Simulated slide tracheoplasty for congenital tracheal stenosis using three-dimensional printed models.
The slide tracheoplasty (STP) is the standard treatment for severe congenital tracheal stenosis (CTS). Understanding the features of the tracheal stenosis in each case and choosing an appropriate incision design are very important for successfully executing the procedure. The present study aimed to evaluate the advantages of three-dimensional (3D) printed models of the trachea for improving CTS. Three-D tracheal models were created using computed tomography (CT) data from ten patients undergoing STP for CTS. Simulated surgery was performed using the hollow models after reinforcing with them with a coating of gum spray. Clinical outcomes, including patient survival, postoperative surgical interventions, and time required for STP, were compared with the corresponding values in the last ten patients before the introduction of 3D model simulations. All ten patients for whom simulated surgery using a 3D tracheal model were conducted achieved good airway patency after their STP. The surgeons reported feeling that the 3D model simulations were highly effective although there was no significant difference in the clinical outcomes of the groups with or without simulated STP. The models were useful not only for surgical planning but also for sharing important information among the multidisciplinary team and the patients' family. Our experience using 3D tracheal models demonstrated several features enabling improvement in the surgical treatment of CTS.


Reversible restriction of vesicular stomatitis virus in permissive cells treated with inhibitors of prostaglandin biosynthesis.
Indomethacin, a potent nonsteroidal inhibitor of prostaglandin synthetase (cyclooxygenase) reduced yields of infectious vesicular stomatitis virus in HEp-2 cells more than 99% if added to cultures at levels of 10(-3)M either before or after infection. Other permissive cell lines differed according to the treatment period and drug level required for restricting productive infections. The inhibitory effect of indomethacin was progressively reduced if infection of cells was delayed for increasing times after drug removal. Strong inhibition of viral replication also occurred in cells treated with the cyclooxygenase antagonists naproxen, phenylbutazone, and oxyphenylbutazone whereas phenacetin, which does not block cyclooxygenase function, was inactive. Enhanced viral replication occurred in indomethacin-treated HEp-2 cultures when these cells were subsequently exposed to such substances as prostaglandin E1, cyclic AMP, or insulin. Conversely, indomethacin-treated cells remained restrictive for VSV if they were subsequently exposed to metabolic inhibitors of functional DNA (actinomycin D or mitomycin C), messenger RNA synthesis (alpha-amanitin), or protein synthesis (cycloheximide) at concentrations that normally do not compromise viral replication. Pretreatment of HEp-2 cells with mitomycin C markedly shifted the dose response for indomethacin-mediated inhibition of VSV from a 90% inhibitory dose of about 10(-4)M to one of 10(-9)M or lower. These findings suggest that preexisting host factors essential for replication of VSV, although rendered nonfunctional by the drug indomethacin, can be replenished unless their synthesis is blocked by various classes of metabolic inhibitors.


Transcutaneous Electrical Neuromuscular Stimulation (TENS) Along with Traditional Dysphagia Therapy in Patients with Posterior Stroke: A Case Study.
Swallowing is a complicated, multilevel and neuromuscular physiological function. Transcutaneous neuromuscular electrical stimulation is a relatively new therapeutic intervention for the treatment of swallowing disorders. The aim was to administer and focus on pre and post therapy effects of traditional dysphagia therapy and electrical stimulation (TENS) in 2 participants with posterior stroke. Electrical current along with traditional dysphagia therapy on regular intervals with adequate current levels post stroke. These cumulative therapeutic strategies helped in improving the swallowing mechanism. TENS is one of the new therapeutic technique that has greater advantage along with traditional dysphagia therapy, which promises a lot of scope in cases with acute cerebrovascular accidents.


Microsurgical Reconstruction of Extensive Lower Lip Defects: An Algorithm for Free Flap Selection and Functional Outcomes.
Large defects of the lower lip pose a difficult challenge for any reconstructive surgeon. When there is limited local tissue available to resurface the defects, free flaps are the preferred option. We reported our experience in the reconstruction of extensive lower lip defects. The authors propose a new algorithm for microsurgical technique selection and assessment of the functional outcomes obtained. A retrospective review of all microsurgical reconstructions of extensive lower lip defects by the senior author for 10 years was performed. The functional outcomes assessed included speech, feeding, and oral continence. Patients were stratified according to their status of simultaneous mandible resection (none, marginal, segmental). Fifty-one patients were included in this study. Almost all patients (96.1%) achieved intelligible speech. Only 1 patient experienced severe drooling. Most patients could eat a solid or soft diet (72.5%). Mandible resection was associated with the worst feeding outcomes. Microsurgical reconstruction of extensive lip defects is safe and provides good results. Free flap selection should take into account the location of the defect, the resected structures, and the body mass index of the patient. Feeding status seems to be inversely correlated with the amount of mandibular resection.


Alpha-thalassaemia caused by a poly(A) site mutation reveals that transcriptional termination is linked to 3' end processing in the human alpha 2 globin gene.
We have investigated the process of transcriptional termination in the duplicated human alpha globin genes which lie 4 kb apart on chromosome 16. In the human erythroleukemic cell line, K562, which expresses high levels of alpha globin, nuclear run-off experiments suggest that termination occurs within a region of 600 bp past the poly(A) site of both alpha 1 and alpha 2 globin genes. However, a thalassaemic alpha 2 globin gene with a non-functional poly(A) site AAUAAG, when transfected into HeLa cells, not only fails to 3' end process but also fails to terminate transcription. Studies on both steady-state RNA and nuclear run-off analysis of the primary transcripts show that transcription of the mutant alpha 2 globin gene reads through into the intergenic sequence past the normal termination site. These results demonstrate that transcriptional termination and 3' end processing of mRNA are coupled events for the alpha 2 globin gene.


ITGA5 promotes tumor angiogenesis in cervical cancer.
Integrins are critical to cancer progression. Integrin alpha 5 (ITGA5) is correlated with the prognosis of cervical cancer patients. However, whether ITGA5 plays an active role in cervical cancer progression or not remains unknown. ITGA5 protein expression was detected in 155 human cervical cancer tissues by immunohistochemistry. Data from The Cancer Genome Atlas were utilized to identify risk factors for the overall survival of cervical cancer patients and ITGA5-associated differentially expressed genes. Analyses of single-cell RNA-seq based on Gene Expression Omnibus datasets were performed to show the coexpression of ITGA5 and angiogenesis factors. Tube formation assay, 3D spheroid sprout assay, qRT-PCR, Western Blotting, ELISA, and immunofluorescence were conducted to explore the angiogenic function of ITGA5 in vitro and underlying mechanisms. High ITGA5 level was significantly correlated with increased risk in terms of overall survival and advanced disease stage in cervical cancer patients. ITGA5-associated differentially expressed genes linked ITGA5 to angiogenesis, and immunohistochemistry showed a positive correlation between ITGA5 and microvascular density in cervical cancer tissues. Moreover, tumor cells transfected with ITGA5-targeting siRNA decreased ability to promote endothelial tube formation in vitro. ITGA5/VEGFA coexpression was observed in a tumor cell subpopulation and the decreased endothelial angiogenesis by downregulating ITGA5 could be reversed by VEGFA. Bioinformatics analysis highlighted the PI3K-Akt signaling pathway as downstream of ITGA5. Downregulation of ITGA5 in tumor cells significantly decreased p-AKT and VEGFA levels. Fibronectin (FN1) coated cells or transfected with FN1-targeting siRNA showed fibronectin may play a critical role on ITGA5-mediated angiogenesis. ITGA5 promotes angiogenesis and possibly be a potential predictive biomarker for poor survival of patients in cervical cancer.


Effects of Lactoferrin on Prevention of Acute Gastrointestinal Symptoms in Winter: A Randomized, Double-Blinded, Placebo-Controlled Trial for Staff of Kindergartens and Nursery Schools in Japan.
This study investigated the preventive effects of lactoferrin (LF) on subjective acute gastrointestinal symptoms during the winter in a randomized, double-blinded, placebo-controlled parallel-group comparative trial. The eligible subjects were healthy adults working at kindergartens and nursery schools. We randomized the subjects to the Placebo group (0 mg/day), the Low LF group (200 mg/day), and the High LF group (600 mg/day) for 12 weeks. The prevalence of acute gastrointestinal symptoms was significantly lower in the High LF (13/112 vs. 26/116; p = 0.030) and the Low LF (13/107 vs. 26/116; p = 0.040) groups than in the Placebo group. The adjusted odds ratio for the prevalence of acute gastrointestinal symptoms was 2.78 (95% CI: 1.19-6.47) in the Placebo group compared with the High LF group. LF is useful to prevent acute gastrointestinal symptoms among childcare workers, who mainly consist of women.


Prolonged activation of the baroreflex decreases arterial pressure even during chronic adrenergic blockade.
Previous studies suggest that prolonged electric activation of the baroreflex may reduce arterial pressure more than chronic blockade of alpha(1)- and beta(1,2)-adrenergic receptors. To determine whether central inhibition of sympathetic outflow has appreciable effects to chronically reduce arterial pressure by actions distinct from well-established mechanisms, we hypothesized that chronic baroreflex activation would lower arterial pressure substantially even during complete alpha(1)- and beta(1,2)-adrenergic receptor blockade. This hypothesis was tested in 6 dogs during adrenergic blockade (AB; 18 days) with and without electric activation of the carotid baroreflex (7 days). During chronic AB alone, there was a sustained decrease in the mean arterial pressure of 21+/-2 mm Hg (control: 95+/-4 mm Hg) and an approximately 3-fold increase in plasma norepinephrine concentration (control: 138+/-6 pg/mL), likely attributed to baroreceptor unloading. In comparison, during AB plus prolonged baroreflex activation, plasma norepinephrine concentration decreased to control levels, and mean arterial pressure fell an additional 10+/-1 mm Hg. Because of differences in plasma norepinephrine concentration, we also tested the acute blood pressure-lowering effects of MK-467, a peripherally acting alpha(2)-antagonist. After administration of MK-467, there was a significantly greater fall in arterial pressure during AB (15+/-3 mm Hg) than during AB plus prolonged baroreflex activation (7+/-3 mm Hg). These findings suggest that reflex-induced increases in sympathetic activity attenuate reductions in arterial pressure during chronic AB and that inhibition of central sympathetic outflow by prolonged baroreflex activation lowers arterial pressure further by previously undefined mechanisms, possibly by diminishing attendant activation of postjunctional alpha(2)-adrenergic receptors.


