The mechanism of involuntary visual spatial attention revealed by a new linear computation model.
EEG reveals brain electrical activities with high temporal resolution. Yet, multiple implicit variables may be involved in limited event related potential (ERP) measures. Special computation techniques are needed to recover these parameters. In the study of involuntary visual spatial attention, we may obtain the ERP in valid cued (V), invalid cued (I) and neutral cued (N) conditions. Usually, the effect of involuntary attention is computed by the subtraction model with the assumption that V/I and N are independent. Yet, they should be related. Treating V/I as a function of N, a linear model V(I) = W + GN is assumed, where W and G are implicit in the ERP measures. G is the gain control on the neutral function. Provided G and W are constant over a local brain region, we may use the Total Least Square (TLS) algorithm to compute their values. The values of W and G computed from an involuntary attention experiment data show that multiple implicit variables are involved in obtained ERPs. Here G acts as a "top-down" sensory modulator on the neutral ERPs and W is related to possible newly involved neural activities. The parameters derived from the new linear model also suggest that there are different mechanisms involved in involuntary attention and voluntary allocation of attention.


Acute In Vitro and In Vivo Effects of Dexamethasone in the Vocal Folds: a Pilot Study.
Glucocorticoids (GC)s are commonly employed to treat vocal fold (VF) pathologies. However, VF atrophy has been associated with intracordal GC injections. Dexamethasone-induced skeletal muscle atrophy is well-documented in other tissues and believed to be mediated by increased muscle proteolysis via upregulation of Muscle Ring Finger (MuRF)-1 and Atrogin-1. Mechanisms of dexamethasone-mediated VF atrophy have not been described. This pilot study employed in vitro and in vivo models to investigate the effects of dexamethasone on VF epithelium, thyroarytenoid (TA) muscle, and TA-derived myoblasts. We hypothesized that dexamethasone will increase atrophy-associated gene expression in TA muscle and myoblasts and decrease TA muscle fiber size and epithelial thickness. In vitro, pre-clinical. TA myoblasts were isolated from a female Sprague-Dawley rat and treated with 1 μM dexamethasone for 24-h. In vivo, 15 New Zealand white rabbits were randomly assigned to three treatment groups: (1) bilateral intracordal injection of 40 μL dexamethasone (10 mg/ml; n = 5), (2) volume-matched saline (n = 5), and (3) untreated controls (n = 5). Larynges were harvested 7-days post-injection. Across in vivo and in vitro experimentation, MuRF-1 and Atrogin-1 mRNA expression were measured via RT-qPCR. TA muscle fiber cross-sectional area (CSA) and epithelial thickness were also quantified in vivo. Dexamethasone increased MuRF-1 gene expression in TA myoblasts. Dexamethasone injection, however, did not alter atrophy-associated gene expression, TA CSA, or epithelial thickness in vivo. Dexamethasone increased atrogene expression in TA myoblasts, providing foundational insight into GC induced atrophic gene transcription. Repeated dexamethasone injections may be required to elicit atrophy in vivo. NA Laryngoscope, 133:2264-2270, 2023.


Light at night: effect on the daily clock, learning, memory, cognition, and expression of transcripts in different brain regions of rat.
The rapid increase in urbanization is altering the natural composition of the day-night light ratio. The light/dark cycle regulates animal learning, memory, and mood swings. A study was conducted to examine the effect of different quantity and quality of light at night on the daily clock, learning, memory, cognition, and expression of transcripts in key learning centers. Treatment was similar for experiments one to three. Rats were exposed for 30 days to 12 h light and 12 h dark with a night light of 2 lx (dLAN group), 250 lx (LL), or without night light (LD). In experiment one, after 28 days, blood samples were collected and 2 days later, animals were exposed to constant darkness. In experiment two, after 30 days of treatment, animals were subjected to various tests involving learning, memory, and cognition. In experiment three, after 30 days of treatment, animals were sampled, and transcript levels of brain-derived neurotrophic factor, tyrosine kinase, Growth-Associated Protein 43, Neurogranin, microRNA-132, cAMP Response Element-Binding Protein, Glycogen synthase kinase-3β, and Tumor necrosis factor α were measured in hippocampus, thalamus, and cortex tissues. In experiment four, animals were exposed to night light of 0.019 W/m2 but of either red (640 nm), green (540 nm), or blue (450 nm) wavelength for 30 days, and similar tests were performed as mentioned in experiment 2. While in experiment five, after 30 days of respective wavelength treatments, all animals were sampled for gene expression studies. Our results show that exposure to dLAN and LL affects the daily clock as reflected by altered melatonin secretion and locomotor activity, compromises the learning, memory, and cognitive ability, and alterations in the expression levels of transcripts in the hypothalamus, cortex, and thalamus. The effect is night light intensity dependent. Further, blue light at night has less drastic effects than green and red light. These results could be of the potential use of framing the policies for the use of light at night.


Control of pleural effusions in patients with breast cancer. A randomized trial.
In a controlled randomized trial, 46 patients with pleural effusions secondary to breast cancer were treated at first diagnosis with either intracavitary mustine or talc, to determine which agent produced the more effective pleurodesis. Of the 37 evaluable patients, control of the effusion was achieved in 9/17 (56%) of those treated with mustine and 18/20 (90%) of the talc group (P less than 0.025). This suggests that early treatment with intracavitary talc can effectively palliate this complication of breast cancer.


Increased power generation in impaired lower extremities correlated with changes in walking speeds in sub-acute stroke patients.
Establishing changes in net joint power in the lower extremity of patients during recovery of walking might direct gait training in early stroke rehabilitation. It is hypothesized that (1) net joint power in the lower extremity joints would increase in sub-acute stroke patients following gait rehabilitation, and (2) the improvements in net joint power would be significantly correlated with changes in walking speed. Thirteen sub-acute patients (<3 months from stroke onset) participated in the study. All patients completed 6 weeks of gait training (3 weeks of robotic gait training and 3 weeks of physiotherapy). The gait patterns were analyzed using 3D motion analysis before and after training. The assessed variables were; gait speed and the net peak joint power of the ankle plantar flexors, hip extensors, hip flexors, hip abductors, and knee extensors. Ankle plantar flexor power in the impaired limb and hip extensor power in the unimpaired limb increased significantly following training (133% and 77%, respectively; P<0.002). Improvements (from 20% to 133%) in net joint power of the ankle plantar flexors, hip extensors, hip flexors, and hip abductors of the impaired limb and ankle plantar flexors and hip abductors of the unimpaired limb significantly correlated with the recovery of walking speed following training (0.24 m/s to 0.51 m/s) (r=0.71-0.86). The findings suggested investigations for strengthening the plantar flexors, hip flexors, hip extensors, and hip abductors concentrically, and knee extensors eccentrically in the impaired limb to determine the effectiveness in improving gait performance.


Ultrasound-assisted synthesis of graphene@MXene hybrid: A novel and promising material for electrochemical sensing.
To date, multiple graphene@MXene hybrids have been reported via various synthesis approaches, but almost all the graphene@MXene hybrids inevitably used the reduced graphene oxide that prepared by chemical oxidation/reduction method, which generally involved the complex and dangerous operation procedure, and the highly toxic chemical reagent. How to prepare graphene@MXene hybrid through a simple, safe and eco-friendly synthetic route is highly desired. Compared with traditional synthesis technology, ultrasound synthesis strategy displays the merits of simplicity, low cost and environment protection. Herein, MXene (Ti3C2Tx) nanoflakes coupled with graphene nanosheets (graphene@MXene) were prepared in N-methylpyrrolidone (NMP) by simple ultrasound-assisted liquid-phase exfoliation method for the first time. Besides, the effect of types of solvent with different viscocity, sonication temperature and sonication duration time on the property of graphene@MXene hybrids were systematacially investigated. It is found the liquid-phase exfoliated graphene owned excellent electron transfer ability and the MXene (Ti3C2Tx) nanoflakes possessed outstanding adsorption property, the as-synthesized graphene@MXene hybrid exhibited significant signal synergistic enhancement effect toward the oxidation of hazardous veterinary drug residue compound (chlorpromazine) and food additives (rhodamine B). Based on this, a novel and sensitive electrochemical sensor was fabricated, the linear detection ranges were 5 nM to 0.5 μM for chlorpromazine with sensitivity of 1090 µA μM-1 cm-2, and 10 nM to 2.5 μM for rhodamine B with sensitivity of 440 and 102.14 µA μM-1 cm-2. Besides, the detection limits were evaluated to be as low as 1.25 nM and 2.45 nM for chlorpromazine and rhodamine B, respectively.


Three and six-month outcome following courses of either ECT or rTMS in a population of severely depressed individuals--preliminary report.
Recent studies have strengthened the claim that repetitive transcranial magnetic stimulation (rTMS) is an effective treatment for major depression. The longitudinal outcome of TMS-treated patients, however, has not been described. We report on the 3- and 6-month outcomes of a group of patients treated with either electroconvulsive therapy (ECT) (n = 20) or (rTMS) (n = 21). Patients diagnosed with major depressive disorder with or without psychotic features referred for ECT were randomly assigned to receive either ECT or rTMS. Forty-one patients who responded to either treatment constituted the sample. Patients were followed on a monthly basis and outcomes were determined with the Hamilton Rating Scale for Depression-17 items (HRSD) and the Global Assessment of Functioning (GAF) scales. Medications were routinely prescribed. There were no differences in the 6-month relapse rate between the groups. Overall, 20% of the patients relapsed (four from the ECT group and four from the rTMS group). Patients reported equally low and not significantly different scores in the HRSD (ECT group 8.4 +/- 5.6 and TMS group 7.9 +/- 7.1) and the GAF (ECT group 72.8 +/- 12 and TMS group 77.8 +/- 17.1) at the 6-month follow up. Patients treated with rTMS do as well as those treated with ECT at the 3- and 6-month follow-up points. These data suggest that the clinical gains obtained with rTMS last at least as long as those obtained with ECT.


Autoimmune autonomic nervous system imbalance and conditions: Chronic fatigue syndrome, fibromyalgia, silicone breast implants, COVID and post-COVID syndrome, sick building syndrome, post-orthostatic tachycardia syndrome, autoimmune diseases and autoimmune/inflammatory syndrome induced by adjuvants.
Chronic fatigue syndrome (CFS), fibromyalgia, silicone breast implants syndrome (SBIs), COVID and post-COVID syndrome (PCS), sick building syndrome (SBS), post-orthostatic tachycardia syndrome (POTS), autoimmune diseases and autoimmune/inflammatory syndrome induced by adjuvants (ASIA) are frequently accompanied by clinical symptoms characteristic for dysautonomia: severe fatigue, dizziness, fogginess, memory loss, dry mouth and eyes, hearing dysfunction, tachycardia etc. The recent discovery of an imbalance of autoantibodies against G protein-coupled receptors (GPCR) in some autoimmune diseases, post-COVID syndrome, SBIs allowed researchers to assume the novel mechanism in these conditions - autoimmune autonomic nervous system imbalance. In this review, all data published on an imbalance of autoantibodies against GPCR, clinical symptoms and pathogenic mechanisms in CFS, Fibromyalgia, SBIs, COVID and PCS, SBS, POTS, and some autoimmune diseases were analyzed. Possible criteria to diagnose the autoimmune autonomic nervous system imbalance were created.


