Synthesis and reactivity of new bis(N-heterocyclic carbene) iridium(I) complexes.
New complexes of the type trans-[IrCl(η(2)-COE)(NHC)2] (COE = cis-cyclooctene; NHC = N-heterocyclic carbene) have been prepared in one step from the reaction of ca. 4 equiv of NHC or [AgCl(NHC)] with [IrCl(η(2)-COE)2]2 in benzene. These new complexes have been characterized by techniques including NMR and IR spectroscopy, X-ray crystallography, and elemental analysis. Exposing trans-[IrCl(COE)(I(i)Pr(Me))2] to CO yielded trans-[IrCl(CO)(I(i)Pr(Me))2], which is the only bis(NHC) analogue of Vaska's complex trans-[IrCl(CO)(PPh3)2] known to date. The synthesis of trans-[Ir(CO)(I(i)Pr(Me))2(R)] (R = MeO, PhCC, OSiPh3, O2CPh) complexes has been achieved via deprotonation reactions involving the new hydroxide species trans-[Ir(OH)(CO)(I(i)Pr(Me))2].


Primary immunodeficiency for the primary care provider.
Primary immunodeficiencies are a group of heterogeneous disorders resulting from defects affecting the function of ≥1 parts of the immune system. Current estimates of the prevalence of primary immunodeficiency disease are one in 1200 patients. In Ontario, where the average general practitioner follows 1300 to 2000 patients, an estimated two patients will have primary immunodeficiency. With new primary immunodeficiencies being described at an exponential rate, and those previously described becoming better understood, it is challenging for health care providers to stay up to date. Knowledge gaps delay diagnosis and treatment, leading to increased morbidity and mortality. The present review aims to provide the primary care provider with the tools necessary to recognize primary immunodeficiency and assist in establishing diagnoses.


Trochanteric fractures. Influence of reduction and implant position on impaction and complications.
A review of roentgenograms and charts was made of 532 trochanteric fractures treated by the sliding-screw technique. According to Evans' modified classification, 65% of the fractures were unstable. There was no breakage or bending of implants. Twenty (3.8%) reoperations were performed because of technical complications or nonunion. The Singh index revealed more unstable fractures and technical complications in hips with Grades 1-3 than in hips with Grades 4-6. Reoperation was more frequent if the screw tip was within 8 mm from the subchondral line in the superolateral quadrant or in the anteroproximal quadrant than if the screw ended farther from the subchondral line. Fifty-five (10.8%) of the lag screws migrated 2 mm or more. Postoperatively, the neck-shaft angle decreased more in unstable fractures than in stable fractures. The decrease in neck-shaft angle was less when the proximal fragment impinged medially on the shaft fragment. Unstable fractures with this type of reduction also impacted less than hips with anatomic reduction or medial reduction of the shaft fragment. Weight bearing did not significantly influence the degree of impaction.


Metronomic chemotherapy: possible clinical application in advanced hepatocellular carcinoma.
Hepatocellular carcinoma (HCC) is a hypervascular highly angiogenic tumor usually associated with liver cirrhosis. Vascular endothelial growth factor plays a critical role in vascular development in HCC. In contrast to the treatment of early-stage HCC, the treatment options for advanced HCC are limited and prognosis is often poor, which contributes to this tumor type being the third leading cause of cancer-related deaths worldwide. Metronomic chemotherapy, which was originally designed to inhibit angiogenesis, involves low-dose chemotherapeutic agents administered in a frequent regular schedule with no prolonged breaks and minimizes severe toxicities. We reviewed the potential effects and impact of metronomic chemotherapy in preclinical studies with HCC models and in patients with advanced HCC, especially when combined with a molecular targeted agent. Metronomic chemotherapy involves multiple mechanisms that include antiangiogenesis and antivasculogenesis, immune stimulation by reducing regulatory T cells and inducing dendritic cell maturation, and possibly some direct tumor cell targeting effects, including the cancer stem cell subpopulation. The total number of preclinical studies with HCC models shows impressive results using metronomic chemotherapy-based protocols, especially in conjunction with molecular targeted agents. Four clinical trials and two case reports evaluating metronomic chemotherapy for HCC indicate it to be a safe and potentially useful treatment for HCC. Several preclinical and clinical HCC studies suggest that metronomic chemotherapy may become an alternative type of chemotherapy for advanced unresectable HCC and postsurgical adjuvant treatment of HCC.


Impact of childhood life events and trauma on the course of depressive and anxiety disorders.
Data on the impact of childhood life events and childhood trauma on the clinical course of depressive and anxiety disorders are limited. Longitudinal data were collected from 1209 adult participants in the Netherlands Study of Depression and Anxiety (NESDA). Childhood life events and trauma at baseline were assessed with a semi-structured interview and the clinical course after 2 years with a DSM-IV-based diagnostic interview and Life Chart Interview. At baseline, 18.4% reported at least one childhood life event and 57.8% any childhood trauma. Childhood life events were not predictive of any measures of course trajectory. Emotional neglect, psychological and physical abuse, but not sexual abuse, were associated with persistence of both depressive and comorbid anxiety and depressive disorder at follow-up. Emotional neglect and psychological abuse were associated with a higher occurrence of a chronic course. Poor course outcomes were mediated mainly through a higher baseline severity of depressive symptoms. Childhood trauma, but not childhood life events, was associated with an increased persistence of comorbidity and chronicity in adults with anxiety and/or depressive disorders. More unfavourable clinical characteristics at baseline mediate the relationship between childhood trauma and a poorer course of depressive and anxiety disorders.


Characterization of temperature-induced phase transitions in five polymorphic forms of sulfathiazole by terahertz pulsed spectroscopy and differential scanning calorimetry.
The far-infrared properties of all five known polymorphic forms of the drug sulfathiazole have been studied by terahertz pulsed spectroscopy and low-frequency Raman spectroscopy. The observed spectra of the different polymorphs are distinctly different. Terahertz pulsed spectroscopy proves to be a rapid and complementary alternative to other physical characterization techniques reported in the literature for distinguishing between the five forms. Variable-temperature measurements (293-473 K) of all polymorphic forms have been performed. The phase transitions observed have been related to thermal analysis data. Form I is the form stable at high temperature of sulfathiazole with a melting point of about 475 K. Form II melts at around 470 K and recrystallizes at higher temperatures to form I. Forms III, IV, and V all convert to form I via a solid-solid phase transition at temperatures below 450 K. The phase transitions can be monitored by terahertz pulsed spectroscopy. Polymorphic impurities of the samples can be detected in the room temperature spectra and their effect on the phase transition behavior can be studied.


Magnitude estimation of inspiratory resistive loads in children with life-threatening asthma.
The perception of inspiratory resistive (R) loads was studied in nonasthmatic children and in children with a history of life-threatening asthma. It was hypothesized that the children with life-threatening asthma would have a reduced sensitivity to added mechanical loads as measured by magnitude estimation of resistive loads (ME). The subjects were screened from the experimenter and seated in a sound-isolated room in a lounge chair facing an oscilloscope, and they respired through a nonbreathing valve with the inspiratory port connected to the loading manifold. The oscilloscope displayed the inspiratory V, and each subject was required to inspire to the same peak V for each breath. The subject's inspiratory background R was measured by the interrupter method. Five magnitudes of R loads and no-load were presented randomly 10 times each for a single inspiration after the illumination of a light cue. The subjects were initially given a training trial breathing to the V target. The loads were presented in two trials. The load was estimated using the modified Borg scale. The slope of the log-log relationship between R load magnitude and the ME is a measure of the sensitivity of the subject to R loads. The slope for children with life-threatening asthma was significantly less than that for asthmatic and nonasthmatic children. There were no significant differences in the slope related to race, sex or age in the nonasthmatic children or in the asthmatic children. The reduced sensitivity to increased R loads suggests that these children are at risk of a life-threatening asthmatic attack in part because of an underestimation or delay in the perception of the increased mechanical load that occurs during an asthmatic attack.


Nanochannel with uniform and Janus surfaces: shear thinning and thickening in surfactant solution.
On basis of molecular simulation of confined surfactant solutions, we show that by adding chemical patterns on the inner surface of nanochannels dynamical properties of the confined surfactant solutions could be modified from shear thinning to shear thickening. To this end, we select uniformly hydrophobic and hydrophilic surfaces as well as a stripe-patterned Janus surface as three prototype confining surfaces of nanochannels. In all three nanochannels, when the surfactant solution is under relatively low shear rates, it shears thin. Under moderate shear rates, a sharp decrease in the shear viscosity could occur due to surfactant morphology transition. Under relatively high shear rates, a shear-thinning-to-thickening transition can emerge due to the tendency of stratification normal to the confining surface. Our simulation study offers a guide to steering dynamic properties of surfactant fluids in nanofluidic devices through engineering surfaces of nanochannels by design.