Brain energization in response to deep brain stimulation of subthalamic nuclei in Parkinson's disease.
Deep brain stimulation (DBS) of the subthalamic nucleus (STN) is an effective treatment in a subgroup of medically refractory patients with Parkinson's disease (PD). Here, we compared resting-state (18)F-fluorodeoxyglucose (FDG) positron emission tomography images in the stimulator off (DBS_OFF) and on (DBS_ON) conditions in eight PD patients in an unmedicated state, on average 2 years after bilateral electrode implantation. Global standardized uptake value (SUV) significantly increased by ∼11% in response to STN-DBS. To avoid any bias in the voxel-based analysis comparing DBS_ON and DBS_OFF conditions, individual scan intensity was scaled to a region where FDG-SUV did not differ significantly between conditions. The resulting FDG-SUV ratio (FDG-SUVR) was found to increase in many regions in response to STN-DBS including the target area of surgery, caudate nuclei, primary sensorimotor, and associative cortices. Contrary to previous studies, we could not find any regional decrease in FDG-SUVR. These findings were indirectly supported by comparing the extent of areas with depressed FDG-SUVR in DBS_OFF and DBS_ON relatively to 10 normal controls. Altogether, these novel results support the prediction that the effect of STN-DBS on brain activity in PD is unidirectional and consists in an increase in many subcortical and cortical regions.


ROS mediated EGFR/MEK/ERK/HIF-1α Loop Regulates Glucose metabolism in pancreatic cancer.
To investigate the glycometabolism associated mechanism in invasion and metastasis of pancreatic cancer, We screened out genes involved in anaerobic glycolysis headed by HIF-1α,using pre-established a pair of pancreatic cancer cell lines. In this study, we further detected the glucose metabolism state not only in the cells but all also in two groups of patients with different SUVmax on 18F-FDG PET/CT. The data suggests that ROS mediated EGFR/MEK/ERK/HIF-1α loop is activated in high glucose metabolic samples both in vitro and in vivo: The increasing of HIF-1α expression is controlled by activation of EGFR/MEK/ERK pathway in hypoxia condition, HIF-1α inhibits excessive release of ROS, the reduction of ROS further activates EGFR to form a positive feedback loop. This difference is closely related to invasion and metastasis capacity of pancreatic cancer, and can be rescued by separate or combined inhibition of EGFR or HIF-1α in various degree. These results indicate a new clue to develop therapy of pancreatic cancer by regulating the glucose metabolism.


Automatic Detection of Thyroid and Adrenal Incidentals Using Radiology Reports and Deep Learning.
Computed tomography (CT) is commonly performed when evaluating trauma patients with up to 55% showing incidental findings. Current workflows to identify and inform patients are time-consuming and prone to error. Our objective was to automatically identify thyroid and adrenal lesions in radiology reports using deep learning. All trauma patients who presented to an accredited Level 1 Trauma Center between January 2008 and January 2019 were included. Radiology reports of CT scans that included either a thyroid or adrenal gland were obtained. Preprocessing included word tokenization, removal of stop words, removal of punctuation, and replacement of misspellings. A word2vec model was trained using 1.4 million radiology reports. Both training and testing reports were selected at random, manually reviewed, and were considered the gold standard. True positive cases were defined as any lesions in the thyroid or adrenal gland, respectively. Training data was used to create models that would identify reports that contained either thyroid or adrenal lesions. Our primary outcomes were sensitivity and specificity of the models using predetermined thresholds on a separate testing dataset. A total of 51,771 reports were identified on 35,859 trauma patients. A total of 1,789 reports were annotated for training and 500 for testing. The thyroid model predictions resulted in a 90.0% sensitivity and 95.3% specificity. The adrenal model predictions resulted in a 92.3% sensitivity and a 91.1% specificity. A total of 240 reports were confirmed to have thyroid incidentals (mean age 69.1 yrs ± 18.9, 35% M) and 214 reports with adrenal incidentals (mean age 68.7 yrs ± 16.9, 50.5% M). Both the thyroid and adrenal models have excellent performance with sensitivities and specificities in the 90s. Our deep learning model has the potential to reduce administrative costs and improve the process of informing patients.


Macro- and micro-structural cerebellar and cortical characteristics of cognitive empathy towards fictional characters in healthy individuals.
Few investigations have analyzed the neuroanatomical substrate of empathic capacities in healthy subjects, and most of them have neglected the potential involvement of cerebellar structures. The main aim of the present study was to investigate the associations between bilateral cerebellar macro- and micro-structural measures and levels of cognitive and affective trait empathy (measured by Interpersonal Reactivity Index, IRI) in a sample of 70 healthy subjects of both sexes. We also estimated morphometric variations of cerebral Gray Matter structures, to ascertain whether the potential empathy-related peculiarities in cerebellar areas were accompanied by structural differences in other cerebral regions. At macro-structural level, the volumetric differences were analyzed by Voxel-Based Morphometry (VBM)- and Region of Interest (ROI)-based approaches, and at a micro-structural level, we analyzed Diffusion Tensor Imaging (DTI) data, focusing in particular on Mean Diffusivity and Fractional Anisotropy. Fantasy IRI-subscale was found to be positively associated with volumes in right cerebellar Crus 2 and pars triangularis of inferior frontal gyrus. The here described morphological variations of cerebellar Crus 2 and pars triangularis allow to extend the traditional cortico-centric view of cognitive empathy to the cerebellar regions and indicate that in empathizing with fictional characters the cerebellar and frontal areas are co-recruited.


Intracranial electroencephalography with subdural and/or depth electrodes in children with epilepsy: techniques, complications, and outcomes.
Intracranial electroencephalographic monitoring with subdural and/or depth electrodes is widely used for the surgical localization of epileptic foci in patients with intractable partial epilepsy; however, data on safety and surgical outcome with this technique are still inadequate. The aims of this study were to assess the morbidity of intracranial recordings and the surgical outcomes in epileptic children. We retrospectively reviewed the clinical data for 137 children with epilepsy (mean age at implantation: 12.6 ± 3.8 years) who underwent intracranial monitoring with the implantation of strip or grid subdural electrodes and/or intracerebral depth electrodes from September 2004 to September 2011 at a tertiary epilepsy center in China. Complications were classified using five grades of severity (including mortality) and were further classified as either minor or severe. Outcome was classified according to Engel's classification. Regression analysis was performed to identify risk factors for complications. The mean duration of implantation was 5.3 ± 1.3 days. Among the 133 patients who underwent resection, 65 (48.9%) were seizure free (Engel Class I) at last known follow-up, which was >2 years after surgery for all patients. Also, 31 (23.3%) patients had a significant reduction in seizures (Engel Class II). Complications of any type were documented in 29 (21.7%) patients; 15 of these patients had intracranial hematoma. The results of multivariate analysis showed that the only independent risk factor for intracranial hematoma was number of electrode contacts. The most common pathologic diagnosis was focal cortical dysplasia (n=58). Our results showed that intracranial electroencephalographic monitoring in children provides good surgical outcomes and the level of risk is acceptable. When using this technique strategies such as using as few electrode contacts as possible should be adopted to minimize the risk of intracranial hematoma.


Distinct metabolite profiles of adiposity indices and their relationships with habitual diet in young adults.
Obesity is characterized as overall or regional adiposity accumulation. However, the metabolic status underlying fat accumulation was not well understood. We sought to identify metabolite profiles based on their correlations with body mass index (BMI), body fat percentage (BFP), waist circumference (WC), and visceral adiposity index (VAI) in young Chinese adults (19-37 years old), and their associations with dietary consumption were also explored. A total of 86 plasma samples were analyzed using untargeted lipidomics and metabolomics approaches. Metabolite profiles of adiposity indices were identified using random forest modelling. Ridge regression was used to generate metabolite scores. Overall, 30, 46, 30, and 20 metabolites correlated with BMI, BFP, WC, and VAI, respectively, which resulted in metabolite scores for each index. Top three enriched categories of the identified metabolites were glycerophospholipids, glycerolipids, and sphingolipids, with some specific metabolites (such as phosphatidylserine (37:2), phatidylethanolamine (42:4), and ceramide (40:0)) exclusively associated with overall adiposity, and some other metabolites exclusively associated with abdominal adiposity indices, e.g., triradylglycerol (45:0, 52:4, and 35:0) and diacylglycerol (38:4, 36:3, and 36:5). Moreover, metabolite scores were negatively associated with the intake of food rich in protein or fiber, while they were positively associated with food rich in carbohydrate, with similar results for adiposity indices. We observed unique metabolite profiles of regional or overall fat deposition in young adults. Glycerophospholipids, glycerolipids, or sphingolipids may be involved in the regulation of adiposity accumulation, affected by dietary exposures.


Clinical results and manometric studies after rectal flap advancement for infra-levator trans-sphincteric fistula-in-ano.
Eleven patients with infra-levator trans-sphincteric fistula-in-ano underwent fistula excision with rectal flap advancement. The clinical results were assessed by interview and the physiological function determined by ano-rectal manometry. Nine patients underwent paired studies before and 5 (range 2 to 6) months after operation. Median maximum resting anal pressure was 84 (48-135) cm water before operation and 76 (29-139) cm water after operation (P = N.S.). Median maximum squeeze pressure was 112 (64-290) cm water before operation and 88 (44-316) cm water after operation (P = N.S.). The median sphincter length was preserved after operation. There was one clinical failure following the development of an abscess under the flap. All patients are continent and there have been no recurrences. We conclude that rectal flap advancement is an acceptable way to cure more complex fistula-in-ano. Good functional results are achieved by maintaining anal sphincter function together with preservation of the integrity of the anal margin.


Ethical challenges in end-stage dementia: Perspectives of professionals and family care-givers.
In Israel, caring for people with end-stage dementia confined to home is mainly done by home care units, and in some cases by home hospice units, an alternative palliative-care service. Because life expectancy is relatively unknown, and the patient's decision-making ability is poor, caring for this unique population raises ethical dilemmas regarding when to define the disease as having reached a terminal stage, as well as choosing between palliative and life-prolonging-oriented care. Exploring and describing differences and similarities of professional staff members' (PSMs') and family caregivers' perceptions of caring for people with end-stage dementia in two different settings. Qualitative research, using semi-structured interviews analyzed through a thematic content-analysis approach. Sixty-four interviews were conducted (24 PSMs and 40 family caregivers) in two care-settings-home hospice unit and home care unit. The study was approved by the Ethics Committee (BBL00118-17). We found dilemmas regarding palliative care to be the main theme, including definition of the disease as terminal, choosing "comfort" over "life-prolonging," clarifying patients' wishes and deciding whether or not to use artificial feeding. Both PSMs and family caregivers deal with ethical dilemmas and have reached different conclusions, both legitimate. Comprehending dementia as a terminal disease influenced participants' perceptions of the relevancy of palliative care for people with end-stage dementia. Discrepancies between PSMs and family caregivers in caring for people with end-stage dementia were found in both home hospice unit and home care unit environments, raising potential conflicts regarding decisions for end-of-life care. Communication between PSMs and family caregivers is crucial for the discussion about the discrepancies regarding the unique dilemmas of caring for people with end-stage dementia and bridging the gap between them. Lack of communication and resources can hamper the provision of an acceptable solution for quality and equality of care in the best interest of people with end-stage dementia.


