI participants exhibited significantly higher rates of failure (18%). Subgroups (n = 20) of effort-screened participants matched for demographics and disability level were compared regarding neuropsychological performance and neuropsychiatric self-report. Both TBI groups exhibited limited neuropsychological impairment, relative to the C-HC participants. The V-TBI group exhibited pronounced neuropsychiatric symptomology compared with the other participant groups. The implications of these findings are discussed for evaluation in the context of disability and litigation.
Characteristics of stuttering in Dutch‐speaking individuals

Clinical diagnostic procedures to distinguish stuttering from non‐stuttering individuals partially rely on the observation of characteristics of stuttered words or syllables. The purpose of this study was to examine the sensitivity and specificity of such a procedure, and to describe the observed characteristics of stuttered words. Methods involved the recording of the frequency, duration, and physical tension of stuttered words in conversational speech samples (total 43 100 words) and in an oral reading task (total 43 100 words). In this manner, 351 native Dutch speaking people, aged 8–53, who stutter were compared to a group of non‐stuttering peers (n = 80). Findings suggest that applying a criterion of 3% stuttered words in conversational speech makes it possible to distinguish stuttering from non‐stuttering individuals with high sensitivity (.9345) and perfect specificity (1.0000). Frequency, duration, and physical tension accompanying stuttered words are described for the group of stuttering participants, and these characteristics were compared to the group of non‐stuttering speakers.
The blue light receptor complex WC-1/2 of Schizophyllum commune is involved in mushroom formation and protection against phototoxicity.

Blue light is necessary for initiation of mushroom formation in Schizophyllum commune. The genome of this basidiomycete contains homologues of the blue light receptor genes wc-1 and wc-2 of Neurospora crassa. Here, it is shown that inactivation of either or both of these genes in S. commune results in a blind phenotype. Mushroom formation was abolished in dikaryons and they formed symmetrical instead of asymmetrical colonies. Development was restored in a temperature dependent way in a Δwc-2Δwc-2 strain by introducing a construct encompassing the wc-2 gene under control of the promoter of the heat shock gene hsp3. A genome-wide expression analysis showed that the transcription factor genes c2h2 and hom1 as well as many hydrophobin genes are downregulated in light-grown colonies of the Δwc-2Δwc-2 mutant when compared with the wild-type dikaryon. Inactivation of wc-1 and/or wc-2 also resulted in sensitivity of the mycelium to intense light. Monokaryotic mutant strains only survived exposure to 6500 lux of light by growing into the agar. Expression analysis indicates that the photosensitivity of the Δwc-1 and Δwc-2 strains is due to lower levels of photolyase and ferrochelatase.
On EMDR: Eye movements during retrieval reduce subjective vividness and objective memory accessibility during future recall

In eye movement desensitization and reprocessing (EMDR), a treatment for post-traumatic stress disorder (PTSD), patients make eye movements (EM) during trauma recall. Earlier experimental studies found that EM during recall reduces memory vividness during future recalls, and this was taken as laboratory support for the underlying mechanism of EMDR. However, reduced vividness was assessed with self-reports that may be affected by demand characteristics. We tested whether recall+EM also reduces memory vividness on a behavioural reaction time (RT) task. Undergraduates (N=32) encoded two pictures, recalled them, and rated their vividness. In the EM group, one of the pictures was recalled again while making EM. In the no-EM group one of the pictures was recalled without EM. Then fragments from both the recalled and non-recalled pictures, and new fragments were presented and participants rated whether these were (or were not) seen before. Both pictures were rated again for vividness. In the EM group, self-rated vividness of the recalled+EM picture decreased, relative to the non-recalled picture. In the no-EM group there was no difference between the recalled versus non-recalled picture. The RT task showed the same pattern. Reduction of memory vividness due to recall+EM is also evident from non-self-report data.
Polyethylenimine‐coated albumin nanoparticles for BMP‐2 delivery

Nanoparticle (NP)‐based delivery has gained importance for improving the potency of therapeutic agents. The bovine serum albumin (BSA) NPs, obtained by a coacervation process, was modified by electrostatic adsorption of cationic polyethylenimine (PEI) to NP surfaces for delivery of bone‐inducing growth factor, bone morphogenetic protein‐2 (BMP‐2). Different concentrations of PEI were utilized for coating BSA NPs to stabilize the colloidal system and to control the release of BMP‐2. The NPs were characterized by size and zeta potential measurements, as well as by Scanning Electron Microscopy and Atomic Force Microscopy. The encapsulation efficiency was typically >90% in all NP preparations. In vitro release kinetics showed that the PEI concentration used for coating the NPs efficiently controlled the release of BMP‐2, demonstrating a gradual slowing, sustained release pattern during a 10‐day study period. The bioactivity of the encapsulated BMP‐2 and the toxicity of the NPs were examined by the alkaline phosphatase (ALP) induction assay and the MTT assay, respectively, using C2C12 cells. The results indicated that PEI was the primary determinant of NP toxicities, and BSA NPs coated with 0.1 mg/mL PEI demonstrated tolerable toxicity, retained the bioactivity of BMP‐2, and efficiently slowed the release rate of BMP‐2. We conclude that BMP‐2 encapsulated in BSA NPs might be an efficient way to deliver the protein for in vivo bone induction.
Candida albicans transcription factor Rim101 mediates pathogenic interactions through cell wall functions

