Analysis of the Black Racial Identity Attitude scale in a substance-abusing population.
Racial attitude characteristics of African Americans may have important implications for patient-therapist matching in substance abuse treatment. The Black Racial Identity Attitude Scale (BRIAS) is a questionnaire used to measure racial identity attitudes. This study tested the stability and internal consistency of the BRIAS in an African-American substance-abusing population. This is the first known test of the BRIAS in a clinical population. African-American veterans (n = 53) were administered the BRIAS to test for stability over time and internal consistency. Initial analysis of the instrument revealed that a majority of items were not stable over time. Using the initial results, we removed 26 problematic items. Three modified scales remained, each having marginal test-retest reliability. Two of the modified scales had moderately adequate internal consistency, and the third was minimally adequate. We found that the BRIAS did not demonstrate sufficient internal consistency or stability in this population to adequately identify the constructs of the Nigrescence Racial Identity Development theory of William Cross, Jr. There is a growing recognition of the need to explore the extent of racial, ethnic, and cultural factors in substance abuse behavior and treatment; therefore, we recommend that further attention be directed toward developing an instrument to reliably and accurately measure identity constructs among African-American clinical subjects.


Prevention of malignant seeding at drain sites after invasive procedures (surgery and/or thoracoscopy) by hypofractionated radiotherapy in patients with pleural mesothelioma.
Literature data show that mesothelioma cells can implant along the surgical pathway of invasive procedures such as thoracotomy and thoracoscopy. We investigated the use of hypofractionated radiotherapy for preventing such malignant seeding. Thirty-two consecutive patients diagnosed with pleural mesothelioma were included in the present retrospective study. All patients underwent surgery and/or thoracoscopy for diagnosis, staging or talc pleurodesis. They were treated with electron external beam radiation therapy (21 Gy in 3 fractions over 1 week), directed to the surgical pathway after the invasive procedure. After completion of radiation treatment, 20 of 32 patients (63%) underwent chemotherapy. After a mean follow-up of 13.6 months (range 3-41) from the end of radiation therapy, no patient had tumour progression in the treated area. The treatment was well tolerated, as only erythema grade I (Radiation Therapy Oncology Group, RTOG, scale) was noted in 11 patients. Seventeen patients died of disease with local progression after a mean survival time of 12.6 months (range 3-27); thirteen patients are alive with disease after a mean follow-up of 13.9 months (range 4-41); two patients are alive without evidence of disease after a mean follow-up of 16.50 months (range 6-27). The present study shows the efficacy and safety of local radiotherapy in preventing malignant seeding after thoracoscopy in patients with pleural mesothelioma although larger prospective trials are probably still needed to validate this treatment approach.


Using topological equivalence to discover stable control parameters in biodynamic systems.
In order to better understand the mechanisms that contribute to low back pain, researchers have developed mathematical models and simulations. A mathematical model including neuromuscular feedback control is developed for a person balancing on an unstable sitting apparatus, the wobble chair. When the application of a direct method fails to discover appropriate controller gain parameters for the wobble chair, we show how topological equivalence can be used to indirectly identify appropriate parameter values. The solution is found by first transforming the wobble chair into the Acrobot, another member of the same family of topologically equivalent dynamical systems. After finding appropriate gain parameters for the Acrobot, a continuous transformation is performed to convert the Acrobot back to the wobble chair, during which the gain parameters are adjusted to maintain stability. Thus, we demonstrate how topological equivalence can be used to indirectly solve a problem that was difficult to solve directly.


The risk assessment profile score identifies trauma patients at risk for deep vein thrombosis.
The identification of trauma patients at risk for the development of deep venous thrombosis (DVT) at the time of admission remains difficult. The purpose of this study is to validate the risk assessment profile (RAP) score to stratify patients for DVT prophylaxis. All patients admitted from November 1998 thru May 1999 were evaluated for enrollment. We prospectively assigned patients as low risk or high risk for DVT using the RAP score. High-risk patients received both pharmacologic and mechanical prophylaxis. Low-risk patients received none. Surveillance duplex Doppler scans were performed each week of hospitalization or if symptoms developed. Hospital charges for prophylaxis were used to determine the savings in the low-risk group. Statistical differences between the risk groups for each factor of the RAP and development of DVT were determined by the chi-squared test, with significance at a probability value of less than .05. There were 102 high-risk (64%) and 58 low-risk (36%) individuals studied. Eleven of the high-risk group (10.8%) experienced the development of DVT (asymptomatic, 64%). None of the low-risk group was diagnosed with DVT. Five of the 16 RAP factors were statistically significant for DVT. Eliminating prophylaxis and Doppler scans in low-risk patients resulted in a total savings of $18,908 in hospital charges. The RAP score correctly identified trauma patients at increased risk for the development of DVT. Despite prophylaxis, the high-risk group warrants surveillance scans. Withholding prophylaxis in low-risk patients can reduce hospital charges without risk.


Methodology for rendering household budget and individual nutrition surveys comparable, at the level of the dietary information collected.
To describe the methodology applied in order to render comparable, at the level of the dietary information collected, the household budget survey (HBS) and individual nutrition survey (INS) data from four European countries (Belgium, Greece, Norway and the United Kingdom). In Belgium, data from the HBS of 1987-88 were compared with data from the Belgian Interuniversity Research on Nutrition and Health collected from 1980 to 1985. In Greece, data from the HBS undertaken in 1993-94 in the greater Athens area were compared with data collected around 1994 in the same region, in the context of the Greek segment of the European Prospective Investigation on Cancer and Nutrition study. In Norway, data from the HBS carried out in 1992, 1993 and 1994 were compared with the NORKOST study conducted in 1993-94. In the United Kingdom, data from four HBSs carried out in 1985, 1986, 1987 and 1988 were compared with the National Dietary and Nutritional Survey of British adults conducted in 1987-88. INS-generated data were converted into 'HBS-like' estimates with the application of yield factors for weight changes during cooking, recipe-based calculations and edible proportion coefficients taking into account weight changes during the food preparation. The 'HBS-like' estimates thus obtained were compared with the original HBS values, after applying an adjustment factor for food spoiled or given to pets. The methodological considerations overviewed in the present paper indicate that a number of issues need to be taken into account before a proper comparison of the dietary data collected through surveys implemented with varied methodologies is carried out.


Successful outcome after antibiotic treatment of postamniocentesis membrane rupture and chorioamnionitis in multiple pregnancy.
Postamniocentesis chorioamnionitis is usually managed with induction of labor to prevent maternal sepsis and related morbidity and mortality. We report a case of chorioamnionitis in a triplet pregnancy after midtrimester genetic amniocentesis, in which multiple antibiotic treatment (ampicillin 2 g i.v. loading dose followed by 1 g i.v. every 6 hr; clindamycin 900 mg i.v. every 8 hr; gentamicin 120 mg i.v. loading dose followed by 100 mg i.v. every 8 hrs; and erythromycin 500 mg i.v. every 6 hr) for 7 days and delivery of the presumably infected triplet A successfully reversed the clinical symptomatology, allowing prolongation of pregnancy until 26 weeks and survival of the remaining fetuses. At age 2 years, both infants are doing well and are meeting their developmental milestones. The viable outcome of this management strategy suggests that antibiotic treatment and expectancy may be an option in selected cases of postamniocentesis chorioamnionitis in multiple pregnancies.


Perifusion of rat pituitaries: requirements for optimal GnRH-stimulated LH release.
Perifusion of rat hemipituitaries was used as an in vitro model for luteinizing hormone (LH) release in response to gonadotropin-releasing hormone (GnRH). LH release during continuous stimulation with GnRH (10(-7) M) was inhibited by EGTA (1.5 or 5 mM given 1 h prior to GnRH) or by D-600 (methoxyverapamil, 1 mM, given concomitantly with GnRH). These findings suggested that GnRH-stimulated LH release was a Ca2+-dependent process. Inhibition of LH release caused by Ca2+ chelation with EGTA was reversed when hemipituitaries were returned to medium without EGTA. Elevation of medium K+ (to 50 mM, without GnRH) stimulated Ca2+-dependent LH release during the 1st h. GnRH-stimulated LH release was 60% inhibited by cycloheximide (25 micrograms/ml) after the 1st h. LH release was not stimulated by dibutyryladenosine 3',5'-cyclic monophosphate (DBcAMP), although this cyclic nucleotide was shown to have biological activity and to enter pituitary cells as judged by its ability to stimulate prolactin release from the same tissue. The data suggest that optimal LH release in response to GnRH requires extracellular Ca2+ and depends on protein synthesis.


[Myocardial infarction and intraventricular conduction disorders].
The diagnosis of myocardial ischemia is not confine to the alteration of the RS-T segment and of the T wave. Conduction disorders at any level can be caused by the ischemia itself and contribute to the diagnosis, as well as the ventricular arrhythmias. On the other hand, conduction blocks do not hinder or hide the diagnosis of ischemia. The primary and secondary characteristics of the T wave and RS-T segment are discussed. The relevance of the knowledge of ventricular activation vectors in bundle branch blocks is shown, as well as their alteration in case of associated myocardial infarction. Emphasis is made on the importance of the deductive method in the electrocardiographic interpretation.


[Physico-chemical properties and heterogeneity of Alcaligenes faecalis polysaccharide].
Two species of O-antigenic molecules with following sedimentation characteristics S(o)20, W 1,25.10(-13) S, D(o)20, W 9,7.10(-7) cm2/s, M 8000 and S(o)20, W 2,5.10(-13) S, D(o)20, W 5.10(-7) cm2/s, M 23,000-30,000 were detected in the cell wall of the strain Alcaligenes faecalis, a representative species of conditionally pathogenic microorganisms with unidentified taxonomic position. "Light" and "heavy" types of molecules have a lipopolysaccharide nature and show no differences in the monosaccharide composition of the polysaccharide moiety, structural organization of O-chain, or lipid A fatty-acid composition.