Comparison of cerebrospinal fluid tau, ptau(181), synuclein, and 14-3-3 for the detection of Creutzfeldt-Jakob disease in clinical practice.
Creutzfeldt-Jakob disease (CJD) is the leading human prion disease and is a major public health concern, with the risk of secondary iatrogenic transmission. Screening for CJD is often based on the detection of 14-3-3 protein in cerebrospinal fluid (CSF) through western blot assay and, in a second step, on a more specific method such as RT-QuIC (Real-Time Quaking-Induced Conversion). Alternatives to the detection of 14-3-3 in CSF have recently been proposed, specifically CSF tau proteins, tau/p-tau(181) ratio, and alpha-synuclein. In the present work, we compare the diagnostic performance of these biomarkers with that of 14-3-3 protein in a cohort of suspected CJD patients. Our results indicate that tau detection is the most effective and suitable approach for routine disease detection in a clinical setting. Combination with other biomarkers does not improve overall performance, while the tau/p-tau(181) ratio remains useful for differentiating Alzheimer's from CJD. In the end, the performance of tau protein detection in CSF reached 78% sensitivity and 80% specificity for the detection of CJD. It is interesting to note that the use of an automated method with a high concentration range allows for rapid and accurate results, which is very useful in clinical practice and allows for confirmatory testing such as RT-QuIC without delay.


The interaction between MC4R gene variant (rs17782313) and dominant dietary patterns on depression in obese and overweight women: a cross sectional study.
Previous studies have shown that the minor allele (C allele) for melanocortin 4 receptor (MC4R) rs17782313 may be associated with depressed mood. Moreover, dietary patterns have potentially adverse effects on depression. This study investigates the interactions between the MC4R gene variant (rs17782313) and dietary patterns on depression among Iranian obese and overweight women. A total of 289 Iranian overweight and obese women, aged 18-50 years, were enrolled in this cross-sectional study. Biochemical, anthropometric, and body composition indices were assessed in all participants. Moreover, MC4R rs17782313, by the restriction fragment length polymorphism (PCR-RFLP) method, and depression, using the 21-item Depression Anxiety Stress Scales (DASS) questionnaire, were assessed. Food intakes were assessed by completing a 147-item semi-quantitative food frequency questionnaire (FFQ). By the use of factor analysis, 2 major dietary patterns were extracted: healthy dietary pattern (HDP) and unhealthy dietary pattern (UDP). Binary logistic analysis showed that individuals with minor allele risk (CC) with high adherence to the unhealthy pattern increased odds for depression (OR: 8.77, 95%CI: -0.86-18.40, P: 0.07), after controlling for confounders. Also, a logical inverse relationship was observed between CT genotype and HDP on depression in the crude and adjusted models (OR: -0.56, 95% CI: -3.69-2.57, P: 0.72) (OR: -4.17, 95% CI: -9.28-0.94, P: 0.11), although this interaction was not statistically significant. According to the above findings, adherence to unhealthy food intake pattern increases odds of depression in MC4R risk allele (C allele) carriers. To confirm these findings, more studies are needed in the form of clinical trials and prospective studies with higher sample sizes.


Parental Beliefs, Logistical Challenges, and Improvement Opportunities for Vaccination among Children Ages 19-35 Months Experiencing Homelessness.
To examine parental beliefs and logistical challenges to early childhood vaccination completion as well as opportunities to support improved vaccine uptake among families experiencing homelessness. A cross-sectional survey was conducted between February 2018 and October 2019 with parents of children ages 19-35 months old experiencing homelessness. Participants were recruited from 10 locations that serve families experiencing homelessness in Washington, DC and by referral from other participants. Vaccination records were obtained from health care providers to determine the child's up-to-date (UTD) status with a combined 7-vaccine series. Of 135 children of participants, only 69 (51.1%) were UTD. Most participants had at least 1 concern about childhood vaccines and at least 1 logistical barrier to completing vaccination (57% and 85.9%, respectively). The most frequent barriers were getting a convenient appointment time (46.3%), remembering appointments (44.8%), and commuting to appointments (44.4%). Although only 53.3% of the participants' children attended a licensed daycare center and only 43.7% received benefits from the Special Supplemental Nutrition Program for Women, Infants, and Children (WIC), use of either of these programs that routinely assess vaccination status was associated with over 3 times higher adjusted odds of being UTD (aOR 3.4, 95% CI 1.6-7.3, and aOR 3.1, 95% CI 1.4-6.5, respectively). Logistical barriers to accessing primary care services are common among children experiencing homelessness, underscoring the importance of health care providers offering vaccines at every opportunity. Government-regulated programs are useful for promoting vaccination, and enrollment should be encouraged because many children experiencing homelessness may not access them.


Arriving at the postmodern medical consultation.
The analysis of the medical consultation is characterised by mainly prescriptive attempts to recommend 'best practice'. As the role of the individual in society has gained prominence, the power relationships in medical practice have had to change to reflect the increasing recognition of autonomy and self-determination. Medical discourse is at a junction, having to relinquish authoritarianism and grapple with the concept of sharing information and decisions in an area where complex and uncertain data exist, albeit often without full disclosure. The writing of Foucault and Lyotard and the concept of postmodernism fit well with the idea that the consultation between doctors and patients is increasingly becoming a contested space that occupies multiple voices, such as that of the media, the pharmaceutical industry, government-led guidelines and that of the profession. Creating the circumstances and the means for creating an effective dialogue in the postmodern consultation is the prime task for physicians.


[The Bier block as an experimental tool to differentiate peripheral and central effects of analgesics on people].
In this study the technique of intravenous regional anesthesia (Bier block) was evaluated as an experimental tool to differentiate peripheral and central effects of analgesics. Touch and pain thresholds were assessed under control conditions and during a prolonged Bier block. In addition, models of experimental pain and hyperalgesia were used (Capsaicin injection, histamine iontophoresis, pinch). No signs of impaired function of Adelta- und C-fibers were found during a Bier block of up to 30 min after onset of ischemia. In contrast, Abeta-mediated touch sensation declined significantly. On the basis of these results, peripheral mechanisms of action could be verified for low-dose lidocaine and for morphine in the Bier block setting. The Bier-block setting can be successfully employed to differentiate peripheral and central modes of action of analgesics.


Transient expression of the transformed phenotype stimulated by 12-O-tetradecanoyl phorbol-13-acetate.
The objective of the present work was to determine whether a short-term perturbation of cells by 12-O-tetradecanoyl phorbol-13-acetate (TPA) treatment caused shape changes identical to those found in oncogenic transformation. A cell line derived from the rat respiratory tract epithelium, 1000 W, was used, in which shape changes had been identified previously as the cells underwent transformation during long-term growth in vitro. These changes corresponded to a steeper rise of the cell from the substrate and a smoothing of the surface contours throughout the periphery of the cell. The phenotype was measured by maximum likelihood estimation, based on the values of several geometrical shape descriptors. With continuous TPA treatment, the cells adopted a transformed phenotype by 2 h. The effect was maximal by 5 h but began to decline by 10 h. Shape change in the opposite direction was stimulated by treatment with the protein kinase C inhibitor staurosporine, and its effects were counteracted if the cells were simultaneously exposed to TPA. No appreciable metabolism of [20-3H]TPA occurred until 24 h after treatment. Enumerating the shape descriptors whose values composed the transformed phenotype indicated that the TPA-stimulated changes were qualitatively similar to those accompanying oncogenic transformation. The subsequent alterations, however, involved few of the variables that composed the transformed phenotype and therefore did not represent a true reversal of the change. Changes observed up to 5 h were not dependent on new RNA synthesis but required continued protein synthesis.


Assessing the effects of different prebiotic dietary oligosaccharides in sheep milk ice cream.
The objective of this study was to assess the effects of different prebiotic dietary oligosaccharides (inulin, fructo-oligosaccharide, galacto-oligossacaride, short-chain fructo-oligosaccharide, resistant starch, corn dietary oligosaccharide and polydextrose) in non-fat sheep milk ice cream processing through physical parameters, water mobility and thermal analysis. Overall, the fat replacement by dietary prebiotic oligosaccharides significantly decreased the melting time, melting temperature and the fraction and relaxation time for fat and bound water (T22) while increased the white intensity and glass transition temperature. The replacement of sheep milk fat by prebiotics in sheep milk ice cream constitutes an interesting option to enhance nutritional aspects and develop a functional food.


Complete Sequence of the Closed Circular Extrachromosomal Element of Naegleria jadini Willaert and Ray (Strain ITMAP400).
Amoebae of the Naegleria genus carry all ribosome-encoding DNA on closed circular extrachromosomal elements (CERE). We report the sequence of the CERE of Naegleria jadini (strain Willaert and Ray).


Mass spectrometric investigations on lactate adduction to equine myoglobin.
Research focused on determining the fundamental mechanisms by which lactate influences color stability has not considered a direct effect of lactate on myoglobin. Thus, the objective of this study was to use Matrix Assisted Laser Desorption Ionization-Time of Flight Mass Spectrometry to examine lactate adduction to myoglobin. Equine oxymyoglobin and equine carboxymyoglobin (0.15mM) were incubated with sodium lactate (200mM) at 4 degrees C, pH 5.6 in 50mM sodium citrate buffer or at 37 degrees C, pH 7.4 in 50mM sodium phosphate buffer, simulating typical meat storage and physiological conditions, respectively. Controls consisted of myoglobin plus a volume of deionized water equivalent to that used to deliver the lactate treatments. No peaks corresponding to lactate-Mb adducts could be detected in the mass spectra of samples incubated up to 360min at pH 7.4, 37 degrees C or 8days at pH 5.6 and 4 degrees C. Our results suggest that lactate did not form covalent adducts with equine oxy- and carboxy-myoglobin.


