Miracle-dz/UniFAR-FTUs huggingface dataset:
Ineffective quinidine therapy in early onset epileptic encephalopathy with KCNT1 mutation

Ineffective Quinidine Therapy in Early Onset Epileptic Encephalopathy With KCNT1 Mutation Pin Fee Chong, MD, Ryoko Nakamura, MD, Hirotomo Saitsu, MD, PhD, Naomichi Matsumoto, MD, PhD, and Ryutaro Kira, MD, PhD Bearden et al reported an impressive antiepileptic effect of quinidine on 1 patient initiated at 25 months with KCNT1 (c.1283G>A; p.Arg428Gly, R428Q) mutation diagnosed with epilepsy of infancy with migrating focal seizures (EIMFS). R428Q was proven to be a gain-of-function pathogenic KCNT1 mutation, with an increase of current observed in electrophysiological study. The reported patient was completely seizure free and showed improved psychomotor development. Due to the promising effect, we started the therapy on an unclassified early onset epileptic encephalopathy patient who had the same R428Q mutation. The patient is currently a 6-year-old male who was born at term with no family history of neurologic disorders. He was brought to us at 6 weeks of life with seizures characterized by a brief episode of staring and right hemiclonic seizures. Interictal electroencephalogram (EEG) showed multifocal sharp waves, and ictal EEG at 3 months displayed rhythmic delta-wave activity in bilateral occipital areas. Intracranial magnetic resonance imaging was normal at 1 month. At 4 years, whole exome sequencing revealed a heterozygous de novo KCNT1 R428Q mutation by a previously published method (Patient 11). Seizure control was refractory to multiple antiepileptic drugs, with seizure frequency peaking at 200 times/day. Ketogenic diet and vagal nerve stimulation reduced the seizure frequency to half. He was bedridden with poor neurodevelopment. Quinidine therapy was started at 5 years. The dose was titrated slowly, adjusted by monitoring the trough serum levels of quinidine at the range of 1.5 to 3.0 lg/ml. The patient was monitored for side effects, and no major adverse event was noted. Frequency of daily seizures was recorded, with monthly seizure frequency before and after quinidine therapy presented in the Figure. Contrary to expectations, quinidine was ineffective in seizure reduction. Seizure frequency per month after quinidine therapy was 103 6 27.7, compared to 106 6 13.3 for the same period before. In a recent literature concerning KCNT1-positive epilepsies, whereas quinidine showed 80% seizure reduction in one 3-year-old EIMFS patient (K629N), it was ineffective in an 11-year-old patient with unclassified epilepsy (Y796H). Therapy initiation at a later age and electroclinical syndrome other than EIFMS are possible reasons for poor response to quinidine in our case. Earlier
Subjective evaluations and objective measurements of the ischial-ramal containment prosthesis.

We examined 12 transfemoral amputees, 6 using the IRC socket and 6 the QL socket, to confirm whether the ischial-ramal containment (IRC) socket is truly superior to the quadrilateral (QL) socket. In subjective evaluation, the IRC group was significantly better in the total score and in items of comfort, that is, to sit on a chair and lumbar lordosis at heel off (Mann-Whitney test, P < 0.05), better but not significant in the items of comfortable to wear, comfortable to go up and down stairs, and truncal sway during stance phase. By computed tomography, the femur of the IRC group was kept in a position significantly more medial than that of the QL group (Mann-Whitney test, P < 0.05); but no significant difference in gluteal medial muscle atrophy ratios between the two groups was found (Mann-Whitney test, P > 0.05). By X-ray, the stump of the IRC group was maintained significantly more adducted during one foot standing on the prosthesis (Mann-Whitney test, P < 0.05), but the lateral force ratio during mid-stance of the IRC group was smaller, but not significantly, than that of the QL group. Physiological cost index (PCI), an indirect simple method for evaluating oxygen consumption of gait, had no significant difference between the two groups (Mann-Whitney test, P > 0.05), and a multiple regression analysis revealed that the stump length ratio and lateral force ratio during mid-stance were significant explanatory variables for predicting PCI (adjusted R square: 0.87, F-value: 11.85, P < 0.05). The results of this study have revealed that the advantage of the IRC socket is a tender feeling of the stump, but that the metabolic efficiency is not superior to the QL socket at the most comfortable speed.
Do Panic Symptom Profiles Influence Response to a Hypoxic Challenge in Patients With Panic Disorder? A Preliminary Report