Association Between Use of Anti-gout Preparations and Dementia: Nested Case-Control Nationwide Population-Based Cohort Study.
Objectives: Gout is the most common form of inflammatory arthritis and was found to be independently associated with incident dementia in the elderly. However, the associations between anti-gout preparations and dementia were not well-studied. Methods: Data were collected from Taiwan's National Health Insurance Research Database (NHIRD). A 2005-2013 retrospective cohort study was conducted, and all investigated subjects were identified by International Statistical Classification of Diseases and Related Health Problems, 9th Revision, Clinical Modification. Conditional logistic regression was used to evaluate the odds ratio of dementia in relation to different gout preparations (benzbromarone, allopurinol, sulfinpyrazone, probenecid) and number of days of anti-gout preparation use, after adjustment for potential confounding variables. Results: A total of 3,242 gout patients with and without dementia were selected from the NHIRD and included in the final analysis after 1:1 matching for age, gender, and diagnosis year of gout. In the anti-gout preparations, only use of Benzbromarone decreased the risk of dementia (adjusted OR, 0.81; 95% CI, 0.68-0.97). The result of the subgroup analysis revealed a trend toward a lower risk of dementia with longer use of benzbromarone. Use of benzbromarone for ≥180 days showed a significantly lower risk of dementia (adjusted OR, 0.72; 95% CI, 0.58-0.89). Moreover, the protective effect was more pronounced in males compared with females. Conclusion: This cohort study reveals that gout patients taking benzbromarone are at a decreased risk of developing incident dementia, especially with longer use and in male. Further prospective trials are warranted to confirm our findings.


National and Regional Variation in Local Primary Care Physician Density Relative to the Uninsured and the Affordable Care Act.
This study is the first to examine primary care physician (PCP) density relative to the uninsured at the local level prior to and after insurance expansion under the Affordable Care Act. Primary care physician density is associated with access to care, lower inpatient and emergency care, and primary care services. However, access to primary care among the uninsured may be limited due to inadequate availability of PCPs. Core-Based Statistical Area (CBSA) data from the Area Health Resource File were retrospectively examined before and after Medicaid expansion. Multiple logistic regressions were modeled for PCP density with predictor interaction effects for percentage uninsured, Medicaid expansion status, and US Census regions. Medicaid expansion CBSAs had significantly lower proportions of uninsured and higher PCP density compared with their nonexpansion counterparts. Nationally, increasing proportions of the uninsured were significantly associated with decreasing PCP density. Most notably, there is an expected 32% lower PCP density in Western Medicaid expansion areas with many uninsured (90th percentile) compared with those with few uninsured (10th percentile). Areas expanding Medicaid with greater proportions of people becoming insured postexpansion had significantly fewer PCPs. Areas with greater proportions of the uninsured may have reduced access to primary care due to the paucity of PCPs in these areas. Efforts to improve access should consider a lack of local PCPs as a limitation for ensuring accessible and timely care. Health care and policy leaders should focus on answers to improve the local availability of primary care clinicians in underserved communities.


The phylogenetic and evolutionary analyses of detoxification gene families in Aphidinae species.
Detoxification enzymes play significant roles in the interactions between insects and host plants, wherein detoxification-related genes make great contributions. As herbivorous pests, aphids reproduce rapidly due to parthenogenesis. They are good biological materials for studying the mechanisms that allow insect adaptation to host plants. Insect detoxification gene families are associated with insect adaptation to host plants. The Aphidinae is the largest subfamily in the Aphididae with at least 2483 species in 256 genera in 2 tribes: the Macrosiphini (with 3/4 of the species) and the Aphidini. Most aphid pests on crops and ornamental plants are Aphidinae. Members of the Aphidinae occur in nearly every region of the world. The body shape and colour vary significantly. To research the role that detoxification gene families played in the process of aphid adaptation to host evolution, we analyzed the phylogeny and evolution of these detoxification gene families in Aphidinae. In general, the P450/GST/CCE gene families contract, whereas the ABC/UGT families are conserved in Aphidinae species compared to these families in other herbivorous insects. Genus-specific expansions of P450 CYP4, and GST Delta have occurred in the genus Acyrthosiphon. In addition, the evolutionary rates of five detoxification gene families in the evolution process of Aphidinae are different. The comparison of five detoxification gene families among nine Aphidinae species and the estimated relative evolutionary rates provided herein support an understanding of the interaction between and the co-evolution of Aphidinae and plants.


Feline Infectious Peritonitis: Immunohistochemical Features of Ocular Inflammation and the Distribution of Viral Antigens in Structures of the Eye.
Feline infectious peritonitis (FIP) is a serious, widely distributed systemic disease caused by feline coronavirus (FCoV), in which ocular disease is common. However, questions remain about the patterns of ocular inflammation and the distribution of viral antigen in the eyes of cats with FIP. This study characterized the ocular lesions of FIP including the expression of glial fibrillary acidic protein and proliferating cell nuclear antigen by Müller cells in the retina in cases of FIP and to what extent macrophages are involved in ocular inflammation in FIP. Immunohistochemistry for FCoV, CD3, CD79a, glial fibrillary acidic protein, calprotectin, and proliferating cell nuclear antigen was performed on paraffin sections from 15 naturally occurring cases of FIP and from controls. Glial fibrillary acidic protein expression was increased in the retina in cases of FIP. Müller cell proliferation was present within lesions of retinal detachment. Macrophages were present in FIP-associated ocular lesions, but they were the most numerous inflammatory cells only within granulomas (2/15 cats, 13%). In cases of severe inflammation of the ciliary body with damage to blood vessel walls and ciliary epithelium (3/15, 20%), some macrophages expressed FCoV antigens, and immunolabeling for calprotectin on consecutive sections suggested that these FCoV-positive macrophages were likely to be recently derived from blood. In cases of severe and massive inflammation of most ocular structures (4/15, 26%), B cells and plasma cells predominated over T cells and macrophages. These results indicate that gliosis can be present in FIP-affected retinas and suggest that breakdown of the blood-ocular barrier can allow FCoV-bearing macrophages to access the eye.


Skewed X-inactivation in a Female Carrier with X-linked Chronic Granulomatous Disease.
Chronic granulomatous disease (CGD) is a primary immunodeficiency caused by defective phagocytic NADPH oxidase, causing a complete lack or significant decrease in the production of microbicidal reactive oxygen metabolites. It mainly affects male children; however, there are scarce reports of adult females diagnosed with X-linked-CGD attributed to an extremely skewed X-chromosome inactivation. This condition is characterized by severe and recurrent infections that usually develop after childhood. In clinical practice, physicians who usually confront these patients should suspect this entity and differentiate it from a secondary immunodeficiency. Here, we report a 38-year-old Mexican female with juvenile-onset X linked-CGD, caused by a de novo mutation and extremely skewed X-inactivation, whose clinical features were similar to those in patients with classic X-linked-CDG.


Copy number variations of the KAT6A gene are associated with body measurements of Chinese sheep breeds.
Copy number variation (CNV) is one kind of genomic structure variations and presents as gains and losses of genomic fragments. More recently, we have made an atlas of CNV maps for livestock. In the future, it is a primary focus to determine the phenotypic effects of candidate CNVs. Lysine Acetyltransferase 6 A (KAT6A) is a protein coding gene and plays a critical role in many cellular processes. However, the effects of KAT6A CNVs on sheep body measurements remains unknown. In this study, we performed quantitative polymerase chain reaction (qPCR) to detect the presences and distributions of three CNV regions within KAT6A gene in 672 sheep from four Chinese breeds. Association analysis indicated that the three CNVs of KAT6A gene were significantly associated with body measurement(s) in Small-tailed Han sheep (STH) and Hu sheep (HU) (p < 0.05), while no effects on Large-tailed Han sheep (LTH) were observed (p > 0.05) were observed. Additionally, only one CNV was significantly associated with body measurement (body length) in Chaka sheep (CK) (p < 0.05). Our study provided evidence that the CNV(s) of KAT6A gene could be used as candidate marker(s) for molecular breedings of STH, HU, and CK breeds.


Differentiation and regulation of the corticotropic pituitary cell.
A number of primary diseases of the pituitary with adrenocorticotropin dysregulation have been recognized. A few genetic defects have been identified as causes of secondary adrenocortical insufficiency. Much less is known about the ontogeny of corticotrophic tumours leading to a hypercorticolaemic state. To improve the diagnosis and treatment of these disorders, a better understanding of the mechanisms of corticotrophic pituitary cell differentiation and regulation is of clear interest. Studies using molecular tools have enhanced our knowledge over recent years, and a few reports of considerable relevance are summarized in this review.