Influence of spontaneous and surgical menopause on atherogenic metabolic risk.
We evaluated serum total-, LDL-, HDL-, cholesterol and triglycerides in 858 women. Sixty-seven were in premenopause, 307 in perimenopause, 326 in spontaneous menopause, and 158 women underwent hysterectomy. Of these, 101 had bilateral ovariectomy, 24 with unilateral ovariectomy and 33 with retention of both ovaries. After correcting for chronological age and body mass index by variance analysis, it was found that total-, LDL- and HDL-cholesterol significantly increased during menopause without changes in the total cholesterol/HDL-cholesterol, LDL-cholesterol/HDL-cholesterol and triglycerides/HDL-cholesterol ratio. The changes gradually occurred during the months preceding spontaneous cessation of menses. Atherogenic metabolic risk (as relative risk of high total and LDL-cholesterol, estimated by logistic regression analysis) significantly increased in all groups of women in reference to premenopause. The risk observed in surgical menopause with bilateral ovariectomy was higher than in spontaneous menopause, and conservation of ovaries in hysterectomized women seems to protect only partially against such an increase.


Psychological origins of the Industrial Revolution: Why we need causal methods and historians.
Did affluence lead to psychological changes such as reduced discounting, and did these changes facilitate the innovation associated with the Industrial Revolution? I argue that claims of this sort are best made when they can be supported by causal evidence and good psychological measurement. When we have neither identifying variation nor adequate measures, the toolbox of psychologists is not useful.


Possible association of Toll-like receptor 9 polymorphisms with cytokine levels and posttraumatic symptoms in individuals with various types of orthopaedic trauma: early findings.
Although TLR9 polymorphisms may be associated with cytokine dysregulation, its role in regulation of cytokines due to bodily trauma or in relation to acute stress symptoms or posttraumatic stress symptoms (ASS/PTS) has not been evaluated. To assess serum cytokine levels and levels of ASS and PTS in relation to four common TLR9 single-nucleotide polymorphisms (SNPs) in individuals with various types of orthopaedic trauma. Forty-eight accident-injured individuals, aged 20-60 years were studied. Serum cytokine levels and TLR9 SNPS (1486T/C, 1237T/C, 1174G/A and 2848G/A) were assessed together with intensity of ASS and PTS symptoms. Statistically significant higher serum levels of IL-12 and IL-1β (p<.05) were found in individuals heterozygous for TLR9-1237 (TC) than in individuals expressing the most common TLR9-1237 type (TT), while differences in levels of IL-6 were not significant. Also, marginally significant levels of IL-6 were found in individuals expressing the common TLR9-1174 (GG) compared with individuals homozygous (AA) or heterozygous (GA) for this SNP. They also had non-significant higher intensity of ASS symptoms. A trend of higher PTS levels in individuals expressing the most common type TLR9-1174 (GG) was found, contrary to homozygous (AA) and heterozygous individuals (GA). The results of this pilot study suggest that accident-injured individuals with certain TLR9 polymorphisms express higher levels of pro-inflammatory cytokines (IL-1β, IL-6 and IL-12). The associations of TLR9 SNPSs with increased risk of ASS or PTS should be further studied in larger groups of such patients.


Impact of a one-stop rapid access venous ulcer clinic on inpatient admissions.
Venous leg ulcers (VLU) are prevalent and require a large investment of resources to manage. We investigated whether the introduction of a rapid access see-and-treat clinic for VLU patients affected rates of unplanned inpatient admissions with VLU. The Hospital Inpatient Enquiry database was consulted for data on admission rates, length of stay, bed-days used, and costs, across a 4-year period; 2 years since the introduction of the clinic, and the 2 years prior as a control. Two hundred and eighteen patients admitted with VLU accounted for 2,529 inpatient bed-days, 4.5 (2-6) admissions per month, and a median hospital stay of 7 (4-13) days across the study period. Median admissions decreased from 6 (2.5-8.5) per month before, to 3.5 (2-5) after introduction of the clinic (p = 0.04). Bed-day usage fell from 62.5 (27-92.5), to 36.5 (21-44) days per month (p = 0.035). Admissions and bed-day usage for inpatient management of VLU fell after commencing a one-stop, rapid access clinic.


Body mass index and sex differences for mortality in hospitalized COVID-19 patients: a path analysis using a brazilian national database.
Previous studies have shown that associations between obesity and other comorbidities favor worse outcomes in COVID-19. However, it is not clear how these factors interrelate and whether effects on men and women differ. We conducted an observational, cross-sectional study using a national COVID-19 inpatient database. We studied differences in direct and indirect effects of obesity and comorbidities according to sex and body mass index (BMI) categories in hospitalized COVID-19 patients in Brazil using path analysis models and logistic regression. For men, path analysis showed a direct association between BMI and death and a negative correlation of death and chronic cardiovascular disease (CCD). For women, the association of BMI and death was indirect, mediated by admission to the ICU and comorbidities and association with CCD was non-significant. In the logistic regression analyses, there was a positive association between death and BMI, age, diabetes mellitus, kidney and lung diseases and ICU admission. We highlight the need to consider the distinct impact of obesity and sex on COVID-19, of monitoring of BMI and of the design for specific male-targeted approaches to manage obesity.


The effect of vinblastin and vincristin on single nerve fibres.
The perfusion of the node of Ranvier with vinblastin or vincristin reduces the amplitude of the action potential within a few seconds. Vincristins is 10fold more active than vinblastin. Upon withdrawal, the effect is promptly reversible and its is antagonized by acetylcholine.


NLRP3 is its own gatekeeper: a group hug of NLRP3 monomers controls inflammation.
A recent study by Hochheiser et al. describes the cryo-electron microscopy (cryoEM) structure of an autoinhibited nucleotide-binding domain-, leucine-rich repeat (LRR)- and pyrin domain-containing protein 3 (NLRP3) decamer that assembles via LRR interactions and is further stabilized by the small-molecule NLRP3-specific inhibitor CRID3 binding into a cleft within the NACHT domain. The study provides a springboard for the development of novel NLRP3-based therapies.


Superoxide dismutase activity confers (p)ppGpp-mediated antibiotic tolerance to stationary-phase Pseudomonas aeruginosa.
Metabolically quiescent bacteria represent a large proportion of those in natural and host environments, and they are often refractory to antibiotic treatment. Such drug tolerance is also observed in the laboratory during stationary phase, when bacteria face stress and starvation-induced growth arrest. Tolerance requires (p)ppGpp signaling, which mediates the stress and starvation stringent response (SR), but the downstream effectors that confer tolerance are unclear. We previously demonstrated that the SR is linked to increased antioxidant defenses in Pseudomonas aeruginosa We now demonstrate that superoxide dismutase (SOD) activity is a key factor in SR-mediated multidrug tolerance in stationary-phase P. aeruginosa Inactivation of the SR leads to loss of SOD activity and decreased multidrug tolerance during stationary phase. Genetic or chemical complementation of SOD activity of the ΔrelA spoT mutant (ΔSR) is sufficient to restore antibiotic tolerance to WT levels. Remarkably, we observe high membrane permeability and increased drug internalization upon ablation of SOD activity. Combined, our results highlight an unprecedented mode of SR-mediated multidrug tolerance in stationary-phase P. aeruginosa and suggest that inhibition of SOD activity may potentiate current antibiotics.


Ethnic 'hyperamylasaemia': clarification by isoamylase analysis.
Total serum amylase and its pancreatic (P-type) and salivary (S-type) isoamylase activities were measured in 92 individuals without pancreatic or salivary disease. They were divided into three ethnic sub-groups resident in the UK, namely native Britons, Asians and West Indians. The mean total amylase activity was highest in West Indians (383 U/l), intermediate in Asians (317 U/l) and lowest in Britons (179 U/l). Nine of the 28 Asians and 8 of the 16 West Indians had total amylase activities above the upper end of the reference range for Britons. Such a finding, if accompanied by abdominal symptoms, could lead to exhaustive pancreatic investigation in these ethnic groups unless the appropriate reference range is used. Isoenzyme analysis by inhibitor and electrophoretic techniques indicated that the increase in total amylase was due to increase in S-type isoamylase, P-type isoamylase or both. There was a good correlation between results by the two methods. These differences in serum amylase seem to be genetically determined.


[Mental disorders and professional determinants. Study of the time relationship between the beginning of professional life and the first disorder in teachers].
Analysis of the temporal relation between the beginning of mental illness and the beginning of professional life, according to a comparative anamnestic method applied to a group of teachers (N. = 94) and a matching control group of psychiatric paired out-patients (N. = 95). The results show that the distribution of illness prior to professional activity is linked with the diagnostic category and not with professional determinants, psychosis proving to be more impairing than neurosis. A high-risk age group for first incidence of psychotic disease was found.


Metastatic Ewing sarcoma to the heart simulating adriamycin cardiotoxicity.
A 20-year-old man with metastatic Ewing Sarcoma developed severe congestive heart failure. Because he had been treated with a large amount of Adriamycin, the diagnosis was initially thought to be Adriamycin cardiotoxicity. However, ante- and post-mortem studies revealed the presence of massive cardiac metastases. At post-mortem, there was no evidence of Adriamycin cardiotoxicity. This case emphasizes that cardiac metastases must be considered in the differential diagnosis of heart failure in patients treated with Adriamycin.


Gene drive by Fusarium SKC1 is dependent on its competing allele.
The Fusarium verticillioides SKC1 gene driver is transmitted to offspring in a biased manner through spore killing. The mechanism that allows SKC1 to kill non-SKC1 offspring while sparing others is poorly understood. Here we report that gene drive by SKC1 is dependent on SKC1's competing allele. We propose that SKC1's competing allele influences the ability of a genome defense process to detect SKC1, and we provide evidence that this genome defense process is meiotic silencing by unpaired DNA (MSUD). Our findings suggest that the successful deployment of gene drivers to control pathogenic fungi will require researchers to consider how competing alleles influence the ability of gene drivers to be detected by genome defense processes.