pH‐responsive transcription factors of the Rim101/PacC family govern virulence in many fungal pathogens. These family members control expression of target genes with diverse functions in growth, morphology and environmental adaptation, so the mechanistic relationship between Rim101/PacC and infection is unclear. We have focused on Rim101 from Candida albicans, which we find to be required for virulence in an oropharyngeal candidiasis model. Rim101 affects the yeast–hypha morphological transition, a major virulence requirement in disseminated infection models. However, virulence in the oropharyngeal candidiasis model is independent of the yeast–hypha transition because it is unaffected by an nrg1 mutation, which prevents formation of yeast cells. Here we have identified Rim101 target genes in an nrg1Δ/Δ mutant background and surveyed function using an overexpression‐rescue approach. Increased expression of Rim101 target genes ALS3, CHT2, PGA7/RBT6, SKN1 or ZRT1 can partially restore pathogenic interaction of a rim101Δ/Δ mutant with oral epithelial cells. Four of these five genes govern cell wall structure. Our results indicate that Rim101‐dependent cell wall alteration contributes to C. albicans pathogenic interactions with oral epithelial cells, independently of cell morphology.
CYLD is a crucial negative regulator of innate immune response in Escherichia coli pneumonia

Bacteraemic pneumonia is a common cause of sepsis in critically ill patients today and is characterized by dysregulation of inflammation. The genetic factors predisposing to bacteraemic pneumonia are not yet fully understood. Innate immunity is pivotal for host defence against invading bacteria, and nuclear factor‐kappa B (NF‐κB) is central to bacteria‐induced inflammation and immune responses. The deubiquitinating enzyme CYLD has been identified as a key negative regulator for NF‐κB. In the present study, we investigated the role of CYLD in innate immune response in Escherichia coli pneumonia. Upon E. coli inoculation, Cyld−/− mice were hypersusceptible to E. coli pneumonia with higher mortality. Innate immune response to E. coli was enhanced in Cyld−/− cells and mice. Cyld−/− cells exhibited enhanced NF‐κB activation upon E. coli inoculation, and the enhanced NF‐κB activation by E. coli was abolished by perturbing IκB kinase (IKK) signalling. Furthermore, IKK inhibitor rescued Cyld−/− mice from lethal infection during E. coli pneumonia along with reduced inflammation. Taken together, these data showed that CYLD acts as a crucial negative regulator for E. coli pneumonia by negatively regulating NF‐κB. These findings provide novel insight into the regulation of bacteraemic pneumonia and related diseases and may help develop novel therapeutic strategies for these diseases.
Select host cell proteins coelute with monoclonal antibodies in protein a chromatography

The most significant factor contributing to the presence of host cell protein (HCP) impurities in Protein A chromatography eluates is their association with the product monoclonal antibodies (mAbs) has been reported previously, and it has been suggested that more efficacious column washes may be developed by targeting the disruption of the mAbs–HCP interaction. However, characterization of this interaction is not straight forward as it is likely to involve multiple proteins and/or types of interaction. This work is an attempt to begin to understand the contribution of HCP subpopulations and/or mAb interaction propensity to the variability in HCP levels in the Protein A eluate. We performed a flowthrough (FT) recycling study with product respiking using two antibody molecules of apparently different HCP interaction propensities. In each case, the ELISA assay showed depletion of select subpopulations of HCP in Protein A eluates in subsequent column runs, while the feedstock HCP in the FTs remained unchanged from its native harvested cell culture fluid (HCCF) levels. In a separate study, the final FT from each molecule's recycling study was cross‐spiked with various mAbs. In this case, Protein A eluate levels remained low for all but two molecules which were known as having high apparent HCP interaction propensity. The results of these studies suggest that mAbs may preferentially bind to select subsets of HCPs, and the degree of interaction and/or identity of the associated HCPs may vary depending on the mAb. © 2012 American Institute of Chemical Engineers Biotechnol. Prog. , 2012