African wild dog movements show contrasting responses to long and short term risk of encountering lions: analysis using dynamic Brownian bridge movement models.
Prey depletion is a threat to the world's large carnivores, and is likely to affect subordinate competitors within the large carnivore guild disproportionately. African lions limit African wild dog populations through interference competition and intraguild predation. When lion density is reduced as a result of prey depletion, wild dogs are not competitively released, and their population density remains low. Research examining distributions has demonstrated spatial avoidance of lions by wild dogs, but the effects of lions on patterns of movement have not been tested. Movement is one of the most energetically costly activities for many species and is particularly costly for cursorial hunters like wild dogs. Therefore, testing how top-down, bottom-up, and anthropogenic variables affect movement patterns can provide insight into mechanisms that limit wild dogs (and other subordinate competitors) in resource-depleted ecosystems. We measured movement rates using the motion variance from dynamic Brownian Bridge Movement Models (dBBMMs) fit to data from GPS-collared wild dogs, then used a generalized linear model to test for effects on movement of predation risk from lions, predictors of prey density, and anthropogenic and seasonal variables. Wild dogs proactively reduced movement in areas with high lion density, but reactively increased movement when lions were immediately nearby. Predictors of prey density had consistently weaker effects on movement than lions did, but movements were reduced in the wet season and when dependent offspring were present. Wild dogs alter their patterns of movement in response to lions in ways that are likely to have important energetic consequences. Our results support the recent suggestion that competitive limitation of wild dogs by lions remains strong in ecosystems where lion and wild dog densities are both low as a result of anthropogenic prey depletion. Our results reinforce an emerging pattern that movements often show contrasting responses to long-term and short-term variation in predation risk.


Clinical efficacy of a two-year oral health programme for infants and toddlers in Singapore.
Dental caries, which is prevalent in Singapore preschoolers, is a disease that has a major impact on children's health and places a high cost on the society and health services. Oral health programmes for young children implemented in some parts of the world have been shown to be effective in the prevention of dental caries. We aimed to examine the clinical efficacy of a two-year oral health programme for infants and toddlers in Singapore. 90 children and their caregivers participated in the programme, and 64 children, who were 24 months older than the intervention group at the initial visit, were recruited as controls in a quasi-experimental study design. We evaluated the presence of severe early childhood caries (SECC) and d3mfs in the control group at the initial visit and in the intervention group after the completion of the two-year programme. Some children in the intervention (7.8%) and control (31.3%) groups (p < 0.001) had SECC (difference 23.5%, 95% confidence interval 11%-36%). A higher percentage of children in the intervention group had d3mfs = 0 and habits associated with low risk for caries. The odds of SECC in the control group were three times higher than that for the intervention group, and the effect was significant (p = 0.037) after adjustment for other significant risk factors. The preventive oral health programme in Singapore was successful in reducing SECC among infants and toddlers when targeted behaviour modifications were implemented.


Fetal response to sound stimulation: preliminary report exploring use of sound stimulation in routine obstetrical ultrasound examinations.
An artificial larynx was used to sound-stimulate 693 human fetuses with gestational age ranging from 21 to 42 weeks. Fetuses were monitored, with simultaneous ultrasound, for immediate, increased motor activity after the stimulus. Each was scored as either demonstrating for startle response or having no visible response to the stimulus. Four zones of gestational development were determined: nonstartle zone (gestation age below 24 weeks), in which none reacted; transitional zone A (24 to 27 weeks), in which 30% reacted, transitional zone B (27 to 30 weeks), in which 86% reacted; and startle zone (above 31 weeks), in which 96% reacted. A review of the 17 patients not responding to sound in the startle zone, revealed a wide spectrum of complications of pregnancy in eight, including sepsis, meconium aspiration, short umbilical cord, abruption of the placenta, bradycardia, and death, while nine were without recorded abnormalities. Sound stimulation designed to elicit a startle response on ultrasound may have some potential benefit in identifying fetuses at risk or needing closer physiologic evaluation. Adding sound stimulation to the routine ultrasound study may warrant further study.


Feasibility of ventilator-assisted tubeless anesthesia for video-assisted thoracoscopic surgery.
General anesthesia providing one-lung ventilation (OLV) with double-lumen endotracheal intubation has been considered inevitable for thoracic surgery. However, with the recent trend of less invasive surgical technique and enhanced recovery after surgery, tubeless anesthesia has been performed in various thoracic surgeries. The aim of this study was to establish a feasible and safe strategy of ventilator-assisted tubeless anesthesia in video-assisted thoracoscopic surgeries (VATS) based on single-institution experiences. We retrospectively reviewed the medical records of patients who underwent tubeless VATS from November 2019 to December 2021. Perioperative anesthetic and surgical variables as well as complications were reported. Seventeen patients with a median age of 29 and American Society of Anesthesiologists physical status I to II underwent video-assisted pulmonary wedge resection under monitored anesthesia care (MAC) using propofol and remifentanil. Mechanical ventilation was applied in synchronized intermittent mandatory ventilation with pressure support mode through facemask if respiratory support was required. During the operation, none of the patients showed hypoxemia or involuntary movement interfering operation. No patients were converted to general anesthesia or open thoracotomy unintentionally. All patients were discharged on median 2 days postoperatively without complications. Ventilator-assisted tubeless VATS is a feasible and safe option in low-risk patients undergoing video-assisted pulmonary wedge resection.


Primary Ureteral Stump Carcinoma: Rare Presentation and Management.
Primary ureteral stump carcinoma is a rare occurrence in patients who receive radical nephrectomy for renal cell carcinoma (RCC). Only 11 previous cases have been reported in the literature. We report a case of synchronous bilateral RCC and colon adenocarcinoma with the subsequent development of primary ureteral stump carcinoma that was treated with robotic ureterectomy and bladder cuff excision. To our knowledge, this is the first reported case of this presentation.


Comparison of Bone Tunnel and Cortical Surface Tendon-to-Bone Healing in a Rabbit Model of Biceps Tenodesis.
Many orthopaedic surgical procedures involve reattachment of a single tendon to bone. Whether tendon-to-bone healing is better facilitated by tendon fixation within a bone tunnel or on a cortical surface is unknown. The purpose of this study was to evaluate tendon-healing within a bone tunnel compared with that on the cortical surface in a rabbit model of biceps tenodesis. Thirty-two rabbits (24 weeks of age) underwent unilateral proximal biceps tenodesis with tendon fixation within a bone tunnel (BT group) or on the cortical surface (SA [surface attachment] group). Postoperatively, rabbits were allowed free-cage activity without immobilization. All rabbits were killed 8 weeks after surgery. Healing was assessed by biomechanical testing, microcomputed tomography (micro-CT), and histomorphometric analysis. Biomechanical testing demonstrated no significant difference between the groups in mean failure loads (BT: 56.8 ± 28.8 N, SA: 55.8 ± 14.9 N; p = 0.92) or stiffness (BT: 26.3 ± 16.6 N/mm, SA: 32.3 ± 9.6 N/mm; p = 0.34). Micro-CT analysis demonstrated no significant difference between the groups in mean volume of newly formed bone (BT: 69.3 ± 13.9 mm, SA: 65.5 ± 21.9 mm; p = 0.70) or tissue mineral density of newly formed bone (BT: 721.4 ± 10.9 mg/cm, SA: 698.6 ± 26.2 mg/cm; p = 0.07). On average, newly formed bone within the tunnel represented only 5% of the total new bone formed in the BT specimens. Histological analysis demonstrated tendon-bone interdigitation and early fibrocartilaginous zone formation on the outer cortical surface in both groups. In contrast, minimal tendon-bone bonding was observed within the tunnel in the BT specimens. Tendon fixation in a bone tunnel and on the cortical surface resulted in similar healing profiles. For tendons placed within a bone tunnel, intratunnel healing was minimal compared with the healing outside the tunnel on the cortical surface. The creation of large bone tunnels, which can lead to stress risers and increase the risk of fracture, may not be necessary for biceps tenodesis procedures.


The CLARION study design and status update: a long-term, registry-based study evaluating adverse events of special interest in patients with relapsing multiple sclerosis newly started on cladribine tablets.
To describe the design of the CLARION post-approval safety study (EU PAS Register number, EUPAS24484) and provide a status update, including characteristics of patients included up to 1 May 2021. CLARION aims to further evaluate adverse events of special interest in patients who are newly initiating treatment with cladribine tablets for relapsing multiple sclerosis (MS). The study population consists of two cohorts: patients newly initiating cladribine tablets (cladribine cohort) and patients newly initiating oral fingolimod tablets (comparator fingolimod cohort), with an aim to include 8000 patients (4000 patients per cohort). The study relies on secondary use of data from pre-existing MS registries/data sources (except in Germany, where primary data collection is performed). The study is projected to last 15 years, with an anticipated 5-year inclusion period. Study outcomes are: malignancies; severe infections; tuberculosis; progressive multifocal leukoencephalopathy; other opportunistic infections; herpes zoster; severe lymphopenia (Grade ≥ 3); and treatment discontinuation. As of 1 May 2021, 2393 patients were included in CLARION from seven participating MS registries/data sources (cladribine cohort, n = 1266; fingolimod cohort, n = 1127). The majority of patients are female (cladribine cohort, 72.5%; fingolimod cohort, 68.0%), with mean age at onset of MS of 31.5 years for the cladribine cohort and 30.9 years for the fingolimod cohort. The majority of patients in both cohorts had relapsing MS (cladribine cohort, 92.1%; fingolimod cohort, 93.5%). By providing further information on adverse events of special interest during long-term follow-up, CLARION will assist neurologists and patients regarding treatment decision-making for management of relapsing MS.


Efficacy and safety analyses across 4 subgroups combining low and high age and body mass index groups in Japanese phase 3 studies of dulaglutide 0.75 mg after 26 weeks of treatment.
In 855 Japanese patients with type 2 diabetes receiving once weekly dulaglutide 0.75 mg in 3 phase 3 studies, the effects on efficacy and safety at week 26 (last observation carried forward) were investigated in a post hoc descriptive analysis of subgroups of age (<65 years [young], ≥65 years [elderly]) and body mass index (BMI [<25 kg/m2, ≥25 kg/m2]). The 4 subgroups were as follows: 1) the young/low-BMI subgroup (Y/L) (n = 255); 2) the young/high-BMI subgroup (Y/H) (n = 386), 3) the elderly/low-BMI subgroup (E/L) (n = 137), and 4) the elderly/high-BMI subgroup (E/H) (n = 77). The mean changes from baseline in glycated hemoglobin (HbA1c) and body weight, respectively, were -1.69% and -0.29 kg in the Y/L subgroup; -1.48% and -0.09 kg in the Y/H subgroup; -1.68% and -0.20 kg in the E/L subgroup; and -1.72% and -0.26 kg in the E/H subgroup. The incidences of nausea and hypoglycemia, respectively, were 6.7% and 11.0% in the Y/L subgroup; 7.0% and 8.0% in the Y/H subgroup; 10.2% and 18.2% in the E/L subgroup; and 3.9% and 22.1% in the E/H subgroup. Dulaglutide improved HbA1c regardless of age or BMI; a higher incidence of hypoglycemia was observed in elderly patients compared to younger patients.