Objective This study e-amined how panic symptom profiles affect response to a hypo-ic laboratory challenge in patients with panic disorder. Methods Seven patients whose naturally occurring panic attacks were characterized by prominent respiratory symptoms (Resp subgroup) were compared and contrasted with seven patients who did not report respiratory symptoms during panic attacks (NonResp subgroup). All were administered a novel 12% O2 challenge and assessed with measures of tidal volume, respiratory rate, end-tidal CO2, anxiety, and panic symptoms. Results Although the Resp and NonResp subgroups showed equivalent increases in an-iety and panic symptoms, the Resp subgroup showed greater fluctuation in tidal volume during and after the challenge as well as overall lower levels of end-tidal CO2. Conclusions Our results suggest the importance of panic symptom profiles in determining respiratory responses to a hypo-ic challenge in patients with panic disorder. These findings are discussed in light of current theories of panic disorder, with particular attention to respiratory disturbances in this disorder.
Regulation of STRA13 by the von Hippel-Lindau Tumor Suppressor Protein, Hypoxia, and the UBC9/Ubiquitin Proteasome Degradation Pathway*

In this study, we focus on different modes of regulation of STRA13, a human ortholog of the mouse basic helix-loop-helix transcriptional factor, previously identified by us as a new von Hippel-Lindau tumor suppressor gene (VHL) target. The gene was overexpressed in VHL-deficient cell lines and tumors, specifically clear cell renal carcinomas and hemangioblastomas. Introduction of wild type VHL transgene into clear cell renal carcinoma restored low level expression of STRA13. Overexpression was also detected in many common malignancies with an intact VHL gene, suggesting the existence of another, VHL-independent pathway of STRA13 regulation. Similar to many other von Hippel-Lindau tumor-suppressor protein (pVHL) targets, the expression of STRA13 on the mRNA level was hypoxia-sensitive, indicating oxygen-dependent regulation of the gene, presumably through the pVHL/hypoxia-inducible factor 1 (HIF-1) pathway. The yeast two-hybrid screening revealed interaction of the STRA13 protein with the human ubiquitin-conjugating enzyme (UBC9) protein, the specificity of which was confirmed in mammalian cells. By adding the proteasome inhibitor acetyl-leucinyl-leucinyl-norleucinal, we demonstrated that the 26 S proteasome pathway regulates the stability of pSTRA13. Co-expression of STRA13 and UBC9 led to an increase of the pSTRA13 ubiquitination and subsequent degradation. These data established that UBC9/STRA13 association in cells is of physiological importance, presenting direct proof of UBC9 involvement in the ubiquitin-dependent degradation of pSTRA13. Hypoxia treatment of mammalian cells transiently expressing STRA13 protein showed that stability of pSTRA13 is not affected by hypoxia or VHL. Thus, STRA13, a new pVHL target, is regulated in cells on multiple levels. We propose that STRA13 may play a critical role in carcinogenesis, since it is a potent transcriptional regulator, abundant in a variety of common tumors.
Heavy metals, islet function and diabetes development

Heavy metals have been known to possess many adverse health effects for a long time. Uncontrolled industrialization breaks out heavy metal pollution in the world. Heavy metal pollutants damage organ functions and disrupt physiological homeostasis. Diabetes mellitus is growing in prevalence worldwide. Several studies have indicated that the deficiency and efficiency of some essential trace metals may play a role in the islet function and development of diabetes mellitus. Some toxic metals have also been shown to be elevated in biological samples of diabetes mellitus patients. In the present work, we review the important roles of heavy metals in islet function and diabetes development in which the in vitro, in vivo, or human evidences are associated with exposure to zinc, arsenic, cadmium, mercury, and nickel. Through this work, we summarize the evidence which suggests that some heavy metals may play an important role in diabetes mellitus as environmental risk factors.
Knowledge, attitudes, and practices about tuberculosis and choice of communication channels in Thailand.