Black Soldier Fly Larva Fat in Broiler Chicken Diets Affects Breast Meat Quality.
This study aimed to evaluate the dose-dependent effect of black soldier fly (BFL) larvae fat inclusion in broiler chicken diets on breast meat quality. Four hundred 1-day-old male birds (Ross 308) were assigned to the following four treatments (10 replicates with 10 birds each): HI0, a basal diet without dietary fat inclusion, and HI03, HI06, and HI09, basal diets enriched with 30 g/kg, 60 g/kg, and 90 g/kg of BSF larvae fat, respectively. Principal component analysis showed noticeable differentiation between the selected plant, animal, and insect-origin dietary fats. The BSF fat exhibits a strong relationship with saturated fatty acids (SFAs), resulting in a high concentration of C12:0 and C14:0. The fatty acid (FA) profile in breast muscle obtained from broilers fed diets with increasing insect fat inclusion showed a significant linear effect in terms of C12:0, C15:0, C18:2, C18:3n6, and total FAs. The proportion of dietary insect fat had a quadratic effect on meat color. The water-holding capacity indices have stayed consistent with the meat color changes. Throughout the experiment, favorable growth performance results were noticed in HI06. The present study confirmed that BSF larvae fat negatively affects the n3 level in meat. However, the physicochemical indices related to consumer acceptance were not altered to negatively limit their final decision, even when a relatively high inclusion of insect fat was used.


COVID-19 Presenting with Seizures.
This case report examines a male with no previous history of seizures initially admitting to the medical service later upgraded to ICU after respiratory failure developing multiple episodes of seizures. Laboratory values on admission, neurological investigations, as well as review of current literature on COVID-19 encephalitis is provided.


Resistance to Eimeria bovis produced after chemotherapy of experimental infections in calves.
Eighteen Holstein-Friesian four week old calves were inoculated with 5 X 10(5) sporocysts of Eimeria bovis by stomach tube. The calves were divided into three equal groups. The first group was treated with monensin, 1 mg kg-1 body weight daily, from the 10th-20th day inclusive after infection; the second group was treated with amprolium, 10 mg kg-1 body weight daily, for the same period of time and the third group acted as infected controls. Both drugs were for the most part effective in preventing clinical signs, in suppressing reduced rates of weight and in reducing oocyst production. The calves of all three groups were resistant to the second infection given 35 days after the first infection with E. bovis as measured by rates of weight gain, fecal oocyst output and lack of clinical signs.


Optimal allocation in annual plants with density-dependent fitness.
We study optimal two-sector (vegetative and reproductive) allocation models of annual plants in temporally variable environments that incorporate effects of density-dependent lifetime variability and juvenile mortality in a fitness function whose expected value is maximized. Only special cases of arithmetic and geometric mean maximizers have previously been considered in the literature, and we also allow a wider range of production functions with diminishing returns. The model predicts that the time of maturity is pushed to an earlier date as the correlation between individual lifetimes increases, and while optimal schedules are bang-bang at the extremes, the transition is mediated by schedules where vegetative growth is mixed with reproduction for a wide intermediate range. The mixed growth lasts longer when the production function is less concave allowing for better leveraging of plant size when generating seeds. Analytic estimates are obtained for the power means that interpolate between arithmetic and geometric mean and correspond to partially correlated lifetime distributions.


Magnetic fields exhibit a positive impact on lipid and biomass yield during phototrophic cultivation of Spirulina sp.
This study aimed to investigate the effects of magnetic field (MF) application (1, 12 and 24 h day -1) to Spirulina sp. LEB 18 in different photosynthesis cycles (dark and/or light) during short (15 days) and long periods (50 days) of cultivation. MF application was performed via two sources: ferrite magnets and solenoids. At the end of cultivation, the biomass was characterized in terms of lipids, proteins, and carbohydrates. In the 15 day cultures, the highest maximum biomass concentrations (2.06 g L-1 and 1.83 g L-1) were observed when 30 mT was applied for 24 h day -1 or 12 h day -1 (on the light cycle), respectively. MF application throughout cultivation (24 h day -1) for more than 30 days is not recommended. In all conditions, there was an increase in the lipid concentration (from 14 to 45%). The protein profile suggested important changes in photosystems I and II due to MF application. Cell morphology was not altered by MF application. In conclusion, the effects on the metabolism of Spirulina sp. are directly related to the photosynthesis cycle and time period in which the MF was applied.


Giant aneurysms of coronary arteries and saphenous vein grafts: angiographic findings and histopathological correlates.
Giant aneurysms that develop in native coronary arteries or saphenous vein grafts are morphologically defined as abnormally expanded outpouching vascular structures >4 cm in diameter. The location, morphology, and content of giant aneurysms account for adverse cardiovascular effects. Two cases of giant aneurysms were studied comprehensively by noninvasive and invasive cardiac methods and subsequent histopathology. The first patient had a giant aneurysm that developed over a course of several years in a saphenous vein graft whereas the second patient had a giant aneurysm occurring within a native coronary artery. Accompanying clinical and angiographic findings are described. Atherosclerosis and thrombosis were among the prominent histopathological findings. Atherosclerosis and associated thrombosis within giant aneurysms result in obstruction of flow, distal embolization, and development of acute coronary syndromes including recurrent ischemic chest pain, unstable angina, and acute myocardial infarction. The options for clinical management of giant coronary or vein graft aneurysms include surgical excision, percutaneous coil occlusion and stent deployment, or medical approach.


Treatment of Ischemia-Reperfusion Injury of the Skin Flap Using Human Umbilical Cord Mesenchymal Stem Cells (hUC-MSCs) Transfected with "F-5" Gene.
BACKGROUND Recent studies have shown that skin flap transplantation technique plays an important role in surgical procedures. However, there are many problems in the process of skin flap transplantation surgeries, especially ischemia-reperfusion injury, which directly affects the survival rate of the skin flap and patient prognosis after surgeries. MATERIAL AND METHODS In this study, we used a new method of the "stem cells-gene" combination therapy. The "F-5" gene fragment of heat shock protein 90-α (Hsp90-α) was transfected into human umbilical cord mesenchymal stem cells (hUC-MSCs) by genetic engineering technique. RESULTS The synergistic effects of "F-5" gene and hUC-MSCs in the treatment of ischemia-reperfusion injury of the skin flap were confirmed by histochemical and immunohistochemical methods. CONCLUSIONS This study showed that the hUC-MSCs transfected with "F-5" gene can effectively improve the repair of ischemia-reperfusion injury.


A healthy weight intervention for children in a dental setting: a pilot study.
There are twice as many U.S. children who are overweight or at risk of being overweight as there were 20 years ago. Dental care professionals have an opportunity to provide obesity prevention interventions to their patients. The authors present a dental office-based healthy weight intervention (HWI) protocol designed for all children. Preventive dental office visits are an opportunity for dental care professionals to provide HWIs to children. The authors found that the HWI they described is feasible and can be well-accepted in a pediatric dental care setting. Caregivers and dental care providers said they considered the HWI to be useful, and it was well-accepted by children. Healthy eating and lifestyle behaviors can have a positive effect on systemic health and oral health. Better food choices can reduce dental caries, and the prevention of obesity-related systemic diseases, particularly diabetes, can help patients maintain good oral health.


Detergent and detergent-free methods to define lipid rafts and caveolae.
Lipid rafts and their related membrane vesicular structures, caveolae, are cholesterol- and sphingolipid-rich microdomains of the plasma membrane that have attracted considerable interest because of their ability to concentrate numerous signaling proteins. Efforts to define the proteins that reside in lipid rafts and caveolae as well as investigations into the functional role of these microdomains in signaling, endocytosis, and other cellular processes have led to the hypothesis that they compartmentalize or prearrange molecules involved in regulating these pathways. This chapter describes biochemical approaches for defining lipid rafts and caveolae. Included are detergent- and nondetergent-based fractionations on sucrose-density gradients that isolate buoyant lipid rafts and caveolae as well as caveolin antibody-based immunoisolation of detergent-insoluble membranes that selectively isolates caveolae and not lipid rafts. Also, a general method to disrupt lipid rafts and caveolae using beta-cyclodextrin that is useful for probing the role of these microdomains in cellular processes is described. The advantages and disadvantages of the respective approaches are discussed. Taken together, these methods are useful for defining the role of lipid rafts and caveolae in cell signaling.


Structural Analysis of Glycosylglycerolipids Using NMR Spectroscopy.
Glycosylglycerolipids are essential components of plant and bacterial membranes. These lipids exert central roles in physiological processes such as photosynthesis in plants or to maintain membrane stability in bacteria. They are composed of a glycerol backbone esterified with two fatty acids at the sn-1 and sn-2 positions, and carbohydrate moieties connected via a glycosidic bond at the sn-3 position. Nuclear magnetic resonance (NMR) spectroscopy is a state-of-the-art technique to determine the nature of the bound carbohydrates as well as their anomeric configurations. Here we describe the analysis of intact glycosylglycerolipids by NMR spectroscopy to determine structural details of their sugar head groups without the need of chemical derivatization.


[Correlation between the number of microfilaria ingested and the thickness of the peritrophic membrane of the vector in onchocercosis of the African savannah].
The fact, as previously established, that a great number of microfilariae remain trapped in the peritrophic membrane of S. damnosum, explains the low proportion of microfilariae passing into the hemocoel. However, it doesn't account for the strong "limitation phenomenon" observed in savannah. Histological analysis shows a growth of the peritrophic membrane proportionate to the number of ingested microfilariae. The microfilariae, exciting the digestive epithelium, provoke the liberation of greater quantities of peritrophic substance, thus reinforcing the peritrophic barrier.


Metformin associated lactic acidosis: incidence and clinical correlation with metformin serum concentration measurements.
The reported incidence of metformin associated lactic acidosis (MALA) in type 2 diabetes mellitus (DM) is 3-9 cases per 100,000 patient-years. In clinical practice, 22-94% of patients using metformin have contraindications to metformin, so the incidence of MALA may be higher than reported. To estimate the incidence of MALA in type 2 DM patients by means of metformin serum concentration measurements and investigate the correlation of metformin serum concentration with the clinical outcome of MALA. MALA cases were identified by reviewing the medical records of patients with metformin serum concentrations measured between January 2000 and October 2008. MALA was defined as arterial pH <7·35 and lactate concentration >5·0 mmol/L in patients using metformin. The incidence of MALA was calculated from the number of cases and the at risk population. The correlation coefficient between the metformin and lactate concentration was calculated by linear regression. The relationship between metformin serum concentration, lactate concentration and outcome was examined by calculating the mean metformin and lactate concentration in patients who survived and those who died. The Student's t-test was used to compare groups. In 29 patients metformin serum concentration was measured, 16 had MALA. Eleven of the 16 MALA cases (69%) had risk factors for lactic acidosis in their medical history, 13 cases (81%) had renal failure on admission. The incidence of MALA was estimated at 47 per 100,000 patient-years, this is 5-16 times higher than previously reported. This may be explained by the use of metformin in the presence of risk factors for lactic acidosis. Survivors had a higher metformin serum concentration (18·9 mg/L) than non-survivors (2·9 mg/L, P = 0·006) which can be explained by less severe underlying disease in patients who survived MALA, rather than an effect of metformin itself. The incidence of MALA estimated from metformin serum concentration measurements in type 2 DM patients is 5-16 times higher than reported in literature. MALA is probably caused by the frequent use of metformin in the presence of risk factors for lactic acidosis. Metformin serum concentration measurements may aid in the timely diagnosis and therapy of MALA. The outcome of MALA is determined by the severity of the underlying disease, rather than by metformin itself.