[Results of drug therapy of inoperable non-small cell lung carcinoma with VP 16-213 (Etoposide) and cis-platin. A phase II study].
Forty-six patients with non-small cell lung cancer were treated with a combination of cis-platinum 90 mg/m2 i.v., day 1 and VP 16-213 100 mg/m2 i.v. on days 1, 3 and 5. The overall remission rate was 22% (10 out of 46 patients) with a median remission duration of 7 months. Squamous cell and large cell undifferentiated carcinomas responded to the chemotherapy with a remission rate of 27% (7 out of 26 patients) and 22% (3 out of 13 patients). Seven patients with adeno-carcinoma did not respond to chemotherapy. The overall survival was 7 months (1-27+). The survival time for patients entering remission was 11.5 months (7-27+), for those with stable disease 8.5 months (3-27+), and for patients with progressive disease 5 months (1-9). Performance status of less than 80%, a weight loss of more than 10.0 kg in the last three months before starting treatment and a "major" atelectasis (collapse of at least one superior or inferior lobe) adversely influenced prognosis. Only 1 out of 31 patients with one or more poor prognostic factors came into remission. In contrast, 9 out of 15 patients (60%) without poor prognostic factors had a remission. Stage, limited versus extensive disease, and age did not affect the results. Hematologic and renal toxicity of the combination were mild, but poor subjective tolerance (nausea, vomiting, loss of appetite) was prominent.


Topologically Associating Domains: An invariant framework or a dynamic scaffold?
Metazoan genomes are organized into regions of topologically associating domains (TADs). TADs are demarcated by border elements, which are enriched for active genes and high occupancy architectural protein binding sites. We recently demonstrated that 3D chromatin architecture is dynamic in response to heat shock, a physiological stress that downregulates transcription and causes a global redistribution of architectural proteins. We utilized a quantitative measure of border strength after heat shock, transcriptional inhibition, and architectural protein knockdown to demonstrate that changes in both transcription and architectural protein occupancy contribute to heat shock-induced TAD dynamics. Notably, architectural proteins appear to play a more important role in altering 3D chromatin architecture. Here, we discuss the implications of our findings on previous studies evaluating the dynamics of TAD structure during cellular differentiation. We propose that the subset of variable TADs observed after differentiation are representative of cell-type specific gene expression and are biologically significant.


Adrenomedullin surges are linked to acute episodes of the systemic capillary leak syndrome (Clarkson disease).
Systemic Capillary Leak Syndrome (SCLS) is an extremely rare and life-threatening vascular disorder of unknown etiology. SCLS is characterized by abrupt and transient episodes of hypotensive shock and edema due to plasma leakage into peripheral tissues. The disorder has garnered attention recently because its initial presentation resembles more common vascular disorders including systemic anaphylaxis, sepsis, and acute infections with the Ebola/Marburg family of filoviruses. Although approximately 70-85% of patients with SCLS have a concurrent monoclonal gammopathy of unknown significance (MGUS), any contribution of the paraprotein to acute flares is unknown. To identify circulating factors that might trigger acute SCLS crises, we profiled transcriptomes of paired peripheral blood mononuclear cell fractions obtained from patients during acute attacks and convalescent intervals by microarray. This study uncovered 61 genes that were significantly up- or downregulated more than 2.5-fold in acute samples relative to respective baselines. One of the most upregulated genes was ADM, which encodes the vasoactive peptide adrenomedullin. A stable ADM protein surrogate (pro-ADM) was markedly elevated in SCLS acute sera compared to remission samples or sera from healthy controls. Monocytes and endothelial cells (ECs) from SCLS subjects expressed significantly more ADM in response to proinflammatory stimuli compared to healthy control cells. Application of ADM to ECs elicited protective effects on vascular barrier function, suggesting a feedback protective mechanism in SCLS. Since ADM has established hypotensive effects, differentiating between these dual actions of ADM is crucial for therapeutic applications aimed at more common diseases associated with increased ADM levels.


Clinical performance of high-resolution late gadolinium enhancement imaging with compressed sensing.
To evaluate diagnostic image quality of 3D late gadolinium enhancement (LGE) with high isotropic spatial resolution (∼1.4 mm3 ) images reconstructed from randomly undersampled k-space using LOw-dimensional-structure Self-learning and Thresholding (LOST). We prospectively enrolled 270 patients (181 men; 55 ± 14 years) referred for myocardial viability assessment. 3D LGE with isotropic spatial resolution of 1.4 ± 0.1 mm3 was acquired at 1.5T using a LOST acceleration rate of 3 to 5. In a subset of 121 patients, 3D LGE or phase-sensitive LGE were acquired with parallel imaging with an acceleration rate of 2 for comparison. Two readers evaluated image quality using a scale of 1 (poor) to 4 (excellent) and assessed for scar presence. The McNemar test statistic was used to compare the proportion of detected scar between the two sequences. We assessed the association between image quality and characteristics (age, gender, torso dimension, weight, heart rate), using generalized linear models. Overall, LGE detection proportions for 3D LGE with LOST were similar between readers 1 and 2 (16.30% vs. 18.15%). For image quality, readers gave 85.9% and 80.0%, respectively, for images categorized as good or excellent. Overall proportion of scar presence was not statistically different from conventional 3D LGE (28% vs. 33% [P = 0.17] for reader 1 and 26% vs. 31% [P = 0.37] for reader 2). Increasing subject heart rate was associated with lower image quality (estimated slope = -0.009 (P = 0.001)). High-resolution 3D LGE with LOST yields good to excellent image quality in >80% of patients and identifies patients with LV scar at the same rate as conventional 3D LGE. 2 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2017;46:1829-1838.


Theoretical study of DNA damage recognition via electron transfer from the [4Fe-4S] complex of MutY.
The mechanism of site-specific recognition of DNA by proteins has been a long-standing issue. The DNA glycosylase MutY, for instance, must find the rare 8-oxoguanine-adenine mismatches among the large number of basepairs in the DNA. This protein has a [4Fe-4S] cluster, which is highly conserved in species as diverse as Escherichia Coli and Homo sapiens. The mixed-valent nature of this cluster suggests that charge transfer may play a role in MutY's function. We have studied the energetics of the charge transfer in Bacillus stearothermophilus MutY-DNA complex using multiscale calculation including density functional theory and molecular dynamics. The [4Fe-4S] cluster in MutY is found to undergo 2+ to 3+ oxidation when coupling to DNA through hole transfer, especially when MutY is near an oxoguanine modified base (oxoG). Employing the Marcus theory for electron transfer, we find near optimal Frank-Condon factors for electron transfer from MutY to oxoguanine modified base. MutY has modest selectivity for oxoguanine over guanine due to the difference in oxidation potential. The tunneling matrix element is significantly reduced with the mutation R149W, whereas the mutation L154F reduces the tunneling matrix element as well as the Frank-Condon factor. Both L154F and R149W mutations are known to dramatically reduce or eliminate repair efficiency. We suggest a scenario where the charge transfer leads to a stabilization of the specific binding conformation, which is likely the recognition mode, thus enabling it to find the damaged site efficiently.


Taxane-induced neurotoxicity: Pathophysiology and therapeutic perspectives.
Taxane-derived drugs are antineoplastic agents used for the treatment of highly common malignancies. Paclitaxel and docetaxel are the most commonly used taxanes; however, other drugs and formulations have been used, such as cabazitaxel and nab-paclitaxel. Taxane treatment is associated with neurotoxicity, a well-known and relevant side effect, very prevalent amongst patients undergoing chemotherapy. Painful peripheral neuropathy is the most dose-limiting side effect of taxanes, affecting up to 97% of paclitaxel-treated patients. Central neurotoxicity is an emerging side effect of taxanes and it is characterized by cognitive impairment and encephalopathy. Besides impairing compliance to chemotherapy treatment, taxane-induced neurotoxicity (TIN) can adversely affect the patient's life quality on a long-term basis. Despite the clinical relevance, not many reviews have comprehensively addressed taxane-induced neurotoxicity when they are used therapeutically. This article provides an up-to-date review on the pathophysiology of TIN and the novel potential therapies to prevent or treat this side effect.


Ontogenetic differences in retention of spatial learning tested with the Morris water maze.
Two experiments examined retention of spatial learning in rats using a Morris water maze. Retention was scored in terms of probe trial performance when the platform was removed. Latency to reach the platform location, percent of time in the quadrant that had contained the platform, and relative frequency of visits to the platform location were analyzed. Results of the first experiment showed that preweanlings and juveniles exhibited substantial forgetting at 3- and 7-day retention intervals. Forgetting in adults was much lower than that found in the younger animals, and no differences in amount of forgetting appeared between the 3- and 7-day retention intervals at any age. The second experiment showed that forgetting in juveniles was alleviated by a single training trial administered just prior to the probe trial. These results are discussed in terms of ontogenetic differences in memory processing and measurement issues pertinent to the Morris water maze test procedure.


Audiovisual Mandarin Lexical Tone Perception in Quiet and Noisy Contexts: The Influence of Visual Cues and Speech Rate.
Armed with the theory of embodied cognition proposing tight interactions between perception, motor, and cognition, this study aimed to test the hypothesis that speech rate-altered Mandarin lexical tone perception in quiet and noisy environments could be affected by the bodily dynamic cross-modal information. Fifty-three adult listeners completed a Mandarin tone perception task with 720 tone stimuli in auditory-only (AO), auditory-facial (AF), and auditory-facial-plus-gestural (AFG) modalities, at fast, normal, and slow speech rates under quiet and noisy conditions. In AF and AFG modalities, both congruent and incongruent audiovisual information were designed and presented. Generalized linear mixed-effects models were constructed to analyze the accuracy of tone perception across different conditions. In Mandarin tone perception, the magnitude of enhancement of AF and AFG cues across three speech rates was significantly higher than that of the AO cue in the adverse context of noise, yet additional metaphoric gestures did not show significant differences from the facial information. Furthermore, the performance of auditory tone perception at the fast speech rate was significantly better than that at the normal speech rate when the inputs were incongruent between auditory and visual channels in quiet. This study provided compelling evidence showing that integrated audiovisual information plays a vital role not only in improving lexical tone perception in noise but also in modulating the effects of speech rate on Mandarin tone perception in quiet for native listeners. Our findings, supporting the theory of embodied cognition, are implicational for speech and hearing rehabilitation among both young and old clinical populations.