Initial experience with staged buccal graft (Bracka) hypospadias reoperations.
We report outcomes from staged buccal graft urethroplasty after failed hypospadias surgery. When the urethral plate had been excised or was visibly scarred after prior surgery patients underwent staged buccal graft repair. In the first operation persistent penile curvature was corrected, a proximal cutaneous urethrostomy was created, scarred tissues distally were excised and buccal graft was quilted into place for subsequent urethroplasty. At least 6 months later the now revascularized buccal strip was tubularized and covered with a dartos or tunica vaginalis flap. A total of 25 patients underwent stage 1 repair following an average of 4.4 prior hypospadias surgeries. Complete graft take occurred in 22 (88%) cases while the remaining 3 had focal scar or graft contracture that was successfully patched before tubularization. To date 20 patients have undergone the stage 2. There were no cases of meatal stenosis, neourethral stricture or diverticulum. A fistula occurred in 1 (5%) of 18 cases in which a flap barrier layer was used. Partial glans dehiscence occurred in 4 prepubertal boys with graft obtained from the cheek, and they have undergone successful reoperative glansplasty. All patients completing surgery have a vertical slit neomeatus. Staged buccal graft reoperation reliably creates a well vascularized substitute urethral plate for tubularization with low complication rates and good cosmetic outcomes. Inner lip, which is thinner than cheek, may be a better source of graft for the glanular urethra.


Effect of KN-62, Ca2+/calmodulin-dependent protein kinase II inhibitor, on adriamycin resistance of human ovarian cancer cells.
We examined effects of an isoquinolinesulfonamide derivative, KN-62, on human ovarian cancer cells, NOS3AR, that are resistant to Adriamycin (ADR). MTT assay revealed that 10 microM KN-62 overcame the resistance. KN-62 had little effect on GST activity. In studies on the intracellular accumulation of ADR, KN-62 increased the ADR contents in the resistant cells close to the level seen in the sensitive cells. These results suggest that the reversal of the resistance against ADR in ovarian cancer cells by KN-62 is mainly due to higher accumulation of ADR in NOS3AR cells. Furthermore, we detected Ca2+/calmodulin-dependent protein kinase II (CaM kinase II) in NOS3AR cells since KN-62 is a specific inhibitor of the kinase. In this paper, we discussed on modulation of ADR-resistance by KN-62.


[Cohort fertility of men and women in the Federal Republic of Germany. A measurement with data from empirical social research].
The availability of mates and the consequences for cohort fertility by sex in Germany is analyzed using pooled data from various fertility surveys conducted since 1900. "All German male cohorts born before 1930 have a greater number of children than their female counterparts. German men up to cohorts around 1930 experienced favourable conditions of the marriage market due to the consequences of the two World Wars.... The general decline of births beginning around 1970 will, however, turn around this relative position. Leaving the preferred age-difference between spouses unchanged smaller female cohorts will now be able to select partners from greater (and older) cohorts of potential male partners. These changing relative positions are already visible in the differences between male and female cohort fertility." (SUMMARY IN ENG)


Evaluation of waist circumference to predict general obesity and arterial hypertension in women in Greater Metropolitan Belo Horizonte, Brazil.
This study examined the capacity of waist circumference (WC) to identify subjects with overweight (BMI >/=25) and obesity (BMI >/=30), in agreement with internationally recommended levels of action. Data were obtained from 791 women, 15-59 years old. After identifying overweight and obesity according to WC values, sensitivity and specificity were calculated to verify whether WC could be a good risk predictor for hypertension. Associations were tested by linear regression and logistic regression, controlling for confounding. WC cut-off points of 80cm and 88cm correctly identified 89.8% and 88.5% of women with overweight and obesity, respectively. Abdominal obesity (WC >/=88cm) was statistically associated with hypertension in the multivariate analysis (OR = 2.88; 95% CI: 1.77-4.67). Hypertension was identified with a sensitivity of 63.8% and 42.8%, and with a specificity of 68.0% and 83.3%, for WC >/=80 and >/=88, respectively. The proposed cut-off points for abdominal obesity can potentially distinguish individuals at risk for future obesity, but has only moderate power to predict individuals with high blood pressure.


Improved cutaneous melanoma survival stratification through integration of 31-gene expression profile testing with the American Joint Committee on Cancer 8th Edition Staging.
Cutaneous melanoma (CM) survival is assessed using averaged data from the American Joint Committee on Cancer 8th edition (AJCC8). However, subsets of AJCC8 stages I-III have better or worse survival than the predicted average value. The objective of this study was to determine if the 31-gene expression profile (31-GEP) test for CM can further risk-stratify melanoma-specific mortality within each AJCC8 stage. This retrospective multicenter study of 901 archival CM samples obtained from patients with stages I-III CM assessed 31-GEP test predictions of 5-year melanoma-specific survival (MSS) using Kaplan-Meier and Cox proportional hazards. In stage I-III CM population, patients with a Class 2B result had a lower 5-year MSS (77.8%) than patients with a Class 1A result (98.7%) and log-rank testing demonstrated significant stratification of MSS [χ2 (2df, n = 901) = 99.7, P < 0.001). Within each stage, 31-GEP data provided additional risk stratification, including in stage I [χ2 (2df, n = 415) = 11.3, P = 0.004]. Cox regression multivariable analysis showed that the 31-GEP test was a significant predictor of melanoma-specific mortality (MSM) in patients with stage I-III CM [hazard ratio: 6.44 (95% confidence interval: 2.61-15.85), P < 0.001]. This retrospective study focuses on Class 1A versus Class 2B results. Intermediate results (Class 1B/2A) comprised 21.6% of cases with survival rates between Class 1A and 2B, and similar to 5-year MSS AJCC stage values. Data from the 31-GEP test significantly differentiates MSM into lower (Class 1A) and higher risk (Class 2B) groups within each AJCC8 stage. Incorporating 31-GEP results into AJCC8 survival calculations has the potential to more precisely assess survival and enhance management guidance.


Nutritional niches reveal fundamental domestication trade-offs in fungus-farming ants.
During crop domestication, human farmers traded greater productivity for higher crop vulnerability outside specialized cultivation conditions. We found a similar domestication trade-off across the major co-evolutionary transitions in the farming systems of attine ants. First, the fundamental nutritional niches of cultivars narrowed over ~60 million years of naturally selected domestication, and laboratory experiments showed that ant farmers representing subsequent domestication stages strictly regulate protein harvest relative to cultivar fundamental nutritional niches. Second, ants with different farming systems differed in their abilities to harvest the resources that best matched the nutritional needs of their fungal cultivars. This was assessed by quantifying realized nutritional niches from analyses of items collected from the mandibles of laden ant foragers in the field. Third, extensive field collections suggest that among-colony genetic diversity of cultivars in small-scale farms may offer population-wide resilience benefits that species with large-scale farming colonies achieve by more elaborate and demanding practices to cultivate less diverse crops. Our results underscore that naturally selected farming systems have the potential to shed light on nutritional trade-offs that shaped the course of culturally evolved human farming.


ELISA detection of IL-1 beta in human sera needs independent confirmation. False positives in hospitalized patients.
The detection of cytokines in human sera has become an accepted index of disease activity in various diseases, including sepsis. However, little attention has been paid to the specificity of these measurements. Using a sensitive sandwich enzyme-linked immunoassay (ELISA), we studied IL-1 beta detectability in sera from 419 serum samples randomly obtained from our clinical laboratory. In initial studies, 6.7% of samples were positive (n = 24, 0.1 to 1.0 ng/ml, and n = 5, 1 to 80 ng/ml). However, attempts to further characterize positive samples revealed that over 90% were falsely positive. For example, samples fractionated on Sephadex G-75 demonstrated IL-1 beta "detectability" near the void volume, and negative samples, spiked with rIL-1 beta, eluted at approximately 17 kD. To determine if this detectability was due to heterophillike antibodies, 23 of 29 "positive" samples were retested in the presence of nonimmune mouse serum. Only 2 of 23 previously positive samples were still positive. Importantly, mouse serum had no effect upon normal human serum spiked with rIL-1 beta. Furthermore, blinded samples sent to a reference laboratory also demonstrated false positive IL-1 beta detection in selected samples. Taken together, these data demonstrate that the presence of nonspecific immunoactivity in sera may confound cytokine assays of human biologic material and suggest that, when possible, a second means of confirming ELISA-positive samples be used.