Steroid induced exocytosis: the human sperm acrosome reaction.
By a combination of organic precipitation and high pressure liquid chromatography, human sperm acrosome reaction inducing activity has been purified from the fluid aspirated from preovulatory human ovarian follicles and identified as 4-pregnen-3,20-dione (progesterone) and 4-pregnen-17 alpha-ol-3,20-dione (17 alpha-hydroxyprogesterone). It is argued that progesterone is present at the site of fertilization of placental mammals in concentrations sufficient for activity, and hence provides a mechanism of inducing the acrosome reaction, an exocytotic event, in vivo.


Osteoblastic cell response to thin film of poorly crystalline calcium phosphate apatite formed at low temperatures.
The response of osteoblastic cells to a thin film of poorly crystalline calcium phosphate apatite crystals (PCA) was examined in vitro. The PCA thin film was prepared on polystyrene culture dishes using highly metastable calcium phosphate ion solution at low temperatures. The PCA thin film was formed through fusion and transformation of granular calcium phosphate particles, which had initially formed on the surface, into a film of calcium phosphate apatite crystal. The PCA thin film was used for cell culture without additional surface treatment. The osteoblastic cell behaviors including adhesion, proliferation, expression of the marker genes, and calcified matrix formation were examined on the PCA thin film using primary osteoblasts or MC3T3-E1 cells. The cells were well attached and had spread in a slender shape over the PCA thin film. The extent of cell proliferation on the PCA thin film is as much as on the plain dishes. In addition, a much larger number of calcified nodules had formed on the PCA thin film than on the plain dish. The expression of the marker genes such as alkaline phosphatase, osteocalcin, osteopontin, osteonectin was apparent. These results demonstrate that the osteoblasts exhibit a full spectrum of cellular activity including the adequate differentiation on the PCA thin film. Therefore, a PCA thin film can be used as a coating material for biomaterials where the surface is not adequate for inducing the full activity of bone cells.


Racial and ethnic disparities in periodontal health among adults seeking dental care in rural North Carolina communities: A retrospective study.
Population studies consistently demonstrate a greater prevalence of chronic diseases, including oral diseases, among underrepresented minorities. This retrospective study aimed to measure and describe the prevalence and extent of periodontitis among adults seeking dental care within an academic practice-based network in rural North Carolina. This study used de-identified electronic health record (EHR) data from 2011 to 2017 of adult dentate patients (aged ≥30 years) seeking dental care who received a comprehensive periodontal examination at one of nine networked clinical centers. Periodontitis prevalence was calculated using CDC/AAP case definitions, along with extent (%) scores for periodontal parameters. Comparisons focused on age, sex, race, ethnicity, tobacco use, diabetes status, payer or insurance status, plaque scores, and the number of teeth. EHR data for 10,544 adult patients (60.5% female) indicated 79.8% had some form of periodontitis. This patient population was diverse: 22.6% Black, 4.4% American Indian, and 53.8% White, with 4.8% self-identified as Hispanic. Patients 50 years and older showed greater mean extent scores for clinical attachment levels relative to patients 30 to 49 years. Males exhibited greater periodontitis than females (p = 0.001). Blacks showed significantly (p < 0.001) greater periodontitis prevalence relative to Whites. Hispanics also showed a greater prevalence of periodontitis (p < 0.001) relative to non-Hispanics. Significantly greater periodontitis was also noted for tobacco users (p < 0.001) but not for diabetes or payer status. A multiple logistic regression analysis of periodontitis prevalence confirmed significant associations for periodontitis for age, sex, race, ethnicity, tobacco use, high plaque scores, and the number of teeth (p < 0.001), but not diabetes or payer status. The data document that racial and ethnic inequalities in periodontal health occur within the population of adults residing in rural communities in North Carolina and seeking dental care.


Chronic epidural hematoma--report on eight cases and review of the literature.
The authors report eight cases of chronic epidural hematoma, classified according to macroscopical operative findings and histological studies of the hematomas. Clinical, radiological, and pathological findings are described. A review of 63 cases of the literature is presented, and the accepted concepts for classification and management of these lesions are discussed.


Holmium laser enucleation of the prostate (HoLEP) combined with transurethral tissue morcellation: an update on the early clinical experience.
The preliminary experience with 64 patients who have undergone HoLEP combined with intravesical morcellation is presented. The mean preoperative prostate volume was 75.3 cc. The mean laser time was 46.9 minutes and the morcellator time a further 10.5 minutes. A mean total of 35.5 g of tissue was obtained, and 93% of the patients were discharged the day after their surgery without a catheter. The American Urological Association Symptom Score at 1 month was 8.6 and the peak flow rate 23.4 mL/sec. This combination of procedures allows prostate glands of virtually any size to be safely treated transurethrally, and a complete anatomic enucleation of the prostatic adenoma is achieved.


17β-Estradiol induces changes in cytokine levels in head kidney and blood of juvenile sea bass (Dicentrarchus labrax, L., 1758).
The cytokine network is involved in the immune system communication. As estrogens influence the cytokine expression in mammals, this study investigated the impact of exogenous estrogenic pollutants on selected cytokines in Dicentrarchus labrax. The gene expression of Interleukin 6, Tumour Necrosis Factor α, Transforming Growth Factor β1 and Interleukin 1β was assessed and accomplished with protein measurements in the blood for the last two. Impacts through 17β-estradiol mainly occurred at the beginning of organ regionalisation, thus falling together with a developmentally induced increase of Interleukin 1β and Tumour Necrosis Factor α gene expression in 102 dph fish. 17β-estradiol depressed this modification after 35 days of exposure and the cytokine gene expression tended to be generally down-regulated independently of the 17β-estradiol concentrations after 56 days of exposure. This impact was confirmed at the protein level, showing that 17β-estradiol affects the fine control of the cytokine network in sea bass.


The effects of the COVID-19 pandemic on psychological stress in breast cancer patients.
The majority of breast cancer patients are severely psychologically affected by breast cancer diagnosis and subsequent therapeutic procedures. The COVID-19 pandemic and associated restrictions on public life have additionally caused significant psychological distress for much of the population. It is therefore plausible that breast cancer patients might be particularly susceptible to the additional psychological stress caused by the pandemic, increasing suffering. In this study we therefore aimed to assess the level of psychological distress currently experienced by a defined group of breast cancer patients in our breast cancer centre, compared to distress levels pre-COVID-19 pandemic. Female breast cancer patients of all ages receiving either adjuvant, neoadjuvant, or palliative therapies were recruited for the study. All patients were screened for current or previous COVID-19 infection. The participants completed a self-designed COVID-19 pandemic questionnaire, the Stress and Coping Inventory (SCI), the National Comprehensive Cancer Network® (NCCN®) Distress Thermometer (DT), the European Organization for Research and Treatment of Cancer (EORTC) QLQ C30, and the BR23. Eighty-two breast cancer patients were included. Therapy status and social demographic factors did not have a significant effect on the distress caused by the COVID-19 pandemic. The results of the DT pre and during COVID-19 pandemic did not differ significantly. Using the self-designed COVID-19 pandemic questionnaire, we detected three distinct subgroups demonstrating different levels of concerns in relation to SARS-CoV-2. The subgroup with the highest levels of concern reported significantly decreased life quality, related parameters and symptoms. This monocentric study demonstrated that the COVID-19 pandemic significantly affected psychological health in a subpopulation of breast cancer patients. The application of a self-created "COVID-19 pandemic questionnaire" could potentially be used to help identify breast cancer patients who are susceptible to increased psychological distress due to the COVID-19 pandemic, and therefore may need additional intensive psychological support. DRKS-ID: DRKS00022507 .


Distally based sural fasciomusculocutaneous flap for treatment of wounds of the distal third of the leg and ankle with exposed internal hardware.
Soft tissue reconstruction of the distal third of the lower limb with exposure of the internal hardware is a challenging problem with several potential complications, such as exposure of the fracture line, fracture instability and bacterial contamination. The treatment of these lesions usually consists of substitution of the internal hardware with external fixation devices and further flap coverage. We propose a different reconstructive approach, characterized by harvesting a sural fasciomusculocutaneous flap on the exposed internal hardware once a sterile ground has been obtained. Four patients were retrospectively analyzed. Soft tissue reconstruction was achieved in all cases. In one case hardware removal was necessary for complete healing. The sural fasciomusculocutaneous flap is a safe alternative to other pedicled and free flaps. Moreover, it allows direct coverage of internal fixators, thus completing the reconstruction in less time. This flap fits best to the morphology of the wound and internal hardware, leaving the main vascular trunk of the leg intact and at the same time providing a reliable vascular supply.


Oxygen sensitivity of photosynthesis and photorespiration in different photosynthetic types in the genus Flaveria.
Two major indicators were used to access the degree of photorespiration in various photosynthetic types of Flaveria species (C3, C3-C4, C4-like, and C4): the O2 inhibition of photosynthesis measured above the O2 partial pressure which gives a maximum rate, and O2- and light-dependent whole-chain electron flow measured at the CO2 compensation point (Γ). The optimum level of O2 for maximum photosynthetic rates under atmospheric levels of CO2 (34 Pa) was lower in C3 and C3-C4 species (ca. 2 kPa) than in C4-like and C4 species (ca. 9 kPa). Increasing O2 partial pressures from the optimum for photosynthesis up to normal atmospheric levels (ca. 20 kPa) caused an inhibition of photosynthesis which was more severe under lower CO2. This inhibition was calculated as the O2 inhibition index (ΘA, the percentage inhibition of photosynthesis per kPa increase in O2). From measurements of 18 Flaveria species at atmospheric CO2, the ΘA values decreased from C3 (1.9-2.1) to C3-C4 (1.2-1.6), C4-like (0.6-0.8) and C4 species (0.3-0.4), indicating a progressive decrease in apparent photorespiration in this series. With increasing irradiance at Γ under atmospheric levels of O2, and increasing O2 partial pressure at 300 μmol quanta·m-2·s-1, there was a similar increase in the rate of O2 evolution associated with whole-chain electron flow (Jo2, calculated from chlorophyll fluorescence analysis) in the C3 and C3-C4 species compared to a much lower rate in the C4-like and C4 species. The results indicate that there is substantial O2-dependent electron flow in C3 and C3-C4 species, reflecting a high level of photorespiration compared to that in C4-like and C4 species. Consistent with these results, there was a significant decrease in Γ from C3 (6-6.2 Pa) to C3-C4 (1.0-3.0 Pa), to C4-like and C4 species (0.3-0.8 Pa), indicating a progressive decrease in apparent photorespiration. However, C3 and C3-C4 species examined had high intrinsic levels of photorespiration with the latter maintaining low apparent rates of photorespiration and lower Γ values, primarily by refixing photorespired CO2. The C4-like and C4 Flaveria species had low, but measurable, levels of photorespiration via selective localization of ribulose-1,5-bisphosphate carboxylase in bundle sheath cells and operation of a CO2 pump via the C4 pathway.