INTRODUCTION The aim of this study was to assess tuberculosis (TB) knowledge, attitudes, and practices in both the general population and risk groups in Thailand. METHODOLOGY In a cross-sectional survey, a general population (n = 3,074) and family members of a TB patient (n = 559) were randomly selected, using stratified multistage sampling, and interviewed. RESULTS The average TB knowledge score was 5.7 (maximum = 10) in the Thai and 5.1 in the migrant and ethnic minorities general populations, 6.3 in Thais with a family member with TB, and 5.4 in migrants and ethnic minorities with a family member with TB. In multivariate linear regression among the Thai general population, higher education, higher income, and knowing a person from the community with TB were all significantly associated with level of TB knowledge. Across the different study populations, 18.6% indicated that they had undergone a TB screening test. Multivariate logistic regression found that older age, lower education, being a migrant or belonging to an ethnic minority group, residing in an area supported by the Global Fund, better TB knowledge, having a family member with TB, and knowing other people in the community with TB was associated having been screened for TB. CONCLUSION This study revealed deficiencies in the public health knowledge about TB, particularly among migrants and ethnic minorities in Thailand. Sociodemographic factors should be considered when designing communication strategies and TB prevention and control interventions.
Highly Accurate Dual-Band Cellular Field Potential Acquisition For Brain–Machine Interface

Cellular field potential includes local field potential (LFP, 0.1 Hz–200 Hz) and spike potential (SP, 200 Hz–10 kHz). In physiological studies of the brain, SP signal has been the focus. Various circuits have been reported to acquire SP signals in brain–machine interface (BMI) systems over the years. Recent study shows that the LFP signal plays important roles in modulating many profound neuronal mechanisms in the brain. It is important for new BMI design to record the dual-band signal accurately, which demands acquisition circuits to have low noise and good linearity in both bands. In this paper, we report the design of a dual-band acquisition integrated circuit (IC) for microelectrode recording. The novel design uses a continuous- time (CT) front-end with chopping to suppress the noise, and a discrete-time (DT) back-end to achieve good linearity. A prototype monolithic acquisition IC is fabricated in a 0.35 <formula formulatype="inline"><tex Notation="TeX">$\mu{\rm m}$</tex></formula> CMOS process. It has 16 acquisition channels and an 11 bit successive-approximation (SAR) analog-to-digital converter (ADC). Silicon measurements show that every channel has <formula formulatype="inline"><tex Notation="TeX">$29.2\,{\rm nV}/{\rm Hz}^{0.5}$</tex></formula> noise and <formula formulatype="inline"><tex Notation="TeX">${<}0.1\%$</tex></formula> nonlinearity. The good linearity effectively prevents the aliasing and mixing between the two bands. For LFP signals, the recording noise is <formula formulatype="inline"> <tex Notation="TeX">$0.9\,{\mu}{\rm V}_{\rm rms}$</tex></formula>. For SP signals, the recording noise is <formula formulatype="inline"><tex Notation="TeX">$2.9\,{\mu}{\rm V}_{\rm rms}$</tex></formula>. Important to the microelectrode recording, the new design has high input impedance <formula formulatype="inline"><tex Notation="TeX">$(320~{\rm M}\Omega$</tex></formula> at <formula formulatype="inline"> <tex Notation="TeX">$1\,{\rm kHz})$</tex></formula>, high common-mode rejection ratio (CMRR) <formula formulatype="inline"><tex Notation="TeX">$({> 110}~{\rm dB})$</tex></formula> and power-supply rejection ratio (PSRR) <formula formulatype="inline"> <tex Notation="TeX">$({> 110}~{\rm dB})$</tex></formula>. Noise-efficiency factor (NEF) of the acquisition channel is 6.6. The IC is experimented with rat cardio-myocytes recording.
Study on removal effects of filling materials and broken files from root canals using pulsed Nd:YAG laser.

OBJECTIVES The aims of this study were to investigate the capability of removing the filling materials or broken files from root canals with pulsed Nd:YAG laser irradiation at three parameters, and to evaluate the temperature rises on root surfaces and morphological changes of root canal walls in vitro. SUMMARY BACKGROUND DATA There has been no report on removing the filling materials and broken instruments from root canals with laser irradiation. MATERIALS AND METHODS Thirty-six extracted human incisors were divided into two groups of 18 each. Eighteen root canals were shaped and obturated with gutta-percha and root canal sealer. In another 18 specimens, 3-mm long fractures of files were performed intentionally during root canal preparation. A pulsed Nd:YAG laser irradiation was performed repeatedly at three parameters of 1, 2, and 3 W to remove the filling materials or file fragments. Temperature rises on root surfaces during laser irradiation were measured by thermography, and the remaining of obturated materials and morphological changes of root canal walls were evaluated by stereoscopy and scanning electron microscopy. RESULTS In more than 70% of the teeth, the obturated materials were completely removed by laser, and in more than 55% of the teeth, the broken files were successfully removed. Temperature rises ranging from 17 degrees C to 27 degrees C were measured from 6 to 11 repeated times. CONCLUSION These results demonstrated that a pulsed Nd:YAG laser irradiation has the capability of removing the obturated materials in root canals and is useful for removing the broken files in same if the counter-measure reducing the temperature rise is performed.
Impact of preinjury warfarin use in elderly trauma patients.