Sodium appetite and 24-hour variations in fluid balance, mean arterial pressure and heart rate in SHR and WKY on various sodium diets.
Young spontaneously hypertensive rats (SHR) and Wistar-Kyoto rats (WKY) were compared with respect to firstly, sodium (Na) appetite during 'rest', mild social stress and adrenocorticotrophic hormone (ACTH) injections and secondly, diurnal patterns of water intake, urine output, mean arterial pressure (MAP) and heart rate (HR) while on various Na diets: 0.5 mmol Na (LNa), 5 or 12-13 mmol Na (CNa), 50 (HNa) or 120 mmol Na (vHNa) per 100 g food. Sodium appetite and water intake, being 50% higher in SHR than in WKY (4-4.5 versus 2.5-3 mmol Na/100 g body weight per day), was modestly increased by both social stress and ACTH, more so in WKY. With regard to influences of the various Na diets, daytime resting MAP was modestly lowered in LNaSHR and slightly increased in vHNaSHR compared with CNaSHR, but about equal in all WKY groups. Food and water consumption was concentrated to the active night period, but even high Na water intakes caused no signs of sustained hypervolaemia, as intake bouts were eliminated by urine within 30-40 min in both SHR and WKY. However, the vHNa diet in particular in SHR increased drinking frequency; each drinking bout induced such rapid, 5-10 min long neurogenic MAP and HR increases that they could not be ascribed to blood volume expansion per se. The diurnal MAP-HR patterns in SHR therefore varied markedly with the Na diets, with a considerably raised average MAP in the vHNa group, even though resting daytime MAP was nearly the same as in CNaSHR.(ABSTRACT TRUNCATED AT 250 WORDS)


Distinct mechanisms of B and T lymphocyte accumulation generate tumor-draining lymph node hypertrophy.
Tumor-draining lymph nodes (TDLNs) often enlarge in human cancer patients and in murine tumor models, due to lymphocyte accumulation and lymphatic sinus growth. B lymphocytes within TDLNs can drive lymph node hypertrophy in response to tumor growth, however little is known about the mechanisms directing the preferential accumulation of B lymphocytes relative to T cells in enlarging TDLNs. To define why B and T lymphocytes accumulate in TDLNs, we quantified lymphocyte proliferation, apoptosis, entry, and exit in TDLNs versus contralateral non-TDLNs (NTDLNs) in a footpad B16-F10 melanoma mouse model. B and T lymphocyte proliferation and apoptosis were increased as the TDLNs enlarged, although relative rates were similar to those of NTDLNs. TDLN entry of B and T lymphocytes via high endothelial venules was also modestly increased in enlarged TDLNs. Strikingly, the egress of B cells was strongly reduced in TDLNs versus NTDLNs, while T cell egress was modestly decreased, indicating that regulation of lymphocyte exit from TDLNs is a major mechanism of preferential B lymphocyte accumulation. Surface sphingosine-1-phosphate receptor 1 (S1PR1) which binds S1P and signals lymphocyte egress, exhibited greater downregulation in B relative to T lymphocytes, consistent with preferential retention of B lymphocytes in TDLNs. TDLN lymphocytes did not activate surface CD69 expression, indicating a CD69-independent mechanism of downregulation of S1PR1. B and T cell trafficking via afferent lymphatics to enter TDLNs also increased, suggesting a pathway for accumulation of tumor-educated lymphocytes in TDLNs. These mechanisms regulating TDLN hypertrophy could provide new targets to manipulate lymphocyte responses to cancer.


Condylomata acuminata in pre-pubertal children.
The medico-legal significance of anogenital warts as a marker of sexual abuse in children is unclear. This review article presents three case reports and discusses the possible modes of transmission of papilloma virus in children. Although genital warts can indicate sexual abuse, non-sexual transmission may also occur.


The spouse's positive effect on the stroke patient's recovery.
To determine the effect of the presence of a spouse on the stroke patient's adaptation, a retrospective chart review of stroke patients who had completed rehabilitation was conducted. The convenience sample comprised 67 stroke patients of a family practice service who received rehabilitation at Pitt County Memorial Hospital Rehabilitation Center in Greenville, NC, over a 45-month period. Roy's Adaptation Model was the theoretical framework for the inquiry. The Barthel Index measured the functioning level, or adaptation, of the patients on discharge from rehabilitation. It was hypothesized that patients who had a stroke and completed a rehabilitation program would achieve a higher level of adaptation if they had a spouse than would comparable patients without a spouse. This hypothesis was supported by the findings; the average Barthel Index score on discharge was 7.5 points higher in patients who had a spouse (Wilcoxon chi-square = 4.17, p < .05). The implications for nurses are presented.


Human immunodeficiency virus infection of T-lymphoblastoid cells reduces intracellular pH.
Alterations in plasma membrane function are induced by many cytopathic viruses, including human immunodeficiency virus type 1 (HIV-1). These alterations can result in changes in the intracellular content of ions and other small molecules and can contribute to cytolysis and death of the infected cell. The pH-sensitive fluorescent probe 2',7'-bis(2-carboxyethyl)-5,6-carboxyfluorescein-acetoxymethyl ester was used to quantitate intracellular pH (pHi) in HIV-1-infected T cells. Infection of cells from the CD4+ T-lymphoblastoid line HUT-78 (RH9 subclone) with HIV-1 strain LAI resulted in a significant decrease of pHi, from approximately 7.2 in mock-infected cells to below 6.7 by day 4 after infection, when cells were undergoing acute cytopathic effects. The pHi in persistently infected cells that survived the acute cytopathic effects of HIV-1 was approximately 6.8 to 7.0. Studies with amiloride, an inhibitor of the Na+/H+ exchange system, suggest that HIV-1-induced intracellular acidification in lymphocytes is due, in part, to dysfunction of this plasma membrane ion transport system. The alterations in pHi may mediate certain cytopathic effects of HIV-1, thereby contributing to depletion of CD4+ T lymphocytes in patients with AIDS.


Revealing the Diet of Generalist Insect Predators in Strawberry Fields: Not Only Pests, But Other Predators Beware.
Generalist invertebrate predators contribute to pest management in agriculture, providing an important ecosystem service, particularly in organically managed fields. DNA-based methods to study food webs and feeding interactions in unrestricted field conditions have transformed dietary analysis of generalist predators. In this study, we used MiSeq next-generation sequencing (NGS) technology and universal arthropod primers to investigate the diet of several generalist insect predators collected in commercial organic Florida strawberry fields from November 2017 to March 2018. Of 12 predator insect taxa, Geocoris spp. (Say) (Hemiptera: Geocoridae) was the most abundant early in the growing season (November) and was collected consistently until the end of the season (early March). DNA sequences from 105 predator samples were matched to 44 arthropod families, and of these, 17 were categorized as pest families, 10 as nonpest or nonpredator families, and 17 as predator families. Drosophilidae was the most detected pest family, and Dolichopodidae was the most detected predator family. Prey diversity differed among the predators. Chrysoperla spp. (Neuroptera: Chrysopidae) consumed more prey earlier in the season than did other predators, whereas the other predators consumed a greater diversity of other predators regardless of month. Our results showed a high amount of intraguild predation, but also that predators are contributing to pest suppression in organic strawberries and providing an important biological control service in Florida organic strawberries.


Maternal and neonatal circulating visfatin concentrations in patients with pre-eclampsia and a small-for-gestational age neonate.
Maternal circulating visfatin concentrations are higher in patients with a small-for-gestational-age (SGA) neonate than in those who delivered an appropriate-for-gestational age (AGA) neonate or in those with pre-eclampsia. It has been proposed that enhanced transfer of visfatin from the foetal to maternal circulation may account for the high concentrations of maternal visfatin observed in patients with an SGA neonate. The aims of this study were: (1) to determine whether cord blood visfatin concentrations differ between normal neonates, SGA neonates and newborns of pre-eclamptic mothers; and (2) to assess the relationship between maternal and foetal circulating visfatin concentrations in patients with an SGA neonate and those with pre-eclampsia. This cross-sectional study included 88 pregnant women and their neonates, as well as 22 preterm neonates in the following groups: (1) 44 normal pregnant women at term and their AGA neonates; (2) 22 normotensive pregnant women and their SGA neonates; (3) 22 women with pre-eclampsia and their neonates; and (4) 22 preterm neonates delivered following spontaneous preterm labour without funisitis or histologic chorioamnionitis, matched for gestational age with infants of pre-eclamptic mothers. Maternal plasma and cord blood visfatin concentrations were determined by ELISA. Non-parametric statistics were used for analyses. (1) The median visfatin concentration was lower in umbilical cord blood than in maternal circulation, in normal pregnancy, SGA and pre-eclampsia groups (p<0.001 for all comparisons); (2) the median cord blood visfatin concentrations did not differ significantly between term AGA or SGA neonates, infants of mothers with pre-eclampsia and their gestational-age-matched preterm AGA neonates; (3) maternal and cord blood visfatin concentrations correlated only in the normal term group (r=0.48, p=0.04). Circulating visfatin concentrations are lower in the foetal than in the maternal circulation and did not significantly differ between the study groups. Thus, it is unlikely that the foetal circulation is the source of the high maternal visfatin concentrations reported in patients with an SGA neonate.


