Miracle-dz/UniFAR-FTUs huggingface dataset:
Stepwise verification of bone regeneration using recombinant human bone morphogenetic protein-2 in rat fibula model

Objectives The purpose of this study was to introduce our three experiments on bone morphogenetic protein (BMP) and its carriers performed using the critical sized segmental defect (CSD) model in rat fibula and to investigate development of animal models and carriers for more effective bone regeneration. Materials and Methods For the experiments, 14, 16, and 24 rats with CSDs on both fibulae were used in Experiments 1, 2, and 3, respectively. BMP-2 with absorbable collagen sponge (ACS) (Experiments 1 and 2), autoclaved autogenous bone (AAB) and fibrin glue (FG) (Experiment 3), and xenogenic bone (Experiment 2) were used in the experimental groups. Radiographic and histomorphological evaluations were performed during the follow-up period of each experiment. Results Significant new bone formation was commonly observed in all experimental groups using BMP-2 compared to control and xenograft (porcine bone) groups. Although there was some difference based on BMP carrier, regenerated bone volume was typically reduced by remodeling after initially forming excessive bone. Conclusion BMP-2 demonstrates excellent ability for bone regeneration because of its osteoinductivity, but efficacy can be significantly different depending on its delivery system. ACS and FG showed relatively good bone regeneration capacity, satisfying the essential conditions of localization and release-control when used as BMP carriers. AAB could not provide release-control as a BMP carrier, but its space-maintenance role was remarkable. Carriers and scaffolds that can provide sufficient support to the BMP/carrier complex are necessary for large bone defects, and AAB is thought to be able to act as an effective scaffold. The CSD model of rat fibula is simple and useful for initial estimate of bone regeneration by agents including BMPs.
BMP type I receptor ALK2 is essential for proper patterning at late gastrulation during mouse embryogenesis

Bone morphogenetic proteins (BMPs) have multiple functions during vertebrate development. Previously, it was shown that BMP type I receptor ALK2 (also known as ACVRI, ActRI, or ActRIA) was important for normal mouse gastrulation by deleting exon 4 or exon 5 of Alk2. Recently, flanking exon 7 by loxP sites generated a conditional allele for Alk2. To assess whether the deletion of exon 7 causes functional null of ALK2, and does not produce a dominant negative form or a partially functional form of ALK2, we performed a comparative analysis between Alk2 homozygous mutant embryos with an exon 5 deletion (Alk2Δ5/Δ5) and embryos with an exon 7 deletion (Alk2Δ7/Δ7). Both Alk2Δ5/Δ5 and Alk2Δ7/Δ7 mutants showed identical morphological gastrulation defects. Histological examinations and molecular marker analyses revealed identical abnormal gastrulation phenotypes in Alk2Δ5/Δ5 and Alk2Δ7/Δ7 mutants. Although Fgf8 was expressed in the primitive streak of Alk2Δ5/Δ5 and Alk2Δ7/Δ7 mutants, Brachyury, Wnt3a, and Tbx6 were dramatically downregulated in Alk2Δ5/Δ5 and Alk2Δ7/Δ7 mutants. These results indicate that deletion of exon 7 for Alk2 leads to a functionally null mutation in vivo, and Alk2 is crucial for sustaining the proper gastrulation events in early mouse embryogenesis. Developmental Dynamics 236:512–517, 2007. Published 2006 Wiley‐Liss, Inc.
Sexual rest and post‐meiotic sperm ageing in house mice

Fertilization by aged sperm can result in adverse fitness consequences for both males and females. Sperm storage during male sexual rest could provide an environment for post‐meiotic sperm senescence causing a deterioration in the quality of stored sperm, possibly impacting on both sperm performance (e.g. swimming ability) and DNA quality. Here, we compared the proportion of sperm with fragmented DNA, an indicator of structural damage of DNA within the sperm cell, among males that had been sexually rested for approximately 2 months, to that of males that had mated recently. We found no evidence of intra‐epididymal sperm DNA damage or any impairment in sperm performance, and consequently no evidence of post‐meiotic sperm senescence. Our results suggest that male house mice are likely to possess mechanisms that function to ensure that their sperm reserves remain stocked with ‘young’, viable sperm during periods of sexual inactivity. We also discuss the possibility that our experimental design leads to no difference in the age of sperm among males from the two mating treatments. Post‐meiotic sperm senescence is especially relevant under sperm competition. Thus, we sourced mice from populations that differed in their levels of post‐copulatory sexual selection, enabling us to gain insight into how selection for higher sperm production influences the rate of sperm ageing and levels of DNA fragmentation. We found that males from the population that produced the highest number of sperm also had the smallest proportion of DNA‐fragmented sperm and discuss this outcome in relation to selection acting upon males to ensure that they produce ejaculates with high‐quality sperm that are successful in achieving fertilizations under competitive conditions.
Spreading the word: non-autonomous effects of apoptosis during development, regeneration and disease