BACKGROUND This study examined the hypothesis that elderly trauma patients on warfarin before injury will have increased morbidity and mortality compared with elderly trauma patients not on warfarin. METHODS From 1993 to 1995, trauma patients were grouped by age and presence or absence of warfarin use before injury. Groups were analyzed with respect to Injury Severity Score, Trauma Registry and Injury Severity Score, Glasgow Coma Scale score, Intensive Care Unit days, hospital days, units of blood transfused, and mortality rates. Statistical analysis was completed by using the Student's t test. RESULTS Records of 61 patients administered warfarin and 800 patients not administered warfarin were available for analysis. There were no statistically significant differences between patients on prehospital warfarin and those not on prehospital warfarin. CONCLUSION This study indicates that elderly trauma patients on warfarin before injury do not have increased morbidity and mortality compared with elderly trauma patients not on warfarin.
Adrenocortical Responses to ACTH in the Neonatal Rat : The Effect of Hypoxia from Birth on Corticosterone , StAR , and PBR Abbreviated Title : Neonatal Hypoxia and Adrenal Function

The adrenocortical response to hypoxia may be a critical component of the adaptation to this common neonatal stress. Little is known about adrenal function in vivo in hypoxic neonates. The purpose of this study was to evaluate adrenocortical responses to ACTH in suckling rat pups exposed to hypoxia from birth to 5-7 days of age, compared to normoxic controls. We also evaluated potential cellular controllers of steroidogenic function in situ. In 7 day-old pups at 0800 h, hypoxia from birth resulted in increased basal (12.2 1.4 ng/ml; N=12) and ACTH-stimulated (94.0 9.4 ng/ml; N=14) corticosterone levels, as compared to normoxic controls (basal=8.3 0.5 ng/ml; N=11; stimulated=51.3 3.8 ng/ml; N=8). This augmentation occurred despite no significant difference in plasma ACTH levels in normoxic vs. hypoxic pups before (85 4 vs. 78 8 pg/ml) or after (481 73 vs. 498 52 pg/ml) porcine ACTH injection (20 g/kg). This effect was similar in the afternoon at 6 days of age, and even greater at 5 days of age at 0800 h. The aldosterone response to ACTH was not augmented by exposure to hypoxia from birth. Adrenocortical hypoxia-inducible factor (HIF-1 ) mRNA was undetectable by RT-PCR. Steroidogenic acute regulatory (StAR) protein in adrenal subcapsules (zona fasciculata/reticularis) was augmented by exposure to hypoxia; this effect was greatest at 5 days of age. Peripheral-type benzodiazepine receptor (PBR) protein was also increased at 6 and 7 days of age in pups exposed to hypoxia from birth. We conclude that hypoxia from birth results in an augmentation of the corticosterone, but not aldosterone response to ACTH. This effect appears to be mediated at least in part, by an increase in controllers of mitochondrial cholesterol transport (StAR and PBR), and to occur independently of measurable changes in Page 3 --R00501-2002 R1 endogenous plasma ACTH. The augmentation of the corticosterone response to acute increases in ACTH in hypoxic pups is likely to be an important component of the overall physiological adaptation to hypoxia in the neonate.
Long-Term Gain After Team-Based Learning Experience in a Pediatric Clerkship

Background: Team-based learning (TBL) increases student engagement, value of teamwork, and performance on standardized evaluations. Purpose: The authors implemented a 3rd-year pediatric TBL curriculum, evaluating its effect on satisfaction, engagement, value of teamwork, and short-term and long-term academic performance. Method: Students evaluated the TBL curriculum and core lectures through satisfaction, engagement and value of team surveys. Scores on short-term and long-term examinations were compared to historical data. Results: The first implementation year, students were less likely to enjoy TBL sessions compared to lectures. The 2nd year, this difference lessened. Through both years, students reported dramatic increases in classroom engagement during TBL compared to lecture. Students developed a greater value for teams after participating in TBL. Short-term and long-term examination scores improved significantly. Conclusions: Both short-term and long-term performance improved with implementation of TBL, emphasizing the benefits of a curriculum that allows students to critically engage with material.
Network-on-chip service guarantees on the kalray MPPA-256 bostan processor