Association of hypertension with symptoms of benign prostatic hyperplasia.
We determined whether the intensity of benign prostatic hyperplasia (BPH) symptoms and arterial hypertension are associated. Baseline data from a large sample of men seeking treatment for BPH symptoms were analyzed retrospectively. BPH symptom intensity (assessed by the International Prostatic Symptom Score [I-PSS] or urinary flow rate [Qmax]) and blood pressure were determined in 9,857 patients with BPH. Normotension was defined as a diastolic blood pressure of 90 mm Hg or less, the absence of the diagnosis hypertension and the lack of antihypertensive medication (in 4,725). Hypertension was concomitantly defined as a diastolic blood pressure of greater than 90 mm Hg (in 1,727), being diagnosed with hypertension (1,950) or the current prescription of anti-hypertensive drugs (3,360 patients). When age and presence of hypertension were used as the independent explanatory variables, each year of age contributed 0.13 points and measured hypertension 1.60 points to I-PSS as the dependent response variable. Similar results were obtained with Qmax as the dependent response variable. In a logistic regression procedure using age, I-PSS and Qmax as the independent explanatory variables, each year of age and each I-PSS point significantly increased the risk of being hypertensive by 5.3% and 5.0%, respectively, while Qmax did not yield a statistically significant contribution to that risk. We conclude that a significant, age independent association exists between BPH symptoms and hypertension. This finding indicates a common pathophysiological factor for both disease states such as increased sympathetic activity.


An event-related potential study of semantic congruity and repetition in a sentence-reading task: effects of context change.
This experiment examined the joint effects of semantic congruity and repetition on event-related brain potentials (ERPs) elicited in a sentence priming task. In an initial training phase, subjects were familiarized with a list of 60 congruous and incongruous sentences. During the second phase, ERPs were recorded as subjects silently read a set of 180 unconnected sentences. One third of the sentences were presented exactly as they had been seen in training (Old sentences), one third were presented for the first time (Completely New sentences), and one third involved a re-pairing of the frames and completions of the congruous and incongruous Old sentences (New Pair sentences). The N400 congruity effect was reduced for Old as compared with Completely New and New Pair sentence completions. These results suggest that N400 reflects processes that are sensitive to both existing semantic associations and representations of previous episodes that include the context of the eliciting stimulus. A late positive component (LPC) involving a sustained positive shift in the waveform after 600 ms was largest for incongruous completions and occurred somewhat earlier for Old sentences. This pattern of results is consistent with the notion that the LPC is an index of episodic retrieval and elaborative processes. The data also suggest the presence of an early onset slow positive shift that is only evident for New Pair congruous sentences.


Primary non-skeletal intracranial cartilaginous neoplasms: report of a chondroma and a mesenchymal chondrosarcoma.
The clinical and pathological features of two rare, primary non-skeletal intracranial cartilaginous tumours, a chondroma and a mesenchymal chondrosarcoma, are presented. The literature with respect to clinical, pathological, and possible pathogenetic features is reviewed. The chondroma was successfully resected and the patient has had no recurrence since the operation in 1956. The clinical course of the mesenchymal chondrosarcoma was characterized by rapidly recurring tumour, slowed somewhat by cobalt therapy and frequent surgical interventions. Death occurred some 16 months after the initial resection. There were no metastases.


Another Perspective on Fasciculations: When is it not Caused by the Classic form of Amyotrophic Lateral Sclerosis or Progressive Spinal Atrophy?
Fasciculations are visible, fine and fast, sometimes vermicular contractions of fine muscle fibers that occur spontaneously and intermittently. The aim of this article is to discuss the main causes for fasciculations and their pathophysiology in different sites of the central/peripheral injury and in particular to disprove that the presence of this finding in the neurological examination is indicative of amyotrophic lateral sclerosis. Undoubtedly, most fasciculations have a distal origin in the motor nerve both in normal subjects and in patients with motor neuron disease. Most of them spread to other dendritic spines often producing an antidromic impulse in the main axon. The clinical and neurophysiological diagnosis must be thorough. It may often take long to record fasciculations with electroneuromyography. In other cases, temporal monitoring is necessary before the diagnosis. The treatment, which may be adequate in some cases, is not always necessary.


Gene trapping with GFP: the isolation of developmental mutants in the slime mold Polysphondylium.
In order to study how a cell mass undergoes a transition from one symmetry to another in the slime mold Polysphondylium, we developed a genetic screen in which mutant phenotype and gene expression can easily be visualized in the living organism. The screen combines restriction enzyme-mediated integration (REMI) [1,2] and green fluorescent protein (GFP) [3] expression. In REMI, a restriction enzyme is electroporated along with linearized vector into cells, thus determining the site of plasmid insertion and often increasing the integration frequency. A set of transforming plasmids carrying the GFP coding sequence in three reading frames was used for transformation. The plasmids were constructed so that GFP could be expressed only under control of a host promoter. Living transformants expressing GFP spatially and temporally could be rapidly identified in a very large background of non-expressing cells and fruiting bodies. The phenotypes of representative mutants range from cells that cannot aggregate and initiate cell-cell interactions, through mutant fruiting bodies, to apparently wild-type fruiting bodies expressing GFP in all or a subpopulation of cells. The ability to screen mutant living cells and tissues for GFP expression is rapid and effective and likely to have application in many transformable systems where screening by gene and promoter trapping is essential for understanding temporal and spatial gene regulation.


Grey-Scale Analysis Improves the Ultrasonographic Evaluation of Thyroid Nodules.
Ultrasonography is the main imaging method for the workup of thyroid nodules. However, interobserver agreement reported for echogenicity and echotexture is quite low. The aim of this study was to perform quantitative measurements of the degree of echogenicity and heterogeneity of thyroid nodules, to develop an objective and reproducible method to stratify these features to predict malignancy.A retrospective study of patients undergoing ultrasonography-guided fine-needle aspiration was performed in an University hospital thyroid center. From January 2010 to October 2012, 839 consecutive patients (908 nodules) underwent US-guided fine-needle aspiration. In a single ultrasound image, 3 regions of interest (ROIs) were drawn: the first including the nodule; the second including a portion of the adjacent thyroid parenchyma; the third, the strap muscle. Histogram analysis was performed, expressing the median, mean, and SD of the gray levels of the pixels comprising each region. Echogenicity was expressed as a ratio: the nodule/parenchyma, the nodule/muscle, and parenchyma/muscle median gray ratios were calculated. The heterogeneity index (HI) was calculated as the coefficient of variation of gray histogram for each of the 3 ROIs. Cytology and histology reports were recorded.Nodule/parenchyma median gray ratio was significantly lower (more hypoechoic) in nodules found to be malignant (0.45 vs 0.61; P = 0.002) and can be used as a continuous measure of hypoechogenicity (odds ratio [OR] 0.12; 95% confidence interval [CI] 0.03-0.49). Using a cutoff derived from ROC curve analysis (<0.46), it showed a substantial inter-rater agreement (k = 0.74), sensitivity of 56.7% (95% CI 37.4-74.5%), specificity of 72.0% (67.8-75.9%), positive likelihood ratio (LR) of 2.023 (1.434-2.852), and negative LR of 0.602 (0.398-0.910) in predicting malignancy (diagnostic odds ratio 3.36; 1.59-7.10). Parenchymal HI was associated with anti-thyroperoxidase positivity (OR 19.69; 3.69-105.23). The nodule HI was significantly higher in malignant nodules (0.73 vs 0.63; P = 0.03) and, if above the 0.60 cutoff, showed sensitivity of 76.7% (57.7-90.1%), specificity of 46.8% (42.3-51.4%), positive LR of 1.442 (1.164-1.786), and negative LR of 0.498 (0.259-0.960).Evaluation of nodule echogenicity and echotexture according to a numerical estimate (nodule/parenchyma median gray ratio and nodule HI) allows for an objective stratification of nodule echogenicity and internal structure.