Well-Defined NHC-Ni Complexes as Catalysts: Preparation, Structures and Mechanistic Studies in Cross-Coupling Reactions.
Developmental studies are ongoing to discover a way to utilise new N-heterocyclic carbene (NHC)-Ni complexes as catalysts. Using a bulky NHC ligand, it is possible to synthesise an NHC/phosphine-mixed heteroleptic Ni(II) complex, which can serve as an excellent catalyst for various cross-coupling reactions. During the study of the reaction mechanisms using these Ni complexes, NHC-Ni(I) complexes were accidentally discovered, and it was observed that they exhibit excellent catalytic activity for cross-coupling reactions. The possibility of the presence of NHC-Ni(I) intermediates in these catalytic reaction pathways has been experimentally demonstrated. Depending on the type of reaction, dinuclear Ni(I) and mononuclear Ni(I) complexes can function as intermediates. The results of the investigation of each reaction mechanism are summarised, and the prospects are described.


Multidimensional, High Precision Measurements of Beam Single Spin Asymmetries in Semi-inclusive π^{+} Electroproduction off Protons in the Valence Region.
High precision measurements of the polarized electron beam-spin asymmetry in semi-inclusive deep inelastic scattering (SIDIS) from the proton have been performed using a 10.6 GeV incident electron beam and the CLAS12 spectrometer at Jefferson Lab. We report here a high precision multidimensional study of single π^{+} SIDIS data over a large kinematic range in Bjorken x, fractional energy, and transverse momentum of the hadron as well as photon virtualities Q^{2} ranging from 1-7 GeV^{2}. In particular, the structure function ratio F_{LU}^{sinϕ}/F_{UU} has been determined, where F_{LU}^{sinϕ} is a twist-3 quantity that can reveal novel aspects of emergent hadron mass and quark-gluon correlations within the nucleon. The data's impact on the evolving understanding of the underlying reaction mechanisms and their kinematic variation is explored using theoretical models for the different contributing transverse momentum dependent parton distribution functions.


A province-wide HIV initiative to accelerate initiation of treatment-as-prevention and virologic suppression in British Columbia, Canada: a population-based cohort study.
In 2010, HIV treatment as prevention (TasP), encompassing widespread HIV testing and immediate initiation of free antiretroviral treatment (ART), was piloted under the Seek and Treat for Optimal Prevention of HIV/AIDS initiative (STOP) in British Columbia, Canada. We compared the time from HIV diagnosis to treatment initiation, and from treatment initiation to first virologic suppression, before (2005-2009) and after (2010-2016) the implementation of STOP. In this population-based cohort study, we used longitudinal data of all people living with an HIV diagnosis in BC from 1996 to 2017. We included those aged 18 years or older who had never received ART and had received an HIV diagnosis in the 2005-2016 period. We defined the virologic suppression date as the first date of at least 2 consecutive test results within 4 months with a viral load of less than 200 copies/mL. Negative binomial regression models assessed the effect of STOP on the time to ART initiation and suppression, adjusting for confounders. All p values were 2-sided, and we set the significance level at 0.05. Participants who received an HIV diagnosis before STOP (n = 1601) were statistically different from those with a diagnosis after STOP (n = 1700); 81% versus 84% were men (p = 0.0187), 30% versus 15% had ever injected drugs (p < 0.0001), and 27% versus 49% had 350 CD4 cells/μL or more at diagnosis (p < 0.0001). The STOP initiative was associated with a 64% shorter time from diagnosis to treatment (adjusted mean ratio 0.36, 95% confidence interval [CI] 0.34-0.39) and a 21% shorter time from treatment to suppression (adjusted mean ratio 0.79, 95% CI 0.73-0.85). In a population with universal health coverage, a TasP intervention was associated with shorter times from HIV diagnosis to treatment initiation, and from treatment initiation to viral suppression. Our results show accelerating progress toward the United Nations' 90-90-90 target of people with HIV who have a diagnosis, those who are on antiretroviral therapy and those who are virologically suppressed, and support the global expansion of TasP to accelerate the control of HIV/AIDS.


Spectroelectrochemical study of cytochrome c oxidase: pH and temperature dependences of the cytochrome potentials. Characterization of site-site interactions.
The cytochrome a and a3 sites in uninhibited, detergent-solubilized cytochrome c oxidase have been studied under a wide range of conditions using thin-layer spectroelectrochemistry. The observed absorbance changes at the alpha and Soret absorbance maxima have been used together to estimate the extents of reduction of cytochromes a and a3, using the absorbance properties of these cytochromes deduced from previous measurements employing ligand inhibition of cytochrome a3. The resulting Nernst plots, combined with the results of parallel studies on the carbon monoxide-inhibited enzyme (Ellis, W. R., Jr., Wang, H., Blair, D. F., Gray, H. B., and Chan, S. I. (1986) Biochemistry 25, 161-167; Wang, H., Blair, D. F., Ellis, W. R., Jr., Gray, H. B., and Chan, S. I. (1986) Biochemistry 25, 167-171), indicate that the cytochrome a site participates in anticooperative thermodynamic interactions which involve all three of the other metal sites in the protein. Using an analysis which resolves the intrinsic thermodynamic properties of the cytochromes from the effects of the intersite interactions, the pH, temperature, and ionic strength dependences of the cytochrome reduction potentials have been measured. The standard entropy of reduction of cytochrome a in the native enzyme is large and negative, in agreement with measurements on the carbon monoxide-inhibited enzyme. The reduction potential of cytochrome a is only moderately (less than -30 mV/pH unit) dependent upon pH, which implies that its reduction is linked to the uptake, on the average, of only about 0.5 protons at pH 7.0, and significantly less at the higher pH values relevant to the mitochondrial matrix. The thermodynamic properties of cytochrome a3 were found to be different in the two enzyme batches studied: in one batch, the cytochrome a3 reduction potential decreased steeply (about -56 mV/pH unit) with increasing pH, indicating stoichiometric (1 H+/e-) coupling of protonation to reduction. In the other batch, the cytochrome a3 potential was insensitive to pH below pH 7.5 and decreased at higher pH values in a manner suggesting coupling to an ionizable group with pKa near 7.8. The temperature dependence of the cytochrome a3 reduction potential indicates that its standard entropy of reduction is more positive than that of myoglobin, another high-spin metalloprotein heme, and significantly more positive than that of cytochrome a.(ABSTRACT TRUNCATED AT 400 WORDS)


The neurolinguistic approach to awake surgery reviewed.
Intraoperative direct electrical stimulation (DES) is increasingly used in patients operated on for tumours in critical language areas. Although a positive impact of DES on postoperative linguistic outcome is generally advocated, the literature is only scantily documented with information about the linguistic methods applied in awake surgery. This article critically reviews the neurolinguistic procedures currently used in awake studies. Based on an extensive review of the literature, an overview is given of the language mapping techniques applied in brain tumour surgery. Studies investigating linguistic testing and outcome in awake surgery were analysed. Information about the timing of the assessment(s), the linguistic tasks, the linguistic stimuli and the indication for awake surgery was also discussed. Intraoperative DES remains the 'gold standard' for language mapping, but pre- and postoperative non-invasive mapping methods are important adjuncts. In the pre- and postoperative phase, standardised linguistic test batteries are generally used to assess language function. In the intraoperative phase, only naming and number counting are commonly applied. Most often no detailed information about the linguistic stimuli is provided and no standardised protocols measuring different linguistic levels have been described. Awake surgery with DES is a useful tool for preserving linguistic functions in patients undergoing surgery in critical brain regions. However, no studies exist that apply a well-balanced and standardised linguistic protocol to reliably identify the critical language zones. The availability of a standardised linguistic protocol might substantially increase intraoperative comfort and might improve outcome and quality of life.


Triglyceride glucose index: A new biomarker in predicting cardiovascular risk.
Insulin resistance can be assessed by the Triglyceride-Glucose Index (TyG), a simple, low-cost, and easy-to-apply method. To assess the predictive capacity of the TyG index about cardiovascular risk and identify its cutoff point in a population at cardiometabolic risk. Cross-sectional study with 264 individuals at cardiometabolic risk (54.9% women, age: 43.1 ± 16.3 years). Demographic, anthropometric, clinical-laboratory, and lifestyle data were collected. The TyG index was determined using the formula Ln [fasting triglycerides (mg/dL) × fasting plasma glucose (mg (dL)/2]. The ten-year cardiovascular risk was assessed by the Framingham risk score (FRS). The receiver operating characteristic curve (ROC) was used to define the cutoff point for the TyG index, and the associations were tested by Poisson regression. ROC curve analysis indicated an area under the curve of 0.678 (95% CI = 0.618-0.734; p < 0.001), with a cutoff of 9.04 (sensitivity = 62.5%, specificity = 66.7%, positive predictive value = 29.4% and negative predictive value = 88.9%). Elevated TyG values (≥9.04) were positively associated with cardiometabolic risk factors (total cholesterol, LDL, VLDL, uric acid, alanine aminotransferase, aspartate aminotransferase, waist-hip ratio, systolic blood pressure, HOMA-IR, smoking, metabolic syndrome, diabetes, and hepatic steatosis). After adjustment for confounding factors, individuals with high TyG showed an increase of 69% (RP = 1.69; 95%CI = 1.03-2.78) in the prevalence of intermediate/high risk by FRS, compared to those with low TyG. The TyG index showed a good predictive capacity for cardiovascular risk in ten years assessed by the FRS.