Apoptosis, in contrast to other forms of cell death such as necrosis, was originally regarded as a ‘silent’ mechanism of cell elimination designed to degrade the contents of doomed cells. However, during the past decade it has become clear that apoptotic cells can produce diverse signals that have a profound impact on neighboring cells and tissues. For example, apoptotic cells can release factors that influence the proliferation and survival of adjacent tissues. Apoptosis can also affect tissue movement and morphogenesis by modifying tissue tension in surrounding cells. As we review here, these findings reveal unexpected roles for apoptosis in tissue remodeling during development, as well as in regeneration and cancer. Summary: This Review highlights how apoptotic cells impact the surrounding tissue to promote morphogenesis and remodelling through secreted signals during development, regeneration and cancer.
Induction of labor in women that had a previous cesarean delivery

Abstract Objective: This study aims to evaluate factors that predict the likelihood of the success of induction of labor (IOL) in women that had a previous cesarean section (pCS). Methods: Pregnant women with one pCS performed more than 18 months prior were included in this retrospective observational study. Of the 242 eligible women, 234 were enrolled; 120 (51.3%) of these women delivered vaginally (VD), with the remainder receiving a repeat CS. Results: The main reasons for IOL were premature rupture of membranes (PROM) (37.1%) and post-date pregnancy (26.5%). Babies with a birth weight ≥4000 g were more prevalent in women undergoing CS (21/114; 18.4%, p < 0.02) and were associated with the failure of IOL. Uterine rupture during labor (1.3%) occurred in three cases. Having had a previous vaginal delivery (VD) (p = 0.01), not being African (p = 0.022), and receiving IOL for PROM (p = 0.04) with a cervical Bishop score ≥5 (p = 0.015) significantly predicted the occurrence of a VD, with an 15% variance (p < 0.001). An age >35 years appears to not affect the success of induction. Conclusions: A successful IOL should be expected in Caucasian women induced for PROM with a favorable Bishop score.
Long‐term potentiation of GABAergic synaptic transmission in neonatal rat hippocampus

1 The plasticity of GABAergic synapses was investigated in neonatal rat hippocampal slices obtained between postnatal days 3 and 6 using intracellular recording techniques. Ionotropic glutamate receptor antagonists were present throughout the experiments to isolate GABAA receptor‐mediated postsynaptic potentials (GABAA PSPs) or currents (GABAA PSCs). 2 Repetitive depolarizing pulses (20 pulses, 0·5 s duration, at 0·1 Hz, each pulse generating 4‐6 action potentials) induced a long‐term potentiation in the slope and amplitude of the evoked GABAA PSPs and GABAA PSCs. 3 Long‐term potentiation was prevented by intracellular injection of the calcium chelator BAPTA (50 mM), or when the voltage‐dependent calcium channels blockers Ni2+ (50 μM) and nimodipine (10 μM) were bath applied. 4 Repetitive depolarizing pulses induced a persistent (over 1 h) increase in the frequency of spontaneous GABAA PSCs. 5 Repetitive depolarizing pulses induced a long‐lasting increase in the frequency of miniature GABAA PSCs, without altering their amplitude or decay‐time constant. 6 It is concluded that the postsynaptic activation of voltage‐dependent calcium channels leads to a long‐term potentiation of GABAergic synaptic transmission in neonatal rat hippocampus. This form of plasticity is expressed as an increase in the probability of GABA release or in the number of functional synapses, rather than as an upregulation of postsynaptic GABAA receptor numbers or conductance at functional synapses.
Effects of Alzheimer's disease-associated risk loci on cerebrospinal fluid biomarkers and disease progression: a polygenic risk score approach.