Offering Outworld Experiences to In-Patients With Dementia Through Virtual Reality: Mixed Methods Study.
Research has suggested that institutionalization can increase the behavioral and psychological symptoms of dementia. To date, recent studies have reported a growing number of successful deployments of virtual reality for people with dementia to alleviate behavioral and psychological symptoms of dementia and improve quality of life. However, virtual reality has yet to be rigorously evaluated, since the findings are still in their infancy, with nonstatistically significant and inconclusive results. Unlike prior works, to overcome limitations in the current literature, our virtual reality system was co-designed with people with dementia and experts in dementia care and was evaluated with a larger population of patients with mild to severe cases of dementia. Working with 44 patients with dementia and 51 medical experts, we co-designed a virtual reality system to enhance the symptom management of in-patients with dementia residing in long-term care. We evaluated the system with 16 medical experts and 20 people with dementia. This paper explains the screening process and analysis we used to identify which environments patients would like to receive as an intervention. We also present the system's evaluation results by discussing their impact in depth. According to our findings, virtual reality contributes significantly to the reduction of behavioral and psychological symptoms of dementia, especially for aggressive, agitated, anxious, apathetic, depressive, and fearful behaviors. Ultimately, we hope that the results from this study will offer insight into how virtual reality technology can be designed, deployed, and used in dementia care.


The development and psychometric properties of a new scale to measure mental illness related stigma by health care providers: the Opening Minds Scale for Health Care Providers (OMS-HC).
Research on the attitudes of health care providers towards people with mental illness has repeatedly shown that they may be stigmatizing. Many scales used to measure attitudes towards people with mental illness that exist today are not adequate because they do not have items that relate specifically to the role of the health care provider. We developed and tested a new scale called the Opening Minds Scale for Health Care Providers (OMS-HC). After item-pool generation, stakeholder consultations and content validation, focus groups were held with 64 health care providers/trainees and six people with lived experience of mental illness to develop the scale. The OMS-HC was then tested with 787 health care providers/trainees across Canada to determine its psychometric properties. The initial testing OMS-HC scale showed good internal consistency, Cronbach's alpha = 0.82 and satisfactory test-retest reliability, intraclass correlation = 0.66 (95% CI 0.54 to 0.75). The OMC-HC was only weakly correlated with social desirability, indicating that the social desirability bias was not likely to be a major determinant of OMS-HC scores. A factor analysis favoured a two-factor structure which accounted for 45% of the variance using 12 of the 20 items tested. The OMS-HC provides a good starting point for further validation as well as a tool that could be used in the evaluation of programs aimed at reducing mental illness related stigma by health care providers. The OMS-HC incorporates various dimensions of stigma with a modest number of items that can be used with busy health care providers.


Penetrating craniofacial injury in a pediatric patient.
Penetrating craniofacial injuries are rare especially in the pediatric age group. They are potentially life-threatening and challenging injuries. We describe an unusual trauma in a 30-month-old child who suffered a craniofacial injury caused by TV antenna. Clinical examination and radiological investigation showed the antenna penetrating the hard palate, left posterior nasal choana, sphenoid sinus, and skull base, up to pituitary fossa. There was no evidence of great vessels injury that confirmed by cerebral angiography. Transpalatal approach was used to remove the antenna and repair the skull base defect. There was no neurological or visual activity deficit postoperatively. The child developed diabetes insipidus that is well controlled using desmopressin.


Comparative Analyses between Skeletal Muscle miRNAomes from Large White and Min Pigs Revealed MicroRNAs Associated with Postnatal Muscle Hypertrophy.
The molecular mechanism regulated by microRNAs (miRNAs) that underlies postnatal hypertrophy of skeletal muscle is complex and remains unclear. Here, the miRNAomes of longissimus dorsi muscle collected at five postnatal stages (60, 120, 150, 180, and 210 days after birth) from Large White (commercial breed) and Min pigs (indigenous breed of China) were analyzed by Illumina sequencing. We identified 734 miRNAs comprising 308 annotated miRNAs and 426 novel miRNAs, of which 307 could be considered pig-specific. Comparative analysis between two breeds suggested that 60 and 120 days after birth were important stages for skeletal muscle hypertrophy and intramuscular fat accumulation. A total of 263 miRNAs were significantly differentially expressed between two breeds at one or more developmental stages. In addition, the differentially expressed miRNAs between every two adjacent developmental stages in each breed were determined. Notably, ssc-miR-204 was significantly more highly expressed in Min pig skeletal muscle at all postnatal stages compared with its expression in Large White pig skeletal muscle. Based on gene ontology and KEGG pathway analyses of its predicted target genes, we concluded that ssc-miR-204 may exert an impact on postnatal hypertrophy of skeletal muscle by regulating myoblast proliferation. The results of this study will help in elucidating the mechanism underlying postnatal hypertrophy of skeletal muscle modulated by miRNAs, which could provide valuable information for improvement of pork quality and human myopathy.


Once-daily umeclidinium/vilanterol 125/25 mcg in COPD: a randomized, controlled study.
Combination long-acting bronchodilator therapy may be more effective than long-acting bronchodilator monotherapy in chronic obstructive pulmonary disease (COPD). To compare the efficacy and safety of once-daily umeclidinium/vilanterol (UMEC/VI) 125/25 mcg with placebo and UMEC or VI monotherapy in COPD. This was a double-blind, placebo-controlled, parallel-group study. A total of 1493 patients were randomized (3:3:3:2) to 24 weeks of treatment with UMEC/VI 125/25 mcg, UMEC 125 mcg, VI 25 mcg, or placebo once-daily via dry powder inhaler. Primary efficacy endpoint was trough forced expiratory volume in one second (FEV1) on Day 169 (23-24 h post-dose). Additional lung-function, symptomatic and health-related quality of life endpoints were also assessed. Safety evaluations included: adverse events, vital signs, electrocardiography and clinical laboratory measurements. All active treatments significantly improved trough FEV1 vs placebo (0.124-0.238 L, all p<0.001). Improvements with UMEC/VI 125/25 mcg were significantly greater than for UMEC 125 mcg or VI 25 mcg (0.079 L and 0.114 L; both p≤0.001). Improvements for UMEC/VI 125/25 mcg vs placebo were observed for the transition dyspnea index (1.0 unit; p<0.001), rescue albuterol use at Weeks 1-24 (-1.5 puffs/day) and St. George's Respiratory Questionnaire (-3.60 units, p<0.001). No safety signals were observed. Once-daily UMEC/VI 125/25 mcg was well tolerated and provided greater improvements in lung function, health status, and dyspnea scores compared with monotherapy components and placebo over 24 weeks. This study supports the use of UMEC/VI 125/25 mcg for the maintenance treatment of COPD. protocol number: DB2113361; ClinicalTrials.gov identifier: NCT01313637.


[Vitamin A requirement of growing swine. 1. Effect of vitamin A supply on growth of piglets and fattening swine].
For the purpose of ascertaining the vitamin A requirement seven experiments with 303 pigs in the live weight range between 6.5 and 114 kg were made. In three experiments under in practice conditions we checked the standard vitamin A supplement to the mixed feed with 1,732 pigs (live weight range between 8.5 and 110 kg). The supplement to vitamin-A-free rations and to those poor in or free of carotene amounted to between 0 and 8,000 IU/kg feed. Above that, between 0 and 16 mg beta-carotene and 1,000 mg nitrite/kg feed were supplemented. As long as the vitamin A store in the liver during weaning amounted to greater than 50 IU and greater than 100 IU/g at the beginning of fattening, feed intake, live weight growth and feed expenditure were not influenced by the supplement of vitamin and provitamin resp. The supplement of 250 IU resulted in the same weight growth from weaning to the end of fattening as that of 4,000 IU. Nitrite supplement had a negative effect at 250 IU, at 500 IU vitamin A consumption and weight growth tended to be only insignificantly lower. The methaemoglobin content decreasing in the course of the experiment reflects the adaptation of the pigs to the nitrite load. The consumption and growth depression caused by vitamin A deficiency could be observed from the 7th week of the experiment when casein-swelling starch rations were fed, but from the 13th week of the experiment only when cereal-soybean oilmeal rations were fed. The weight of liver, spleen, kidneys, heart and brain was not influenced by vitamin A supply. The same applies to the body composition and retention with the exception of two deficiency piglets, which contained less fat in the empty body than the control animals.


Preliminary testing of the Swedish version of the Assessment of Interprofessional Team Collaboration Scale (AITCS-S).
Interprofessional collaboration might improve healthcare processes and outcomes; however, it has been found that most instruments that aim to measure collaboration have undergone limited testing. The assessment of interprofessional team collaboration scale (AITCS) is one questionnaire that aims to evaluate collaboration, but it has not yet been extensively tested. The aim of this study was to translate and to cross-culturally adapt the AITCS for use in Sweden, to describe floor and ceiling values, and to investigate the AITCS in terms of reliability, face, and content validity. The study included a total of 349 participants working in team-based pain rehabilitation. The participants were asked to fill in the Swedish version of the AITCS (AITCS-S) at baseline. Of these, 73 participants also completed the AITCS-S two weeks later. The results showed that the content and face validity were good. Internal consistency varied from 0.79 to 0.96 and judged to be acceptable to excellent. Test-retest stability showed excellent stability with intraclass correlation values above 0.75 for all subscales. This study concludes that the Swedish version of the AITCS is a reliable and valid questionnaire. Further psychometric investigations might be undertaken in order to attempt to develop shorter versions of the AITCS-S.