Role of neoadjuvant treatment in cT3N0M0 rectal cancer.
The aim of the study was to evaluate the pathological response (pTNM), local relapse and overall survival (OS) in clinical T3N0M0 (cT3N0M0) rectal cancer after a neoadjuvant chemoradiotherapy (CHT-RT) with 5-fluorouracil (5-FU) continuous infusion (c.i.) (+/- oxaliplatin) or bolus or capecitabine (an oral fluorpyrimidine). A secondary endpoint was to identify the local relapse rate and OS in those patients also receiving an adjuvant chemotherapy. From January 2000 to January 2006, 48 consecutive cT3N0M0 rectal cancer cases neoadjuvantly treated were retrospectively examined. Variables considered were age, gender, modality of 5-FU administration and tumour site. Median age was 64 years (range, 22-84 years) and the male:female ratio was 28:20. All the patients received the full course of CHT-RT. Twenty-eight patients received c.i. 5-FU neoadjuvant chemotherapy, 17 received bolus 5-FU administration and 3 patients received capecitabine-based therapy. The mean number of chemotherapy weeks was 4.9 (range, 2-6). A total of 85.4% of patients were operated on without relevant postoperative complications but another 4 are awaiting surgery. Twenty-one patients had a lower (< or = 5 cm from the anal verge) and 27 had a middle rectal lesion (from 6 to 10 cm). In those patients with the lower site of lesion, a sphincter-saving (SS) procedure was achieved in 88.9%. Downstaging was reported in 66.7%. Ninety percent of cases are still free from progression after a median follow-up of 22.1 months; 7.5% are dead. The down-staging, the good level of SS and the disease-free survival (DFS) obtained here suggests that a neoadjuvant therapy may also be useful for stage II rectal cancer at diagnosis. The use of a postoperative chemotherapy should probably be outlined better.


Studies on glutathione S-transferases important for sperm function: evidence of catalytic activity-independent functions.
Our earlier studies reported the identification of a rat testicular protein of 24 kDa with significant similarity at the N-terminus with Mu class glutathione S-transferases (GSTs). Treatment of goat sperm with antisera against this protein identified immunoreactive sites on the spermatozoa and inhibited in vitro fertilization of goat oocytes by the antibody-treated sperm. The above observations indicated the presence of GST-like molecule(s) important for fertility related events on goat spermatozoa. In this study, we report the purification of goat sperm GSTs (GSP1) which were purified by glutathione affinity chromatography and were enzymically active towards 1-chloro-2,4,-dinitrobenzene, a general GST substrate, and ethacrynic acid, a substrate for Pi class GSTs. GSP1 resolved into three major components on reverse-phase HPLC: peaks 1 and 2 with molecular masses of 26.5 kDa and peak 3 with a molecular mass of 25.5 kDa, as determined by SDS/PAGE. Multiple attempts to obtain N-terminal sequences of the first two peaks failed, indicating N-terminal block; however, they reacted to specific anti-Mu-GST antisera on Western blots and ELISA, and not to anti-Pi-GST antisera, which provides evidence for the presence of Mu-GST-reactive sites on peaks 1 and 2. The third component showed 80% N-terminal similarity with human and rat GSTP1-1 over an overlap of 15 amino acids, and reacted to anti-Pi-specific antisera in ELISA. Sperm labelled with antibodies against a 10-mer and an 11-mer peptide, designed from the N-terminal sequences of Mu and Pi class GSTs respectively, showed the presence of both Mu- and Pi-GST on goat sperm surface at distinct cellular domains. Selective inhibition of Pi class GST by the Pi-specific antisera, either at 0 h or at 3 h after initiation of sperm capacitation, leads to a reduction in fertilization rates. In contrast, the inhibition of Mu class GST by specific antisera at 0 h does not inhibit fertilization, although such treatment at 3 h after the initiation of capacitation reduces fertilization rates. The results indicate that both Pi- and Mu-GSTs are involved in fertilization, but the Mu-GST sites essential for fertilization are exposed only after 3 h of capacitation. The enzymic activity of GSP1 or live spermatozoa is not inhibited by the two antisera. The inability of the antibodies to cause such inhibition indicates that the reduction in fertilization rates and acrosome reaction caused by the antibodies is through a mechanism which does not interfere with the catalytic activity of the molecule. Therefore we established the presence of Pi and Mu class GST on goat sperm, their localization and their possible function in fertility-related events.


[Development in ontogeny of the effect of ACTH fragment 4-7 on rat learning].
Studies have been made of the effect of ACTH fragment 4-7 on learning in rats in early postnatal ontogenesis, as well as of the possibility of preservation of early learning during administration of this peptide to adult animals. It was shown that conditioned reaction of active avoidance practically cannot be formed in normal 13-15-day animals; however, administration of ACTH 4-7 increases the number of animals exhibiting adequate reactions. Weak effect of ACTH 4-7 in 12-15-day animals, in older ones (20-24 days) is changed by a significant stimulating effect.


Older people's experiences of patient-centered treatment for chronic pain: a qualitative study.
Older adults with chronic pain who seek treatment often are in a health care environment that emphasizes patient-directed care, a change from the patriarchal model of care to which many older adults are accustomed. To explore the experiences of older adults seeking treatment for chronic pain, with respect to patient-directed care and the patient-provider relationship. In-depth interviews with 15 Caucasian older adults with chronic pain who had been evaluated at a university-based pain clinic. All interviews were audiotaped and the transcripts were analyzed using a grounded theory based approach. Older adults with chronic pain vary in their willingness to be involved in their treatment decisions. Many frequently participate in decisions about their pain treatment by asking for or refusing specific treatments, demanding quality care, or operating outside of the patient-provider relationship to manage pain on their own. However, others prefer to let their provider make the decisions. In either case, having a mutually respectful patient-provider relationship is important to this population. Specifically, participants described the importance of "being heard" and "being understood" by providers. As some providers switch from a patriarchal model of care toward a model of care that emphasizes patient activation and patient-centeredness, the development and cultivation of valued patient-provider relationships may change. While it is important to encourage patient involvement in treatment decisions, high-quality, patient-centered care for older adults with chronic pain should include efforts to strengthen the patient-provider relationship by attending to differences in patients' willingness to engage in patient-directed care and emphasizing shared decision-making.


Huntingtin interacting protein 1 induces apoptosis via a novel caspase-dependent death effector domain.
Huntington disease is a devastating neurodegenerative disease caused by the expansion of a polymorphic glutamine tract in huntingtin. The huntingtin interacting protein (HIP-1) was identified by its altered interaction with mutant huntingtin. However, the function of HIP-1 was not known. In this study, we identify HIP-1 as a proapoptotic protein. Overexpression of HIP-1 resulted in rapid caspase 3-dependent cell death. Bioinformatics analyses identified a novel domain in HIP-1 with homology to death effector domains (DEDs) present in proteins involved in apoptosis. Expression of the HIP-1 DED alone resulted in cell death indistinguishable from HIP-1, indicating that the DED is responsible for HIP-1 toxicity. Furthermore, substitution of a conserved hydrophobic phenylalanine residue within the HIP-1 DED at position 398 eliminated HIP-1 toxicity entirely. HIP-1 activity was found to be independent of the DED-containing caspase 8 but was significantly inhibited by the antiapoptotic protein Bcl-x(L), implicating the intrinsic pathway of apoptosis in HIP-1-induced cell death. Co-expression of a normal huntingtin fragment capable of binding HIP-1 significantly reduced cell death. Our data identify HIP-1 as a novel proapoptotic mediator and suggest that HIP-1 may be a molecular accomplice in the pathogenesis of Huntington disease.


Study of charged particle activation analysis (II): Determination of boron concentration in human blood samples.
Boron Neutron Capture Therapy (BNCT) is a radiotherapy for the treatment of intractable cancer. In BNCT precise determination of 10B concentration in whole blood sample before neutron irradiation of the patient, as well as accurate neutron dosimetry, is crucial for control of the neutron irradiation time. For this purpose ICP-AES and neutron induced prompt γ-ray analysis are generally used. In Ibaraki Neutron Medical Research Center (iNMRC), an intense proton beam will be accelerated up to 8 MeV, which can also be used for Charged Particle Activation Analysis (CPAA). Thus, in this study, we apply the CPAA utilizing the proton beam to non-destructive and accurate determination of 10B concentration in whole blood sample. A CPAA experiment is performed by utilizing an 8 MeV proton beam from the tandem accelerator of Nuclear Science Research Institute in Japan Atomic Energy Agency. The 478 keV γ-ray of 7Be produced by the 10B(p, α)7Be reaction is used to quantify the 10B in human blood. The 478 keV γ-ray intensity is normalized by the intensities of the 847 keV and 1238 keV γ-rays of 56Co originating from Fe in blood. The normalization methods were found to be linear in the range of 3.27 μg 10B/g to 322 μg 10B/g with correlation coefficients of better than 0.9999.


Trends of testis-sparing surgery for pediatric testicular tumors in South China.
Testis-sparing surgery is not popular in South China. This study aimed to investigate this procedure for pediatric testicular tumors. Children with testicular benign tumors were retrospectively analyzed from January 2001 to June 2015 in the Sun Yat-sen University Cancer Center (SYSUCC) and the First Affiliated Hospital (SYSU-1st). Follow-up was performed until June 2016, and the proportions of TSS in the two hospitals during the different periods were compared. Forty-seven children with testicular benign tumors were enrolled, and 16 cases underwent testis-sparing surgery. All patients were cured and discharged, which included mature teratoma (n = 37), testicular adrenal rest tumors (n = 4), epidermal cysts (n = 3), granulomatous inflammation (n = 2) and adenomatoid tumors (n = 1). Inguinal testis-sparing surgery was performed in 16 children, and no recurrence was detected during follow-up. It was performed more frequently in SYSUCC than in SYSU-1st (P = 0.031), and the tumor size of these patients was smaller than those of patients who underwent radical orchiectomy (P = 0.044). Moreover, testis-sparing surgery has become more common in the past 5 years, although differences over time have not reached significance (P = 0.051). Testis-sparing surgery is reliable, and tumor size and special hospitals affect its success. Additionally, its use has become more popular in recent years. However, advocacy is still needed for the use of this technique in pediatric testicular benign tumors that are small sized.


Cohort profile: Biomarkers related to folate-dependent one-carbon metabolism in colorectal cancer recurrence and survival - the FOCUS Consortium.
The overarching goal of the FOCUS (biomarkers related to folate-dependent one-carbon metabolism in colorectal cancer (CRC) recurrence and survival) Consortium is to unravel the effect of folate and folate-mediated one-carbon metabolism (FOCM) biomarkers on CRC prognosis to provide clinically relevant advice on folate intake to cancer patients and define future tertiary prevention strategies. The FOCUS Consortium is an international, prospective cohort of 2401 women and men above 18 years of age who were diagnosed with a primary invasive non-metastatic (stages I-III) CRC. The consortium comprises patients from Austria, two sites from the Netherlands, Germany and two sites from the USA. Patients are recruited after CRC diagnosis and followed at 6 and 12 months after enrolment. At each time point, sociodemographic data, data on health behaviour and clinical data are collected, blood samples are drawn. An increased risk of cancer recurrences was observed among patients with higher compared with lower circulating folic acid concentrations. Furthermore, specific folate species within the FOCM pathway were associated with both inflammation and angiogenesis pathways among patients with CRC. In addition, higher vitamin B6 status was associated with better quality of life at 6 months post-treatment. Better insights into the research on associations between folate and FOCM biomarkers and clinical outcomes in patients with CRC will facilitate the development of guidelines regarding folate intake in order to provide clinically relevant advice to patients with cancer, health professionals involved in patient care, and ultimately further tertiary prevention strategies in the future. The FOCUS Consortium offers an excellent infrastructure for short-term and long-term research projects and for combining additional biomarkers and data resulting from the individual cohorts within the next years, for example, microbiome data, omics and multiomics data or CT-quantified body composition data.