Polymorphisms in the NQO1, GSTT and GSTM genes are associated with coronary heart disease and biomarkers of oxidative stress.
It was hypothesized that the presence of genetic polymorphisms that decrease activity of the detoxification enzymes glutathione-S-transferase (GST) and quinone oxido-reductase (NQO1) may contribute to heart disease and affect biomarkers of coronary health and oxidative stress. Sixty-seven patients with angiographically confirmed coronary heart disease (CHD) and 63 healthy controls were genotyped for polymorphisms in the GST isoforms Mu and Theta (GSTM and GSTT respectively) and NQO1. Participants' blood levels of homocysteine (Hcy), C-reactive protein (CRP), oxidized low density lipoprotein (LDL) and total antioxidant capacity (TAOX) were measured. TAOX levels were significantly lower in women than men (P < or = 0.001) and this finding was more marked in the control group (P < or = 0.001). Hcy levels were higher in CHD patients (P=0.003 vs. control) which was mostly attributed to female patients (P=0.034 case vs. control). GSTM polymorphisms were present with greater frequencies in CHD cases with the odds ratio (OR) for GSTM equal to 3.77 vs. control. CHD patients also have an increased incidence of both GSTM and GSTT null polymorphisms (OR=5.13). In contrast, NQO1 polymorphisms were protective in CHD patients (OR=0.18 vs. control), which when stratified for genotype was due to heterozygous individuals. Significantly higher C-reactive protein levels occurred in CHD patients with lower NQO1 activity (P=0.001), however, due to the large variations in CRP levels seen in CHD patients; the clinical importance of this difference is unclear. Smokers with the GSTM null polymorphism were more likely to have CHD than non-smokers expressing the GSTM null polymorphism (OR=3.54, P=0.079). We conclude that a lack of activity in the detoxification enzymes NQO1 and GSTM, and biomarker levels are strongly associated with coronary heart disease with sex as a mitigating factor.


[« I was moved by an absolute urgency: I had to know what had always been kept from me »].
In certain family configurations, the secrecy of origins is fiercely maintained. The revelation can then occur suddenly, causing a radical upheaval for the person concerned. This is what happened to Alexandre Mercier, who agreed to share his experience with us.


The effects of contextual and structural factors on patient safety in nursing units.
Because of limited research on patient safety from a macrolevel perspective, our understanding of how to reduce the risk of system failures that impact patient safety outcomes in Taiwanese healthcare organizations is limited. We conducted this study to explore the relationships between macrolevel factors and patient safety outcomes. Structural contingency theory was used as the framework for the study. A cross-sectional design was used, and data were collected from self-administered questionnaires. Head nurses and registered nurses working in 64 in-patient nursing units at three hospitals participated in the study. A tailored design method was used for data collation, and the data collection lasted 3 weeks during the winter of 2010. Data were aggregated from the individual to the unit level, and path analysis was used to examine the hypothesized model. Sixty-two head nurses (96.8%) and 977 staff nurses (72%) completed and returned the questionnaire. Eta-squared coefficient (η), interitem consistency (rwg), and F ratio results showed that data at the individual level are appropriate for aggregating to the unit level. These findings show that nursing units with high degrees of professional autonomy, comparatively higher proportions of nursing experts, and relatively large unit sizes tend to have higher rates of medication errors. In addition, we found high degrees of unit technology associated with higher rates of medication errors and patient falls. These findings suggest a link between macrolevel factors and patient safety outcomes. This study shows that redesigning continuing education programs encourages nurses to participate in patient safety training and understand the nursing unit characteristics that enhance patient safety outcomes to improve the patient safety of nursing units.


Atrichia with papular lesions resulting from novel compound heterozygous mutations in the human hairless gene.
Atrichia with papular lesions is a rare form of complete, irreversible alopecia that is inherited in an autosomal recessive manner. Several studies have implicated mutations in the human hairless gene as the underlying cause of this disorder. We describe two novel heterozygous mutations in exons 3 and 8 of the hairless gene in a 2-year-old Caucasian boy with complete alopecia of his scalp. These novel mutations add to the growing literature of mutations in the hairless gene found in nonconsanguineous families and expands the allelic series of mutations in this gene.


Race Roundtable Series: Structural Racism in Palliative Care.
This series will focus on addressing the intersection of race and racism in palliative care through a series of roundtable discussions with interdisciplinary clinicians, researchers, educators, and leaders in palliative care. These short discussions are intended to stimulate readers to examine issues of race and racism within the field of hospice and palliative care - in the various forms that it appears - as well as serve as a continual call to action to facilitate and promote equity.


Activation of TRPV3 Regulates Inflammatory Actions of Human Epidermal Keratinocytes.
Transient receptor potential (TRP) ion channels were first characterized on neurons, where they are classically implicated in sensory functions; however, research in recent decades has shown that many of these channels are also expressed on nonneuronal cell types. Emerging findings have highlighted the role of TRP channels in the skin, where they have been shown to be important in numerous cutaneous functions. Of particular interest is TRPV3, which was first described on keratinocytes. Its functional importance was supported when its gain-of-function mutation was linked to Olmsted syndrome, which is characterized by palmoplantar keratoderma, periorifacial hyperkeratosis, diffuse hypotrichosis and alopecia, and itch. Despite these exciting results, we have no information about the role and functionality of TRPV3 on keratinocytes at the cellular level. In this study, we identified TRPV3 expression both on human skin and cultured epidermal keratinocytes. TRPV3 stimulation was found to function as a Ca2+-permeable ion channel that suppresses proliferation of epidermal keratinocytes and induces cell death. Stimulation of the channel also triggers a strong proinflammatory response via the NF-κB pathway. Collectively, our data show that TRPV3 is functionally expressed on human epidermal keratinocytes and that it plays a role in cutaneous inflammatory processes.


Identification of the influence of distal inputs on mercury loading across the mid Great Lakes region using chemical sediment chronologies.
Sediment cores from 47 inland lakes in Michigan, USA were used to assess spatial and temporal trends in loadings of mercury (Hg). Focusing/background corrected accumulation rates and inventories and peak concentrations were used to examine: 1) responses of loadings to post-1990 reductions in emissions, 2) if spatial trends are consistent with modeled Hg deposition and 3) evidence for local and distal inputs. Results showed that decreases in concentrations and anthropogenic accumulation rates of Hg were consistent with recent reductions in emissions of Hg. Most lakes exhibiting a decreasing trend were located within an area with the most emission sources. Not all lakes showed the decreasing trend with some showing increases or no change. These lakes tended to be in the northern portion of the state. In all lakes, current concentrations of Hg remain greater than long-term, historical, background concentrations. Sub-regional mean inventories and mean decadal accumulation rates exhibited a south to north gradient, consistent with previously modeled spatial trends. However, individual lake inventories and rates of accumulation compared at shorter times scales varied among lakes. Evidence for event deposition (e.g., volcanic eruptions, manufacturing) was also variable among lakes. These results suggest influence of more distal inputs of Hg, perhaps driven by well-mixed, global sources. Cause(s) of variability on shorter time scales (e.g., events) needs further work. Finally, the results reveal that understanding risks to humans and ecosystems due to exposure to Hg and developing effective abatement policy is challenging.


[Molecular phylogeny of deer (Cervidae: Artiodactyla)].
Sequences of mitochondrial genes 12S and 16S rRNA (2 445 bp) and the region of the nuclear beta-spectrin gene (828 bp) were analyzed in members of the family Cervidae and in other artiodactyls. Several molecular synapomorphies characteristic both of Cervidae and musk deer have been found. According to our data, Cervidae is a sister clade to Bovidae, which are very close to Moschidae. The family Giraffidae is exterior to this common clade, while Antilocapridae occupies a more basal position. The family Cervidae proper splits into three clades including the genera Cervus and Muntiacus (1), Capreolus, Hydropotes, Alces (2), and Rangifer, Odocoileus, and the remaining genera (3). In general, our phylogenetic reconstructions conform to the results of earlier molecular genetic studies, but substantially differ from the traditional taxonomy of Ruminantia.


Elucidating the role of circNFIB in myocardial fibrosis alleviation by endogenous sulfur dioxide.
To investigate the role of circNFIB in the alleviation of myocardial fibrosis by endogenous sulfur dioxide (SO2). We stimulated cultured neonatal rat cardiac fibroblasts with transforming growth factor-β1 (TGF-β1) and developed an in vitro myocardial fibrosis model. Lentivirus vectors containing aspartate aminotransferase 1 (AAT1) cDNA were used to overexpress AAT1, and siRNA was used to silence circNFIB. The SO2, collagen, circNFIB, Wnt/β-catenin, and p38 MAPK pathways were examined in each group. In the in vitro TGF-β1-induced myocardial fibrosis model, endogenous SO2/AAT1 expression was significantly decreased, and collagen levels in the cell supernatant and type I and III collagen expression, as well as α-SMA expression, were all significantly increased. TGF-β1 also significantly reduced circNFIB expression. AAT1 overexpression significantly reduced myocardial fibrosis while significantly increasing circNFIB expression. Endogenous SO2 alleviated myocardial fibrosis after circNFIB expression was blocked. We discovered that circNFIB plays an important role in the alleviation of myocardial fibrosis by endogenous SO2 by inhibiting the Wnt/β-catenin and p38 MAPK pathways. Endogenous SO2 promotes circNFIB expression, which inhibits the Wnt/β-catenin and p38 MAPK signaling pathways, consequently alleviating myocardial fibrosis.