The developmental inter-relationships between activity, novelty preferences, and delay discounting in male and female rats.
Increased locomotion, novelty-seeking, and impulsivity are risk factors associated with substance use. In this study, the inter-relationships between activity, novelty preferences, and delay discounting, a measure of impulsivity, were examined across three stages: juvenile/early adolescence (postnatal Day [P] 15, 19, and 42 for activity, novelty, and impulsivity, respectively), adolescent/late adolescent (P28, 32, 73), and adult (P90, 94, 137) in male and female rats. Our estimates of impulsive choice, where animals were trained to criterion, revealed an age × sex interaction where early adolescent females had the lowest levels of impulsivity. The relationships of activity and novelty to impulsivity significantly changed across age within each sex. Early adolescent males with high activity, but low novelty preferences, were more impulsive; however, low activity and high novelty preferences were related to high impulsivity in adult males. Female activity gradually increased across age, but did not show a strong relationship with impulsivity. Novelty preferences are moderately related to impulsivity into adulthood in females. These data show that males and females have different developmental trajectories for these behaviors. Males show greater sensation-seeking (e.g., activity) and risky behavior (e.g., novelty preferences) earlier in life, whereas these behaviors emerge during adolescence in females.


Parents' and children's ratings of sleep behavior, excitement, and tiredness: a 10-week longitudinal study.
In a 10-week longitudinal study, 29 parents and their children kept daily records of the children's sleep behaviors, excitement levels, and tiredness levels. Although the hypothesized increase in sleep behaviors such as sleepwalking and restlessness during the week of Christmas did not occur, children rated as more excitable by their parents and themselves exhibited a higher frequency of sleep behaviors. Positive associations were also found between averaged tiredness ratings and sleep scores. The results support previous findings of an association between arousal characteristics of children and their sleep behavior. Moderate validity coefficients were obtained for parents' and children's ratings of excitement, tiredness, and nocturnal waking.


Occupational physical activity and risk of adenocarcinomas of the esophagus and stomach.
Physical activity may have a role in many cancers, but little is known about its effect on esophageal and gastric adenocarcinoma risk. We investigated occupational physical activity and esophageal and gastric adenocarcinoma risk in a population-based, case-control study including 212 esophageal, 264 gastric cardia and 389 distal gastric cancer cases, and 1,330 controls in Los Angeles County. Lifetime occupational histories were obtained during in-person interviews, and total lifetime occupational activity (Total Activity Index) was calculated using US Census job codes classified as sedentary, or moderately or highly physically active. Average Annual Activity Index was a per-year Total Activity Index counterpart. Unconditional logistic regression was used to calculate odds ratios, 95% confidence intervals and trend tests adjusting for gender, race, age, birthplace, education, smoking, body mass index (BMI) and number of years worked. Esophageal adenocarcinoma risk tended to decrease with increasing Total Activity Index (OR = 0.67, 95% CI = 0.38,1.19 for highest versus lowest quartile), but neither gastric cardia nor distal gastric cancer was associated with the Total Activity Index. This inverse association held for esophageal adenocarcinoma (OR = 0.61, 95% CI = 0.38,0.99 for highest vs. lowest quartile) and modest associations were observed for gastric cardia (OR = 0.76, 95% CI = 0.49,1.18) and distal gastric cancer (OR = 0.77, 95% CI = 0.52,1.14) when based on Average Annual Activity Index before age 65 years. Analyses stratified by gender, race, age, BMI, education and years worked provided similar results. We found a modest protective effect of Total Activity Index on esophageal adenocarcinoma. Future studies with more complete information on occupational and recreational physical activity are needed to confirm and further investigate the suggested protective effect of physical activity on these tumor types.


Aberrant connectivity of lateral prefrontal networks in presymptomatic Huntington's disease.
In clinically presymptomatic individuals with the Huntington's disease (HD) gene mutation, functional neuroimaging data have suggested a dysfunction of multiple cortical and subcortical regions including the prefrontal and parietal cortex, as well as the striatum. Although it has been hypothesized that these activation differences most likely reflect aberrant corticostriatal circuits, the functional coupling of neural networks associated with cognitive performance has not been investigated so far. In this study, we used functional magnetic resonance imaging (fMRI) and multivariate analytic techniques to investigate memory-related patterns of functional connectivity in healthy controls (n=16) and pre-HD individuals (n=16). Independent component analyses (ICA) revealed distinct bilateral frontostriatal and frontoparietal networks that were activated during a verbal working memory paradigm in both healthy controls and pre-HD subjects. Compared with healthy controls, pre-HD individuals exhibited lower functional connectivity in left lateral prefrontal and parietal regions as well as in the bilateral putamen. Functional connectivity indices in the left putamen were negatively correlated with the CAG repeat size and the UHDRS behavioral score, and positively correlated with the predicted years to manifest symptom onset. The connectivity of the right putamen was negatively correlated with the UHDRS motor score. In pre-HD individuals, these results suggest an early frontostriatal and frontoparietal deficit of dissociable functional networks associated with executive processing.


Balanced Chromosomal Rearrangement Detection by Low-Pass Whole-Genome Sequencing.
Balanced chromosomal rearrangements (or balanced chromosome abnormalities, BCAs) are common chromosomal structural variants. Emerging studies have demonstrated the feasibility of using whole-genome sequencing (WGS) for detection of BCA-associated breakpoints, but the requirement for a priori knowledge of the rearranged regions from G-banded chromosome analysis limits its application. The protocols described here are based on low-pass WGS for detecting BCA events independent from chromosome analysis, and has been validated using genomic data from the 1000 Genomes Project. This approach adopts non-size-selected mate-pair library (3∼8 kb) with 2∼3 μg DNA as input, and requires only 30 million read-pairs (50 bp, equivalent to 1-fold base-coverage) for each sample. The complete procedure takes 13 days and the total cost is estimated to be less than $600 (USD) per sample. © 2018 by John Wiley & Sons, Inc.


Evaluation of the short form of "Experience in Close Relationships" (Revised, German Version "ECR-RD12") - A tool to measure adult attachment in primary care.
Attachment theory helps us to understand patients´ health behavior. Attachment styles might explain patient differences in coping behavior, self-treatment, or patient-provider relationships. In primary care time constrains are relevant. A short instrument may facilitate screening and assessment in daily medical practice. The aim of this study was to evaluate a 12-item short version of the Experience in Close Relationships-revised (ECR-R-D) to be used in primary care settings. We included 249 patients from ten general practices in central Germany into a cross-sectional study. Exploratory factor analysis was performed to evaluate the factor structure of the ECR-items. Cronbach's alpha was used to assess internal consistency. The results related to the short form of the ECR are in line with those of the German full-length version of the measure (ECR-RD 36). Internal consistencies were in an adequate range. The ECR short form can be recommended as a screening measure of attachment styles in primary care.


BP and Renal Outcomes in Diabetic Kidney Disease: The Veterans Affairs Nephropathy in Diabetes Trial.
Proteinuric diabetic kidney disease frequently progresses to ESRD. Control of BP delays progression, but the optimal BP to improve outcomes remains unclear. The objective of this analysis was to evaluate the relationship between BP and renal outcomes in proteinuric diabetic kidney disease. BP data from all 1448 randomized participants in the Veterans Affairs Nephropathy in Diabetes Trial were included in a post hoc analysis. The associations of mean on-treatment BP with the primary end point (decline in eGFR, ESRD, or death), renal end point (decline in eGFR or ESRD), rate of eGFR decline, and mortality were measured. The median (25th, 75th percentile) follow-up time was 2.2 (1.2, 3.0) years. There were 284 primary end points. In univariate analyses, both mean systolic and mean diastolic BPs were strongly associated (P<0.001) with the primary end point. After multivariate adjustment, the hazard of developing the primary end point became progressively higher as mean systolic BP rose from <120 to ≥ 150 mmHg (P=0.02), with a significantly higher hazard ratio for 140-149 versus 120-129 mmHg (1.51 [1.06, 2.15]; P=0.02). There was also a significant association of mean diastolic BP with the hazard of developing the primary end point (P<0.01), with a significantly higher hazard ratio when mean diastolic BP was 80-89 versus 70-79 mmHg (1.54 [1.05, 2.25]; P=0.03); there was also a strong trend when mean diastolic BP was <60 mmHg. Associations between BP and both renal end point and rate of eGFR decline were similar to those with the primary end point. No association of BP with mortality was observed, possibly because of the limited number of mortality events. In patients with proteinuric diabetic kidney disease, mean systolic BP ≥ 140 mmHg and mean diastolic BP ≥ 80 mmHg were associated with worse renal outcomes.


New inotropic concepts: rationale for and differences between calcium sensitizers and phosphodiesterase inhibitors.
Positive inotropic compounds may be harmful in the long-term treatment of chronic congestive heart failure because they may induce a calcium overload, unwanted changes in cross-bridge kinetics and an acceleration in heart rate. As a result of all three alterations, energy consumption would be increased. Different pharmacological modes of action may have different effects on the molecular mechanisms underlying the positive inotropic effect, and hence on myocardial energy consumption. Therefore, we studied the effects of a variety of cardiotonic agents on the heat released from small guinea pig papillary muscles contracting isometrically at an experimental temperature of 21 degrees C and a stimulation frequency of 12 per minute using rapid antimony-bismuth thermopiles. We were able to define the economy of muscle contraction, which was lowest with phosphodiesterase inhibitors and highest with calcium sensitizers. Compared with an increase in extracellular calcium concentration, beta 1-adrenoceptor stimulators and phosphodiesterase inhibitors profoundly decrease the economy of myocardial contraction, and calcium-sensitizers (pimobendan and EMD-53998) slightly increase myocardial economy, whereas ouabain and the calcium channel agonist BAY K 8644 have no effect on this parameter. In addition, we provide evidence that acceleration of heart rate may be harmful not only from an energetic point of view: an increase in heart rate may also decrease the contractility of the failing human myocardium (inverse force-frequency relationship). Taking these observations into consideration, an "optimal' positive inotropic compound should have no, or even negative, chronotropic effects, should not be mediated by increases in calcium transients, and should decelerate, rather than accelerate, cross-bridge kinetics.


Defining resident abuse within the culture of long-term care institutions.
Although researchers have identified the presence of resident abuse within long-term carefacilities, it has not come under the same scrutiny as have other aspects of abuse against older adults. This is due, in part, to the difficulty in defining the phenomenon. The purpose of this study was to articulate a definition of resident abuse as perceived by registered nurses working in long-term care institutions. Ethnoscience was the method used to answer this question. The five categories of resident abuse characteristics--perception of hurtfelt by older residents, acts of omission or commission, context of care, intentional or unintentional, and behavioral clusters--that emerged through semistructured interviews and focus groups reflect the descriptions given by participants. Identifying a common definition of resident abuse suggests that assessment and intervention to reduce episodes of it are more likely to be effective.