Effects of arsenic species and concentrations on arsenic accumulation by different fern species in a hydroponic system.
Two hydroponic experiments were conducted to evaluate factors affecting plant arsenic (As) hyperaccumulation. In the first experiment; two As hyperaccumulators (Pteris vittata and P. cretica mayii) were exposed to 1 and 10 mg L(-1) arsenite (AsIII) and monomethyl arsenic acid (MMA) for 4 wk. Total As concentrations in plants (fronds and roots) and solution were determined In the second experiment P. vittata and Nephrolepis exaltata (a non-As hyperaccumulator) were exposed to 5 mgL(-1) arsenate (AsV) and 20 mgL(-1) AsIIIfor 1 and 15 d. Total As and AsIII concentrations in plants were determined Compared to P. cretica mayii, P. vittata was more efficient in arsenic accumulation (1075-1666 vs. 249-627mg kg(-1) As in the fronds) partially because it is more efficient in As translocation. As translocation factor (As concentration ratio in fronds to roots) was 3.0-5.6 for P. vittata compared to 0.1 to 4.8 for P. cretica. Compared to N. exaltata, P. vittata was significantly more efficient in arsenic accumulation (38-542 vs. 4.8-71 mg kg(-1) As in thefronds) as well asAs translocation (1.3-5.6 vs. 0.2-0.5). In addition, P. vittata was much more efficient in As reduction from AsV to AsIII (83-84 vs. 13-24% AsIII in the fronds). Little As reduction occurred after 1-d exposure to AsV in both species indicates that As reduction was not instantaneous even in an As hyperaccumulator. Our data were consistent with the hypothesis that both As translocation and As reduction are important for plant As hyperaccumulation.


Evaluation of cardiorespiratory effects of combinations of dexmedetomidine and atropine in cats.
The cardiovascular effects of dexmedetomidine alone or in combination with atropine were studied in six cats. Cats underwent four treatments in a randomized crossover design as follows: DEX15, saline+dexmedetomidine 15microg/kg; DEX30, saline+dexmedetomidine 30microg/kg; ADEX15, atropine+dexmedetomidine 15microg/kg; ADEX30, atropine+dexmedetomidine 30microg/kg. Pulse rate (PR) and systolic arterial pressure (SAP) decreased in DEX15 and DEX30. Premedication with atropine was effective in preventing bradycardia (PR<100 beats/min) and resulted in a biphasic effect in blood pressure. Hypertension was followed by a gradual decrease in SAP. Rate pressure product decreased in DEX15 and DEX30 whereas in ADEX15 and ADEX30 it remained within baseline values for at least 60min. Although premedication with atropine in cats sedated with dexmedetomidine prevents bradycardia, it induces hypertension and increases myocardial oxygen consumption. The magnitude of cardiovascular effects produced by dexmedetomidine in cats does not seem to be dose-related.


Pregnancy outcomes in women with polycystic ovary syndrome: a metaanalysis.
The purpose of this study was to examine which maternal and neonatal complications are associated with polycystic ovary syndrome (PCOS) in pregnant women. The studies that were included compared pregnancy outcomes between women with PCOS and those without diagnosed PCOS. Our primary outcomes included gestational diabetes mellitus, pregnancy-induced hypertension, and preeclampsia. Secondary outcomes included cesarean delivery rates, operative vaginal delivery rates, preterm delivery, small-for-gestational-age (SGA) infants and large-for-gestational-age infants. We found that PCOS in pregnancy was associated with higher rates of gestational diabetes mellitus, pregnancy-induced hypertension, preeclampsia, preterm delivery, cesarean delivery, operative vaginal delivery, SGA, and large-for-gestational age. Only gestational diabetes mellitus, pregnancy-induced hypertension, preeclampsia, preterm delivery, and SGA infants were found to be statistically significant. This metaanalysis confirms the higher association of pregnancy complications and PCOS compared with patients who do not have PCOS. Additionally, there may be a stronger association between PCOS and hypertensive disorders than has been shown previously.


Country adherence to WHO recommendations to improve the quality of HIV diagnosis: a global policy review.
Ensuring a correct and timely HIV diagnosis is critical. WHO publishes guidelines on HIV testing strategies that maximise the likelihood of correctly determining one's HIV status. A review of national HIV testing policies in 2014 found low adherence to WHO guidelines. We updated this review to determine adherence to current recommendations. We conducted a comprehensive policy review through April 2018. We extracted data on HIV testing strategies, recommendations on HIV retesting prior to antiretroviral therapy (ART) initiation and pre-exposure prophylaxis (PrEP)-related HIV testing information. Descriptive analyses disaggregated by region were conducted to ascertain adherence to recommendations and to describe testing strategy characteristics. Of 91 policies included, 26% (n=24/91) adhered to WHO recommendations. Having a two-assay testing strategy to rule-in HIV infection as opposed to the recommended three-assay testing strategy was a major reason for non-adherence. Of 72 country policies providing sufficient information, 31% (n=22) recommended retesting for HIV prior to initiating ART. Of 25 countries and two regions reporting PrEP-related HIV testing guidelines, almost all recommended testing prior to initiating PrEP and every 3 months during PrEP use. Global adherence to WHO recommendations for HIV testing strategies have improved since 2014 but remain low. We found adherence existed on a continuum. Such a system provides insights into how countries can move towards adherence by making relatively minor changes to testing strategies. Guidance from WHO on the role of new HIV testing technologies within testing algorithms and identifying ways to simplify testing guidance is warranted.


G-6A polymorphism of the angiotensinogen gene and its association with left ventricular mass in asymptomatic young adults from a biethnic community: the Bogalusa Heart Study.
Angiotensinogen (AGT), the precursor of angiotensin II and a rate limiting factor in the renin-angiotensin system, is implicated in left ventricular hypertrophy, as angiotensin II is a potent stimulator of cardiac growth. A genetic variant (G-6A) in the proximal promoter region of the AGT gene may be particularly important for changes in left ventricular mass (LVM). However, previous findings associating this variant with LVM among relatively older adults with cardiovascular morbidity are inconsistent and contradictory. This study examined the effect of G-6A polymorphism on LVM in a biethnic (African American and white), community-based sample of 362 asymptomatic younger adults (mean age 32.5 years, 71% white, 39% male). Two-dimensional M-mode echocardiography was used to assess LVM, and the indexation of LVM for height(2.7) (LVMI) was used to adjust for body size. The frequency of the variant A(-6) allele was higher in subjects of African American than in white ethnicity (0.819 v 0.439, P < .0001), with carriers (GA+AA) representing 97.0% of African American as compared to 66.6% of white subjects. After adjusting for age, ethnicity (for total sample), gender, body mass index, systolic BP, and homeostasis model assessment index of insulin resistance, mean levels for both LVM and LVMI showed a significant decreasing trend with increasing gene dosage of the A(-6) allele in white subjects, African American subjects, and the total sample. These results indicate that the A(-6) allele frequency differs markedly between African Americans and white individuals, and that the variant allele modulates LVM and LVMI in a beneficial manner in asymptomatic young adults of white and African American ethnicities.


Long-term-desensitization of prostacyclin receptors is independent of the C-terminal tail.
Persistent stimulation of the G(s) protein-coupled prostacyclin receptor (IP-R) causes its slow desensitization in a variety of cell types, a significant desensitization requiring several hours. To evaluate the role of the human IP-R C-terminus in desensitization and agonist-induced internalization, a C-terminally truncated hIP-receptor was generated. The C-terminal 68 amino acid residues were deleted by introduction of a stop codon for exchange of the original S319 codon (termed D318 mutant). Wild-type (WT) and truncated receptor were expressed in COS1 cells. Pretreatment of cells with the stable prostacyclin mimetic cicaprost (200 nM) desensitized cAMP production via WT and D318 receptors to similar extents. The cAMP response of WT and D318, respectively, was reduced by approximately 50% of maximal cAMP formation after 8 hr of continuous agonist stimulation, indicating significant long-term desensitization. Moreover, agonist-promoted sequestration of WT and D318 C-terminally tagged with green fluorescent protein was demonstrated, indicating that receptor internalization was not prevented by truncation of the C-terminus. These results demonstrated that long-term desensitization and sequestration of hIP-R did not depend on structures located in the hIP-R C-terminus.


Design of a dynamic transcranial magnetic stimulation coil system.
To study the brain activity at the whole-head range, transcranial magnetic stimulation (TMS) researchers need to investigate brain activity over the whole head at multiple locations. In the past, this has been accomplished with multiple single TMS coils that achieve quasi whole-head array stimulation. However, these designs have low resolution and are difficult to position and control over the skull. In this study, we propose a new dynamic whole-head TMS mesh coil system. This system was constructed using several sagittal and coronal directional wires. Using both simulation and real experimental data, we show that by varying the current direction and strength of each wire, this new coil system can form both circular coils or figure-eight coils that have the same features as traditional TMS coils. Further, our new system is superior to current coil systems because stimulation parameters such as size, type, location, and timing of stimulation can be dynamically controlled within a single experiment.


Physical exercise modulates the astrocytes polarization, promotes myelin debris clearance and remyelination in chronic cerebral hypoperfusion rats.
White matter damage is the main pathological feature of chronic cerebral hypoperfusion (CCH) and glial activation is crucial in this process. Physical exercise has protective effects on CCH, but the mechanism is unclear. Therefore, this study focuses on investigating the influence of physical exercise on activated astrocytes polarization and its role in CCH. Rats were given wheel running 48 h after 2VO (2 vessel occlusion) surgery. The cognitive function was evaluated by Morris water maze and novel object recognition test. Inflammatory cytokines expressions were detected by ELISA. Astrocytes polarization was analyzed by immunofluorescence. Myelin debris clearance and remyelination were detected by immunofluorescence and transmission electron microscopy. Astrocytes were activated and mainly switched to A1 phenotype in rats 2 and 3 months after 2VO. Myelin debris deposition and limited remyelination can be observed at the corresponding time. Whereas physical exercise can improve the cognitive function of 2VO rats, downregulate the expression of inflammatory factors IL-1α, C1q and TNF, upregulate the release of TGFβ, and promote activated astrocytes transformation from A1 to A2 phenotype. In addition, it can also enhance myelin debris removal and remyelination. These findings suggest that the benefits of physical exercise on white matter repair and cognition improvement may be related to its regulation of astrocytes polarization, which contributes to myelin debris clearance and effective remyelination in CCH.


A Promising Route Towards Improvement of Homeless Young People's Access to Mental Health Services: The Creation and Evolution of an Outreach Service Network in Montréal.
Youth homelessness is a complex phenomenon as well as an important public health issue often compounded by mental illness of varying severity, in turn creating numerous deleterious consequences. While emergency health services usage remains high, access to mental health services is arduous and conventional interventions often fall short on providing integrated care and seldom lead to sustained positive outcomes for this group. From this observation, clinicians in Montreal, Canada, initiated collaborative meetings, eventually attended by a growing number of institutional and community stakeholders working with homeless youth. Acknowledging the unique needs of this population, the Réseau d'intervention de proximité auprès des Jeunes de la Rue (RIPAJ) or Montreal Homeless Youth Network was created to engage and seamlessly connect youth with the right resources within the network including mental health services amongst others. The genesis, philosophy and unique features of RIPAJ that allow for effective and cohesive interventions as well as future directions are discussed.