Is there added value to adding ARB to ACE inhibitors in the management of CKD?
Antagonism of the rennin-angiotensin-aldosterone-system (RAAS) decreases BP and reduces proteinuria in chronic kidney disease. BP is decreased approximately 5 mmHg when angiotensin II blockers are added to angiotensin-converting enzyme (ACE) inhibitors and is less than typically seen when other agents are added to existing ACE inhibitor regimens. Dual RAAS blockade results in additional reduction in proteinuria. Clinically insignificant increases in hyperkalemia and modest decreases in GFR occur. Data regarding long-term preservation of renal function are lacking. We suggest dual RAAS blockade be used in patients with chronic kidney disease with residual proteinuria on maximal ACE inhibitor or angiotensin II blocker therapy, anticipating additional data with ongoing trials.


Summary of the National Institute on Aging-sponsored conference on depressive symptoms and cognitive complaints in the menopausal transition.
The National Institutes of Health and The North American Menopause Society sponsored a symposium to understand the impact of the menopausal transition on mood symptoms and cognitive disorders and to identify research priorities for further investigation. The symposium was divided into a morning session on depressive symptoms and an afternoon session on cognitive function. There were four speakers per session, and each session covered four methodological approaches, including longitudinal cohort studies, randomized intervention trials, pharmacological challenge studies, and clinical diagnosis. Interactive panel discussions focused on translating research findings to clinical practice. Most women do not experience serious depressive symptoms during the menopausal transition, but a subgroup of women is at increased risk. Slight changes in memory function and processing speed are evident during the menopausal transition, and physiological factors associated with hot flashes may contribute to memory problems. Clinical trial evidence indicates that estradiol therapy can be effective in treating perimenopausal depression. There is some limited evidence of a cognitive benefit with estrogen-alone therapy in younger postmenopausal women and stronger evidence that certain forms of combination hormone therapy produce modest deficits in verbal memory in younger postmenopausal women. Routine evaluation of depressive symptoms in perimenopausal women is warranted by the literature. Quick and valid screening tools for assessing depression in the clinic are available online and free of charge. Identifying a cognitively neutral or beneficial combination therapy for the treatment of menopausal symptoms in naturally postmenopausal women is an important goal for future research.


Design, facile synthesis and anthelmintic activity of new O-substituted 6-methoxybenzothiazole-2-carbamates. Part II.
In the framework of pursuing the design and synthesis of a new series of substituted 6-methoxybenzothiazole-2-carbamates as potential anthelmintics, and as a continuation of the expended efforts in part I, we have set out to develop novel compounds with enhanced anthelmintic activity by blocking the 6-position of benzothiazole with side chains of different polarities. Guided by the findings in part I, and reporting the paramphistomicidal activity of oxadiazoline derivatives V and VI, we aimed to synthesize target benzothiazoles designed to comprise some planar heterocyclic ring systems, namely, 1,3,4-oxadiazoles and 1,2,4-triazoles, bearing a variety of hydrophobic and hydrophilic components. The synthesis of the desired compounds was primarily achieved by cyclization of 6-acetohydrazide, 1. The in vitro paramphistomicidal activity of all synthesized carbamates was evaluated. Four synthesized carbamates exhibited notable activity. Compound 24, methyl 6-[(5-(4-bromophenacylsulfanyl)-[1,3,4]-oxadiazol-2-yl)methoxy]benzothiazole-2-carbamate, displayed an equipotent effect to the reference drug oxyclozanide at a concentration of 80 μg mL-1; compounds 9, 10 and 23 showed high orders of anthelmintic effect. A structural computational study on the polar nature and hydrophilic-lipophilic properties of the synthesized carbamates was undertaken to discuss their structure-activity relationship (SAR). Besides, pharmacophore mapping was performed using eight active compounds as a training set. The generated pharmacophore model revealed five common features and was validated using fenbendazole, triclabendazole and triclabendazole sulfoxide.


TUBB4A mutations result in specific neuronal and oligodendrocytic defects that closely match clinically distinct phenotypes.
Hypomyelinating leukodystrophies are heritable disorders defined by lack of development of brain myelin, but the cellular mechanisms of hypomyelination are often poorly understood. Mutations in TUBB4A, encoding the tubulin isoform tubulin beta class IVA (Tubb4a), result in the symptom complex of hypomyelination with atrophy of basal ganglia and cerebellum (H-ABC). Additionally, TUBB4A mutations are known to result in a broad phenotypic spectrum, ranging from primary dystonia (DYT4), isolated hypomyelination with spastic quadriplegia, and an infantile onset encephalopathy, suggesting multiple cell types may be involved. We present a study of the cellular effects of TUBB4A mutations responsible for H-ABC (p.Asp249Asn), DYT4 (p.Arg2Gly), a severe combined phenotype with hypomyelination and encephalopathy (p.Asn414Lys), as well as milder phenotypes causing isolated hypomyelination (p.Val255Ile and p.Arg282Pro). We used a combination of histopathological, biochemical and cellular approaches to determine how these different mutations may have variable cellular effects in neurons and/or oligodendrocytes. Our results demonstrate that specific mutations lead to either purely neuronal, combined neuronal and oligodendrocytic or purely oligodendrocytic defects that closely match their respective clinical phenotypes. Thus, the DYT4 mutation that leads to phenotypes attributable to neuronal dysfunction results in altered neuronal morphology, but with unchanged tubulin quantity and polymerization, with normal oligodendrocyte morphology and myelin gene expression. Conversely, mutations associated with isolated hypomyelination (p.Val255Ile and p.Arg282Pro) and the severe combined phenotype (p.Asn414Lys) resulted in normal neuronal morphology but were associated with altered oligodendrocyte morphology, myelin gene expression, and microtubule dysfunction. The H-ABC mutation (p.Asp249Asn) that exhibits a combined neuronal and myelin phenotype had overlapping cellular defects involving both neuronal and oligodendrocyte cell types in vitro. Only mutations causing hypomyelination phenotypes showed altered microtubule dynamics and acted through a dominant toxic gain of function mechanism. The DYT4 mutation had no impact on microtubule dynamics suggesting a distinct mechanism of action. In summary, the different clinical phenotypes associated with TUBB4A reflect the selective and specific cellular effects of the causative mutations. Cellular specificity of disease pathogenesis is relevant to developing targeted treatments for this disabling condition.


Biochemical pathway for the biosynthesis of the CuA center in bacterial cytochrome c oxidase.
The di-copper center CuA is an essential metal cofactor in cytochrome oxidase (Cox) of mitochondria and many prokaryotes, mediating one-electron transfer from cytochrome c to the site for oxygen reduction. CuA is located in subunit II (CoxB) of Cox and protrudes into the periplasm of Gram-negative bacteria or the mitochondrial intermembrane space. How the two copper ions are brought together to build CoxB·CuA is the subject of this review. It had been known that the reductase TlpA and the metallochaperones ScoI and PcuC are required for CuA formation in bacteria, but the mechanism of copper transfer has emerged only recently for the Bradyrhizobium diazoefficiens system. It consists of the following steps: (a) TlpA keeps the active site cysteine pair of CoxB in its dithiol state as a prerequisite for metal insertion; (b) ScoI·Cu2+ rapidly forms a transient complex with apo-CoxB; (c) PcuC, loaded with Cu1+ and Cu2+ , dissociates this complex to CoxB·Cu2+ , and a second PcuC·Cu1+ ·Cu2+ transfers Cu1+ to CoxB·Cu2+ , yielding mature CoxB·CuA . Variants of this pathway might exist in other bacteria or mitochondria.


Vascular matrix metalloproteinase-2-dependent cleavage of calcitonin gene-related peptide promotes vasoconstriction.
Matrix metalloproteinase (MMP)-2 has been historically associated with the process of vascular remodeling through the cleavage of extracellular matrix proteins. However, we recently found that MMP-2 also cleaves the endothelium-derived peptide big endothelin-1, ET-1[1-38] and yields the novel vasoconstrictor ET-1[1-32]. We therefore investigated the effects of MMP-2 inhibitors as potential vasodilators. MMP inhibition with ortho-phenanthroline (0.3 to 30 micromol/L) induced vasorelaxation of isolated rat mesenteric arteries (maximum of relaxation=74.5+/-27.6% at 30 micromol/L). However, phosphoramidon (0.3 to 30 micromol/L), which inhibits some metalloenzymes, but not MMP-2, did not dilate the arteries. Selective inhibition of endogenous MMP-2 with the novel tissue-permeable cyclic peptide CTTHWGFTLC (CTT, 10 micromol/L) also caused vasorelaxation (by 85+/-6%), whereas STTHWGFTLS (10 micromol/L), an inactive CTT analogue, did not dilate the arteries. Interestingly, the vasorelaxation that results from MMP-2 inhibition was endothelium-independent. Thus, we examined whether MMP-2 acted on peptides derived from the smooth muscle or the perivascular nerves. Recombinant human MMP-2 cleaved calcitonin gene-related peptide (CGRP) specifically at the Gly(14)-Leu(15) peptide bond and reduced the vasodilatory potency of CGRP by 20-fold. Inhibition of MMP-2 increased the amount of intact CGRP in arteries and enhanced vasorelaxation induced by anandamide, which stimulates CGRP release. Vasorelaxation in response to MMP-2 inhibition was abolished by CGRP[8-37], a selective CGRP receptor antagonist, and by capsaicin, which depletes arterial perivascular nerves of CGRP. We conclude that vascular MMP-2 cleaves endogenous CGRP and promotes vasoconstriction. These data suggest a novel mechanism of regulating the vasoactive and, possibly, the neurohormonal actions of CGRP and establish MMP-2 as a modulator of vascular function.