Study on Morphology, Microstructure and Properties of 6063-T6 Aluminum Alloy Joints in MIG Welding.
In this paper, a metal inert gas (MIG) shielded welding method was used for high-quality welding of 6063-T6 aluminum alloy sheet with a thickness of 2.5 mm. The welding process of MIG welding was accurately simulated and the welding temperature field and thermal cycle curve were calculated using a combination of Gaussian body heat source and double ellipsoidal heat source. As the welding current increased from 75 A to 90 A, the reinforcing phase precipitated under the microstructure of the joint gradually became larger and re-solidified into the body, resulting in a reduction in mechanical properties. When the welding current is 85 A, the pitting resistance of weld forming and weld area reaches its optimum. At this time, the tensile strength of the joint is up to 110.9 MPa, the elongation is up to 16.3% and the Vickers Microhardness is up to 46.9 HV.


Simultaneous determination of stable carbon, oxygen, and hydrogen isotopes in cellulose.
A technological development is described through which the stable carbon-, oxygen-, and nonexchangeable hydrogen-isotopic ratios (δ(13)C, δ(18)O, δ(2)H) are determined on a single carbohydrate (cellulose) sample with precision equivalent to conventional techniques (δ(13)C 0.15‰, δ(18)O 0.30‰, δ(2)H 3.0‰). This triple-isotope approach offers significant new research opportunities, most notably in physiology and medicine, isotope biogeochemistry, forensic science, and palaeoclimatology, when isotopic analysis of a common sample is desirable or when sample material is limited.


Interleukin-23 drives expansion of Thelper 17 cells through epigenetic regulation by signal transducer and activators of transcription 3 in lupus patients.
To elucidate the molecular mechanisms underlying pathogenic Th17 cells, we investigated the modulation of epigenetic modifications and its association with SLE. Naive CD4+ T cells were cultured in Th17 polarizing conditions for 5 days and then treated with various cytokines, including IL-23. Expression of Th17 cell-related markers and phosphorylation of signal transducers and activators of transcription (pSTATs) were analysed using flow cytometry and quantitative PCR. Histone modifications were assessed using chromatin immunoprecipitation PCR. T cell phenotypes and pSTATs were analysed in blood samples of patients with SLE (n = 28). Finally, the effects of baricitinib on memory Th17 cells were investigated in SLE patients (n = 12). Stimulation of resting Th17 cells with IL-23 promoted maturation of these cells (P < 0.0001). IL-23 induced pSTAT3, but not pSTAT4, during Th17 cell maturation (P < 0.05). IL-23-induced STAT3 directly bound the RORγT gene locus. This was accompanied by induction of the H3H4me3 permissive mark and reduction of the H3K27me3 repressive mark, leading to enhanced RORγT gene expression. IL-23-induced expansion of Th17 cells and pSTAT3 were suppressed by the addition of baricitinib in a concentration-dependent manner (P < 0.05). In memory Th17 cells from SLE patients, pSTAT3 was hypersensitized by IL-23 stimulation and inhibited by baricitinib (P < 0.05). The results of this study indicate that IL-23/STAT3 signalling plays a fundamental role in Th17 cell maturation through transcriptional and epigenetic modifications in patients with SLE. This mechanism may underlie pathogenic Th17 cell expansion and may lead to identification of novel therapeutic targets for SLE.


Violations and errors during simulation-based driver training.
The effectiveness of virtual driving instruction can increase when techniques that automatically distinguish between violations and errors are available, two behaviours requiring different types of remediation. This study reports the analysis of the objectively measured performance of 520 participants completing a simulation-based training programme. Factor analysis of failure reasons showed that violations and errors were the primary underlying factors. Men committed more violations and women made more errors; the magnitude of sex differences corresponded to the factor loadings. Factor analysis of the mean task completion times yielded a factor that can be described as the extent to which motivation for speed resulted in quicker task execution. Quicker participants completed more tasks, committed more violations, but made fewer errors. Participants reduced errors during forced-paced driving and increased speed during self-paced driving. The authors would recommend exploiting the distinction between violations and errors by developing interfaces and feedback for both types of aberration.


Vitamin D receptor variants and breast cancer risk in the Polish population.
The aim of the study was to determine whether four VDR gene single nucleotide polymorphisms (SNPs: rs1544410, rs731236, rs10735810 and rs4516035) are associated with breast cancer risk in Polish population. Two independent series of female patients were employed: 960 consecutive breast cancer cases, and 800 unselected early onset cases diagnosed under the age of 51. The control group for the consecutive breast cancer cases consisted of 960 healthy, age-matched women with a negative cancer family history. 550 healthy women, aged 51 or less, with negative cancer family history were selected as the independent controls for the early onset breast cancer cases. The frequencies of the VDR polymorphisms in the unselected cases when compared to the respective control population failed to reveal any association between the individual SNPs and disease. Examination of the group of early-onset patients, revealed an association between rs10735810 and increased breast cancer risk. Heterozygous carriers for the change had an OR = 1.73 (95% CI 1.33-2.26, P < 0.0001) and homozygous carriers OR = 2.34 (95% CI 1.71-3.21, P < 0.0001). The remaining three examined SNPs failed to show any association with disease risk. In summary, this study has identified an association between the VDR gene and early onset breast cancer risk in the Polish population.


Dextromethorphan-bupropion (Auvelity) for the Treatment of Major Depressive Disorder.
Depression is a significant cause of morbidity and mortality globally. Although various pharmacologic options exist for depression, treatments are limited by delayed or incomplete therapeutic response, low rates of remission, and adverse effects necessitating effective, fast-acting, and better tolerated alternatives. The purpose of this review is to describe the safety and efficacy of dextromethorphan-bupropion (Auvelity), a Food and Drug Administration approved treatment for major depressive disorder in adults. Dextromethorphan modulates glutamate signaling through uncompetitive antagonism of N-methyl-D-aspartate receptors and sigma-1 agonism, while bupropion increases the bioavailability of dextromethorphan by CYP2D6 inhibition. In a phase 3 trial with dextromethorphan-bupropion 45-105 mg for patients with major depressive disorder saw significant reductions in their Montgomery-Åsberg Depression Rating Scale total scores compared to placebo. A phase 2 trial comparing dextromethorphan-bupropion 45-105 mg to bupropion monotherapy led to significant reduction in Montgomery-Åsberg Depression Rating Scale score. Changes in Montgomery-Åsberg Depression Rating Scale with dextromethorphan-bupropion were seen within two weeks in both clinical trials. Remission and response rates were significantly higher with dextromethorphan-bupropion in both studies. The medication was well-tolerated in both trials, with the most common adverse events being rated as mild-to-moderate. Two long-term, open-label studies with dextromethorphan-bupropion saw large reductions in Montgomery-Åsberg Depression Rating Scale scores that were maintained through 12 and 15 months of treatment. In both long-term studies, remission rates approached 70%, while response rates were greater than 80%. These data suggest that dextromethorphan-bupropion is an effective, fast-acting, and well tolerated option for depression treatment and produced remission in a large percentage of patients.


A Comprehensive Craniofacial Study of 22q11.2 Deletion Syndrome.
The 22q11.2 deletion syndrome (22q11.2DS) is one of the most frequent microdeletion syndromes and presents with a highly variable phenotype. In most affected individuals, specific but subtle facial features can be seen. In this observational study, we aim to investigate the craniofacial and dental features of 20 children with a confirmed diagnosis of 22q11.2DS by analyzing 3-dimensional (3D) facial surface scans, 2-dimensional (2D) clinical photographs, panoramic and cephalometric radiographs, and dental casts. The 3D facial scans were compared to scans of a healthy control group and analyzed using a spatially dense geometric morphometric approach. Cephalometric radiographs were digitally traced, and measurements were compared to existing standards. Occlusal and dental features were studied on dental casts and panoramic radiographs. Interestingly, a general trend of facial hypoplasia in the lower part of the face could be evidenced with the 3D facial analysis in children with 22q11.2DS compared to controls. Cephalometric analysis confirmed a dorsal position of the mandible to the maxilla in 2D and showed an enlarged cranial base angle. Measurements for occlusion did not differ significantly from standards. Despite individual variability, we observed a retruded lower part of the face as a common feature, and we also found a significantly higher prevalence of tooth agenesis in our cohort of 20 children with 22q11.2DS (20%). Furthermore, 3D facial surface scanning proved to be an important noninvasive, diagnostic tool to investigate external features and the underlying skeletal pattern.


Chylothorax following cardiac surgery caused by unusual lymphatic anatomy.
Chylothorax due to injury to the thoracic duct and lymphatic channels during left internal thoracic artery harvest is well described. However, high volume leakage of chyle due to disruption of aberrant thymic collateral lymphatic channel in the anterior mediastinum has not been described previously. We describe such a case which was managed by early surgical exploration, ligation of the aberrant duct, and insertion of a pleuro-peritoneal shunt.


Melatonin impedes Tet1-dependent mGluR5 promoter demethylation to relieve pain.
Melatonin (N-acetyl-5-methoxytryptamine)/MT2 receptor-dependent epigenetic modification represents a novel pathway in the treatment of neuropathic pain. Because spinal ten-eleven translocation methylcytosine dioxygenase 1 (Tet1)-dependent epigenetic demethylation has recently been linked to pain hypersensitivity, we hypothesized that melatonin/MT2-dependent analgesia involves spinal Tet1-dependent demethylation. Here, we showed that spinal Tet1 gene transfer by intrathecal delivery of Tet1-encoding vectors to naïve rats produced profound and long-lasting nociceptive hypersensitivity. In addition, enhanced Tet1 expression, Tet1-metabotropic glutamate receptor subtype 5 (mGluR5) promoter coupling, demethylation at the mGluR5 promoter, and mGluR5 expression in dorsal horn neurons were observed. Rats subjected to spinal nerve ligation and intraplantar complete Freund's adjuvant injection displayed tactile allodynia and behavioral hyperalgesia associated with similar changes in the dorsal horn. Notably, intrathecal melatonin injection reversed the protein expression, protein-promoter coupling, promoter demethylation, and pain hypersensitivity induced by Tet1 gene transfer, spinal nerve ligation, and intraplantar complete Freund's adjuvant injection. All the effects caused by melatonin were blocked by pretreatment with a MT2 receptor-selective antagonist. In conclusion, melatonin relieves pain by impeding Tet1-dependent demethylation of mGluR5 in dorsal horn neurons through the MT2 receptor. Our findings link melatonin/MT2 signaling to Tet1-dependent epigenetic demethylation of nociceptive genes for the first time and suggest melatonin as a promising therapy for the treatment of pain.