Diacylglycerol oil ingestion in type 2 diabetic patients with hypertriglyceridemia.
Coronary arteriosclerotic heart disease frequently develops in patients with diabetes. Decreases in [corrected] serum high-density lipoprotein cholesterol (HDL-C) [corrected] concentration and low-density lipoprotein (LDL) particle size, accompanied by hypertriglyceridemia, are associated with the onset of atherosclerosis. We recently reported that hypertriglyceridemia was significantly improved in patients with type 2 diabetes who ingested diacylglycerol (DAG) oil. The effect on variables, including LDL particle size related to lipid metabolism, however, was not examined. The present study investigated the effects on these variables in more detail. Patients with type 2 diabetes (n = 24) were assigned to receive DAG oil or triacylglycerol oil, and a 3-mo, single-blind, controlled study was performed. Patients replaced cooking oil in their daily diet with DAG or triacylglycerol oil, and anthropometry and blood sampling were performed at monthly intervals. There were no significant differences in calorie intake or amount of test oil ingested between groups. Waist circumference and serum triacylglycerol concentrations were significantly lower and serum concentrations of high-density lipoprotein cholesterol and apolipoprotein-AI were significantly higher in the DAG oil group than in the triacylglycerol oil group. Plasma plasminogen activator inhibitor-1 concentrations were significantly lower in the DAG oil group. LDL particle size tended to increase in the DAG oil group and was significantly larger in patients who had a small initial LDL particle size (<25.5 nm). There were no significant differences in variables related to glucose metabolism or in serum concentration of free fatty acids or total ketone bodies. These results indicate that DAG oil may be useful for patients who have type 2 diabetes in the management of obesity and lipid abnormalities.


Scope insensitivity in contingent valuation of complex environmental amenities.
It has been argued that respondents in contingent valuation (CV) surveys, asked to value complex environmental amenities, will state willingness to pay (WTP) independently of the scope of the project. Such insensitivity to scope would be at odds with rational choice, and could therefore imply that CV is not a theoretically valid method for biodiversity valuation. The scope test in the present CV study was applied to endangered species preservation. Respondents were split in four sub-samples facing different scopes of endangered species preservation. The design allowed for both external and internal scope tests. Furthermore, the tests were split according to elicitation format. Of four external tests of insensitivity to scope, one was rejected, two gave mixed results, depending on either the type of test or elicitation format, and for the last one the null hypothesis could not be rejected. Of five internal tests, insensitivity to scope was rejected in three cases, one test gave mixed results, and one could not be rejected. Survey design features of the CV study, especially an unfamiliar sub-group of endangered species, could explain the apparent insensitivity to scope observed.


Frailty and Cardiovascular Mortality: A Narrative Review.
The goal of the narrative review is to provide an overview of the epidemiology of frailty in cardiovascular disease and cardiovascular mortality and discuss applications of frailty in cardiovascular care of older adults. Frailty is highly prevalent in older adults with cardiovascular disease and is a robust, independent predictor of cardiovascular death. There is a growing interest in using frailty to inform management of cardiovascular disease either through pre- or post-treatment prognostication or by delineating treatment heterogeneity in which frailty serves to distinguish patients with differential harms or benefits from a given therapy. Frailty can enable more individualized treatment in older adults with cardiovascular disease. Future studies are needed to standardize frailty assessment across cardiovascular trials and enable implementation of frailty assessment in cardiovascular clinical practice.


Modulation of arthritis in rats by Toxicodendron pubescens and its homeopathic dilutions.
Toxicodendron pubescens P. Mill (Anacardiaceae) known in homeopathy as Rhus toxicodendron (Rhus tox) is used as an anti-inflammatory medicine in homeopathic practice. In this study, Rhus tox in its crude form and homeopathic dilutions (3cH, 6cH, 30cH, 200cH) was evaluated for effects on Complete Freund's Adjuvant (CFA) induced arthritis in rats. We assessed the severity of arthritis through observations including inflammatory lesions, body and organ weight and hematological parameters including C-reactive protein (CRP). Blinded radiological analysis of the affected joints and pain intensity determination was also carried out. Rhus tox protected rats from CFA-induced inflammatory lesions, body weight changes and hematological alterations. Rhus tox protected against radiological joint alterations due to arthritis. Arthritic pain scores were also favorably affected by Rhus tox. All the dilutions of Rhus tox including crude form showed anti-arthritic activity. The maximum protective effect was evident in the crude form at 10mg/kg/day, by mouth. This study supports claims in the homeopathic literature on the role of Rhus tox and its ultra dilutions in the treatment of arthritis and associated pain. Further study is needed to explain this anti-arthritic effect of Rhus tox.


Hepatoprotective effect of linagliptin against liver fibrosis induced by carbon tetrachloride in mice.
The current study aimed to investigate linagliptin for its potential role in the prevention of liver fibrosis progression. Balb-C mice were randomly allocated into five groups (10 each): (i) control; (ii) mice were injected intraperitoneally with 50 μL carbon tetrachloride (CCl4) in corn oil in a dose of 0.6 μL/g three times per week for four weeks; (iii) linagliptin was administered orally in a daily dose of 10 mg/kg simultaneously with CCl4; (iv) silymarin was administered orally in a daily dose of 200 mg/kg concomitantly with CCl4; and (v) only linagliptin was administered. Hepatic injury was manifested in the CCl4 group by elevation of biochemical parameters (alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP)), and hepatic fibrosis was evident histopathologically by increased METAVIR score and immunostaining expression of alpha-smooth muscle actin (α-SMA), as well as increased liver tissue oxidative stress parameters, transforming growth factor-β1 (TGF-β1), and mammalian target of rapamycin (mTOR). Linagliptin was able to stop the progression of liver fibrosis, evident histopathologically with reduced METAVIR score and α-SMA expression. The possible mechanism may be via suppression of oxidative stress, TGF-β1, and mTOR, which was associated with improvement of serum biochemical parameters ALT and AST. In conclusion, linagliptin might help to protect the liver against persistent injury-related consequences.


A highly sensitive detection method for immunohistochemistry using biotinylated tyramine.
A highly sensitive method for light microscopic immunohistochemistry is described. The increased sensitivity compared with current methodologies is based on the horseradish peroxidase-catalysed deposition of biotinylated tyramine at the sites of immunoreactivity, followed by the detection of the biotin with streptavidin biotin horseradish peroxidase complex. This method is of general applicability in immunohistochemistry and has several important advantages over currently used immunohistochemical detection procedures. The most significant advantage is that several antibodies which to data have been non-reactive, even in antigen-retrieval formalin-fixed, was-embedded sections, now show strong and reproducible immunoreactivity using biotinylated tyramine amplification. In addition, many other antibodies can be used at significantly higher dilutions.


A 6-month follow-up after constraint-induced movement therapy with and without transfer package for patients with hemiparesis after stroke: a pilot quasi-randomized controlled trial.
To investigate the long-term effects of the 'transfer package' in constraint-induced movement therapy, which is an optional protocol to facilitate actual use of the trained affected arm in activities of daily living. A pilot quasi-randomized controlled trial with a blinded single assessor with six-month follow-up. Hospitalized care at university hospital. Twenty-one post-stroke patients were quasi-randomized to either a group with transfer package during constraint-induced movement therapy or a control group (without transfer package). The transfer package group received 4.5 hours of intensive task training and 0.5 hours of transfer package whereas the control group received 5.0 hours of intensive task training per day during 10 consecutive weekdays. Arm function was measured with Fugl-Meyer Assessment and Amount of Use score of Motor Activity Log. Twenty-three patients were quasi-randomized, but data from two patients were missing from the long-term follow-up. Both groups showed increase in arm function postintervention. However, at six months' follow-up only the transfer package group showed consistent increase in arm function (with transfer package group versus control group; Fugl-Meyer Assessment, mean (± SD) from 48.6 ± 7.8 (preintervention) to 55.7 ± 4.5 (postintervention) and 59.0 ± 3.6 (six months postintervention) versus from 49.1 ± 5.5 to 52.8 ± 6.0 and 53.3 ± 4.9, P= 0.003; Amount of Use scale of Motor Activity Log, mean from 1.3 ± 0.55 (preintervention) to 2.12 ± 0.55 (postintervention) and 2.79 ± 0.98 (six months postintervention) versus from 1.18 ± 0.70 to 1.61 ± 0.54 and 1.65 ± 0.68, P= 0.002). Our results confirmed the long-term effects of the transfer package in constraint-induced movement therapy.


Synthesis, structure-activity relationships and molecular docking studies of phenyldiazenyl sulfonamides as aromatase inhibitors.
The exploration of innovative aromatase inhibitors represents an important approach for the identification of new therapeutic treatments of breast cancer. In this respect, a series of phenyldiazenyl sulfonamides was designed, synthesized and tested. Compounds 3b, 3f and 5f showed an aromatase inhibition in the micromolar range and were evaluated in vitro on the human breast cancer cell line MCF7 by MTT assay, cytotoxicity assay (LDH release), cell cycle analysis and apoptosis, revealing a dose-dependent inhibition profile. In particular, 3f displayed the best reduction in terms of metabolic activity and an anti-proliferative effect on MCF7 cells, being blocked in the G1/S phase checkpoint. Moreover, computational studies were carried out to better understand at a molecular level of detail the rationale behind the effective binding to the active site of aromatase of the more active inhibitor 3f. The obtained results allow to consider this compound as an interesting lead for the development of a new class of non-steroidal aromatase inhibitors.


Response mechanisms to ocean warming exposure in Effrenium voratum (Symbiodiniaceae).
Ocean warming is an extreme environment event that has profound and lasting impacts on Symbiodiniaceae. However, their response mechanisms to elevated temperature exposure are poorly understood. In this study, the physiological and transcriptional responses of Effrenium voratum (Symbiodiniaceae) to ocean warming were examined. After exposure to 30 °C, no significant variations in growth, chlorophyll a, or photosynthetic and respiration rates were observed, while a higher temperature (34 °C) significantly reduced these physiological measurements. Meanwhile, lipid content and fatty acid composition were altered at high temperature (i.e., elevated degree of fatty acid saturation). Such biochemical constituents likely contributed to the mitigation of the negative effects of elevated temperatures. Furthermore, higher expression levels of genes related to the synthesis and elongation of fatty acids were detected at high temperature. The adjustment of lipids and fatty acid composition may be a potential mechanism by which E. voratum may survive under future global warming. ONE SENTENCE SUMMARY: The adjustment of lipids and fatty acid composition may be a potential mechanism by which E. voratum acclimate to future global warming.