Integration of Single-Cell RNA Sequencing and Bulk RNA Sequencing Reveals That TAM2-Driven Genes Affect Immunotherapeutic Response and Prognosis in Pancreatic Cancer.
Tumor-associated macrophages M2 (TAM2), which are highly prevalent infiltrating immune cells in the stroma of pancreatic cancer (PC), have been found to induce an immunosuppressive tumor microenvironment, thus enhancing tumor initiation and progression. However, the immune therapy response and prognostic significance of regulatory genes associated with TAM2 in PC are currently unknown. Based on TCGA transcriptomic data and single-cell sequencing data from the GEO database, we identified TAM2-driven genes using the WGCNA algorithm. Molecular subtypes based on TAM2-driven genes were clustered using the ConsensusClusterPlus algorithm. The study constructed a prognostic model based on TAM2-driven genes through Lasso-COX regression analysis. A total of 178 samples obtained by accessing TCGA were accurately categorized into two molecular subtypes, including the high-TAM2 infiltration (HMI) cluster and the low-TAM2 infiltration (LMI) cluster. The HMI cluster exhibits a poor prognosis, a malignant tumor phenotype, immune-suppressive immune cell infiltration, resistance to immunotherapy, and a high number of genetic mutations, while the LMI cluster is the opposite. The prognostic model composed of six hub genes from TAM2-driven genes exhibits a high degree of accuracy in predicting the prognosis of patients with PC and serves as an independent risk factor. The induction of TAM2 was employed as a means of verifying these six gene expressions, revealing the significant up-regulation of BCAT1, BST2, and MERTK in TAM2 cells. In summary, the immunophenotype and prognostic model based on TAM2-driven genes offers a foundation for the clinical management of PC. The core TAM2-driven genes, including BCAT1, BST2, and MERTK, are involved in regulating tumor progression and TAM2 polarization, which are potential targets for PC therapy.


Bevacizumab+chemotherapy versus chemotherapy alone in elderly patients with untreated metastatic colorectal cancer: a randomized phase II trial-PRODIGE 20 study results.
Metastatic colorectal cancer frequently occurs in elderly patients. Bevacizumab in combination with front line chemotherapy (CT) is a standard treatment but some concern raised about tolerance of bevacizumab for these patients. The purpose of PRODIGE 20 was to evaluate tolerance and efficacy of bevacizumab according to specific end points in this population. Patients aged 75 years and over were randomly assigned to bevacizumab + CT (BEV) versus CT. LV5FU2, FOLFOX and FOLFIRI regimen were prescribed according to investigator's choice. The composite co-primary end point, assessed 4 months after randomization, was based on efficacy (tumor control and absence of decrease of the Spitzer QoL index) and safety (absence of severe cardiovascular toxicities and unexpected hospitalization). For each arm, the treatment will be consider as inefficient if 20% or less of the patients met the efficacy criteria and not safe if 40% or less met the safety criteria. About 102 patients were randomized (51 BEV and 51 CT), median age was 80 years (range 75-91). Primary end point was met for efficacy in 50% and 58% and for safety in 61% and 71% of patients in BEV and CT, respectively. Median progression-free survival was 9.7 months in BEV and 7.8 months in CT. Median overall survival was 21.7 months in BEV and 19.8 months in CT. The 36-month overall survival rate was 27% in BEV and 10.1% in CT. Severe toxicities grade 3/4 were mainly non-hematologic toxicities (80.4% in BEV, 63.3% in CT). Bevacizumab combined with CT was safe and efficient. Both arms met the primary safety and efficacy criteria.


Chemotherapy in primary osteogenic sarcoma in patients over the age of forty.
In this study, we sought to review the clinical and histopathological features and the chemotherapy regimens in osteogenic sarcoma in patients over 40 years of age, and we aimed at identifying the possible prognostic factors in this particular group of patients. We reviewed 287 patients with osteosarcoma treated between the year 1986 and 2010. Patients from this group who met the following criteria were considered eligible for our study; presence of primary OS, had typical histological and radiographic features of OS, no prior history of cancer or any treatment elsewhere and no prior history of preexisting bone abnormalities. The Kaplan-Meier survival curve for the entire group, with a 95% confidence interval, at two and five years showed the survival rates as 76.2% and 72.8% respectively. The surgical margin was a significant factor affecting the survival. Presence of a pathological fracture also had a significant effect on the survival rate. Osteogenic sarcoma remains a challenging disease to treat. Despite the expectation that elderly patients may not tolerate aggressive modern chemotherapy as the younger patients, we believe that patients with primary OS over the age of 40 should be treated aggressively with effective chemotherapy and complete surgical excision whenever possible. Level IV, therapeutic study.


Long-term consumption of fruits and vegetables and risk of chronic obstructive pulmonary disease: a prospective cohort study of women.
Fruits and vegetables, due to high antioxidant capacity, may protect the lung from oxidative damage caused by tobacco smoke and potentially prevent chronic obstructive pulmonary disease (COPD). Only one study based on baseline diet has examined fruit and vegetable consumption in relation to risk of COPD, and no previous studies have examined long-term diet. We investigated whether long-term fruit and vegetable consumption was associated with COPD incidence among 34 739 women (age 48-83 years) in the population-based prospective Swedish Mammography Cohort. Fruit and vegetable consumption was assessed twice (1987, 1997) with a self-administered questionnaire. Cases of COPD were identified by linkage to the Swedish health register. Cox proportional hazard regression models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs). During follow-up from 2002 to 2014, 1512 women were diagnosed with COPD. Long-term fruit was associated with lower risk of COPD; women in the highest vs lowest quintile of consumption (≥2.5 vs <0.8 servings/day) had a 37% lower risk of COPD (95% CI: 25-48%; P-trend < 0.0001). No association was observed with long-term vegetable intake. Current and ex-smokers with low long-term consumption of fruits (<1 serving/day) in comparison to never smokers with high consumption (≥3 servings/day) had a 38-fold (HR: 38.1; 95% CI: 20.2-71.7) and 13-fold (HR: 12.5, 95% CI: 6.5-24.1) higher risk of COPD, respectively. However, no significant interaction between smoking status and fruit intake in relation to COPD incidence was observed (P-interaction = 0.95). In this prospective cohort of middle-age and older women, long-term consumption of fruits but not vegetables was inversely associated with COPD incidence.


Surface-wave interferometry on single subwavelength slit-groove structures fabricated on gold films.
We apply the technique of far-field interferometry to measure the properties of surface waves generated by two-dimensional (2D) single subwavelength slit-groove structures on gold films. The effective surface index of refraction n(surf) measured for the surface wave propagating over a distance of more than 12 mum is determined to be n(surf) = 1.016+/-0.004, to within experimental uncertainty close to the expected bound surface plasmon-polariton (SPP) value for a Au/Air interface of n (spp) = 1.018. We compare these measurements to finite-difference-time-domain (FDTD) numerical simulations of the optical field transmission through these devices. We find excellent agreement between the measurements and the simulations for n(surf). The measurements also show that the surface wave propagation parameter k(surf) exhibits transient behavior close to the slit, evolving smoothly from greater values asymptotically toward k (spp) over the first 2-3 mum of slit-groove distance x(sg). This behavior is confirmed by the FDTD simulations.


Diagnostic advantage of double immunohistochemistry using two mutation-specific anti-IDH antibodies (HMab-1 and MsMab-1) in gliomas.
Isocitrate dehydrogenase (IDH) mutation is a valuable prognostic marker and a tool for decision-making for glioma treatment. An algorithm for IDH mutation screening was recently proposed--it consists of a two-step process of an initial search for the most common IDH1-R132H mutation using immunohistochemistry (IHC)-based assay, followed by DNA-based analysis of IHC-negative or -equivocal cases. Here, we report that immunohistochemistry using two mutation-specific anti-IDH monoclonal antibodies (mAbs)--an IDH1-R132H-specific mAb (clone HMab-1) and a multi-specific mAb (clone MsMab-1)--is easy and reliable for IDH mutation screening. We investigated the IDH status of 54 grade III gliomas. For the first screening, we used HMab-1 IHC and for the second, (of HMab-1-negative cases) we used MsMab-1 IHC. The double IHC screening results were confirmed using sequence analysis (100% specificity and 100% sensitivity). Thirty of 54 cases (55.6%) had IDH mutations and the remaining 24 were of the IDH wild type; moreover, the screening results predicted grade III glioma prognosis. IDH sequencing procedures are popular but inconsistent across laboratories. By contrast, double IHC screening using HMab-1 and MsMab-1 is very reliable for detecting IDH1/2 mutations and can predict survival in grade III glioma patients.


Animal models in the research of abdominal aortic aneurysms development.
Abdominal aortic aneurysm (AAA) is a prevalent and potentially life threatening disease. Many animal models have been developed to simulate the natural history of the disease or test preclinical endovascular devices and surgical procedures. The aim of this review is to describe different methods of AAA induction in animal models and report on the effectiveness of the methods described in inducing an analogue of a human AAA. The PubMed database was searched for publications with titles containing the following terms "animal" or "animal model(s)" and keywords "research", "aneurysm(s)", "aorta", "pancreatic elastase", "Angiotensin", "AngII" "calcium chloride" or "CaCl(2)". Starting date for this search was set to 2004, since previously bibliography was already covered by the review of Daugherty and Cassis (2004). We focused on animal studies that reported a model of aneurysm development and progression. A number of different approaches of AAA induction in animal models has been developed, used and combined since the first report in the 1960's. Although specific methods are successful in AAA induction in animal models, it is necessary that these methods and their respective results are in line with the pathophysiology and the mechanisms involved in human AAA development. A researcher should know the advantages/disadvantages of each animal model and choose the appropriate model.


Geographic variation of racial/ethnic disparities in colorectal cancer testing among medicare enrollees.
The Medicare population has documented racial/ethnic disparities in colorectal cancer (CRC) screening, but it is unknown whether these disparities differ across geographic regions. Among Medicare enrollees within 8 US states, we ascertained up-to-date CRC screening on December 31, 2003 (fecal occult blood testing in the prior year or sigmoidoscopy or colonoscopy in the prior 5 years). Logistic regression models tested for regional variation in up-to-date status among white versus different nonwhite populations (blacks, Asian/Pacific Islanders [APIs], Hispanics). We estimated regression-adjusted region-specific prevalence of up-to-date status by race/ethnicity and compared adjusted white versus nonwhite up-to-date prevalence across regions by using generalized least squares regression. White versus nonwhite up-to-date status varied significantly across regions for blacks (P = .01) and APIs (P < .001) but not Hispanics (P = .62). Whereas the white versus black differences in proportion up-to-date were greatest in Atlanta (Georgia), rural Georgia, and the San Francisco Bay Area of California (range, 10%-16% differences, blacks<whites); there were no significant white versus black differences in Connecticut, Seattle (Washington) or Iowa. Whereas APIs had significantly lower up-to-date prevalence than whites in Michigan and the California regions of San Francisco, Los Angeles, and San Jose (range, 4%-15% differences, APIs<whites), APIs in Hawaii had higher up-to-date status than whites (52% vs 38% P < .001). White versus Hispanic differences were substantial but homogeneous across regions (range, 8%-16% differences, Hispanics<whites). In contrast to nonwhites, there was little geographic variation in up-to-date status among whites. Significant geographic variation in up-to-date status among black and API Medicare enrollees is associated with heterogeneous racial/ethnic disparities for these groups across US regions.