The reasons dissociative disorder patients self-injure.
Most individuals with dissociative disorders (DDs) report engaging in self-injury. The present study aimed to understand the reasons for self-injury among a clinical sample of 156 DD patients enrolled in the TOP DD Network study. Participants answered questions about self-injury, including a prompt asking how often they are aware of the reasons they have urges to self-injure, as well as a prompt asking them to list three reasons they self-injure. Six themes of reasons for self-injury, each with subthemes, were identified in the qualitative data: (1) Trauma-related Cues, (2) Emotion Dysregulation, (3) Stressors, (4) Psychiatric and Physical Health Symptoms, (5) Dissociative Experiences, and (6) Ineffective Coping Attempts. Participants reported that they were able to identify their reasons for self-injuring sometimes (60.26%) or almost always (28.85%), with only 3.20% unable to identify any reasons for their self-injury. Results suggest that the vast majority of DD patients (92.31%) reported being at least partially unaware of what leads them to have self-injury urges, and many individuals with DDs experience some reasons for self-injury that are different from those with other disorders. The treatment implications of these findings are discussed.


Maxillary single-tooth replacement utilizing a novel ceramic restorative system: results to 30 months.
This study reports on the first longitudinal results of an alumina (70%)-zirconia (30%) ceramic restorative system for implant-supported, single-tooth replacement in the anterior maxillary jaw. Eighteen patients (9 men, 9 women, mean age = 42.4 years) were treated with 22 implants placed into 19 extraction sockets and 3 residual ridges. Eight implants were immediately loaded with nonoccluding provisional prostheses. All implants were definitively loaded with fully occluding ceramic restorations after osseointegration and soft tissue maturation. Patients were monitored from 7 to 30 months (mean = 18.1 months) after loading. All implants osseointegrated and were successfully restored. One case of abutment screw loosening occurred because of patient parafunction (bruxing), and another patient reported chewing pain attributed to malocclusion. Both problems were successfully resolved without further incidence. Within the context of this study, single-tooth replacement in the anterior maxillary jaw was successfully achieved with alumina-zirconia ceramic single-tooth restorations with up to 30 months of clinical function.


Energy-filtered electron diffraction and high-resolution electron microscopy on short-range ordered structure in GaAs(0.5)Sb(0.5).
Characteristic intensity distribution of diffuse scattering in III-V alloy semiconductor GaAs(0.5)Sb(0.5) epitaxially grown was observed by the energy-filtered electron diffraction method with [110] incidence. The diffuse scattering situates at the one-third positions between the fundamental reflections extending parallel to the q002 direction in the reciprocal space. A high-resolution electron microscope image shows weak contrast modulation corresponding to the diffuse scattering. The image processed with the Fourier transform by selecting the diffuse scattering and a fundamental reflection shows small regions consisting of bright dots being elongated along the (111) planes and aligning on the (002) planes, which are considered to result from the ordering of As and Sb during the growth process. The effect of including the fundamental reflection for imaging the ordered regions in the image processing method is also discussed. Finally, based on the results obtained by energy-filtered electron diffraction and high-resolution electron microscopy, a simple structure model for the short-range ordered structure in GaAs(0.5)Sb0.5 is proposed.


An Abbreviated Diagnostic Maneuver for Posterior Benign Positional Paroxysmal Vertigo.
Benign paroxysmal positional vertigo (BPPV) secondary to canalolithiasis of the posterior semicircular canal is perhaps the most frequent cause of vertigo and dizziness. One of its properties is a high response rate to canalith repositioning maneuvers. However, delays in the diagnosis and treatment of this entity can range from days to years, depending on the setting. Here, we present an abbreviated variation of the Dix-Hallpike maneuver, which can be used to diagnose this disease. It is similar to the standard maneuver but can be performed without an examination bed/table and requires only a backed chair (a difference that we feel is very important in settings where a clinical bed/table is not readily available). A diagnostic assessment study was conducted in 163 patients who presented with vertigo or dizziness. The abbreviated test had fairly good sensitivity (80%) and high specificity (95%) for diagnosing posterior BPPV. This new diagnostic maneuver may serve as a screening procedure for quickly identifying this pathology. This will allow patients to be more directly treated, without requiring unnecessary referrals or full vestibular testing, and will be especially useful in primary care settings or heavily overloaded otolaryngology or neurology departments.


Commentary 1: The Challenging Task of Addressing Power, Control, and Influence in Sibling Relationships After the First Two Decades of Life.
Extending the topic of power, control, and influence in the sibling relationship past the years covered in this issue is not an easy task because most adult siblings neither interact frequently nor live in geographic proximity, although there are considerable ethnic and social class variations. Thus, there are limited opportunities to observe how power is manifested, how siblings control each other and themselves to achieve their goals, nor how siblings influence each other. Comments in this commentary address the challenges presented when considering the trajectory of these dynamics in adult sibling relationships as well as the difficulties sibling dynamics present in carrying out tasks for which an egalitarian relationship is not ideal.


Protease-activated receptor 4 uses anionic residues to interact with alpha-thrombin in the absence or presence of protease-activated receptor 1.
Thrombin activates protease-activated receptor 1 (PAR1) faster than protease-activated receptor 4 (PAR4) due to a hirudin-like sequence in the exodomain of PAR1 that binds thrombin's exosite I. However, recombinant exodomain studies indicate that PAR4 does have extended contacts with alpha-thrombin that influence PAR4's kinetics of cleavage. In this report, the role of an anionic cluster (Asp(57), Asp(59), Glu(62), and Asp(65)) in the exodomain of PAR4 is examined for its influence on cleavage and activation of PAR4 on cells in the absence or presence of PAR1. Alpha-thrombin induces wild-type PAR4 (PAR4-wt) calcium flux with an EC(50) of 110 nM, whereas mutation of the four anionic residues (PAR4-AAAA) increases the EC(50) to 641 nM. In contrast, PAR4-wt and PAR4-AAAA are activated by gamma-thrombin with similar EC(50) values (588 and 449 nM, respectively; p = 0.48), suggesting a role for alpha-thrombin's exosite I in PAR4 activation. Coexpression of PAR1 lowered the EC(50) of cleavage for PAR4-wt from 321 to 26 nM and for PAR4-AAAA from 1.5 microM to 360 nM. Individual point mutations at Asp(57), Asp(59), Glu(62), and Asp(65) show that PAR4-D57A is activated by alpha-thrombin with the same EC(50) as PAR4-wt (140 nM) whereas PAR4-D59A is the same as PAR4-AAAA (699 nM). Glu(62) and Asp(65) contribute to alpha-thrombin recognition, but to a lesser extent. This report shows that PAR4 uses its anionic cluster to interact with alpha-thrombin and that this interaction is important even in the presence of PAR1.


[Massive therapy and transplant of autologous bone marrow in childhood lymphomas and solid tumors. State of the art and perspectives].
The role of massive therapy followed by autologous bone marrow transplantation (ABMT) in pediatric tumours is reviewed. The rationale of such an approach based on dose-response relationship in clinical oncology, the usefulness of total body irradiation (TBI) as a part of conditioning regimens, and phase I and II trials with high dose drug combinations are discussed. The results of ABMT in lymphomas, sarcomas, neuroblastomas and other tumours are critically analyzed with special emphasis on prognostic factors, differences among conditioning regimens, intensive therapy morbidity and marrow purging procedures. Finally future perspectives and questions still unsolved are briefly summarized.


Photoemission spectroscopy and atomic force microscopy investigation of vapor-phase codeposited silver/poly(3-hexylthiophene) composites.
Nanocomposite matrices of silver/poly(3-hexylthiophene) (P3HT) were prepared in ultrahigh vacuum through vapor-phase codeposition. Change in microstructure, chemical nature, and electronic properties with increasing filler (Ag) content were investigated using in situ XPS and UPS, and ambient AFM. At least two chemical binding states occur between Ag nanoparticles and sulfur in P3HT at the immediate contact layer, but no evidence of interaction between Ag and carbon (in P3HT) was found. AFM images reveal a change in Ag nanoparticles size with concentration which modifies the microstructure and the average roughness of the surface. Under codeposition, P3HT largely retains its conjugated structures, which is evidenced by the similar XPS and UPS spectra to those of P3HT films deposited on other substrates. We demonstrate here that the magnitude of the barrier height for hole injection (epsilon(v)(F)) and the position of the highest occupied band edge (HOB) with respect to the Fermi level of Ag may be controlled and changed by adjusting the metal (Ag) content in the composite. Furthermore, UPS reveals distinct features related to the C 2p (sigma states) in the 5-12 eV regions, indicating the presence of ordered P3HT, which is different from solution processed films.


Extraneural sclerosing perineurioma of the buccal mucosa: a case report and clinicopathologic review.
The perineurioma is an infrequently encountered benign peripheral nerve sheath tumor composed of a clonal proliferation of perineurial cells. Rare cases of perineurioma have been reported in the oral cavity. An extraneural sclerosing perineurioma arising in the buccal mucosa of a 17-year-old male is presented. Histopathologically, the tumor is composed of a well circumscribed nodular proliferation of spindle cells arranged in a storiform growth pattern, in some areas subtly arranged around vascular channels. The tumor cells reveal positive immunostaining for epithelial membrane antigen (EMA), collagen type IV and vimentin, and negative immunostaining for S-100 protein, consistent with a perineurial origin. To the best of our knowledge, this case represents the first report of an extraneural sclerosing perineurioma involving the oral cavity.


Hybrid optimal descriptors as a tool to predict skin sensitization in accordance to OECD principles.
Skin sensitization (allergic contact dermatitis) is a widespread problem arising from the contact of chemicals with the skin. The detection of molecular features with undesired effect for skin is complex task owing to unclear biochemical mechanisms and unclearness of conditions of action of chemicals to skin. The development of computational methods for estimation of this endpoint in order to reduce animal testing is recommended (Cosmetics Directive EC regulation 1907/2006; EU Regulation, Regulation, 1223/2009). The CORAL software (http://www.insilico.eu/coral) gives good predictive models for the skin sensitization. Simplified molecular input-line entry system (SMILES) together with molecular graph are used to represent the molecular structure for these models. So-called hybrid optimal descriptors are used to establish quantitative structure-activity relationships (QSARs). The aim of this study is the estimation of the predictive potential of the hybrid descriptors. Three different distributions into the training (≈70%), calibration (≈15%), and validation (≈15%) sets are studied. QSAR for these three distributions are built up with using the Monte Carlo technique. The statistical characteristics of these models for external validation set are used as a measure of predictive potential of these models. The best model, according to the above criterion, is characterized by nvalidation=29, r2validation=0.8596, RMSEvalidation=0.489. Mechanistic interpretation and domain of applicability for these models are defined.