Validation of calcaneus trabecular microstructure measurements by HR-pQCT.
Assessment of calcaneus microstructure using high-resolution peripheral quantitative computed tomography (HR-pQCT) might be used to improve fracture risk predictions or to assess responses to pharmacological and physical interventions. To develop a standard clinical protocol for the calcaneus, we validated calcaneus trabecular microstructure measured by HR-pQCT against 'gold-standard' micro-CT measurements. Ten human cadaveric feet were scanned in situ using HR-pQCT (isotropic 82μm voxel size) at 100, 150 and 200ms integration times, and at 100ms integration time following removal of the calcaneus from the foot (ex vivo). Dissected portions of these bones were scanned using micro-computed tomography (micro-CT) at an isotropic 17.4μm voxel size. HR-pQCT images were rigidly registered to those obtained with micro-CT and divided into multiple 5mm sided cubes to evaluate and compare morphometric parameters between the modalities. Standard HR-pQCT measurements (derived bone volume fraction (BV/TVd); trabecular number, Tb.N; derived trabecular thickness, Tb.Thd; derived trabecular spacing, Tb.Spd) and corresponding micro-CT voxel-based measurements (BV/TV, Tb.N, Tb.Th, Tb.Sp) were compared. A total of 108 regions of interest were analysed across the 10 specimens. At all integration times HR-pQCT BV/TVd was strongly correlated with micro-CT BV/TV (r2=0.95-0.98, RMSE=1%), but BV/TVd was systematically lower than that measured by micro-CT (mean bias=5%). In contrast, HR-pQCT systematically overestimated Tb.N at all integration times; of the in situ scans, 200ms yielded the lowest mean bias and the strongest correlation with micro-CT (r2=0.61, RMSE=0.15mm-1). Regional analysis revealed greater accuracy for Tb.N in the superior regions of the calcaneus at all integration times in situ (mean bias=0.44-0.85mm-1; r2=0.70-0.88, p<0.001 versus mean bias=0.63-1.46mm-1; r2≤0.08, p≥0.21 for inferior regions). Tb.Spd was underestimated by HR-pQCT compared to micro-CT, but showed similar trends with integration time and the region evaluated as Tb.N. HR-pQCT Tb.Thd was also underestimated and moderately correlated (r2=0.53-0.59) with micro-CT Tb.Th, independently from the integration time. Stronger correlations, smaller biases and error were found in the scans of the calcaneus ex vivo compared to in situ. Calcaneus trabecular BV/TVd and trabecular microstructure, particularly in the superior region of the calcaneus, can be assessed by HR-pQCT. The highest integration time examined, 200ms, compared best with micro-CT. Weaker correlations for microstructure at inferior regions, and also with lower integration times, might limit the use of the proposed protocol, which warrants further investigation in vivo.


[Renal changes caused by pentavalent antimonial (Glucantime) hypersensitivity in American tegumentary leishmaniasis. Report of a case].
The authors report one case of leishmaniasis in a 60 year old patient who developed renal failure after treatment with Glucantime. With the interruption of these drug the patient recovered her normal renal function, and a new treatment with Amphotericin B was tried with complete cicatrization of the lesions.


Significant polyp and early colorectal cancer - SPECC: The role of the Colorectal Cancer Clinical Nurse Specialist (CNS): promoting patient-centred care.
The colorectal Clinical Nurse Specialist (CNS) makes an important contribution to the care of individuals diagnosed with a significant polyp and early colorectal cancer (SPECC). This paper offers an expert opinion on the role of the CNS in SPECC, informed by relevant literature. A CNS can support the patient through the diagnostic and treatment pathway acting as the patient's advocate as a core member of the multidisciplinary team. They will offer support and information to help patients understand their diagnosis, make choices about their available treatment options and help them to feel prepared for any treatment undertaken. By providing care that is respectful of, and responsive to, individual patient preferences, needs and values, the CNS can play an important role in promoting patient-centred care.


American Association of Clinical Endocrinology Consensus Statement: Addressing Stigma and Bias in the Diagnosis and Management of Patients with Obesity/Adiposity-Based Chronic Disease and Assessing Bias and Stigmatization as Determinants of Disease Severity.
To focus on the intersection of perception, diagnosis, stigma, and weight bias in the management of obesity and obtain consensus on actionable steps to improve care provided for persons with obesity. The American Association of Clinical Endocrinology (AACE) convened a consensus conference of interdisciplinary health care professionals to discuss the interplay between the diagnosis of obesity using adiposity-based chronic disease (ABCD) nomenclature and staging, weight stigma, and internalized weight bias (IWB) with development of actionable guidance to aid clinicians in mitigating IWB and stigma in that context. The following affirmed and emergent concepts were proposed: (1) obesity is ABCD, and these terms can be used in differing ways to communicate; (2) classification categories of obesity should have improved nomenclature across the spectrum of body mass index (BMI) using ethnic-specific BMI ranges and waist circumference (WC); (3) staging the clinical severity of obesity based on the presence and severity of ABCD complications may reduce weight-centric contribution to weight stigma and IWB; (4) weight stigma and internalized bias are both drivers and complications of ABCD and can impair quality of life, predispose to psychological disorders, and compromise the effectiveness of therapeutic interventions; (5) the presence and of stigmatization and IWB should be assessed in all patients and be incorporated into the staging of ABCD severity; and (6) optimal care will necessitate increased awareness and the development of educational and interventional tools for health care professionals that address IWB and stigma. The consensus panel has proposed an approach for integrating bias and stigmatization, psychological health, and social determinants of health in a staging system for ABCD severity as an aid to patient management. To effectively address stigma and IWB within a chronic care model for patients with obesity, there is a need for health care systems that are prepared to provide evidence-based, person-centered treatments; patients who understand that obesity is a chronic disease and are empowered to seek care and participate in behavioral therapy; and societies that promote policies and infrastructure for bias-free compassionate care, access to evidence-based interventions, and disease prevention.


Calmodulin antagonists inhibit the mitochondrial pyruvate dehydrogenase complex.
Calmodulin antagonists, including phenothiazine, sulfonamide, butyrophenone, and imidazolium derivatives, were in vitro inhibitors of pea mitochondrial pyruvate dehydrogenase complex activity. Inhibition was observed both during direct assay of the partially purified complex and during assay of pyruvate oxidation by isolated, intact mitochondria. When tested against the purified complex, the sulfonamide compound N-(6-aminohexyl)-5-chloro-1-naphthalene sulfonamide (W-7) was a competitive inhibitor with respect to coenzyme A and an uncompetitive inhibitor with respect to NAD and pyruvate. Inhibition of a process as crucial as mitochondrial respiration should serve to emphasize the care necessary in interpretation of whole-organism calmodulin antagonist studies.


Mycorrhizal infection of wild oats: maternal effects on offspring growth and reproduction.
The objective of this study was to determine whether infection of Avena fatua L. plants by the mycorrhizal fungus Glomus intraradices Schenck & Smith could influence the vigor of the offspring generation. Two experiments demonstrated that mycorrhizal infection of the maternal generation had slight but persistent positive effects on offspring leaf expansion in the early stages of growth. In two other experiments, mycorrhizal infection of mother plants had several long lasting effects on their offspring. Offspring produced by mycorrhizal mother plants had greater leaf areas, shoot and root nutrient contents and root:shoot ratios compared to those produced by non-mycorrhizal mother plants. Moreover, mycorrhizal infection of mother plants significantly reduced the weight of individual seeds produced by offspring plants while it increased the P concentrations of the seeds and the number of seeds per spikelet produced by offspring plants. The effects of mycorrhizal infections of maternal plants on the vigor and performance of offspring plants were associated with higher seed phosphorus contents but generally lighter seeds. The results suggest that mycorrhizal infection may influence plant fitness by increasing offspring vigor and offspring reproductive success in addition to previously reported increases in maternal fecundity.


Diagnosis and treatment of high-grade astrocytoma.
High-grade astrocytomas include the most common adult central nervous system (CNS) tumor, glioblastoma multiforme, and anaplastic astrocytoma--a highly aggressive cancer with short median survival despite maximal multimodality therapy. Diagnosis is by clinical and radiographic findings confirmed by histopathology. Standard-of-care therapy includes surgical resection, radiotherapy, and temozolomide. Nearly all patients who have high-grade astrocytomas develop tumor recurrence or progression after this multimodality treatment. Two treatment challenges are molecular/genetic heterogeneity of tumors and limited CNS tumor delivery. It is probable that targeted therapies will be most effective in combination with one another or with cytotoxic therapies. This article discusses diagnosis and current treatment of high-grade astrocytomas.


Prospective assessment of changing from placebo to IFN beta-1a in relapsing MS: the PRISMS study.
The efficacy of interferon (IFN) beta has been shown in several placebo-controlled, parallel-group studies in relapsing-remitting multiple sclerosis (RRMS). PRISMS, the largest such study to date, clearly demonstrated the efficacy of IFN beta-1a on all outcome measures over 2 years during the placebo-controlled, parallel-group phase. However, this study's placebo-crossover design also provided us with a unique opportunity to conduct a prospective within-group assessment, eliminating the impact of inter-patient variability. At the start of year 3, patients receiving placebo during years 1-2 were re-randomized in a dose-blinded fashion to receive IFN beta-1a, 22 or 44 mcg subcutaneously three times weekly, during years 3 and 4. Clinic visits occurred 3-6 monthly and T2 MRI scans were obtained after 1 and 2 years on therapy. Comparison of the mean relapse count per patient over 2 years (the primary outcome measure) during time on placebo (years 1 and 2) with that during active treatment (years 3 and 4) revealed a decrease from 2.6 to 1.2 in both dose groups (54% relative reduction; p<0.001). Disability progression, T2 MRI lesion activity and accumulation of T2 lesion burden were also significantly improved with therapy (p<0.01). No new safety issues were noted. These data provide further support for IFN beta-1a's efficacy in RRMS. The ability to detect significant treatment effects with reduced patient numbers in this type of before/after analysis, may be due to the reduction in inter-patient variability.


Serum cortisol and dehydroepiandrosterone sulfate responses to adrenocorticotropin stimulation in premature infants.
ACTH stimulation tests were performed in 15 premature infants in a serial fashion at the ages of 5--10 days and 27--31 days. Six of the 15 had subsequent ACTH stimulation tests at 6--8 weeks and/or 12--13 weeks. The pre- and post-ACTH serum cortisol and dehydroepiandrosterone sulfate (DHAS) levels were determined by radioimmunoassay. The mean basal levels of cortisol, 55 ng/ml, and DHAS, 4108 ng/ml, were significantly higher (P less than 0.05 and P less than 0.025, respectively) at 5--10 days than those of 24 ng/ml and 1858 ng/ml, respectively, at 27--31 days. The mean net change (delta) of cortisol after ACTH at 5--10 days, 95 ng/ml, increased significantly to 148 ng/ml at 27--31 days. However, deltaDHAS did not differ significantly between the two periods (1514 ng/ml vs. 972 ng/ml). Therefore, deltaDHAS/deltacortisol was lower (P less than 0.05) at 27--31 days than at 5--10 days. No further significant changes were observed after 4 weeks of age in the levels of the two steroids. There was little correlation of basal levels between cortisol and DHAS, nor between deltacortisol and deltaDHAS at any age period we studied. There were four infants whose mothers had prenatal steroid treatment for the prevention of hyaline membrane disease and their values were not different from the other infants.