Development of a control system for the teat-end vacuum in individual quarter milking systems.
Progress in sensor technique and electronics has led to a decrease in the costs of electronic and sensor components. In modern dairy farms, having udders in good condition, a lower frequency of udder disease and an extended service life of dairy cows will help ensure competitiveness. The objective of this study was to develop a teat-end vacuum control system with individual quarter actor reaction. Based on a review of the literature, this system is assumed to protect the teat tissue. It reduces the mean teat-end vacuum in the maximum vacuum phase (b) to a level of 20 kPa at a flow rate of 0.25 L/min per quarter. At flow rates higher than 1.50 L/min per quarter, the teat-end vacuum can be controlled to a level of 30 kPa, because in this case it is desirable to have a higher vacuum for the transportation of the milk to the receiver. With this system it is possible for the first time to supply the teat end with low vacuum at low flow rates and with higher vacuum at increasing flow rates in a continuous process with a three second reaction-rate on individual quarter level. This system is completely automated.


Factors associated with the intensity of anxiety and depression symptoms in health workers of two centres of reference for COVID 19 patient care in Antioquia, Colombia - A latent class analysis.
To classify the staff of two reference institutions for COVID-19 care in Antioquia according to the intensity of anxiety and depression symptoms, and to determine the factors associated with these classes. Cross-sectional study in which the GAD-7, PHQ-9, fear of COVID-19, and the Copenhagen Burnout scale were used. Latent class analysis was performed to identify the classes, and the factors associated with these were determined using multinomial logistic regression. 486 people participated. The three-class model had the best fit: class I with low scores on the scales; class II with mild degrees of anxiety and depression, and intermediate levels of fear of COVID-19 and perceived stress; and class III with moderate and severe degrees of anxiety, depression, and perceived stress. The factors associated with belonging to class III were age (OR = 0.94; 95%CI, 0.91-0.96), change of residence to avoid exposing relatives (OR = 4.01; 95%CI, 1.99-8.09), and a history of depressive disorder (OR = 3.10; 95%CI, 1.27-7.56), and anxiety (OR = 5.5; 95%CI, 2.36-12.90). Factors associated with class II were age (OR = 0.97; 95%CI, 0.95-0.99), history of depressive disorder (OR = 3.41; 95%CI, 1.60-7.25), living with someone at risk of death from COVID-19 (OR = 1.86; 95%CI, 1.19-2.91), family member being healthcare staff (OR = 1.58; 95%CI, 1.01-2.47), and change of residence to avoid exposing relatives (OR = 1.99; 95%CI, 1.11-3.59). Three classes of participants were obtained, two of them with anxiety and depression symptoms. Younger age and a history of mental disorder were factors associated with the two classes of symptomatic patients; other factors may be causes or consequences of the symptoms.


Long-term clinical course of normotensive preperimetric glaucoma.
To evaluate the long-term clinical course of normotensive preperimetric glaucoma (PPG). We retrospectively analysed 130 eyes of 130 patients initially diagnosed as having preperimetric normal tension glaucoma and followed these cases for at least 5 years with reliable visual field (VF) examinations by standard automated perimetry. When the VF defect (VFD) met Anderson-Patella's criteria on three or more consecutive examinations, and consistently met the criteria on subsequent examinations, we concluded that a glaucomatous VFD was present. Predictive factors for developing a VFD were assessed. Seventy-one eyes (54.6%) developed a glaucomatous VFD during the follow-up period. The mean deviation slope varied from -0.90 to 0.41 dB/year. A Cox proportional hazard model showed that having a greater initial pattern SD (p=0.005), the presence of optic disc haemorrhage (p=0.022) and higher mean intraocular pressure (IOP) prior to developing a VFD (p=0.039) were related to developing a VFD. Our findings confirmed that the mean IOP, but not the IOP fluctuation, is strongly associated with the development of a VFD in cases of PPG.


Spontaneous ameloblastic fibro-odontoma in a female mouse.
A spontaneous ameloblastic fibro-odontoma is described in a 73-wk-old female mouse. The tumor was located in the molar mandibular region. The diagnosis was made on the basis of the histologic presence of odontogenic epithelial tissue embedded in mesodermal tissue resembling dental papilla, and containing in addition dentin and enamel. The positive reaction for keratin and vimentin confirmed the presence of ectodermal and mesodermal elements respectively in the tumor.


Sperm-mediated DNA lesions alter metabolite levels in spent embryo culture medium.
Paternal genetic alterations may affect embryo viability and reproductive outcomes. Currently it is unknown whether embryo metabolism is affected by sperm-mediated abnormalities. Hence, using a mouse model, this study investigated the response to paternally transmitted DNA lesions on genetic integrity and metabolism in preimplantation embryos. Spent embryo culture media were analysed for metabolites by nuclear magnetic resonance spectroscopy and embryonic genetic integrity was determined by terminal deoxynucleotidyl transferase dUTP nick-end labelling (TUNEL) assay on embryonic Day 4.5 (E4.5). Metabolic signatures were compared between normally derived embryos (control) and embryos derived from spermatozoa carrying induced DNA lesions (SDL). SDL embryos showed a significant reduction in blastocyst formation on E3.5 and E4.5 (P<0.0001) and had an approximately 2-fold increase in TUNEL-positive cells (P<0.01). A cohort of SDL embryos showing delayed development on E4.5 had increased uptake of pyruvate (P<0.05) and released significantly less alanine (P<0.05) to the medium compared with the corresponding control embryos. On the other hand, normally developed SDL embryos had a reduced (P<0.001) pyruvate-to-alanine ratio compared with normally developed embryos from the control group. Hence, the difference in the metabolic behaviour of SDL embryos may be attributed to paternally transmitted DNA lesions in SDL embryos.


[The state of the endometrium and myometrium in patients with ovarian tumors and tumor-like growths].
The study was concerned with the condition of the endometrium and myometrium in relation to the histological pattern of ovarian tumor and tumor-like growth and patient's age. Polyps, glandular atypical hyperplasia and endometrial adenocarcinoma were more frequent in cases of ovarian malignancies than in patients with benign tumors and tumor-like growth. On the whole, pathomorphologic alterations in corpus uteri were observed in one-third of patients with ovarian growth (271 out of 913, i.e. 29.6%).


Normal Basal Epithelial Cells Stimulate the Migration and Invasion of Prostate Cancer Cell RM-1 by TGF-β1/STAT3 Axis in vitro.
Basal epithelial cells are absent in distant prostate cancer. This study aimed to investigate whether basal epithelial cells could suppress migration and invasion of prostate cancer cells to become a new treatment strategy for prostate cancer. Basal epithelial cells were identified by immunofluorescence with anti-p63. Wound healing assays or transwell assays were used to explore the effects of basal epithelial cells, TGF-β1, SB431542 (inhibitor of TGF-β type I receptor) or stattic (inhibitor of phosphorylated STAT3) on migration or invasion of mouse prostate cancer cell (RM-1). Concentration of TGF-β1 was measured by ELISA assay. HE staining was used to investigate cell morphology. Immunocytochemistry with anti-p63 was used to identify basal epithelial cells. Levels of STAT3, p-STAT3 (Ser727) and proteins associated with EMT were measured with Western blot assay. Cell proliferation was measured with MTT or CCK8 assay. Normal basal epithelial cells acquired from mouse prostate were specific to anti-p63 and more than 90%. Basal epithelial cells and RM-1 could both secrete TGF-β1. Basal epithelial cells and TGF-β1 promoted the migration and invasion of RM-1 through changing the cell morphology and up-regulating expression of ZEB1, N-cadherin, vimentin, snail and p-STAT3 (Ser727), at the same time down-regulating E-cadherin of RM-1. SB431542 strongly suppressed migration, invasion as well as the expressions of EMT relevant proteins and p-STAT3 (Ser727) of co-cultured RM-1. In addition, stattic suppressed proliferation, migration and invasion of non-treated RM-1 and co-cultured RM-1. Our study suggests that normal basal epithelial cells might stimulate the migration and invasion of RM-1 by TGF-β1/STAT3 axis which could be suppressed by inhibitor of TGF-β receptor and inhibitor of p-STAT3. So, basal epithelial cells might not become a treatment strategy for prostate cancer, but our results could provide some researching references for other diseases which include basal epithelial cells such as prostatic intraepithelial neoplasia, prostatic hyperplasia, cervical cancer, or urinary bladder cancer.


[Incidence of squamous cell carcinoma of the skin in the city of Tubarao (SC)--Brazil in the years 2000, 2003, and 2006].
A worldwide increasing trend in the incidence of squamous cell carcinoma of the skin has been observed but there are no studies regarding the incidence of this cancer in the Southern region of the State of Santa Catarina. To establish epidemiological data regarding squamous cell carcinoma of the skin in Tubarao (state of Santa Catarina). Anatomopathological reports, positive for squamous cell carcinoma of the skin, found in laboratories of the city of Tubarao, were analyzed regarding year, age, gender, site, histological subtype, largest diameter, and biopsy margins. The annual incidence was calculated using the number of neoplasias found and the estimated population for the years 2000, 2003, and 2006. The incidence of squamous cell carcinoma of the skin per 100,000 habitants was 50.86 for the year 2000, 71.16 for 2003 and 94.39 for 2006. There was no gender dominance, the face was the most frequent location affected in both genders, and the most common histological subtype was well differentiated tumor. The detected incidence of squamous cell carcinoma of the skin surpassed the incidence estimated in the literature. There was a considerable increase in its incidence; the variables age and location agreed with information found in the literature but gender distribution differed.