BACKGROUND Several risk loci for Alzheimer's disease (AD) have been identified during recent years in large-scale genome-wide association studies. However, little is known about the mechanisms by which these loci influence AD pathogenesis. OBJECTIVE To investigate the individual and combined risk effects of the newly identified AD loci. METHODS Association of 12 AD risk loci with AD and AD-related cerebrospinal fluid (CSF) biomarkers was assessed. Furthermore, a polygenic risk score combining the effect sizes of the top 22 risk loci in AD was calculated for each individual among the clinical and neuropathological cohorts. Effects of individual risk loci and polygenic risk scores were assessed in relation to CSF biomarker levels as well as neurofibrillary pathology and different biochemical measures related to AD pathogenesis obtained from the temporal cortex. RESULTS Polygenic risk scores associated with CSF amyloid-β42 (Aβ42) levels in the clinical cohort, and with soluble Aβ42 levels and γ-secretase activity in the neuropathological cohort. The γ-secretase effect was independent of APOE. APOE-ε4 associated with CSF Aβ42 (p < 0.001) levels. For the other risk loci, no significant associations with AD risk or CSF biomarkers were detected after multiple testing correction. CONCLUSIONS AD risk loci polygenically contribute to Aβ pathology in the CSF and temporal cortex, and this effect is potentially associated with increased γ-secretase activity.
A profile of multiple sclerosis: The New York State Multiple Sclerosis Consortium

We have obtained a current profile of multiple sclerosis (MS) in New York State through a centralized patient registry and standardized data collection instrument associated with the New York State Multiple Sclerosis Consortium of 12 MS centers located throughout the state. Data from the first 3019 patients with clinically definite MS revealed a clear relationship between MS disease type, duration of disease, and severity of physical disability. Patients with relapsing disease had disease durations approximately half as long as those with progressive forms of the disease (means approximately 6 years versus 11 years). The majority of patients with relapsing disease had Expanded Disability Status Scale (EDSS) scores of 4.0 or less (self-sustained, fully ambulatory), whereas the majority of patients with progressive disease types had EDSS scores of 6.0 or greater (at least unilateral assist for walking). These findings emphasize the importance of early intervention in patients with relapsing disease to slow or prevent the accumulation of physical disability associated with progressive types of disease. Progressive disease was associated with lack of full-time employment and being disabled before the age of 60 years. Patients with relapsing disease were more likely to be employed and have private forms of insurance, whereas patients with progressive types of disease were more likely to have government-supported insurance to cover medical expenses.
Treatment non‐adherence in teenage and young adult cancer patients: a preliminary study of patient perceptions

Objectives: Non‐adherence (NA) by adolescents receiving cancer treatment is believed to be a major problem. However, adequate measures of NA have not been developed. The purpose of this study was to (1) assess the internal reliability of a new scale reflecting low‐risk NA behaviours, (2) examine whether the scores on this scale were associated with high‐risk NA behaviours and (3) assess the relationship between NA behaviours and patient attitudes towards stopping treatment.
Computed tomography-guided trigeminal tractotomy-nucleotomy in the management of vagoglossopharyngeal and geniculate neuralgias.

OBJECTIVE Vagoglossopharyngeal and geniculate neuralgias are less frequently seen types of cranial neuralgias. Their causes and symptomatology are similar to those of trigeminal neuralgia; however, the complex anatomic relationship between the intermedius, vagal, and glossopharyngeal nerves leads to difficulties in the diagnosis and management of neuralgias originating from these cranial nerves. Numerous procedures have been used to treat intractable neuralgias of the VIIth, IXth, and Xth cranial nerves: 1) extracranial sectioning of the cranial nerves, 2) percutaneous thermal rhizotomy, 3) intracranial glossopharyngeal and vagal rhizotomies, 4) microvascular decompression, and 5) percutaneous trigeminal tractotomy-nucleotomy (TR-NC) or nucleus caudalis dorsal root entry zone operation. We propose that computer-guided TR-NC may be the first-choice operation for patients with glossopharyngeal, vagal, or geniculate neuralgia. PATIENTS AND METHODS Nine patients suffering from idiopathic vagoglossopharyngeal neuralgia (six patients) and geniculate neuralgia (three patients) were managed at our clinic. Computed tomography-guided percutaneous trigeminal TR-NC was performed for these nine patients. RESULTS Excellent (six patients) or good (three patients) pain control was obtained in each patient. Complications included temporary ataxia in two patients after TR-NC. CONCLUSION The risk:benefit ratio should be evaluated individually to select the appropriate treatment procedure for patients with vagoglossopharyngeal and geniculate neuralgias. Computed tomography-guided percutaneous TR-NC is an effective and minimally invasive procedure for such patients.
Living With the Stigma of Hepatitis C