Homicide patterns in the Toyama Prefecture, Japan.
Homicides occurring in the Toyama prefecture, Japan, during the past 10 years were reviewed. Between 1985 and 1994, 56 offenders committed 63 homicides. The mean death rate for homicide was 0.55 per 100,000. The ratio of male to female victims was 1:1, while 82% of the assailants were male and 18% were female. The victim and the assailant had a close family relationship in 58.7% of the cases. Dyadic death (homicide followed by suicide) accounted for 27% of all victims. Twenty-nine per cent of the victims were murdered by mentally unstable offenders, and in almost half (44%) of the cases the offender was convicted. Homicides during robbery were rare (only two cases), and there was only one homicide during sexual assault. Death was caused by blunt instrument injury in 38.1% of cases, asphyxia in 31.7%, stabbing in 17.5%, burns in 9.5% and shooting in 3.2% (only two cases). The majority (80%) of homicides occurred at the residence of the victim(s). None of the victims had a history of drug abuse. Social conditions in Toyama prefecture, and their possible relevance to local homicide patterns, are discussed briefly.


A novel endolaparoscopic intragastric partitioning for treatment of morbid obesity.
Morbid obesity is a burgeoning health crisis. Significant morbidity is associated with the current gastric bypass, and, therefore, alternative surgical modalities are desired. A novel minimally invasive surgical technique, endoluminal gastric partitioning, is presented. Ten mongrel dogs underwent endolaparoscopic placement of intragastric mesh. Each circular prosthesis (Surgisis or prolene mesh) was 8 cm in diameter with a 1.5 cm central aperture. The mesh was passed transorally into the gastric lumen and secured with a laparoscopic, intragastric suturing resulting in a 30 to 50 mL proximal gastric reservoir. The operation was successfully completed in all 10 animals. Nine of 10 animals were healthy at the scheduled sacrifice date. In 2 dogs, the intragastric mesh was 100% adherent to the gastric mucosa after 7 days. Four of the final 5 dogs demonstrated some degree of mucosal adherence after 1 week. Endoluminal placement of intragastric mesh appears feasible and safe. Long-term studies are necessary to demonstrate the efficacy and long-term weight loss of this, or alternate intraluminal gastric partitioning techniques.


In vitro biocompatibility of thermally gelling liquid mucoadhesive loaded curcuminoids in colorectal cancer chemoprevention.
Colorectal cancer (CRC) is the third leading cause of cancer death in Taiwan; it ranks top three in the cancer mortality rate. Curcuminoids are derived from the rhizome of Curcuma longa. It has shown anti-cancer activity and apoptosis induction in a variety of cancer cell lines. This aims to study the potential of Poloxamer 407 as the thermogelling and mucoadhesive polymer for development of a site-targeting delivery system to enhance the localized delivery of curcuminoids to the colorectal cells for CRC chemotherapy. The mucoadhesive strength and rheological properties were measured as a function of poloxamer loaded with curcuminoids. The gelation temperature of Poloxamer 407 was found to vary with its concentration and start gelling at 37°C at the concentration of 15.5% (w/v). To ensure gelation at physiological temperature after intra-rectal application, gelation temperature was determined by rheological measurement as well as by its physical appearance. The results indicated that its mucoadhesive strength also shows a dependency on temperature, which appears to be related to the increment in the maximum strength and average strength of the polymer. The results have suggested that Poloxamer 407 could be a potential thermogelling and mucoadhesive polymer for the development of a site-targeting colorectal drug delivery system for curcuminoids in colorectal cancer therapy.


Can endoscopic biopsy specimens be used for reliable Laurén classification of gastric cancer?
The aim of this study was to ascertain whether routine endoscopic biopsy specimens are of sufficient quality and representative enough to enable reliable classification of histologic type, grade of differentiation, and frequency of signet ring cells. As part of a population-based etiologic study of gastric cancer in Sweden, the histologic slides of 687 incident cases were independently reviewed by one pathologist. In 305 cases both biopsy and surgical specimens were available for assessment of sensitivity and specificity of diagnoses on the basis of biopsy specimens, with the classification based on surgical specimens as the gold standard. The sensitivity and specificity of the diagnoses on the basis of biopsy specimens was 86% and 82%, respectively, for detecting the intestinal type, and 87% and 90%, respectively, for the diffuse type of gastric cancer. The percentage agreement between biopsy and surgical specimens with regard to grade of differentiation was 71%. This study shows that misclassification of Laurén type due to random intraobserver variation needs to be taken into account in epidemiologic studies. The degree of misclassification appears to be of similar magnitude regardless of the source material.


Folding and unfolding of a non-fluorescent mutant of green fluorescent protein.
Green fluorescent protein (GFP), from the Pacific jellyfish A. victoria, has numerous uses in biotechnology and cell and molecular biology as a protein marker because of its specific chromophore, which is spontaneously created after proper protein folding. After formation, the chromophore is very stable and remains intact during protein unfolding, meaning that the GFP unfolding process is not the reverse of the original folding reaction; i.e., the principles of microscopic reversibility do not apply. We have generated the mutant S65T/G67A-GFP, which is unable to form the cyclic chromophore, with the goal of investigating the folding, unfolding and competing aggregation of GFP under fully reversible conditions. Our studies have been performed in the presence of GdnHCl. The GFP conformation was monitored using intrinsic tryptophan fluorescence, and fluorescence of bis-ANS. Light scattering was used to follow GFP aggregation. We conclude from these fluorescence measurements, that S65T/G67A-GFP folding is largely reversible. During equilibrium folding, the first step is formation of molten globule, prone to aggregation.


Oligodeoxynucleotides containing CpG motifs can induce T cell-dependent arthritis in rats.
To investigate whether CpG oligodeoxynucleotides (ODNs) can induce or accelerate arthritis in rats. The CpG-induced response was studied by recording joint inflammation, cell activation in draining lymph nodes, and levels of the acute-phase reactant alpha(1)-acid glycoprotein (AGP) in sera. The role of T cells was investigated by in vivo administration of monoclonal antibodies specific for the T cell receptor alpha/beta (TCRalpha/beta), followed by analysis of cell phenotypes by flow cytometry. One intradermal injection of CpG ODN emulsified with Freund's incomplete adjuvant (IFA) induced arthritis in LEW and LEW.1AV1 rats, while the control ODN sequence without CpG motifs or IFA alone did not trigger disease. The CpG/IFA and control-ODN/IFA injections induced lymphoplasia as well as elevated levels of interleukin-1beta and interferon-gamma messenger RNA in lymph nodes. The arthritis was preceded by elevated levels of AGP in serum. In vivo administration of anti-TCRalpha/beta antibodies after disease induction caused decreased expression of the TCR-CD3 complex on circulating T cells and ameliorated the arthritis. We demonstrated that injection with immunostimulatory CpG, both in phosphorothioate-modified and native forms, can induce a T cell-dependent joint-specific inflammation in LEW and LEW.1AV1 rat strains. This arthritis is preceded by signs of activation of the innate immune system. Since unmethylated CG dinucleotides are common in bacterial DNA but rare in mammalian DNA, our results indicate that exposure to bacterial DNA during infection may contribute to arthritis induction by amplifying the innate immune response.


Zinc Therapy in Treatment of Symptomatic Oral Lichen Planus.
Lichen planus is a chronic inflammatory disease, which involves skin, mucous membrane, and nails. Prevalence of oral lichen planus varies between 0.5% and 2.6% of adult population worldwide with overall female preponderance. It is considered as a potentially malignant disorder with rate of transformation to oral cancer varying between 0.5% and 2%. Oral lichen planus may either be unilateral or bilateral, or may involve multiple sites. Although the exact etio-pathogenesis of this condition is unknown, it is believed that stress, use of medications, dental fillings, genetics, immunity, and hypersensitivity reactions may contribute to its pathogenesis. It is a T-cell-mediated autoimmune disorder in which CD8+ T cells are involved which release various cytokines such as tumor necrosis factor-α and interleuking-12 leading to disruption of basement membrane integrity. Zinc activates caspase-3 and DNA fragmentation, resulting in the apoptosis of keratinocytes. By prevention of matrix metalloproteinase (MMP)-1 activation, it inhibits T-cell accumulation in oral lichen planus, and by inhibiting MMP-9 it prevents cleavage of collagen IV resulting in maintaining the integrity of the basement membrane. The present case series describes the use of oral zinc acetate (50 mg) in patients having symptomatic oral lichen planus with favorable outcome in terms of size of lesion and global index score.