Multicentric glioblastoma multiforme occurring in the supra- and the infratentorial regions--case report.
A 74-year-old male was admitted because of severe headache, vertigo, and vomiting. A computed tomographic scan showed heterogeneously enhanced tumors in the supra- and the infratentorial regions, apparently attached to the cerebellar tentorium. He died 2 months after the onset despite external decompression and a ventriculo-peritoneal shunt. The autopsy showed both tumors were intra-axial and not attached to the dura mater including the cerebellar tentorium. The histological diagnosis of either tumor was glioblastoma multiforme. This case could be classified as multicentric gliomas. In the 23 reported cases, including our case, most died soon after the onset of symptoms. Some, however, with low grade tumors had a comparatively long life span after the onset. It is, therefore, important to investigate the histology of these tumors for correct prognosis.


The effect of high-calorie meal consumption on oxidative stress and endothelial dysfunction in healthy male adults.
Several authors have reported the association of postprandial hypertriglyceridemia with oxidative stress, systemic inflammation and endothelial dysfunction. Our aim was to investigate the effect of high-calorie meal on blood markers of oxidative stress and endothelial dysfunction and the association of APOA5 -1131T/C and -250G/A hepatic lipase (HL) polymorphisms with postprandial triglyceride response. This study included 102 healthy male volunteers. All participants consumed a high-calorie meal (823 calories, 50 g fat, 28 g protein, 60 g carbohydrates). Total cholesterol, triglycerides, HDL-cholesterol, LDL-cholesterol, hsCRP, TAS and ICAM-1 were measured at fasting state and postprandially. APOA5 -1131T/C and -250G/A HL polymorphisms were also determined. Postprandial triglycerides were significantly increased (1.4 (1.1-2.1) vs. 2.4 (1.9-3.3) mmol/l, P<0.001). Average triglyceride increase was 1.0+/-0.7 mmol/l (65 %). Concentration of triglycerides, HDL-cholesterol, LDL-cholesterol, TAS and ICAM-1 differed significantly between the fasting state and postprandial measurements (P<0.001). However, those differences were within the limits of analytical imprecision. Other parameters did not change 3 h after the meal. Triglycerides response did not differ respective to the APOA5 and HL polymorphisms. Family history of hypertension and acute myocardial infarction were associated with higher postprandial triglyceride concentrations. Postprandial hypertriglyceridemia is not associated with increased concentrations of hsCRP, TAS and ICAM-1. Furthermore, APOA5 -1131T/C and -250G/A HL polymorphisms are not associated with different postprandial triglyceride response.


Laparoscopic salvage for malfunctioning of peritoneal dialysis catheters.
The aim of this study was to emphasize the efficacy of the laparoscopic surgical method performed for elimination of catheter-induced mechanical complications developing in CAPD patients. Medical records of 31 patients who had undergone CAPD catheter implantation at the Dicle University Medical Faculty Hemodialysis Unit between January 2001 and June 2012 were examined retrospectively. Double-felted spiral Tenckhoff catheters were used in all patients for peritoneal access. We performed a retrospective review of 31 patients who, over an 11-year period, underwent revision of a peritoneal dialysis catheter using laparoscopy. Chronic renal failure requiring dialysis occurred in 31 patients (12 males and 19 female). Ages ranged from 13 to 77 years (mean age 35.8 years). As a conclusion, CAPD is currently a choice to be frequently used in patients with ESRD. In the treatment of CAPD-associated mechanical catheter complications laparoscopic method may be preferred because of patient comfort, short hospital stay, and lesser postoperative complications.


Substitution Pattern Controlled Quantum Interference in [2.2]Paracyclophane-Based Single-Molecule Junctions.
Quantum interference (QI) of electron waves passing through a single-molecule junction provides a powerful means to influence its electrical properties. Here, we investigate the correlation between substitution pattern, conductance, and mechanosensitivity in [2.2]paracyclophane (PCP)-based molecular wires in a mechanically controlled break junction experiment. The effect of the meta versus para connectivity in both the central PCP core and the phenyl ring connecting the terminal anchoring group is studied. We find that the meta-phenyl-anchored PCP yields such low conductance levels that molecular features cannot be resolved; in the case of para-phenyl-coupled anchoring, however, large variations in conductance values for modulations of the electrode separation occur for the pseudo-para-coupled PCP core, while this mechanosensitivity is absent for the pseudo-meta-PCP core. The experimental findings are interpreted in terms of QI effects between molecular frontier orbitals by theoretical calculations based on density functional theory and the Landauer formalism.


Comparison of immunoreactivity of staphylococcal enterotoxin B mutants for use as toxin surrogates.
The development and testing of detection methodologies for biothreat agents are by their very nature complicated by the necessity to handle hazardous materials. Toxoids prepared by thermal or chemical inactivation are often used in place of the native toxin; however, the process of detoxification can decrease the agent's ability to be detected at similar concentrations. One method to overcome this limitation is the use of toxin mutants which have altered amino acid sequences sufficient to abrogate or greatly reduce their toxic activity. While this method of toxoid preparation is much more controlled, there is still no guarantee that the resulting product will be equal in detectability to the native toxin. In this work, we have evaluated the utility of two recombinantly expressed Staphylococcal Enterotoxin B (SEB) mutants, a single point mutant (Y89A), and a mutant with three amino acids changed (L45R, Y89A, Y94A), to act as surrogates for SEB in immunoassays. We evaluated the affinity of a number of anti-SEB monoclonal antibodies (mAb) and an anti-SEB single domain antibody (sdAb) for SEB and its surrogates. One of the mAb's affinity was decreased by a factor of 3000 for the triple mutant, and another mAb's affinity for the triple mutant was decreased by 11-fold while the others bound the mutants nearly as well as they did the native toxin. MAGPIX sandwich immunoassays were used to evaluate the ability of all combinations of the recognition reagents to detect the SEB mutants in comparison to SEB and a chemically inactivated SEB. These results show that recombinant mutants of SEB can serve as much more useful surrogates for this hazardous material relative to the chemically inactivated toxin; however, even the point mutant impacted limits of detection, illustrating the need to evaluate the utility of toxin mutants on a case-by-case basis depending on the immunoreagents being employed.


Comparison of the O Kalpha x-ray emission bands in micro- and mesoporous silica materials and in alpha-quartz.
X-ray emission spectroscopy (XES) at the O Kalpha threshold has been used to investigate the electronic structure of a microporous pure calcined zeolite with the crystal structure of the MFI-type framework (silicalite), a deboronated MFI zeolite (DB-MFI), a pure mesoporous cubic MCM-48 material, a MCM-48 loaded with copper and zinc oxide nanoparticles (CuZnO-MCM-48), and a crystalline layered silicic acid H-RUB-18. For comparison, the XES O Kalpha spectrum of pure alpha-quartz has also been recorded. In the nonresonant energy regime the XES O Kalpha spectra for all these compounds look very similar indicating that the electronic structure of the micro- and mesoporous silica materials is very similar to that of quartz. In the resonant regime, however, the spectra exhibit significant differences. In all the materials under study, the resonant XES O Kalpha spectra recorded at photon energies close to the positions of the O K edges show Raman-type inelastic peaks with an energy loss of 11 eV, originating from electronic excitations within these insulating materials. The prominent features in the XES O Kalpha spectra of alpha-quartz and H-RUB-18 are analyzed by means of quantum chemical ab initio cluster calculations.


Plasma magnesium levels as influenced by cold exposure in fed or fasted sheep.
Eight ewes weighing about 52 kg were used in a 2 X 2 factorial arrangement of treatments replicated with temperature reversal to determine the effect of cold exposure on plasma Mg, Ca, free fatty acids (FFA), glucose and insulin concentrations and on renal clearance of Mg and Ca. Closely sheared ewes were fed a complete mixed diet at either 1.5% of body weight with no pretreatment fast or fed ad libitum followed by fasting 3 days before initiation of temperature treatments. Fasting superimposed on cold exposure reduced (P less than 0.01) plasma Mg at 1 hour after exposure to cold, and this effect continued during the cold treatment period, whereas Mg concentration was not significantly affected in fed sheep. Plasma FFA measured across temperature treatments was increased (P less than 0.01) by fasting. FFA measured across dietary treatments was only slightly increased by cold exposure. Plasma glucose levels of fasting sheep were lower (P less than 0.05) than those of fed sheep; however, levels rose (P less than 0.05) after exposure to cold. A tendency for plasma insulin to increase after cold stress was observed. Renal clearances of Mg and Ca were markedly reduced (P less than 0.01) by fasting, but clearance was not changed by cold stress. These results suggest that exposure to cold (2-5 degrees) and a deficient dietary intake synergistically reduce plasma Mg in sheep.


The characterisation and risk factors of ischaemic heart disease in patients with coeliac disease.
Studies have shown an increased risk of ischaemic heart disease (IHD) in patients with coeliac disease (CD), despite the patients' lack of traditional IHD risk factors. To characterise IHD according to CD status. Data on duodenal or jejunal biopsies were collected in 2006-2008 from all 28 pathology departments in Sweden and were used to define CD (equal to villous atrophy; Marsh stage 3). We used the Swedish cardiac care register SWEDEHEART to identify IHD and to obtain data on clinical status and risk factors at time of first myocardial infarction for this case-only comparison. Logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs). CD patients were compared with general population reference individuals. We identified 1075 CD patients and 4142 reference individuals with subsequent IHD. CD patients with myocardial infarction had lower body mass index (P < 0.001) and cholesterol values (P < 0.001) and were less likely to be active smokers (OR = 0.74; 95% CI = 0.56-0.98) than reference individuals with myocardial infarction. CD patients had less extensive coronary artery disease at angiography (any stenosis: OR = 0.80; 95% CI = 0.66-0.97; three-vessel disease: OR = 0.73; 95% CI = 0.57-0.94); but there was no difference in the proportions of CD patients with positive biochemical markers of myocardial infarction (CD: 92.2% vs. reference individuals: 91.5%, P = 0.766). Despite evidence of an increased risk of IHD and higher cardiovascular mortality, patients with coeliac disease with IHD have a more favourable cardiac risk profile compared with IHD in reference individuals.