Stigma poses significant challenges to those with chronic hepatitis C (CHC), their social networks, communities, and society. This study's purpose was to identify and describe how people lived with CHC and made self-care decisions. Data are presented from interviews and daily recordings of 26 study participants. Experiences of stigma were attributed primarily to misconceptions about the cause and transmission of the disease and its association with illicit drug use. Perceptions and responses to stigma were context-dependent, flexible, and varied over time. Stigma created barriers to access of health services and undermined the social supports required to address self-care needs and illness management. The extent and severity of stigma suggests that interventions to reduce or eliminate stigma will require individual, structural, and systemic changes. Further study is required to clarify the relationship between the trajectory of CHC and the experience and responses to stigma.
Biochemical Changes in Liver and Blood During Liver Fattening in Rats

Excessive fat accumulation in the liver is a common metabolic disorder seen in humans and animals. Fatty liver was induced in the rat by feeding the animals with a sucrose rich diet containing 1% orotic acid for 2-3 weeks. In the sera from fatty liver rats there were significant changes in the level of alanine aminotransferase (+ 68.7%), malic dehydrogenase (+ 77.8%), gamma-glutamyl transpeptidase (- 53.4%) and total lipids (+ 26.6%). There were small to no changes in the levels of aspartate aminotransferase, glucose-6-phosphate dehydrogenase, lactic dehydrogenase, aldolase, malic enzyme, 6-phosphogluconic acid dehydrogenase, alkaline phosphatase and albumin. In fatty liver, significant differences were seen in the levels of glucose 6-phosphate dehydrogenase (+ 235%), malic enzyme (+ 170%), gamma-glutamyl transpeptidase (+ 113%), 6-phosphogluconate dehydrogenase (+ 63%), aspartate aminotransferase (+ 35.6%), malic dehydrogenase (+ 38%), lactic dehydrogenase (+ 37%), and alanine aminotransferase (- 23%). Comparison of the non-fatty part with the fatty part of the fatty liver showed larger changes in the non-fatty part of the liver, suggesting that during the fattening process, there is an induction of enzymes in the liver reaching a peak prior to lipid accumulation, declining thereafter during liver fattening. The increase in NADPH-generating lipogenic enzymes suggests that accumulated fat in the liver is at least partially from de-novo increased synthesis in the liver.
Suppression of Livin Gene Expression by siRNA Leads to Growth Inhibition and Apoptosis Induction in Human Bladder Cancer T24 Cells

Apoptosis deficiency is a hallmark of many cancer cells. Functional suppression of specific antiapoptotic factors might provide a feasible strategy in cancer gene therapy. Livin, the latest found inhibitor of apoptosis protein (IAP) family member, plays important role in cell growth and apoptosis. It has been reported that Livin is highly expressed in bladder cancer tissues. In this study, we found that, unlike other cancer cell lines, there was only Livin-α not Livin-β expression in bladder cancer cell lines. We further investigated the effects of Livin knockdown on human bladder cancer T24 cell growth and apoptosis. We found that small interfering RNA (siRNA) mediated Livin suppression significantly inhibited T24 cell proliferation and colony formation ability. Livin knockdown dramatically increased the T24 cell apoptotic rate in response to different proapoptotic stimuli, such as Mitomycin and TNF-alpha, and this was associated with caspase-3 and caspase-9 activation. These results suggest that Livin knockdown can inhibit cell growth and increase sensitivity to apoptotic stimuli, and might serve as a potent target in bladder cancer gene therapy.
Footwear Traction and Lower Extremity Joint Loading