Primary prevention in chiropractic practice: a systematic review.
Chiropractors are primarily concerned with musculoskeletal disorders but have the responsibility to deal also with prevention in other areas. To establish the prevalence of chiropractors who have a positive opinion on the use of primary prevention (PP), their actual use of PP, and the proportion of patients who consult for PP in relation to (i) musculoskeletal disorders, (ii) public health issues, or (iii) chiropractic treatment for wellness. A systematic search for literature was done using PubMed, Embase, Index to Chiropractic Literature, and Google Scholar and updated on February 15th 2017. Inclusion criteria were: surveys on chiropractors and/or chiropractic patients, information had to be present on PP in relation to the percentage of patients who consult for PP in chiropractic practice or in a chiropractic student clinic, and/or the percentage of chiropractors who reported using PP, and/or information on chiropractors' opinions of the use of PP, in the English, French, or Scandinavian languages. The review followed the PRISMA guidelines. Articles were classified as 'good', 'acceptable' and 'unacceptable' based on scores of quality items. Results from the latter group were not taken into account. Twenty-five articles were included, reporting on twenty-six studies, 19 of which dealt with wellness. The proportion of chiropractors who stated that they had a positive opinion on PP was generally higher than the proportion of chiropractors offering PP. Most chiropractors offered some type of PP for musculoskeletal disorders and more than a half stated that they did so in the public health area but also for wellness. For all types of PP, however, it was rarely stated to be the reason for patients consulting. Regardless the type of PP, the proportion of patients who actually consulted specifically for PP was much smaller than the proportion of chiropractors offering PP. More research efforts have been put into wellness than into prevention of musculoskeletal disorders or public health-related disorders. It therefore seems that parts of the chiropractic profession are in search of an understanding of various aspects of clinical practice over and above its traditional musculoskeletal role. Interestingly, only a small proportion of chiropractic patients consult for PP, despite the readiness of the profession to offer such services.


Comparing cytomegalovirus prophylaxis in renal transplantation: single center experience.
Cytomegalovirus (CMV) presents a serious threat to CMV-seronegative recipients (R-), who have received an organ from a seropositive donor (D+). We compared the effectiveness of three different prophylactic protocols in CMV D+/R- patients and reviewed data on patients who received no prophylaxis. We reviewed 1137 kidney transplantations from 1995 to 2004. Of these, 147 recipients were CMV negative (D+/R-); 125 patients received CMV prophylaxis. Group I received CMV hyperimmune gammaglobulin only, group II received CMV hyperimmune gammaglobulin plus oral ganciclovir, and group III received prophylaxis with oral ganciclovir only. In group I, CMV infection was observed in 31 of 53 patients (59%), and CMV disease was diagnosed in 9 (17%) during the prophylaxis. In the first year post transplant, a total of 41 of 53 patients (77.5%) had primary CMV infection. In group II, CMV infection occurred in 7 of 30 patients (23%), and CMV disease was diagnosed in only 2 (7%) during prophylaxis. In the first year post transplant, a total of 9 of 30 patients (30%) had primary CMV infection. In group III, 9 of 42 patients (21%) developed CMV infection during prophylaxis, and CMV disease was not observed. In the first year post transplant, a total of 13 of 42 patients (30%) had primary CMV infection. In contrast, all 22 CMV D+/R- patients without prophylaxis developed CMV infection (100%); CMV disease was diagnosed in 10 (45%), and 1 patient died. Prophylaxis with hyperimmune gammaglobulin and/or oral ganciclovir significantly reduces CMV infection and disease. Prophylaxis with ganciclovir was significantly more effective than hyperimmune gammaglobulin monoprophylaxis, and more cost effective than combined prophylaxis.


Transcriptional regulation of the gene encoding the human C-type lectin leukocyte receptor AIM/CD69 and functional characterization of its tumor necrosis factor-alpha-responsive elements.
The human activation antigen CD69 is a member of the C-type animal lectin superfamily that functions as a signal-transmitting receptor. Although the expression of CD69 can be induced in vitro on cells of most hematopoietic lineages with a wide variety of stimuli, in vivo it is mainly expressed by T-lymphocytes located in the inflammatory infiltrates of several human diseases. To elucidate the mechanisms that regulate the constitutive and inducible expression of CD69 by leukocytes, we isolated the promoter region of the CD69 gene and carried out its functional characterization. Sequence analysis of the 5'-flanking region of the CD69 gene revealed the presence of a potential TATA element 30 base pairs upstream of the major transcription initiation site and several putative binding sequences for inducible transcription factors (NF-kappa B, Egr-1, AP-1), which might mediate the inducible expression of this gene. Transient expression of CD69 promoter-based reporter gene constructs in K562 cells indicated that the proximal promoter region spanning positions -78 to +16 contained the cis-acting sequences necessary for basal and phorbol 12-myristate 13-acetate-inducible transcription of the CD69 gene. Removal of the upstream sequences located between positions -78 and -38 resulted in decreased promoter strength and abolished the response to phorbol 12-myristate 13-acetate. We also found that tumor necrosis factor-alpha (TNF-alpha) is capable of inducing the surface expression of the CD69 molecule as well as the promoter activity of fusion plasmids that contain 5'-flanking sequences of the CD69 gene, suggesting that this cytokine may regulate in vivo the expression of CD69.(ABSTRACT TRUNCATED AT 250 WORDS)


Stimulated Raman scattering microscopy reveals a unique and steady nature of brain water dynamics.
The biological activities of substances in the brain are shaped by their spatiotemporal dynamics in brain tissues, all of which are regulated by water dynamics. In contrast to solute dynamics, water dynamics have been poorly characterized, owing to the lack of appropriate analytical tools. To overcome this limitation, we apply stimulated Raman scattering multimodal multiphoton microscopy to live brain tissues. The microscopy system allows for the visualization of deuterated water, fluorescence-labeled solutes, and cellular structures at high spatiotemporal resolution, revealing that water moves faster than fluorescent molecules in brain tissues. Detailed analyses demonstrate that water, unlike solutes, diffuses homogeneously in brain tissues without differences between the intra- and the extracellular routes. Furthermore, we find that the water dynamics are steady during development and ischemia, when diffusions of solutes are severely affected. Thus, our approach reveals routes and uniquely robust properties of water diffusion in brain tissues.


Routine blood tests to predict liver fibrosis in chronic hepatitis C.
To verify the usefulness of FibroQ for predicting fibrosis in patients with chronic hepatitis C, compared with other noninvasive tests. This retrospective cohort study included 237 consecutive patients with chronic hepatitis C who had undergone percutaneous liver biopsy before treatment. FibroQ, aspartate aminotransferase (AST)/alanine aminotransferase ratio (AAR), AST to platelet ratio index, cirrhosis discriminant score, age-platelet index (API), Pohl score, FIB-4 index, and Lok's model were calculated and compared. FibroQ, FIB-4, AAR, API and Lok's model results increased significantly as fibrosis advanced (analysis of variance test: P < 0.001). FibroQ trended to be superior in predicting significant fibrosis score in chronic hepatitis C compared with other noninvasive tests. FibroQ is a simple and useful test for predicting significant fibrosis in patients with chronic hepatitis C.


Resting metabolic rate in subjects with paraplegia: the effect of pressure sores.
To determine the overall effect of paraplegia and pressure sores on resting metabolic rate. Unblinded, case-control study using a convenience sample. Hospital primary care setting. Fourteen individuals with paraplegia and pressure sores (PS-Para), 24 with paraplegia in good health (NPS-Para), and 23 non-spinal cord injury (SCI) controls. The planned outcome measures consisted of resting metabolic rate, percent of predicted resting metabolic rate, resting metabolic rate per kilogram body weight, and resting metabolic rate per meter squared body surface area. Post hoc analyses were used to identify the effect of completeness of lesion, smoking, and pressure sores on percent of predicted resting metabolic rate and resting metabolic rate per kilogram body weight. Percent of predicted resting metabolic rate and resting metabolic rate per kilogram body weight were significantly higher in the PS-Para group than in the NPS-Para or control groups (115% +/- 4% vs 100% +/- 2% or 107% +/- 2%, p < .05) and (25.9 +/- 1.2 vs 21.4 +/- 0.6 or 22.5 +/- 0.4 kcal/kg, p < .05, respectively). The resting metabolic rate per meter squared body surface area was significantly higher in the PS-Para group than in NPS-Para group (973 +/- 39 vs 874 +/- 20kcal/m2, p < .05). In the PS-Para group, current smokers had significantly higher resting metabolic rate per kilogram body weight than nonsmokers (27.3 +/- 1.7 vs 24.0 +/- 1.4kcal/kg, p < .01). Controlling for the effects of smoking in a multiple regression model, those in the PS-Para group had significantly (p < .001) greater percent of predicted resting metabolic rate and resting metabolic rate per kilogram body weight than those in the NPS-Para group. These findings indicate that individuals with SCI may have a decreased percent of predicted resting metabolic rate and those with pressure sores may have a hypermetabolic state. This hypermetabolic state is significantly higher than that resulting from smoking. Because ordinary prediction equations for energy expenditure may not be accurate when applied to subjects with paraplegia and pressure sores, quantification of energy needs by indirect calorimetry is recommended.


Supply-side predictors of fatal drug overdose in the Washington/Baltimore HIDTA region: 2016-2020.
Rising rates of fentanyl- and polydrug-involved drug overdose deaths have prompted inquiry into the role of drug supply in fatal overdose outcomes in the United States. To date, however, there have been few empirical investigations of drug enforcement strategies on fatal overdose rates, despite knowledge that both drug use and supply are often geographically distributed. To address this limitation, we examined measures of drug enforcement as predictors of next-year fatal overdose rates in the Washington/Baltimore High Intensity Drug Trafficking Area (W/B HIDTA). We conducted mixed-effects models to examine the role of drug seizures and disruption in drug trafficking organizations (DTOs) and money laundering organizations (MLOs) on fatal overdose rates over a 5-year period (2016-2020) across 45 local jurisdictions in the W/B HIDTA region. Outcomes included any, opioid-involved, and fentanyl-involved fatal overdose. Adjusting for covariates, both the total number of drug seizures and amount of cocaine seized (in dosage units per capita) positively predicted next-year opioid- and fentanyl-involved fatal overdose rates. Disruption to DTO and MLO operations did not significantly predict next-year fatal overdose rates for any outcome. Supply-side enforcement activities alone may have limited impact on reducing fatal overdose rates, but may serve as important markers to identify communities at high risk of fatal overdose and facilitate targeted intervention. Our findings underscore the importance of comprehensive law enforcement approaches that extend beyond drug enforcement to integrate prevention, linkage to treatment, and harm reduction strategies as needed to address the overdose epidemic.