Preliminary examination of cognitive reserve theory in closed head injury.
This investigation was designed to provide preliminary support for cognitive reserve theory in closed head injury (CHI), and demonstrate the effectiveness of using the Oklahoma premorbid intelligence estimate (OPIE) in research and clinical activities. Out of a possible 124 consecutive referrals, 26 patients (N=26) who underwent neuropsychological assessment following brain injury met study inclusion/exclusion criteria. Participants were included if they had exited post-traumatic amnesia (PTA), demonstrated uncompromised upper extremity use, displayed adequate verbal communication, and were judged capable of completing a full neuropsychological evaluation. Participants were divided into a closed head injury-negative premorbid history (CHI-) or closed head injury-positive premorbid history (CHI+) group based upon premorbid variables (e.g., history of alcoholism). Groups did not differ in terms of demographic variables or premorbid IQ. Despite having less severe head injuries, the CHI+ group had a greater pre-post difference for PIQ, and a significantly larger VIQ/PIQ discrepancy than the CHI- group. In conclusion, these findings suggest that the CHI+ group had diminished cognitive reserve secondary to the aggregate effects of premorbid insult, which resulted in greater cognitive decline following an additional stressor (i.e., CHI) than what might otherwise be expected from the head injury alone.


Levodopa has primarily negative influences on postural control in patients with Parkinson's disease.
Patients with Parkinson's disease have better functional status and motor performance under on-drug conditions. However, the administration of levodopa leads to greater postural sway. The present study's primary objective was to determine whether this on-drug problem may be related to a lack of adjustment in postural control mechanisms and body segment rotations. Fourteen patients with Parkinson's disease and 14 controls performed two gaze-shift tasks (40° to the left and 40° to the right, at 0.125 and 0.25Hz) and a stationary gaze task in two sessions (an off-drug session and an on-drug session for the patients, and two off-drug sessions for the controls). At baseline, the "on-drug" patients indeed swayed significantly more than the controls during the gaze-shift tasks. As expected, acute L-dopa administration did not increase eye, head, neck and lower back rotation of the patients during the gaze-shift tasks. Unexpectedly, levodopa appeared to enable the patients to significantly increase the contribution of their postural control mechanisms (relative to controls) during the gaze-shift tasks. However, and as expected, this adjustment was not great enough to enable the patients to maintain their postural sway as well as the controls did. Overall, the administration of levodopa seemed to destabilize the patients - especially with regard to the lower back region. In addition, the patients used hypermetric eye rotations during the gaze-shift tasks under both off- and on-drug conditions. If they had not used these compensatory eye rotations, their unsafe behavior at the hip level might have been even more pronounced. Future research should focus on this lower back weakness.


Analysis of chromosomally normal spontaneous abortions after chorionic villus sampling.
Analysis of patients who spontaneously aborted chromosomally normal pregnancies following chorionic villus sampling (CVS) revealed an overall loss rate of 5.4% but a rate of only 3.2% if the procedure was performed between 9 and 12 menstrual weeks. There is preliminary evidence to suggest that a small but significant risk of infection is related to CVS.


Two 3'-O-β-glucosylated nucleoside fluorometabolites related to nucleocidin in Streptomyces calvus.
The antibiotic nucleocidin is a product of the soil bacterium Streptomyces calvus T-3018. It is among the very rare fluorine containing natural products but is distinct from the other fluorometabolites in that it is not biosynthesised from 5'-fluorodeoxyadenosine via the fluorinase. It seems to have a unique enzymatic fluorination process. We disclose here the structures of two 4'-fluoro-3'-O-β-glucosylated metabolites (F-Mets I and II) which appear and then disappear before nucleocidin production in batch cultures of S. calvus. Full genome sequencing of S. calvus T-3018 and an analysis of the putative biosynthetic gene cluster for nucleocidin identified UDP-glucose dependent glucosyl transferase (nucGT) and glucosidase (nucGS) genes within the cluster. We demonstrate that these genes express enzymes that have the capacity to attach and remove glucose from the 3'-O-position of adenosine analogues. In the case of F-Met II, deglucosylation with the NucGS glucosidase generates nucleocidin suggesting a role in its biosynthesis. Gene knockouts of nucGT abolished nucelocidin production.


A review on toxic and harmful algae in Greek coastal waters (E. Mediterranean Sea).
The Greek coastal waters are subjected to harmful algal bloom (HAB) phenomena due to the occurrence of species characterized as toxic (TX), potentially toxic (PT), and non-toxic, high biomass (HB) producers causing harm at multiple levels. The total number of (TX), (PT) and (HB) algae reported in this work are 61, but only 16 species have been associated with the occurrence of important HABs causing damage in the marine biota and the water quality. These phenomena are sporadic in time, space and recurrence of the causative species, and are related to the anthropogenically-induced eutrophication conditions prevailing in the investigated areas.


Quantitative ultrasound biomicroscopy for the analysis of healthy and repair cartilage tissue.
The increasing spectrum of different cartilage repair strategies requires the introduction of adequate non-destructive methods to analyse their outcome in-vivo, i.e. arthroscopically. The validity of non-destructive quantitative ultrasound biomicroscopy (UBM) was investigated in knee joints of five miniature pigs. After 12 weeks, six 5-mm defects, treated with different cartilage repair approaches, provided tissues with different structural qualities. Healthy articular cartilage from each contralateral unoperated knee joint served as a control. The reflected and backscattered ultrasound signals were processed to estimate the integrated reflection coefficient (IRC) and apparent integrated backscatter (AIB) parameters. The cartilage repair tissues were additionally assessed biomechanically by cyclic indentation, histomorphologically and immunohistochemically. UBM allowed high-resolution visualisation of the structure of the joint surface and subchondral bone plate, as well as determination of the cartilage thickness and demonstrated distinct differences between healthy cartilage and the different repair cartilage tissues with significant higher IRC values and a steeper negative slope of the depth-dependent backscatter amplitude AIBslope for healthy cartilage. Multimodal analyses revealed associations between IRC and the indentation stiffness. Furthermore, AIBslope and AIB at the cartilage-bone boundary (AIBdC) were associated with the quality of the repair matrices and the subchondral bone plate, respectively. This ex-vivo pilot study confirms that UBM can provide detailed imaging of articular cartilage and the subchondral bone interface also in repaired cartilage defects, and furthermore, contributes in certain aspects to a basal functional characterization of various forms of cartilage repair tissues. UBM could be further established to be applied arthroscopically in-vivo.


Individualized treatment strategies and considerations in patients with mild asthma: Discussion of Canadian Thoracic Society guideline recommendations.
To highlight recommendations from the Canadian Thoracic Society (CTS) 2021 asthma guideline for adults and children aged 12 years and older and to address controversies related to the update. The CTS 2021 asthma guideline. Asthma is a common condition encountered in primary care. Poor symptom control and exacerbations contribute substantially to the burden of disease. Practice guidelines have been shifting in recent years toward more aggressive treatment of very mild and mild asthma, with goals of optimizing symptom control and reducing exacerbations. Consider underlying risk of exacerbation, extent of asthma symptoms, adherence levels, and treatment cost when choosing therapy for patients with very mild and mild asthma. The goal of this article is to briefly review the evidence and rationale behind treatment options in the CTS guideline to help physicians make patient-centred decisions.


Competition between Chlamydia psittaci and L cells for host isoleucine pools: a limiting factor in chlamydial multiplication.
L cells (mouse fibroblasts) supported the multiplication of the obligately intracellular parasitic bacterium Chlamydia psittaci (strain 6BC) when incubated in fresh growth medium (medium 199 + 5% fetal calf serum). When incubated in the medium supernatant from a 24-h-old culture of uninfected L cells (24-h used medium), uninfected cells did not divide and infected cells did not provide an adequate environment for the multiplication of C. psittaci, which persisted in a noninfectious latent state within the host cells. The failure of both L cells and chlamydiae to divide resulted from an overall reduction in the rate of protein synthesis by both host and parasite brought about by an insufficiency of the essential amino acid isoleucine in 24-h used medium. The concentration of isoleucine required to activate minimal growth of C. psittaci also minimally stimulated uninfected L cells to divide. The addition of cycloheximide to 24-h used medium also activated the latent chlamydial infection because it stimulated the incorporation of host protein-derived isoleucine into chlamydial protein. The results suggest that the chlamydial parasite and the L-cell host compete for the isoleucine in the soluble pool of the host cell and that the parasite is capable of sequestering isoleucine for its own biosynthetic needs only when the concentration of isoleucine in the host pool rises above the level required to maintain the hose in the stationary state. Extrapolation of the results obtained with the L cell-C. psittaci model system to natural latent chlamydial infections is discussed.


Autoimmune Ascites Responding to Mycophenolate Mofetil: A Case Report.
Ascites is an abnormal accumulation of fluid within the peritoneal cavity. The most common cause of ascites in the United States population is portal hypertension secondary to cirrhosis, accounting for about 80% of the cases. Other etiologies include malignancy, heart failure, tuberculosis, and pancreatic disease. After an extensive literature review, it is to our best knowledge that there have been no cases reported on autoimmune ascites. We present an interesting case of ascites in a 67-year-old Caucasian male with symptoms of recurrent abdominal distention and significant weight gain, refractory to standard therapies. An extensive 3-year long workup was only significant for serum-ascites albumin gradient > 1.1 g/dL, ascitic fluid protein of 3.0 g/dL, and peritoneal biopsies showing minor inflammatory changes. Both common and rare causes of ascites were ruled out. Empiric treatment with mycophenolate mofetil (CellCept) resulted in resolution of symptoms with no need for a repeat paracentesis for > 2 years, suggesting the diagnosis of autoimmune ascites.


[The organization and technology of interaction between health care clinics and comprehensive medical insurance].
Presents the results of realization of public health reforms in some regions of the country. Describes the scheme and stages of introducing obligatory medical insurance, the tasks, functions, and interests of various managing structures of a territory in the progress of reforms. Offers experimentally developed criteria for assessing the readiness of a territory to introduction of obligatory medical insurance, describes the methods and order of monitoring the quality of medical care rendered to insured patients, and outlines alterations in the organization and legal status of public health institutions.