Screening of phytochemical constituents and potential antioxidant, antibacterial and anticancerous activities of Carpesium nepalense seeds oil.
The pharmacological importance and ecofriendly nature of medicinal plants holding a unique edge in the arena of pharmaceutical industries. Therefore, the current research was aimed to evaluate the phytochemical constituents and potential antioxidant, in vitro anticancer and antibacterial activity of Carpesium nepalense seeds essential oil. The analysis performed through Gas chromatography/Mass spectroscopy confirmed the presence of different types of biologically active compounds. At the concentration of 500μg/mL, n-hexane fraction of C. nepalense showed highly significant (P<0.001) antioxidant activity in 2,2-diphenyl-1-picrylhydrazyl, 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid and superoxide assays with the percentage inhibitions of 86.60±1.6%, 82.55±1.0% and 80.50±1.0% respectively. The extract also produced highly significant anticancerous activity against different cell lines at 500μg/mL. The significant antibacterial activity of extract was observed against bacterial strains with the zone of inhibitions of 24.3±0.8, 28.20±0.10, 22.33±0.11 and 33.22±0.10 mm respectively. The significant damage in bacterial cell membranes was also observed in atomic force microscopic analysis. In the light of obtained findings, it is concluded that C. nepalence proved to be a potential candidate as an alternative medicinal agent.


An unusual case of mycosis fungoides presenting as sarcoidosis or granulomatous mycosis fungoides.
The authors describe a case of cutaneous and lymph node granulomas first reported as sarcoidosis. As skin sarcoidlike reactions disappeared, the development of typical histologic and immunopathologic features of cutaneous mycosis fungoides suggested granulomatous mycosis fungoides. This case illustrates the difficulties in differentiating true systemic sarcoidosis associated with mycosis fungoides from sarcoidlike reactions when extensive granulomas obscure the underlying cutaneous lymphoma. This report emphasizes the utility of immunohistochemical analysis to identify the early cutaneous T-lymphomatous infiltrate, initially admixed with epithelioid and giant cell granulomas. This technique also made it possible to characterize a Ki-1-positive anaplastic large-cell lymphoma when the transformation of mycosis fungoides into highly malignant lymphoma occurred in the lymph node.


Generation of monocyte-derived dendritic cells from precursors in rhesus macaque blood.
While the dendritic cells (DCs) of mouse and man have been extensively studied, until recently those of non-human primates remained poorly characterized. We present a method for generating large numbers of DCs from precursors in rhesus macaque blood, based on techniques developed for human blood. For 7 days, a T cell-depleted population of mononuclear cells was cultured in 1% human plasma with GM-CSF and IL-4, both to initiate DC differentiation and to inhibit macrophage development. On day 7, 50% of the culture medium was replaced with a monocyte-conditioned medium (MCM), which is required for the final maturation of the DCs into potent stimulators of the allogeneic MLR. Between 0.5 and 1.0 x 10(6) DCs can be generated from 20 ml of rhesus macaque blood. We compared these cytokine-generated DCs to the adherent macrophages present in the same cultures. Cytokine-generated DCs were considerably more potent at stimulating allogeneic T cells than adherent macrophages. Furthermore, the DCs had a distinct morphology and phenotype, with long processes, high levels of p55, and a characteristic perinuclear collection of intracellular CD68. In contrast, adherent macrophages expressed very low levels of p55, and high diffuse levels of CD68. Macaque DCs generated by this method may be useful in vaccine development and for studies of SIV pathogenesis.


Antibiotic Susceptibility Pattern and Bacterial Spectrum Among Patients with External Eye Infections at Menelik II Referral Hospital in Addis Ababa, Ethiopia.
Eye infections can cause loss or impairment of visual function and can lead to severe impairment. Bacteria are the most common pathogens that affect the structure of the eye. As a result, quick identification of the causative agents and testing of their medication susceptibility are essential for effective treatment of eye infections. This study was intended for determining the extent of bacterial isolates from external eye infections (EEIs) and their susceptibility to antibiotics. A facility-based cross-sectional study was conducted among patients attending Menelik II Referral Hospital. The study comprised patients who had EEIs verified. EEI samples were collected using sterile methods. Bacterial isolates were identified using gram stain, colony morphology, and biochemical tests. The Kirby-Bauer disk diffusion technique was used to conduct a drug susceptibility test. Totally, 323 participants were recruited for this study and 184 bacterial isolates were obtained from 175 (54.5%) participants. The main clinical diagnosis was blepharitis 122 (37.8%), followed by conjunctivitis 73 (22.6%) and keratitis 57 (17.6%). The gram-positive isolates were 171 (92.9%). CoNS with a frequency of 76 (41.3%) was the most common bacterial isolates, followed by S. aureus 67 (36.4%), Viridans streptococcus 16 (8.7%), and Klebsiella species 6(3.3%). Gram-positive isolates were sensitive to tobramycin, gentamicin, chloramphenicol, vancomycin, and ceftriaxone. In contrast, 94.0% of these gram-positive isolates showed resistance to penicillin. Multidrug resistance (MDR) was observed in both gram-positive and negative bacteria at rates of 123 (72%) and 12 (92.1%), respectively. The overall MDR rate among the isolates was 135 (73.4%). In this study, blepharitis was the major EEI, followed by conjunctivitis. The predominant bacterial species isolated from EEIs were CoNS, followed by S. aureus. More than half of the isolates were drug-resistant, with a large number being multidrug-resistant, highlighting the necessity for continued and coordinated surveillance to hunt for infections that are known to be resistant.


Reduced Efficiency and Capacity of Cognitive Control in Autism Spectrum Disorder.
Cognitive control constrains mental operations to prioritize information that reaches conscious awareness and is essential to flexible, adaptive behavior under conditions of uncertainty. Cognitive control can be compromised by neurodevelopmental disorders such as autism spectrum disorder (ASD), which is characterized by the presence of social and communicative deficits, and restricted interests/repetitive behaviors. Although prior investigations have attempted to elucidate the nature of cognitive control in ASD, whether there is an underlying information processing deficit associated with cognitive control remains unclear. This study challenged cognitive control in 15 high-functioning adults with ASD and 15 typically developing (TD) controls using three novel tasks designed to systematically manipulate uncertainty. We aimed to investigate the efficiency of cognitive control in sequential information processing, cognitive control of nonsequential information processing across a range of cognitive loads and cognitive control capacity under time constraint. Results demonstrated that the ASD group performed less efficiently on sequential and nonsequential information processing, and had reduced cognitive control capacity under time constraint relative to the TD group. These findings suggest that inefficient cognitive control of information processing may be a fundamental deficit in ASD.


Stereoscopic shape discrimination is well preserved across changes in object size.
A single experiment evaluated human observers' ability to discriminate the shape of solid objects that varied in size and orientation in depth. The object shapes were defined by binocular disparity, Lambertian shading, and texture. The object surfaces were smoothly curved and had naturalistic shapes, resembling those of water-smoothed granite rocks. On any given trial, two objects were presented that were either the same or different in terms of shape. When the "same" objects were presented, they differed in their orientation in depth by 25 degrees , 45 degrees , or 65 degrees . The observers were required to judge whether any given pair of objects was the "same" or "different" in terms of shape. The size of the objects was also varied by amounts up to +/-40% relative to the standard size. The observers' shape discrimination performance was strongly affected by the magnitude of the orientation changes in depth - thus, their performance was viewpoint dependent. In contrast, the observers' shape discrimination abilities were only slightly affected by changes in the overall size of the objects. It appears that human observers can recognize the three-dimensional shape of objects in a manner that is relatively independent of size.


Retention of erythrocytes in the spleen: a double-edged process in human malaria.
Splenomegaly is frequent in acute or chronic forms of Plasmodium falciparum malaria, and splenectomy is associated with more frequent fever and parasitaemia. A novel role for the spleen in malaria is indicated by recent epidemiological and experimental data, bringing about a novel paradigm on severe malaria pathogenesis. In Sudanese children, severe malarial anaemia was associated with larger spleen, longer fever duration, and lower parasitaemia than cerebral malaria. These findings are consistent with evolution toward severe malarial anaemia being linked to the presence of a spleen-dependent mechanism that is absent or inefficient in cerebral malaria. An isolated-perfused human spleen model revealed unexpected retention of numerous erythrocytes harbouring young parasite stages (rings), probably through an innate mechanical process. A new paradigm is discussed, whereby the extent of erythrocyte retention in the spleen conditions not only haemoglobin concentration and spleen size but also the rate of parasite load increase. The prediction is that, in nonimmune children, stringent splenic retention of rings and uninfected erythrocytes reduces the risk of cerebral malaria (a complication associated with high parasite loads) but increases the risk of severe malarial anaemia. This hypothesis casts new light on epidemiological, genetic, and experimental studies in malaria pathogenesis.