[Specific features of mammographic visualization of "small" breast tumors developing on the background of fibrocystic disease].
All complications diagnosed at early stages of breast cancer were associated with small tumors, especially with those arising in the aftermath of fibrocystic disease. Hence, our task was to study the XR-semiotics of lesions of less than 15 mm in diameter and of the same origin. 100 mammograms of breast cancer patients with benign disease of the breast were studied. The presence of moderate-to-severe fibrocystic disease significantly affected the visualization of lesions of less than 10 mm in diameter. Since the XR-semiotics of small tumors failed to reveal malignancy features, all lesions visualized by mammography required additional diagnostic procedures using ultrasound and invasive radiology.


Secretion of proinflammatory cytokines by villous chorion tissue in spontaneous abortion.
Secretion of proinflammatory cytokines IL-1 beta, TNF-alpha, IL-6, IFN-alpha, and IFN-gamma by the chorion tissue (8-12 weeks) was studied in normal gestation and spontaneous abortion. The production of IL-1 beta, TNF-alpha, and IFN-alpha virtually did not change in spontaneous abortion, while IFN-gamma was not secreted in all experimental groups. The production of IL-6 increased more than 2-fold in patients with spontaneous abortion during the first trimester. These data confirm the involvement of this cytokine in the reproductive processes and in the pathogenesis of miscarriage.


Change in the Number of Patient Safety Reports Through a 16-Year Patient Safety Initiative: A Retrospective Study Focusing on the Incident Severity and Type in a Japanese Hospital.
To describe the long-term quantitative change in the number of submissions of patient safety reports after the introduction of a patient safety reporting system, focusing on incident severity and type. This study was performed at a tertiary care hospital in Japan. Patient safety reports from 2006 to 2020 were retrospectively reviewed. Incident severity was classified from level 0 (near miss) to level 5 (fatality). The incident types included those related to medication, patient care, drains and catheters, procedures and interventions, examinations, medical devices, and blood transfusions. The study period was divided into 1. 2004-2007; 2. 2008-2014; and 3. 2015-2020 based on the implementation of hospital patient safety strategies. The number of reports per hospital worker was compared among the study periods and the incident levels and types. We analyzed 96,332 reports extracted from the patient safety reporting system of the hospital. The total number of reports per hospital worker has increased over time. The numbers of levels 0 and 1 incidents increased throughout the study period. In addition, levels 3a and 3b incidents increased between periods 2 and 3. All incident types, except for procedure and intervention-related incidents, increased between periods 1 and 2 and between periods 1 and 3. The number of procedure and intervention-related incidents increased between periods 2 and 3, although it did not between periods 1 and 2. We found increases in the number of patient safety reports according to the incident severity and type. This suggests two contextual changes occurring during the cultural maturity process, which reflected the development of organizational patient safety culture in our institution. The first was the establishment of a reporting attitude in the institution. The second was to overcome barriers to patient safety.


Small-scale two-dimensional liquid chromatography for a preparative re-purification of a highly labile tritium-labeled compound.
Tritium-labeled compounds are generally less stable than their non-labeled counterparts. This requires storage at low temperatures, a constant workflow of quality checks, and subsequent re-purifications. As the amount of tritium-labeled material is typically purified in the μg range, repeated injections on analytical-scale ultra high-performance liquid chromatography systems can provide high-resolution re-purification results. Yet, degradants can be undesirably included in the compound isolation because the amount of decomposition can vary dramatically depending on the structure. We report a case of a sensitive molecule that could not be isolated in pure form even though the chromatographic separation was successful. In this case, the use of a small-scale two-dimensional preparative liquid chromatography approach with a direct transfer interface to a second (trapping) column resulted in a highly pure compound (>98% radiochemical purity). This approach combines high chromatographic resolution, accurate control over the re-purification process, minimal sample manipulation, and higher overall safety for the handling of radioactive samples.


[Comparison of the findings of rectal examination and ultrasonographic findings in horses with colic].
The examination of patients suffering from an acute abdomen routinely comprises both clinical and rectal examinations, and is ever more frequently accompanied by an ultrasonographic abdominal examination. The aim of the study was to compare the findings as defined through rectal examination with the results of the ultrasonographic examination for different forms of colic. In a retrospective study, the patient records of the Large Animal Clinic of the University of Leipzig from 2012 and 2013 were analysed, and those of horses suffering from colic were included. Diagnoses made through rectal and ultrasonographic examination were grouped and compared with the diagnoses made during colic surgery or pathologic examination, which served as the gold standard. Horses that underwent conservative treatment had a definitive diagnosis assigned only in cases where a pathognostic rectal finding defined the diagnosis. Based on these data, sensitivity, specificity and positive and negative predictive values were calculated for both techniques. Ultrasonography was more sensitive than rectal examination in cases of small intestinal occlusion (97.1% vs. 50.7%), torsion of the large colon in the long axis (63.2% vs. 26.3%) and dislocation of the large colon into the nephrosplenic space (90.9% vs. 72.7%). Rectal examination was more sensitive than ultrasonographic examination in cases of other types of dislocation of the large colon (96.5% vs. 8.8%) and of constipations of the large colon (93.6% vs. 29.8%). In cases of severe diseases, including small intestinal occlusions and torsions of the large colon, ultrasonography helps to better identify and more precisely diagnose conditions that in most cases require abdominal surgery than rectal examination. Therefore, under hospital conditions, it is highly advisable to include ultrasonography in the routine examination of the equine acute abdomen. However, this technique does not replace the traditional rectal examination, which is superior in the diagnosis of dislocations and constipations of the large colon as well as diseases of the caecum.


Influence of the CleaRing intraocular open capsule device on refractive predictability in cataract surgery.
The marked improvement in cataract surgery and intraocular lens (IOL) quality has led to a decline in posterior capsular opacification (PCO) incidence; however, PCO remains a common complication of cataract surgery. The CleaRing intraocular capsule open device (IOCD) decreases PCO incidence. We aimed to investigate the influence of the CleaRing IOCD on refractive predictability in cataract surgery. We conducted this prospective pilot study at the Wolfson Medical Center, Holon, Israel. Ten eyes of patients who underwent cataract surgery and insertion of an IOL after IOCD implantation into the capsular bag were included. All patients completed 12 months of follow-up, including refraction, measurement of uncorrected (UDVA) and best-corrected distance visual acuity (CDVA), slit-lamp biomicroscopy, and ultrasound biomicroscopy. All the surgeries were uneventful, with no postoperative complications. The IOL was centred in the device and bag in all cases. The mean prediction error at 1 and 12 months postoperatively was +0.28 ± 0.32 D and +0.50 ± 0.32 D, respectively. The mean UDVA was 0.17 ± 0.13 and 0.15 ± 0.11 logMAR, and the mean CDVA was 0.04 ± 0.10 and 0.04 ± 0.06 logMAR, respectively. The manifest refractive cylinders at 12 months postoperatively were compatible with corneal astigmatism. Implantation of the IOCD resulted in a slight, predicted, and stable hyperopic shift with a low standard deviation. The standard deviation of the prediction error demonstrated excellent refractive accuracy and predictability using the IOCD, which was as low as 0.32 D at the 12-month follow-up.


Role of N-cadherin- and integrin-based costameres in the development of rat cardiomyocytes.
Costameres, vinculin-containing structures found in skeletal and cardiac muscle, are thought to anchor the Z-discs of the peripheral myofibrils to the sarcolemma. Several lines of evidence indicate that two different sets of costameres, integrin- and N-cadherin-based, are present in cardiac muscles. In this study, immunoblot analysis was used to study the expression of N-cadherin, alpha-catenin, beta-catenin, vinculin, talin, and laminin in rat cardiac muscles at embryonic days 15 and 19, the day of birth (postnatal day 0), postnatal weeks 1, 2, 3, and 4, and in the adult. Double immunofluorescence microscopy was performed to study the spatial and temporal distribution of these two sets of costameres in rat cardiomyocytes. Costameric staining for N-cadherin, codistributed with beta-catenin, was strong from embryonic day 15 up to postnatal week 2, gradually decreased after postnatal week 3, and was undetectable at postnatal week 4 and in the adult. Confocal microscopy showed that N-cadherin colocalized with alpha-actinin at cortical myofibrils. Double-labeling of beta-catenin and talin indicated the coexistence of N-cadherin/catenin- and integrin/talin-based costameres in rat cardiac muscle. Although beta-catenin and vinculin were co-localized at the costamere of cardiomyocytes from embryonic day 15 to postnatal week 3, staining for beta-catenin or talin was mutually exclusive at all stages examined. These results demonstrate the simultaneous, but mutually exclusive, existence of N-cadherin/catenin- and integrin/talin-based costameres in rat cardiomyocytes between late embryonic stages and postnatal week 3, while only integrin/talin-based costameres were found in adult rats. The N-cadherin/catenin-based costameres in rat cardiac muscles may play a role in myofibrillogenesis similar to that of their counterparts in cultured cardiomyocytes.


Design and performance of a fracture monitoring transducer.
The answer to the question, 'when is a fracture healed?' is not simple, since the healing process is progressive and it is not possible to specify a time when the fracture can be said to have healed. In the past the assessment of fracture healing has, in the main, been subjective, relying upon the skill of the interpreter. A more objective method would be an advantage for many reasons, and since the bone is intended to be load bearing it is reasonable to assess healing by measuring the mechanical integrity of the bone. To do this a 'clamp on' transducer has been developed which, when fitted to the support column of an external fixator, enables the stiffness of a fracture to be determined during the healing process. Over the past 6 years this system has been used for both clinical and research work. It has enabled various forms of treatment to be evaluated in terms of 'rate of healing' and it also indicates the safe point at which the fixator can be removed.


Discovery of novel benzimidazole derivatives as potent p300 bromodomain inhibitors with anti-proliferative activity in multiple cancer cells.
Adenovirus E1A-associated 300-kD protein (p300) bromodomain, which regulates gene expression by recognizing acetylated lysine (KAc) of histone, is a promising target for the treatment of cancer. Herein, a series of potent p300 bromodomain inhibitors with novel CBP30-based scaffolds was discovered through bioisosterism and conformational restriction strategies. The most promising compound 1u showed more potent inhibitory activity (IC50 = 49 nM) against p300 bromodomain and anti-proliferative activity in various cancer cell lines compared to CBP30. Moreover, 1u suppressed the expression of c-Myc and induced G1/G0 phase arrest and apoptosis in OPM-2 cells more potently than CBP30. This study provides new lead compounds for further research on the biological functions of p300.