The efficacy of split-night sleep studies.
Positive airway pressure (PAP) therapy is the most commonly used medical modality to reverse the apneas, hypopneas and inspiratory flow-limited breaths which result in the oxyhemoglobin desaturation, altered sleep architecture, and daytime sleepiness representing the cardinal features of obstructive sleep apnea/hypopnea (OSA/H). Identifying optimal strategies to develop the initial positive airway prescription is of paramount importance to clinicians who evaluate patients with suspected OSA/H. In addition, with the growing appreciation of the clinical and physiologic importance of sleep-disordered breathing, there have been increasing demands on clinical resources to diagnose and treat these patients. The time, hardware, and personnel-intensive nature of in-laboratory polysomnography (PSG) are significant in light of the traditional paradigm that utilizes a full night PSG for a diagnostic evaluation and when indicated, another full night for PAP titration. Efforts to identify time and resource-conserving alternatives to this paradigm have focused on in-laboratory split-night studies, in which the diagnosis of OSA/H can be made, and a positive pressure prescription defined during a single overnight PSG. Case-control studies indicate that, when certain guidelines are applied, split-night PSGs result in prescription efficacy and patient adherence, which are comparable to the traditional two-night strategy. However, prospective, randomized trials designed with adequate power are required to further define the impact of a split-night strategy on clinical outcome. As more information becomes available regarding the factors that determine long-term adherence to positive pressure therapy, the potential for efficient, expeditious treatment, and cost savings with split-night sleep studies will likely receive greater attention.


[No adverse effects on intelligence 6 years after surgery for epilepsy].
To evaluate the long-term effects of epilepsy surgery on intelligence. Prospective descriptive. The group included 20 patients of the Instituut voor Epilepsiebestrijding, Heemstede, and the Epilepsiecentrum Kempenhaeghe, Heeze, the Netherlands, who suffered from medication-resistant epilepsy originating from the temporal lobe, in 9 patients from the left lobe (mean age: 33.1 years), in 11 from the right one (34.6 years). The epilepsy focus was removed surgically (Academic Hospital, Utrecht). The scores on the 'Wechsler adult intelligence scale' (WAIS) were determined before the operation and 6 months, 2 years and 6 years after operation. The mean WAIS IQs before operation were: verbal IQ (VIQ): 111.8 and performance IQ (PIQ): 117.7 in the group treated on the left and VIQ: 113.5 and PIQ: 112.4 in the group treated on the right. The mean gains 6 years after operation were 0.8 and 2.6 VIQ-points and 8.7 and 8.5 PIQ-points respectively. In the patients operated on the left the difference between VIQ and PIQ was significant 2 and 6 years after operation. The increase in IQs remained within what could be expected in retests. Only for the VIQ of patients treated on the left was a smaller retest effect found. These figures show that in the long term epilepsy surgery does not have an adverse outcome on the intelligence.


Intracortical myelin links with performance variability across the human lifespan: results from T1- and T2-weighted MRI myelin mapping and diffusion tensor imaging.
Cerebral myelin maturation and aging-related degradation constitute fundamental features of human brain integrity and functioning. Although mostly studied in the white matter, the cerebral cortex contains significant amounts of myelinated axons. However, how intracortical myelin content evolves during development, decays in aging, and links with cognition remain poorly understood. Several studies have shown the potential of mapping myelin in the cortex by use of T1-weighted (T1w) and T2-weighted (T2w) magnetic resonance imaging signal intensity, which show inverse sensitivity to myelin. Here, we characterized cortical myelin in 339 participants 8-83 years of age using a recently introduced T1w/T2w ratio myelin mapping technique and mean diffusivity (MD) from diffusion tensor imaging. To test for cognitive correlates, we used intraindividual variability (IIV) in performance during a speeded task, a measure recently associated with white matter integrity. The results showed that intracortical myelin maturation was ongoing until the late 30s, followed by 20 relative stable years before declining from the late 50s. For MD, U-shaped paths showing similar patterns were observed, but with fewer maturational effects in some regions. IIV was correlated with both T1w/T2w ratio and MD, mainly indicating that the higher degree of intracortical myelin is associated with greater performance stability. The relations were more prominent with advancing age, suggesting that aging-related cortical demyelination contributes to increased IIV. The T1w/T2w ratio myelin-mapping technique thus seems sensitive to intracortical myelin content in normal development and aging, relates to cognitive functioning, and might constitute an important future tool in mapping normal and clinical brain changes.


Exposure to air pollution is associated with lung hyperinflation in healthy children and adolescents in Southwest Mexico City: a pilot study.
Air pollution produces adverse health effects. The consequences of lifelong daily exposures to atmospheric pollutants upon the respiratory apparatus of healthy children are of considerable clinical importance. We investigated the association between exposure to a highly polluted urban environment with a complex mixture of air pollutants-ozone and particulate matter the predominant ones-and chest x-ray abnormalities in 59 healthy Mexican children who are lifelong residents of Southwest Metropolitan Mexico City (SWMMC), with a negative history of tobacco exposure and respiratory illnesses. Their clinical results and x-ray findings were compared to those of 19 Mexican control children, residents of a low-pollution area, with a similar negative history of tobacco exposure and respiratory illnesses. Ozone concentrations in SWMMC exceeded the U.S. Environmental Protection Agency (U.S. EPA) National Ambient Air Quality Standard (NAAQS) for O(3): 0.08 ppm as 1-h maximal concentration, not to be exceeded more than 4 times a year, on 71% of days in 1986 and 95% in 1997, with values as high as 0.48 ppm. Ozone maximal peaks are usually recorded between 2 and 5 pm coinciding with children's outdoor physical activities. Children in the control group reported no upper or lower respiratory symptomatology. Every SWMMC child complained of upper and/or lower respiratory symptoms, including epistaxis, nasal dryness and crusting, cough, shortness of breath, and chest discomfort. Children aged 7-13 yr had the most symptomatology, while 5- to 6-year olds and adolescents with the lowest number of statistically significant outdoor exposure hours had less respiratory symptoms. Bilateral symmetric mild lung hyperinflation was significantly associated with exposure to the SWMMC atmosphere (p = .0004). Chronic and sustained inhalation of a complex mixture of air pollutants, including ozone and particulate matter (PM), is associated with lung hyperinflation, suggestive of small airway disease, in a population of clinically healthy children and adolescents. Small airways are a target of air pollutants in SWMMC children, with ozone and PM being most likely responsible, based on experimental animal, controlled-chamber, and epidemiological data available. Our main concern is the potential likelihood for the development of chronic lung disease in this highly exposed population.


FVA: Modeling Perceived Friendliness of Virtual Agents Using Movement Characteristics.
We present a new approach for improving the friendliness and warmth of a virtual agent in an AR environment by generating appropriate movement characteristics. Our algorithm is based on a novel data-driven friendliness model that is computed using a user-study and psychological characteristics. We use our model to control the movements corresponding to the gaits, gestures, and gazing of friendly virtual agents (FVAs) as they interact with the user's avatar and other agents in the environment. We have integrated FVA agents with an AR environment using with a Microsoft HoloLens. Our algorithm can generate plausible movements at interactive rates to increase the social presence. We also investigate the perception of a user in an AR setting and observe that an FVA has a statistically significant improvement in terms of the perceived friendliness and social presence of a user compared to an agent without the friendliness modeling. We observe an increment of 5.71% in the mean responses to a friendliness measure and an improvement of 4.03% in the mean responses to a social presence measure.


School-Based Curriculum to Improve Depression Literacy Among US Secondary School Students: A Randomized Effectiveness Trial.
To determine the effectiveness of a universal school-based depression education program. In 2012-2015, we matched 6679 students from 66 secondary schools into pairs by state (Maryland, Delaware, Pennsylvania, Michigan, and Oklahoma) and randomized to the Adolescent Depression Awareness Program (ADAP; n = 3681) or to a waitlist control condition (n = 2998). Trained teachers delivered ADAP as part of the health education curriculum to students aged 14 to 15 years. The primary outcome was depression literacy. Secondary outcomes included mental health stigma and, in a subset of the sample, the receipt of mental health services. Follow-up was at 4 months. ADAP resulted in significantly higher levels of depression literacy among participating students than did waitlist controls, after adjusting for pretest assessment depression literacy (P < .001). Overall, ADAP did not significantly affect stigma (P = .1). After ADAP, students approached 46% of teachers with concerns about themselves or others. Of students who reported the need for depression treatment, 44% received treatment within 4 months of ADAP implementation. ADAP is an effective public health intervention for improving depression literacy among students. Clinicaltrials.gov NCT02099305.


Activation of fast skeletal muscle: contributions of studies on skinned fibers.
The membrane potential of vertebrate twitch fibers closely controls Ca fluxes between intracellular compartments, which in turn control contraction. Recent work on intracellular Ca movement is reviewed in the general context of current efforts to synthesize physiological, biochemical, and structural observations on the contractile mechanism and its regulation, emphasizing the increasing role of functionally skinned fibers in this synthesis. Skinned fiber preparations, with removed or disrupted sarcolemma, bridge the gap between properties of isolated subsystems and their constrained operation in the intact fiber. Recent studies indicate that the surface action potential propagates along the transverse tubules, but not the sarcoplasmic reticulum (SR), which appears to be a distinct intracellular compartment. Voltage-dependent charge movements in the transverse tubules probably control Ca flux across the SR membranes. Current questions concern the mechanism of the signal that bridges the junctional gap between the two membrane systems, the mechanism and properties of the activated Ca efflux to the myofilament space, and the operation of the Ca pump of the SR during activation. New methods applied to intact fibers, cut fibers, skinned fibers, and subcellular systems are yielding the kind of information needed for a complete description of these central steps in excitation-contraction coupling and of Ca regulation of the myofilaments.


Looking Beyond the Terrestrial: The Potential of Seaweed Derived Bioactives to Treat Non-Communicable Diseases.
Seaweeds are a large and diverse group of marine organisms that are commonly found in the maritime regions of the world. They are an excellent source of biologically active secondary metabolites and have been shown to exhibit a wide range of therapeutic properties, including anti-cancer, anti-oxidant, anti-inflammatory and anti-diabetic activities. Several Asian cultures have a strong tradition of using different varieties of seaweed extensively in cooking as well as in herbal medicines preparations. As such, seaweeds have been used to treat a wide variety of health conditions such as cancer, digestive problems, and renal disorders. Today, increasing numbers of people are adopting a "westernised lifestyle" characterised by low levels of physical exercise and excessive calorific and saturated fat intake. This has led to an increase in numbers of chronic Non-communicable diseases (NCDs) such as cancer, cardiovascular disease, and diabetes mellitus, being reported. Recently, NCDs have replaced communicable infectious diseases as the number one cause of human mortality. Current medical treatments for NCDs rely mainly on drugs that have been obtained from the terrestrial regions of the world, with the oceans and seas remaining largely an untapped reservoir for exploration. This review focuses on the potential of using seaweed derived bioactives including polysaccharides, antioxidants and fatty acids, amongst others, to treat chronic NCDs such as cancer, cardiovascular disease and diabetes mellitus.