Background: Traction is influenced by the sole architecture and playing surface, with increases in traction potentially leading to injury. The mechanism as to how or why increased traction could lead to injury remains unknown. Purpose: This study was undertaken to determine how shoes of different sole designs and traction influence knee and ankle joint moments. Study Design: Controlled laboratory study. Methods: Traction testing was performed on 2 shoes of varying sole designs (tread vs smooth) using a robotic testing machine. All testing was conducted on a 60-cm × 90-cm piece of sample track surface. Kinematic and kinetic data were then collected on 13 recreational athletes performing running V-cuts in the 2 different shoe conditions. Five trials per condition were collected with reflective markers placed on the right shank and shoe of each participant. Kinematic and kinetic data were collected using an 8–high-speed camera system and force plate. Results: The coefficient of translational traction and the peak moment of rotation were both significantly higher in the tread shoe compared with the smooth shoe (1.00 vs 0.87 and 23.87 N·m vs 16.12 N·m, respectively). The high-traction shoe had significantly higher peak ankle external rotation moments (89.58 N·m vs 80.17 N·m), peak knee external rotation moments (36.23 N·m vs 32.02 N·m), peak knee adduction moments (224.0 N·m vs 186.8 N·m), and knee adduction angular impulse (2.10 Nms vs 1.83 Nms) compared with the low-traction shoe. Conclusion: Increased shoe traction significantly increased ankle and knee joint moments during a V-cut. Despite the significant difference in traction, no difference in performance was observed. These changes could have an effect on ankle and knee joint injury. Clinical Relevance: Shoes with decreased traction could be used in sports to reduce the joint moments in the knee and ankle and potentially reduce injury without a loss in performance.
Induction of prolonged tenderness in patients with tension‐type headache by means of a new experimental model of myofascial pain

Tenderness is the most prominent abnormal finding in patients with tension‐type headache (TTH). Recently we developed a model of myofascial tenderness using intramuscular infusion of a combination of bradykinin, serotonin, histamine and prostaglandin E2. We aimed to examine tenderness after this combination in patients with episodic TTH (ETTH). Fifteen patients and 15 healthy controls completed the study. Participants received the combination into the non‐dominant trapezius muscle in a randomized, double‐blinded and placebo‐controlled design. Local tenderness and stimulus–response functions, mechanical pain thresholds (PPDT) in the temporal region and on the finger, and total tenderness score (TTS) were recorded. A local, prolonged, and mild to moderate tenderness was reported both in patients (P = 0.001) and in controls (P = 0.001) after the combination compared with the placebo. The response to the combination tended to be increased in patients. The stimulus–response function was leftward shifted after the combination, compared with baseline in both groups. No changes in PPDT or TTS were found after the infusions, whereas baseline PPDTs were decreased in ETTH compared with controls (PPDTfinger: P = 0.033; PPDTtemporal: P = 0.015). Intramuscular infusion of a combination of endogenous substances induced prolonged tenderness in both patients with episodic TTH and healthy subjects. The present results suggest an increased excitability of peripheral muscle afferents in TTH.
Type and location of findings in dental panoramic tomographs in 7–12-year-old orthodontic patients

Abstract Objective The Radiation and Nuclear Safety Authority in Finland has paid attention to the large numbers of dental panoramic tomographs (DPTs), particularly in 7–12-year-old children. The majority of these radiographs are taken for orthodontic reasons. Because of the high radiosensitivity of children, the size of the irradiated field should be carefully chosen to yield the necessary diagnostic information at the lowest possible dose. The purpose of the present study was, therefore, to assess the outcome of DPTs within this age group in terms of type and location of pathological findings. It was also hypothesized that DPTs of orthodontic patients rarely display unrestored caries. Materials and methods Four hundred and forty-one DPTs, taken of 7–12-year-old children in 2010–2014, were randomly sampled. The 413 of them (94%) that had been taken for orthodontic reasons were analysed. Results All pathologic findings were restricted to the tooth-bearing area and there was no pathology in the bone structure or any incidental findings in the region of temporomandibular joint. Unlike hypothesized, 27% of the orthodontic DPTs showed caries in deciduous teeth and 16% in permanent teeth. A sub-sample of 229 DPTs, analysed for developmental dental and occlusal problems, most commonly displayed crowding (50%), positional anomalies and local problems with tooth eruption (32%), as well as hyperodontia (15%). Conclusion Inclusion of only the actual area of interest in the image field should be considered case-specifically as a means to reduce the radiation dose.