Bibrachial plegia due to Lyme radiculopoliomyelitis-myelitis.
Nervous system involvement occurs in up to 15% of patients with Lyme disease, most commonly manifested as cranial neuropathy, lymphocytic meningitis, and or radiculoneuritis. We describe a patient with subacute radiculopoliomyelitis-myelitis matching the selective involvement of the anterior horns and roots of the cervical spinal cord seen on MRI and on electrodiagnostic studies. We demonstrate positive CSF Lyme antibodies and document a near-complete recovery with antibiotics. This case highlights the importance of recognizing an atypical presentation of Lyme disease in the setting of initial radiculitis and or myelitis, particularly given the potential for favorable outcomes with appropriate treatment.


Frontal sinus disease. IV. Cellular response to experimentally-induced infection.
The pathogenesis of chronic frontal sinusitis is poorly understood. The canine frontal sinus model was developed to isolate experimentally the variables involved. We have recently determined that blockage of the naso-frontal duct does not, by itself, produce sinusitis or mucocele experimentally. The purpose of the present investigation is to examine the histological and ultrastructural responses of the sinus mucosa to artificially-induced infection. Bone wax was implanted in the canine frontal sinus via an osteoplastic flap, and subsequently removed three months later. Radiological, histological and ultrastructural analysis of the resultant infected mucosa was performed at periods up to one year. The sinus mucosa did not return to normal up to nine months following removal of the infection-inciting foreign body. Persistent changes included epithelial and submucosal thickening, polypoid degeneration, matting of the ciliary carpet, and "bursting" of the ciliary cell bodies. In the light of this and previous experiments, an insidious cycle of events leading to irreversible frontal sinus disease is postulated, requiring the interplay of at least three variables: the infectious insults, the response of the sinus mucosa, and the variable patency of the nasofrontal duct.


Effect of "re du qing" on the activation, proliferation and membrane fluidity of lymphocytes.
Effects of Chinese Medicinal Preparation "Re Du Qing" (RDQ) on the activation, proliferation and membrane fluidity of T lymphocytes from human peripheral blood were studied by means of 3H-TdR incorporation and DPH fluorescence polarization. The results showed that "RDQ" can: 1) significantly inhibit the activation of T lymphocytes; 2) restrain the proliferation of activated T lymphoblasts in the presence of exogenous interleukin-2 (IL-2); and 3) increase the membrane fluidity of T lymphocytes and antagonize the decreased fluidity of lymphocyte membrane mediated by Con A or PHA. The functional abnormalities of T lymphocytes in some autoimmune diseases such as arthritis and the usefulness of RDQ in the treatment of these diseases were also discussed.


Connective tissue metabolism including cytokines in scleroderma.
Review of the currently published literature on systemic sclerosis emphasizes the role of adhesion molecules, growth factors, immune reactions, and aberrant fibroblast biology and metabolism in effecting vascular and connective tissue alterations in this disease and its variants.


Omnimodal topological polarization of bilayer networks: Analysis in the Maxwell limit and experiments on a 3D-printed prototype.
Periodic networks on the verge of mechanical instability, called Maxwell lattices, are known to exhibit zero-frequency modes localized to their boundaries. Topologically polarized Maxwell lattices, in particular, focus these zero modes to one of their boundaries in a manner that is protected against disorder by the reciprocal-space topology of the lattice's band structure. Here, we introduce a class of mechanical bilayers as a model system for designing topologically protected edge modes that couple in-plane dilational and shearing modes to out-of-plane flexural modes, a paradigm that we refer to as "omnimodal polarization." While these structures exhibit a high-dimensional design space that makes it difficult to predict the topological polarization of generic geometries, we are able to identify a family of mirror-symmetric bilayers that inherit the in-plane modal localization of their constitutive monolayers, whose topological polarization can be determined analytically. Importantly, the coupling between the layers results in the emergence of omnimodal polarization, whereby in-plane and out-of-plane edge modes localize on the same edge. We demonstrate these theoretical results by fabricating a mirror-symmetric, topologically polarized kagome bilayer consisting of a network of elastic beams via additive manufacturing and confirm this finite-frequency polarization via finite element analysis and laser-vibrometry experiments.


Outcomes after induction chemotherapy in patients with acute myeloid leukemia arising from myelodysplastic syndrome.
Secondary acute myeloid leukemia (AML) from an antecedent myelodysplastic syndrome (MDS)/myeloproliferative neoplasm is associated with a poor prognosis. The authors evaluated predictive factors in patients with secondary AML treated with anthracycline-based induction therapy. This was a retrospective review of secondary AML patients treated with induction therapy. Age, International Prognostic Scoring System, Eastern Cooperative Oncology Group performance status, cytogenetics, duration of MDS/myeloproliferative neoplasm, and prior MDS/myeloproliferative neoplasm treatment were evaluated for their impact on complete response (CR), CR with low platelets, and overall survival (OS). The authors evaluated 61 secondary AML patients who received induction chemotherapy; 59% (36 patients) achieved CR/CR with low platelets (95% confidence interval [CI], 46%-71%), and median OS was 6.5 (95% CI, 3.9-8.1) months. Three factors were associated with lower CR/CR with low platelets and OS: poor risk cytogenetics, prior treatment with hypomethylating agents or lenalidomide, and longer time to transformation to AML. Of those treated with hypomethylating agents or lenalidomide, 32% achieved CR/CR with low platelets versus 78% in the group not treated with a hypomethylating agent or lenalidomide (odds ratio [OR], 0.13; 95% CI, 0.04-0.42). Median OS for those treated with a hypomethylating agent or lenalidomide was 3.7 versus 10.5 months for those not treated with a hypomethylating agent or lenalidomide (P < .0001). The CR/CR with low platelets rate for those with intermediate risk cytogenetics was 70% versus 35% for those with poor risk (OR, 4.33; 95% CI, 1.38-13.6). Those with poor risk cytogenetics had a median OS of 2.8 versus 7.5 months for those with intermediate risk (P = .01). Prior treatment with hypomethylating agents or lenalidomide, poor risk cytogenetics, and longer time to transformation to AML are independent negative predictive factors for response and OS in patients with secondary AML after induction therapy.


Influence of formalin fixation on the implant stability quotient and mechanical characteristics of bone.
The implant stability quotient (ISQ) has been widely evaluated in clinical studies and animal experiments. However, accurate measurement is often difficult in animal models. In such cases, measurement of ISQ in bone is needed after formalin fixation. However, it is not yet clear how such fixation influences the measurement. The purpose of this study was to investigate the influence of formalin fixation on ISQ and the mechanical characteristics of bone. Fourteen tibias were harvested from rabbits; the samples from the left (length 60mm, control group) were soaked in saline and the samples from the right (length 60mm, fixation group) were fixed in 10% neutral-buffered formalin at 4°C for 4h. Three-point bending tests were done at 5mm/min to measure the maximum load and total absorbed energy. Twelve titanium implants (Brånemark System(®) Mk-III TiUnite, Nobel Biocare, Sweden) were placed into the edentulous molar site of the mandibles of 2 dogs and the ISQ was measured by Osstell(®) (control group) 3 months later. The implants involved in the bone block were then fixed for 4h (fixation group) and the ISQ measured. The maximum load values did not differ significantly between the control and fixation groups. Total absorbed energy was significantly higher in the control group than in the fixation group. ISQ did not differ significantly between the groups. These results suggest that formalin fixation of bone might affect some of the mechanical characteristics of bone, but not its ISQ.


TGF-β1-activated cancer-associated fibroblasts promote breast cancer invasion, metastasis and epithelial-mesenchymal transition by autophagy or overexpression of FAP-α.
Cancer-associated fibroblasts (CAFs) play an important role in the initiation, metastasis, and invasion of breast cancer. However, whether autophagy acts as a tumor promotion mechanism by inducing epithelial-mesenchymal transition (EMT) is still controversial and remains undefined at the mechanistic levels. In this study, we investigated whether autophagy or FAP-α is required for the invasion, pulmonary metastasis and EMT of breast cancer cells and underlying mechanism. We employed an in vitro model of NIH3T3 fibroblasts treated with H2O2 and confirmed that TGF-β1 could convert fibroblasts into CAFs through autophagy under oxidative stress in the tumor microenvironment. Modulation of autophagy by rapamycin, 3-methyladenine or ATG-5 knockdown regulated the expression of CAFs markers, suggesting a role of autophagy in the tumor promotion mechanism of TGF-β1-induced CAFs activation. Furthermore, we established an indirect co-culture model and a mixed xenograft as a corresponding in vivo model. We demonstrated that TGF-β1-activated CAFs promote tumor invasion, pulmonary metastasis and EMT, which act through autophagy and overexpression of FAP-α in both models, while autophagy inhibitor 3-methyladenine blocked these effects induced by TGF-β1-activated CAFs. Moreover, the co-localization of LC3β and EMT marker vimentin in mixed xenograft also revealed that TGF-β1-activated CAFs promote tumor growth, pulmonary metastasis, and EMT program partly through autophagy. In addition, knockdown of FAP-α resulted in reversed EMT and abolished tumor invasion and pulmonary metastasis induced by TGF-β1-activated CAFs. Taken together, we conclude that both autophagy and FAP-α are required for breast cancer cell invasion and metastasis. Targeting autophagy or FAP-α rather than both can serve as a potential approach to improve the prognosis for human breast cancer.


Investigating group formation: An experiment on the distribution of extraversion in educational settings.
Group formation plays a crucial role in enhancing collaborative learning experiences. This study investigates the impact of extraversion as a criterion for group formation on collaborative learning outcomes. A total of 180 students participated in the experiment and were assigned to groups that were homogeneously or heterogeneously distributed in terms of extraversion. The groups met weekly and worked on group assignments throughout the semesters. The first hypothesis posed the outcomes to be explainable at the group-level. Surprisingly, the results show that groups with a homogeneous distribution of extraversion reported higher levels of group work satisfaction than those with a heterogeneous distribution, in contrast to the second hypothesis and the group hierarchy theory. These findings emphasize the potential of considering personality traits when forming groups and extend the existing literature on group formation. The study takes a critical stance by addressing normative definitions of leadership. Future research is suggested to further enhance collaborative learning experiences using similar interdisciplinary and experimental methods.