Maternal and newborn outcomes of care from community midwives in Pakistan: A retrospective analysis of routine maternity data.
The study aimed to determine the maternal and newborn outcomes of Community Midwives' (CMWs') services in Pakistan as recorded in the provincial Management Information System (MIS) of the government's Maternal Newborn and Child Health (MNCH) program of Sindh province. A descriptive retrospective design was used to examine the monthly reports of CMWs, stored in the MNCH-MIS, for the period of January 2013 to December 2015. A total of 200 CMWs were randomly selected from 23 districts of the Sindh province. The outcomes of the CMWs' services were analyzed, using descriptive statistics. The analysis of data of 23 districts revealed that a total of 103,836 antenatal care were attended by 200 CMWs who were selected for the study. For intranatal care, 23,296 cases were registered, of which 78.3% (n = 18, 233) returned to these CMWs at the time of delivery. During the period, 17,849 were live births. The still birth rate was calculated to be 13.4/1000, the abortion rate was 7.3 per 1000 pregnant women, newborn mortality rate was 12.4/1000 live births, and the maternal mortality ratio was 142.5/100,000 live births. Moreover, the low birth weight newborns were 9% of the total live births. This study indicates that although the outcomes for CMWs are better than for some other cadres in Pakistan, they are still inadequate compared to midwives trained to the international standards. The outcomes presented in this study are in line with the challenges of CMWs survival reported in the earlier studies. This strongly indicate need for improvement in CMWs pre-service and in-service education to meet the international quality standards set by ICM.


Effect of feed withdrawal or challenge with Pasteurella multocida on growth, blood metabolites, circulating growth hormone, and insulin-like growth factor-I concentrations in eight-week-old turkeys.
The daily effects of feed withdrawal or a bacterial disease (Pasteurella multocida; PM) challenge was studied in a slow-growing line of turkeys. The following groups (n = 6 birds/group) were sampled for up to 13 d: untreated control (CON), 4-d feed withdrawal followed by refeeding (FAST), a group that succumbed within the first 2 to 3 d after PM challenge (E-DEAD), a group that succumbed 8 to 9 d after PM challenge (L-DEAD), a group that survived the PM challenge (SUR), and a group treated with both PM challenge and 4-d feed withdrawal followed by refeeding (FAST/CHAL). Daily feed intake and BW gains were markedly reduced in the E-DEAD and L-DEAD groups immediately and 3 d after PM challenge, respectively. Feed intake and BW gain between CON and SUR groups of turkeys were not different throughout the trial. The turkeys in the FAST group followed the expected feed withdrawal and refeeding patterns for feed intake and BW loss or gain. The FAST/CHAL turkeys consumed the minimal amount of feed to maintain BW after refeeding. Plasma uric acid sharply increased 1 d prior to death in both E-DEAD and L-DEAD groups of turkeys. Plasma uric acid also increased each consecutive day during fasting in the FAST and FAST/CHAL groups of turkeys. Plasma growth hormone was measured in only the CON and FAST groups and increased from about 40 to 85 ng/mL in the FAST group during fasting but returned to control levels within 1 d of refeeding. Circulating plasma insulin-like growth factor-I (IGF-I) decreased from about 17 to 5 ng/mL in the PM-challenged (E-DEAD, L-DEAD, and FAST/CHAL groups) and FAST groups. The concentration of IGF-I returned to prefeed withdrawal levels within 3 d of refeeding the FAST group of turkeys. It was concluded that 1) turkey poults that were not susceptible to the PM challenge generally maintained physiological functions at control bird levels, 2) susceptible turkey poults generally exhibited depressed feed intake and BW gains, and 3) poults challenged with both feed withdrawal and PM treatment responded differently than poults challenged with either feed withdrawal or challenge with PM. The depletion of energy intake and mobilization of energy stores in susceptible poults might have contributed to the rate at which PM caused the poults to die.


[How to avoid burnout syndrome in a general surgical service].
Burnout syndrome may affect >50% of physicians and is characterized by feelings of emptiness and negative attitudes towards work and life. The work of surgeons presented some specific causal factors that determine that the physician (as a professional) can "burn out" and suffer from this disease with the consequent social/laborial impact, affecting also the rest of the surgical service. These may include external factors linked to the health organization or to internal factors that are directly dependent on the type of work performed by the hospital surgeon. This study analyzes these causal factors of burnout and offers some simple coping strategies in order to improve the health of professionals.


Exploring the Effects of a Social Robot's Speech Entrainment and Backstory on Young Children's Emotion, Rapport, Relationship, and Learning.
In positive human-human relationships, people frequently mirror or mimic each other's behavior. This mimicry, also called entrainment, is associated with rapport and smoother social interaction. Because rapport in learning scenarios has been shown to lead to improved learning outcomes, we examined whether enabling a social robotic learning companion to perform rapport-building behaviors could improve children's learning and engagement during a storytelling activity. We enabled the social robot to perform two specific rapport and relationship-building behaviors: speech entrainment and self-disclosure (shared personal information in the form of a backstory about the robot's poor speech and hearing abilities). We recruited 86 children aged 3-8 years to interact with the robot in a 2 × 2 between-subjects experimental study testing the effects of robot entrainment Entrainment vs. No entrainment and backstory about abilities Backstory vs. No Backstory. The robot engaged the children one-on-one in conversation, told a story embedded with key vocabulary words, and asked children to retell the story. We measured children's recall of the key words and their emotions during the interaction, examined their story retellings, and asked children questions about their relationship with the robot. We found that the robot's entrainment led children to show more positive emotions and fewer negative emotions. Children who heard the robot's backstory were more likely to accept the robot's poor hearing abilities. Entrainment paired with backstory led children to use more of the key words and match more of the robot's phrases in their story retells. Furthermore, these children were more likely to consider the robot more human-like and were more likely to comply with one of the robot's requests. These results suggest that the robot's speech entrainment and backstory increased children's engagement and enjoyment in the interaction, improved their perception of the relationship, and contributed to children's success at retelling the story.


Neurasthenia, Generalized Anxiety Disorder, and the Medicalization of Worry in a Vietnamese Psychiatric Hospital.
This article examines two forms of the medicalization of worry in an outpatient psychiatric clinic in Ho Chi Minh City, Vietnam. Biomedical psychiatrists understand patients' symptoms as manifestations of the excessive worry associated with generalized anxiety disorder (GAD). Drawing on an ethnopsychology of emotion that reflects increasingly popular models of neoliberal selfhood, these psychiatrists encourage patients to frame psychic distress in terms of private feelings to address the conditions in their lives that lead to chronic anxiety. However, most patients attribute their symptoms to neurasthenia instead of GAD. Differences between doctors' and patients' explanatory models are not just rooted in their understandings of illness but also in their respective conceptualizations of worry in terms of emotion and sentiment. Patients with neurasthenia reject doctors' attempts to psychologize distress and maintain a model of worry that supports a sense of moral selfhood based on notions of obligation and sacrifice.


Differential neuroplastic changes in neocortical movement representations and dendritic morphology in epilepsy-prone and epilepsy-resistant rat strains following high-frequency stimulation.
The epileptogenic-prone (FAST) and epileptogenic-resistant (SLOW) rat strains have become a valuable tool for investigating the neurochemical and neurophysiological basis of epilepsy. This study examined the two strains with respect to their neocortical movement representations and cortical layer III pyramidal cell dendritic morphology in both control and potentiated conditions. FAST and SLOW rats received high-frequency stimulation of the corpus callosum in order to induce long-term polysynaptic potentiation of the transcallosal pathway to the sensorimotor neocortex. Baseline-evoked potentials of this pathway were recorded in the left hemisphere before stimulation, and following 5, 10, 15 and 20 days of high-frequency stimulation. All rats then underwent high-resolution intracortical microstimulation (ICMS) in order to assess functional movement representations of the left caudal forelimb area of the sensorimotor cortex. Immediately following ICMS, the brains were stained with the Golgi-Cox method, and the length, branching and spine density of frontal and occipital neocortical layer III pyramidal neurons were measured. We observed that high-frequency stimulation induced similar increases in polysynaptic potentiation in both rat strains; however, only the FAST strain showed an increase (doubling) in the size of their motor maps. We also observed decreases in dendritic length and branching in the FAST rats, and the opposite profile in the SLOW rats. The potentiated FAST rats also showed an increase in spine density. Our results suggest that differences in susceptibility to epileptogenesis may result in a differential response to stimulation-induced plasticity.


Platelet distribution width: a simple, practical and specific marker of activation of coagulation.
Platelet indices are potentially useful markers for the early diagnosis of thromboembolic diseases. An increase in both mean platelet volume (MPV) and platelet distribution width (PDW) due to platelet activation, resulting from platelet swelling and pseudopodia formation was hypothesized. Platelet indices (MPV and PDW) in three groups of persons, using impedance and optical technology were measured. The first group consisted of patients with established platelet activation and healthy control subjects. The second study group included pregnant women in different trimesters of pregnancy. The effect of storage time on MPV and PDW in blood samples of a third group of randomly chosen patients was also assessed. There was a significant increase in MPV (P<0.001) and PDW (P<0.001) in patients with confirmed platelet activation compared to healthy control subjects. Only PDW showed a significant increase from the first to the third trimester of pregnancy (P=0.009). Temporal changes of MPV and PDW over storage time revealed a significant increase in MPV (P<0.001), in contrast to a significant decrease in PDW (P<0.05). MPV and PDW are simple platelet indices, which increase during platelet activation. PDW is a more specific marker of platelet activation, since it does not increase during simple platelet swelling.


Reading Rate Acceleration: Developmental Aspects.
The relationships between reading rate, decoding, and comprehension during consecutive stages of reading acquisition were examined in this longitudinal study. Participants were followed throughout their first 5 years of elementary school. Substantial gains in comprehension and decoding accuracy were obtained for all 5 grade levels during reading acceleration. This effect was particularly pronounced among poor readers. Reading acceleration may enhance reading performance by promoting a more effective use of cognitive resources. Further analyses revealed 2 stages in the development of the 3 reading subskills. In the first stage (Grades 1 to 3), performance in each subskill was directly related to improvements in that same subskill, whereas in the second stage (Grades 4 to 5), reading rate became a determining factor in reading performance. Second-grade reading rate was the best predictor of reading performance in Grades 4 and 5. This finding indicates that reading rate may play a critical role in the successful acquisition of reading skills. Reading rate could be a useful diagnostic aid, and accelerating reading rate might serve as a remedial tool.