The Kalray MPPA-256 Bostan manycore processor implements a clustered architecture, where clusters of cores share a local memory, and a DMA-capable network-on-chip (NoC) connects the clusters. The NoC implements wormhole switching without virtual channels, with source routing, and can be configured for maximum flow rate and burstiness at ingress. We describe and illustrate the techniques used to configure the MPPA NoC for guaranteed services. Our approach is based on three steps: global selection of routes between end-points and computation of flow rates, by solving the max-min fairness with unsplittable path problem; configuration of the flow burstiness parameters at ingress, by solving an acyclic set of linear inequalities; and end-to-end latency upper bound computation, based on the principles of separated flow analysis (SFA). In this paper, we develop the two last steps, taking advantage of the effects of NoC link shaping on the leaky-bucket arrival curves of flows.
Healing and expression of growth factors (TGF-β and PDGF) in canine radial ostectomy gap containing platelet-rich plasma

Summary Objectives: To evaluate bone healing in an experimental radial ostectomy in dogs treated with autologous platelet-rich plasma (PRP), through histological, densitometric, radiographic studies, as well as expression of growth factors in the ostectomy gap. Methods: Twenty-one dogs were randomly divided into either a control or a PRP group. All underwent unilateral ostectomy of the radius to generate a gap of 2.0 mm, that was stabilized with external skeletal fixation. The ostectomy gap was either filled with PRP or left empty as a control. The radiographic and densitometric studies were performed after surgery, then at intervals until 60 days during the post-surgery period. Histological and immunohistochemical evaluations were performed at seven or 60 days post-surgery. Analyses were performed using a statistical analysis system, and the level of significance was set at p <0.05. Results: The median radiographic healing score in the PRP group increased significantly between day 0 and day 60. Furthermore, at 60 days, the median healing score and the proportion of healed ostectomies in the control group (score 1; 1/6 healed) and the PRP group (score 5; 4/5 healed) were significantly different. There were differences between groups in radiographic and densitometric values at days 45 and 60. The histological evaluation showed advanced bone healing at 60 days in the PRP group and signs of delayed union in the control group. Clinical relevance: Platelet-rich plasma can be used as an adjuvant therapy because it may promote better bone healing of a radial ostectomy treated with external skeletal fixation in dogs.
Engrafted chicken neural tube-derived stem cells support the innate propensity for axonal regeneration within the rat optic nerve.

PURPOSE Injury to the adult optic nerve, caused mechanically or by diseases, is still not reparable because the retinal ganglion cells (RGCs) are not allowed to regrow their axons and die retrogradely, although they possess the intrinsic propensity to regenerate axons in experimental conditions. METHODS In vitro propagated embryonic stem cells derived from the early chicken neural tube (NTSCs) were used to examine whether transplanted NTSCs produce growth-promoting factors and pave the microenvironment, thus facilitating axonal regeneration within the rat optic nerve. RESULTS NTSCs survived within the site where the optic nerve had been cut and continued to be nestin-positive, thus preserving their undifferentiated cell phenotype. Transplanted NTSCs activated the matrix metalloproteases (MMP)-2 and -14 in glial fibrillary acidic protein (GFAP)-positive optic nerve astrocytes. MMP2 production correlated with immunohistochemically visible degradation of inhibitory chondroitin sulfate proteoglycans (CSPGs). In addition, NTSCs produced a panoply of neurite-promoting factors including oncomodulin, ciliary neurotrophic factor, brain-derived neurotrophic factor and crystallins beta and gamma. Cut axons intermingled with NTSCs and passed through the zone of injury to enter the distal optic nerve over long distances, arriving at the thalamus and midbrain. CONCLUSIONS This study showed evidence that paving of the distal optic nerve microenvironment with proteolytically active MMPs and providing stem-cell-derived growth factors is a suitable method for facilitating regenerative repair of the optic nerve. Understanding the molecular mechanisms of this repair has fundamental implications for development of NTSC-based subsidiary therapy after neural injuries.