Development of a biodegradable microfluidic paper-based device for blood-plasma separation integrated with non-enzymatic electrochemical detection of ascorbic acid.
In the present article, we developed an electrochemical microfluidic paper-based device (EμPAD) for the non-enzymatic detection of Ascorbic Acid (AA) concentration in plasma using whole human blood. We combined LF1 blood plasma separation membrane and Whatman grade 1 filter paper to separate plasma from whole blood through wax printing. A screen-printed electrode (SPE) was modified with spherical-shaped MgFe2O4 nanomaterial (n-MgF) to improve the catalytic properties of SPE. The n-MgF was prepared via hydrothermal method, and its material phase and morphology were confirmed via XRD, FTIR, TEM, SEM, and AFM analysis. The fabricated n-MgF/SPE/EμPAD exhibited detection of AA ranging from 0 to 80 μM. The obtained value of the detection limit, limit of quantification, sensitivity, and response time are 2.44 μM, 8.135 μM, 5.71 × 10-3 mA μM-1 cm-2, and 10 s, respectively. Our developed n-MgF/SPE/EμPAD shows marginal interference with the common analytes present in plasma, such as uric acid, glutamic acid, glucose, urea, lactic acid, and their mixtures. Overall, our low-cost, portable device with its user-friendly design and efficient plasma separation capability offers a practical and effective solution for estimating AA concentration from whole human blood in a single step.


The prognostic impact of skeletal muscle status and bone mineral density for resected distal cholangiocarcinoma.
The preoperative body composition and bone mineral density (BMD) have been reported as prognostic factors for several cancers. However, the prognostic impact of the preoperative body composition and BMD for resected distal cholangiocarcinoma (DCC) remains unclear. A total of 111 patients who underwent pancreatoduodenectomy for DCC between 2002 and 2017 were analyzed. The skeletal muscle index (SMI) and BMD were measured by preoperative computed tomography. The optimal cut-off value of the body composition and BMD were selected based on the minimum P-value obtained by the log-rank test. The prognostic significance of the preoperative body composition and BMD was investigated using multivariate analysis. The median values of the SMI (45.7 vs. 36.7 cm2/m2, P < 0.001) and BMD (128.5 vs. 101.0 Hounsfield units [HU], P = 0.005) in male and female were significantly different. The optimal cut-off values for the SMI were 55 cm2/m2 in male and 36 cm2/m2 in female, and those for the BMD were 75 HU in male and 74 HU in female. A multivariate analysis identified low SMI (hazard ratio [HR], 4.340; P = 0.044), low BMD (HR, 5.333; P < 0.001) and microscopic venous invasion (HR, 2.019; P = 0.026) as independent prognostic factors for the survival. A preoperative low SMI and low BMD were independent prognostic factors for resected DCC.


Nerve innervation of the hand and associated nerve dominance aggregates in the somatosensory cortex of a primate (squirrel monkey).
The cutaneous innervation territories of the median, ulnar, and radial nerves to the hand were determined from neurophysiological recordings of peripheral mechanoreceptor axons in adult squirrel monkeys. These territories were then related to cutaneous receptive fields of cortical area 3b neurons to determine how low-threshold inputs from each hand nerve map onto the primary somatosensory cortex. The results indicate that mechanoreceptor axons in each nerve innervate a continuous skin territory covering about 40% of the hand surface. The total territory of each nerve contains subregions of skin that are either autonomously innervated by that nerve or that receive overlapping innervation from more than one nerve. The autonomous, overlap, and total territories of each nerve are relatively constant from hand to hand. In the area 3b cortex, low-threshold afferents from each nerve provide inputs to aggregates of cortical neurons. The cortical aggregates relating to the median and ulnar nerves are arranged as continuous, rostrocaudally oriented bands, whereas aggregates relating to the radial nerve are discontinuous and more patch-like. Similar patterns of bands and patches, and similar compression ratios of skin/cortical area, are seen across different monkeys. These findings demonstrate that the primary somatosensory cortex of normal adult primates contains bands or patches of neurons that are dominantly activated by low-threshold inputs from specific hand nerves. This approach of delineating nerve territories and their related cortical dominance aggregates provides a useful means of analyzing cortical images of nerves and of quantitating peripheral and central patterns of deprivation after nerve injury.


Importance of lean mass in the interpretation of total body densitometry in children and adolescents.
Most studies that use total body dual energy x-ray absorptiometry (DEXA) in children rely on areal bone mineral density (BMD=bone mineral content [BMC]/bone area [BA]) and compare the output with age- and sex-specific normative data. Because this approach is prone to size-related misinterpretation, this study focuses on the interrelations among BMC, body size (height), and lean tissue mass (LTM). This cross-sectional study presents normative total body LTM data in relation to height and BMC for 459 healthy white subjects (249 female), 3 to 30 years of age. Guidelines for DEXA interpretation in children are provided and illustrated for patients with growth hormone deficiency (n=5) and anorexia nervosa (n=5). LTM/height tended to be greater in male than in girls. The BMC/LTM ratio was greater in female than in boys (P<.001), even after adjustment for age and height. Sex-specific reference curves were created for LTM/height, the BMC/LTM ratio, BA/height, and BMC/BA. We recommend that total body DEXA in children should be interpreted in 4 steps: (1) BMD or BMC/age, (2) height/age, (3) LTM/height, and (4) BMC/LTM ratio for height. This allows differentiation of the origin of a low BMD or BMC/age, for example, short stature and primary, secondary, and mixed bone defects.


Treatment of metastatic breast cancer: looking towards the future.
The armamentarium for the treatment of metastatic breast cancer is increasing with the introduction of newer chemotherapeutic agents and the development of molecular targeted therapies. The clinical utility of anthracyclines in advanced breast cancer has been limited by significant adverse events; therefore the taxanes are increasingly used in the metastatic setting. Trastuzumab with a taxane as first-line therapy is now standard of care for patients with human epidermal growth factor receptor 2 (HER2)-positive metastatic breast cancer. Other targeted therapies, including the antiangiogenesis agents such as bevacizumab, are being investigated both as monotherapy and in combination regimens. While the number of available agents is growing rapidly, challenges remain concerning appropriate dose, schedule, treatment duration and management of drug resistance. This paper reviews recent data regarding the established and investigational medical treatments for endocrine-refractory metastatic breast cancer, and presents treatment recommendations.


Absorption of p,p'-dichlorodiphenyldichloroethylene and dieldrin in largemouth bass from a 60-d slow-release pellet and detection using a novel enzyme-linked immunosorbent assay method for blood plasma.
This work describes the uptake of two organochlorine pesticides from slow-release pellets by largemouth bass and the utility of a blood plasma enzyme-linked immunosorbent assay (ELISA) method for exposure verification. We measured blood and tissue levels by gas chromatography/mass spectrometry and by a novel ELISA method, and present a critical comparison of the results.


Influence of State-Level Emergency Planning Policy Requirements on Secondary School Adoption.
Emergency action plans (EAPs) are a critical component in the management of catastrophic sport-related injury. Some state high school athletics associations and state legislation have required that schools develop EAPs, but little research exists on the influence of a statewide policy requirement on local adoption of these policies. To examine the efficacy of a statewide policy requirement on local adoption of an EAP. Cross-sectional study. Online questionnaire. Secondary school athletic trainers were invited to complete a survey (n = 9642); 1136 completed the survey, yielding an 11.7% response rate. Survey responses on the adoption of EAPs along with cardiopulmonary resuscitation and automated external defibrillator (CPR/AED) requirements were cross-referenced with published statewide policies to determine the prevalence of EAP adoption. We evaluated the adoption of emergency action plan components based on the National Athletic Trainers' Association's emergency planning position statement along with CPR/AED requirements to determine component-specific prevalence. We compared the prevalence of EAP and component adoption between states that required EAPs and specific components of EAPs and states without such requirements. Athletic trainers in states that required adoption of an EAP reported including more components of the emergency planning position statement (mean = 8 ± 4, median = 9) than in states without a requirement (mean = 7 ± 4, median = 8). The adoption of EAP components did not differ between states that required specific components of the EAP versus development of the EAP only. However, schools in states with both EAP and CPR/AED training requirements reported higher rates of CPR/AED training implementation (95.5%) than states that only required CPR/AED training (81.6%, prevalence ratio = 1.10, 95% confidence interval = 1.01, 1.20). Based on these data, statewide policy requirements for the development of an EAP may be associated with increasing adoption of EAPs.


The duration of a neuronal trace of an auditory stimulus as indicated by event-related potentials.
Event-related brain potential studies have revealed a component called the mismatch negativity (MMN) in response to occasional deviant stimuli presented in a sequence of homogeneous repetitive, 'standard', stimuli. This negativity probably reflects an automatic neuronal-mismatch process with a neuronal representation of the standard stimulus. The present study aimed at determining the duration of the assumed neuronal representation by varying the inter-stimulus interval (ISI) of a stimulus block. It was assumed that a deviant stimulus can elicit a MMN only when the neuronal representation of the previous standard stimulus still exists. It was found that a clear MMN was elicited by the deviant stimulus when the ISI was 1 or 2 s, but not when the ISI was 4 or 8 s. This suggests that the duration of the neuronal representation involved was less than 4 s.


Speech and language development and disorders in children.
Language disorders are identified when a person has difficulty with expressive language, receptive language, or pragmatic language. Speech disorders are identified when a person's voice, fluency, or articulation call attention to the speaker because his or her speech is sufficiently different from the norm. Speech and language development should be consistent with a child's overall development and can be tracked using typical milestone markers. Differential diagnosis is critical to designing appropriate intervention, which should be tailored to the parents' goals along with the child's clinical and educational needs. Early identification and intervention assist in educational planning and are often associated with better long-term outcomes. Any speech-language therapy plan should be designed with measurable goals and consistent monitoring of progress toward those goals.


Pseudolymphoma of the liver: Report of a case and review of the literature.
We report a case of pseudolymphoma of the liver in a 49-year-old woman without an underlying disease except for liver hemangioma. A 20-mm nodule was incidentally found in segment 2 of the liver by abdominal ultrasonography during a regular follow-up of the hepatic hemangioma. After a series of radiological examinations, a left lateral sectionectomy was performed because malignant hepatic tumor could not be excluded. The patient was discharged uneventfully 7 days after the operation. The pathology examination revealed a pseudolymphoma. No recurrence of the tumor was found 5½ years after the operation. To the best of our knowledge, only 46 cases of pseudolymphoma of the liver have been reported to date. A review of the literature showed that pseudolymphomas occur predominantly in females (89.4%), usually occur as a single tumor (80.4%), are no more than 20 mm in size (90.6%), and are frequently associated with either autoimmune disease or chronic liver disease. Because an accurate diagnosis is difficult to establish, vigilant follow-up is indicated, and surgical intervention is the choice of treatment once the suspiciousness of malignancy has been raised.


An efficient synthesis of aripiprazole, buspirone and NAN-190 by the reductive alkylation of amines procedure.
The reductive alkylation of amines procedure was applied for the synthesis of aripiprazole 1a, buspirone 1b, and NAN-190 1c.