Causes of death in patients with familial polyposis coli (FPC).
Autopsy reports from patients with familial polyposis coli were obtained from the Roswell Park Memorial Institute Registry as well as clinical data on patients with familial polyposis coli with regard to their causes of death. Although the latter group did not undergo autopsy they were the subject of a close follow-up. From this data it is clear that diagnosis at an early age may not diminish the chances of the patient with familial polyposis to develop cancer. Removal of the colonic mucosa does not provide absolute assurance that patients with this condition will be cured, as these patients remain at considerable risk for developing other benign and malignant lesions of the gastrointestinal tract and perhaps also of other organs. Close follow-up of FPC patients who have had surgery for colorectal polyps or cancer is necessary. Other proliferative abnormalities of FPC patients include an abnormal fibroblastic response, tendency to develop adhesions, and the propensity for developing desmoids. Desmoids may follow a slow but unrelenting course with a lethal outcome. Autopsy findings support the view that there should be no distinction between familial polyposis coli and Gardner's syndrome.


Enthesitis in patients with psoriatic arthritis, axial spondyloarthritis and healthy subjects assessed by 'head-to-toe' whole-body MRI and clinical examination.
To investigate the ability of whole-body MRI (WBMRI) to detect axial and peripheral enthesitis in patients with psoriatic arthritis (PsA) and axial spondyloarthritis (axSpA), and in healthy subjects (HS). Furthermore, to develop MRI enthesitis indices based on WBMRI and validate these by use of clinical measures of disease activity. Prospective cross-sectional study of patients with PsA (n=18) and axSpA (n=18) with moderate to high disease activity, and HS (n=12). Enthesitis at 35 individual sites located at upper and lower limbs, chest and pelvis were evaluated by WBMRI and clinical examination, and compared. Three new WBMRI enthesitis indices were developed. WBMRI allowed evaluation of 888 (53%) of 1680 sites investigated, and 19 (54%) of 35 entheses had a readability >70%. The percentage agreement between WBMRI and clinical enthesitis was 49-100%, when compared at the level of the individual entheses. Enthesitis on WBMRI was observed in 148 (17%) of the entheseal sites, and was frequently present at greater trochanters (55%) and Achilles (43%) and supraspinate (23%) tendon insertions in patients and HS. At the first mentioned two locations enthesitis often appeared without clinical signs of enthesitis. Patients and HS differed significantly in one of the new WBMRI enthesitis scores. Patients and HS differed significantly in one of the new WBMRI enthesitis scores, and this score correlated weakly with BASDAI question 4 (tenderness in relation to entheses), BASDAI and patient global (ρ=0.29-0.31, p<0.05). WBMRI is a promising new imaging modality for evaluation of enthesitis in patients with PsA and axSpA, but requires further investigation before clinical use.


Evaluation of Probiotics for Warfighter Health and Performance.
The probiotic industry continues to grow in both usage and the diversity of products available. Scientific evidence supports clinical use of some probiotic strains for certain gastrointestinal indications. Although much less is known about the impact of probiotics in healthy populations, there is increasing consumer and scientific interest in using probiotics to promote physical and psychological health and performance. Military men and women are a unique healthy population that must maintain physical and psychological health in order to ensure mission success. In this narrative review, we examine the evidence regarding probiotics and candidate probiotics for physical and/or cognitive benefits in healthy adults within the context of potential applications for military personnel. The reviewed evidence suggests potential for certain strains to induce biophysiological changes that may offer physical and/or cognitive health and performance benefits in military populations. However, many knowledge gaps exist, effects on health and performance are generally not widespread among the strains examined, and beneficial findings are generally limited to single studies with small sample sizes. Multiple studies with the same strains and using similar endpoints are needed before definitive recommendations for use can be made. We conclude that, at present, there is not compelling scientific evidence to support the use of any particular probiotic(s) to promote physical or psychological performance in healthy military personnel. However, plausibility for physical and psychological health and performance benefits remains, and additional research is warranted. In particular, research in military cohorts would aid in assessing the value of probiotics for supporting physical and psychological health and performance under the unique demands required of these populations.


Vibration of Tympanic Membrane Influenced by Middle Ear Fluid.
The amount and viscosity of middle ear fluid probably influences the vibration function of the tympanic membrane (TM). There has been much research into the mechanisms of hearing loss resulting from middle ear fluid in the previous study. However, further study is required to understand how the middle ear fluid affects the vibration function of the TM. Tests on a TM in a fresh cadaveric human temporal bone specimen under different simulated conditions were carried out. Saline (1 cSt) and silicone oil (100 cSt, 1 000 cSt, 12 500 cSt) were used to simulate middle ear fluid. The fluid approximately contacted 50% or 100% of TM, which was proportional to the fluid amount. Induced by stimulus signal with frequency domain from 0.25 to 8 kHz, the vibration at 6 points of the TM was measured by laser Doppler vibrometer (LDV), respectively. Data acquisition and processing were accomplished by self-developed software. With the increase of the fluid amount, the magnitude of velocity transfer function reduced across all frequencies. The effect of fluid viscosity on the TM vibration varied and reduced in a complicated way when the fluid viscosity changed. Increasing fluid amount will significantly reduce the TM movement. The effect of fluid viscosity on the TM vibration was nonlinear and related to the fluid amount. The vibration at each point on the TM is frequency-dependent.


Hospice Satisfaction Among Patients, Family, and Caregivers: A Systematic Review of the Literature.
Background: Hospice care is an underused form of intervention at the end of life. The experiences of patients, families, and other caregivers are important to consider in thinking about how to encourage greater use of hospice care, through policies and advocacy that promote its benefits. Specifically, patient, family, and other caregiver satisfaction with hospice care is important to understand better. Methods: A PRISMA-guided review of the research on hospice care satisfaction and its correlates among patients, families, and other caregivers. Included in the review is research published over the time period 2000-2023 identifying a hospice care satisfaction finding. Results: Thirty-eight studies were included in the review. Key findings were: (a) higher levels of hospice care satisfaction among patients, families, and other caregivers; and (b) correlates of hospice care satisfaction falling into the categories of communication, comfort, and support. The published literature had fewer findings related to demographic correlates of satisfaction such as age or race/ethnicity and was lacking in comparative research examining satisfaction across different types of hospice care settings. Discussion: Extant research demonstrates a consistently higher level of hospice care satisfaction among patients, families, and other caregivers. This satisfaction appears related to specific aspects of care delivery that involve effective care coordination and communication; pain and symptom management; and emotional support. Strengthening future research involves testing additional interventions aimed at enhancing satisfaction; including more comparative research across hospice care settings; and more studies that include patients as the key respondents.


Collagen hydrolysis by a new Streptomyces species.
A soil streptomycete hydrolysed collagen extracted from bovine Achilles tendon, calf skin, carp swim bladder and rat tail tendon. Enzyme activity was highest with rat tail tendon collagen as substrate. The taxonomy of the streptomycete was studied according to internationally approved methods. Comparative studies revealed that it resembled Streptomyces humidus , S. rochei and S. distatochromogenes in some respects, but differed in many cultural and physiological characteristics. Based on these differences the organism was given a new identity as Streptomyces species A.


Chronic disease and depression in the geriatric population.
A brief review is given of the incidence and nature of psychiatric symptoms, particularly depression, that are associated with chronic physical diseases common in the elderly. A discussion of medical illnesses that mimic depression, and depression presenting as somatic disease, illustrates the challenge of differential diagnosis. Guidelines are presented for the treatment of depression in patients with central nervous system, cardiovascular, hepatic and renal, and gastrointestinal disorders. Pharmacokinetic factors relevant to the use of cyclic and monoamine oxidase inhibitor antidepressants in the elderly are reviewed.


[Detailed mapping of the Hly-region of the plasmid pHly241. Homology of the hemolysis determinants of plasmids pHly241 and pHly195].
Data on the hemolysin synthesis determined by the plasmid pHly241, belonging to the incompatibility group I2, and its derivatives are presented in this paper. The restriction analysis of the pHly241 plasmid has resulted in the detailed mapping of the hly determinant region in the plasmid. The substantial homology has been demonstrated between the regions of the plasmids pHly241 and pHly195 coding for hemolysin synthesis and excretion from the bacterial cell.


Combined tumor genomic profiling and exome sequencing in a breast cancer family implicates ATM in tumorigenesis: A proof of principle study.
Familial breast cancers (BCs) account for 10%-20% of all diagnosed BCs, yet only 20% of such tumors arise in the context of a germline mutation in known tumor suppressor genes such as BRCA1 or BRCA2. The vast genetic heterogeneity which characterizes non BRCA1 and non BRCA2 (or BRCAx) families makes grouped studies impossible to perform. Next generation sequencing techniques, however, allow individual families to be studied to identify rare and or private mutations but the high number of genetic variants identified need to be sorted using pathogenicity or recurrence criteria. An additional sorting criterion may be represented by the identification of candidate regions defined by tumor genomic rearrangements. Indeed, comparative genomic hybridization (CGH) using single nucleotide polymorphism (SNP) arrays allows the detection of conserved ancestral haplotypes within recurrent regions of loss of heterozygosity, common to several familial tumors, which can highlight genomic loci harboring a germline mutation in cancer predisposition genes. The combination of both exome sequencing and SNP array-CGH for a series of familial BC revealed a germline ATM mutation associated with a loss of the wild-type allele in two BC from a BRCAx family. The analysis of additional breast tumors from ten BC families in which a germline ATM mutation had been identified revealed a high frequency of wild-type allele loss. This result argues strongly in favor of the involvement of ATM in these tumors as a tumor suppressor gene and confirms that germline ATM mutations are involved in a subset of familial BC.


Research on Intelligent Monitoring of Boring Bar Vibration State Based on Shuffle-BiLSTM.
Due to its low stiffness, the boring bar used in deep-hole-boring is prone to violent vibration during the cutting process. It is often inaccurate and inefficient to judge the vibration state of the boring bar through artificial experience. To detect the change of the vibration state of the boring bar over time, guide the adjustment of the processing parameters, and avoid wastage of the workpiece and the loss of equipment, it is particularly important to intelligently monitor the vibration state of the boring bar during processing. In this paper, the boring bar is taken as the research object, and an intelligent monitoring technology of the boring bar's vibration state based on deep learning is proposed. Based on grouping convolution, channel shuffle, and BiLSTM, a shuffle-BiLSTM NET model is constructed, which is both lightweight and has a high classification accuracy. The boring experiment platform is built, and 192 groups of cutting experiments are carried out. The three-way acceleration and sound pressure signals are collected, and the signals are processed by smoothed pseudo-Wigner-Ville distribution. The original signals are transformed into a 256 × 256 × 3 matrix obtained by a two-dimensional time-frequency spectrum diagram. The matrix is input into the model to recognize the boring bar's vibration state. The final classification accuracy is 91.2%. A variety of typical deep learning models are introduced for performance comparison, which proves the superiority of the models and methods used in this paper.