Surgical strategy when identifying less than four parathyroid glands during total thyroidectomy: a retrospective cohort study.
Parathyroid glands protection is still controversial in patients with less than 4 parathyroid glands during thyroidectomy. The aim of this study was to investigate the strategy of parathyroid autotransplantation or in situ preservation in patients with 3 parathyroid glands. Consecutive patients who underwent primary total thyroidectomy with bilateral central neck dissection for papillary thyroid carcinoma (PTC) in our center were included retrospectively. Serum calcium and parathyroid hormone (PTH) levels (pg/mL), incidence of hypocalcemia and hypoparathyroidism during 24 months follow-up were compared grouping by the number of parathyroid glands both identified intraoperatively and confirmed postoperatively by pathology. A total of 1,424 patients were included. Serum PTH and calcium levels were lower and the incidence of hypocalcemia was higher in patients with 3 identified parathyroid glands. When excluding patients with accidental parathyroid resection, the results remained similar. Of the 212 patients with 3 identified parathyroid glands, PTH levels at postoperative 12-month in patients underwent autotransplantation were significantly lower than patients with all parathyroid glands preserved in situ (3.65±1.30 vs. 4.67±1.89, P=0.026). The parathyroid function was weaker in patients with 3 parathyroid glands than patients with 4 before and after operation. Parathyroid glands preserved all in situ promoted better recovery of postoperative function in patients with 3 identified parathyroid glands.


TOR controls transcriptional and translational programs via Sap-Sit4 protein phosphatase signaling effectors.
The Tor kinases are the targets of the immunosuppressive drug rapamycin and couple nutrient availability to cell growth. In the budding yeast Saccharomyces cerevisiae, the PP2A-related phosphatase Sit4 together with its regulatory subunit Tap42 mediates several Tor signaling events. Sit4 interacts with other potential regulatory proteins known as the Saps. Deletion of the SAP or SIT4 genes confers increased sensitivity to rapamycin and defects in expression of subsets of Tor-regulated genes. Sap155, Sap185, or Sap190 can restore these responses. Strains lacking Sap185 and Sap190 are hypersensitive to rapamycin, and this sensitivity is Gcn2 dependent and correlated with a defect in translation, constitutive eukaryotic initiation factor 2alpha hyperphosphorylation, induction of GCN4 translation, and hypersensitivity to amino acid starvation. We conclude that Tor signals via Sap-Sit4 complexes to control both transcriptional and translational programs that couple cell growth to amino acid availability.


Neuron-specific enolase serum levels after controlled cortical impact injury in the rat.
The aim of this study was to investigate the time course and the correlation of neuron-specific enolase (NSE) serum levels to the severity of traumatic brain injury in rats. Sixty-five male Wistar rats were subjected to severe cortical impact injury (100 PSI, 2 mm deformation). Blood samples were drawn directly after trauma and after 1, 6, 12, 24, and 48 h in the trauma group. In the sham operated levels animals samples were drawn directly after craniotomy and after 6 and 48 h. Additionally, NSE serum levels after controlled cortical impact at different levels of severity samples (45 PSI, 75 PSI; 2 mm deformity) were compared to sham-operated animals. The severity of the injury was not validated histopathologically. NSE serum levels were estimated with a commercially available enzyme immunoassay (LIA mat Sangtec). The control animals showed a NSE serum level of 8.82 microg/L (mean, n = 10) and the injured animals demonstrated a time-dependent release of NSE into the serum. The highest NSE serum values were detected 6 h after trauma (31.5 microg/L mean, n = 10). In addition, we found a close relationship between NSE serum levels and the severity of traumatic brain injury in the cortical impact model. NSE serum levels reflect in a time-dependent manner the severity of brain trauma induced by cortical impact model in rat.


Investigating the hows and whys of DNA endoreduplication.
Endoreduplication is a form of nuclear polyploidization that results in multiple, uniform copies of chromosomes. This process is common in plants and animals, especially in tissues with high metabolic activity, and it generally occurs in cells that are terminally differentiated. In plants, endoreduplication is well documented in the endosperm and cotyledons of developing seeds, but it also occurs in many tissues throughout the plant. It is thought that endoreduplication provides a mechanism to increase the level of gene expression, but the function of this process has not been thoroughly investigated. Numerous observations have been made of endoreduplication, or at least extra cycles of S-phase, as a consequence of mutations in genes controlling several aspects of cell cycle regulation. However, until recently there were few studies directed at the molecular mechanisms responsible for this specialized cell cycle. It is suggested that endoreduplication requires nothing more elaborate than a loss of M-phase cyclin-dependent kinase activity and oscillations in the activity of S-phase cyclin-dependent kinase.


Descriptive spatial analysis of scrapie-affected flocks in Great Britain between January 1993 and December 2002.
The spatial distribution of sheep flocks in Great Britain with confirmed clinical scrapie between January 1993 and December 2002 inclusive was investigated by using kernel density estimation and a cluster scan test statistic. Six statistically significant clusters were identified: three were lower risk, and were centred on the north-western coast of Scotland, the north-western coast of Wales and the South Yorkshire/Pennine region; three were of higher risk, and were centred in the central south, North Yorkshire and north Cumbria. General knowledge and the results of previous epidemiological studies were used to generate biologically plausible hypotheses that might explain these findings. They included aspects of flock management and disease transmission, and factors associated with the identification of cases, including their detection, recognition and, in particular, reporting levels, as well as diagnosis and animal movements.


[In vitro activity of an antiseptic, chlorquinaldol, against Neisseria gonorrhoeae and Chlamydia trachomatis].
The activity of chlorquinaldol, a derivative of hydroxy-8-quinolein used for local antisepsy, was studied against Neisseria gonorrhoeae and Chlamydia trachomatis. The weak solubility of the product and the special growth conditions of the organisms made an adaptation of the AFNOR norm necessary. For 0.1 to 0.2% (W/V) chlorquinaldol concentrations, a reduction of about 10(4) organisms was obtained after 60 minutes for N. gonorrhoeae and C. trachomatis. However, for technical problems, the concentrations tested were 10 to 100 times lower than the doses usually recommended for this antiseptic.


Linguistic Structure and Meaning Organize Neural Oscillations into a Content-Specific Hierarchy.
Neural oscillations track linguistic information during speech comprehension (Ding et al., 2016; Keitel et al., 2018), and are known to be modulated by acoustic landmarks and speech intelligibility (Doelling et al., 2014; Zoefel and VanRullen, 2015). However, studies investigating linguistic tracking have either relied on non-naturalistic isochronous stimuli or failed to fully control for prosody. Therefore, it is still unclear whether low-frequency activity tracks linguistic structure during natural speech, where linguistic structure does not follow such a palpable temporal pattern. Here, we measured electroencephalography (EEG) and manipulated the presence of semantic and syntactic information apart from the timescale of their occurrence, while carefully controlling for the acoustic-prosodic and lexical-semantic information in the signal. EEG was recorded while 29 adult native speakers (22 women, 7 men) listened to naturally spoken Dutch sentences, jabberwocky controls with morphemes and sentential prosody, word lists with lexical content but no phrase structure, and backward acoustically matched controls. Mutual information (MI) analysis revealed sensitivity to linguistic content: MI was highest for sentences at the phrasal (0.8-1.1 Hz) and lexical (1.9-2.8 Hz) timescales, suggesting that the delta-band is modulated by lexically driven combinatorial processing beyond prosody, and that linguistic content (i.e., structure and meaning) organizes neural oscillations beyond the timescale and rhythmicity of the stimulus. This pattern is consistent with neurophysiologically inspired models of language comprehension (Martin, 2016, 2020; Martin and Doumas, 2017) where oscillations encode endogenously generated linguistic content over and above exogenous or stimulus-driven timing and rhythm information.SIGNIFICANCE STATEMENT Biological systems like the brain encode their environment not only by reacting in a series of stimulus-driven responses, but by combining stimulus-driven information with endogenous, internally generated, inferential knowledge and meaning. Understanding language from speech is the human benchmark for this. Much research focuses on the purely stimulus-driven response, but here, we focus on the goal of language behavior: conveying structure and meaning. To that end, we use naturalistic stimuli that contrast acoustic-prosodic and lexical-semantic information to show that, during spoken language comprehension, oscillatory modulations reflect computations related to inferring structure and meaning from the acoustic signal. Our experiment provides the first evidence to date that compositional structure and meaning organize the oscillatory response, above and beyond prosodic and lexical controls.


Centrally acting anorectic drugs: a clinical perspective.
This paper reviews the anorectic activity and effectiveness of catecholamine and serotoninergic anorectic drugs in the management of obesity. It discusses the clinical implications of the experimental findings and suggests prescribing strategies for effective long-term therapeutic benefit. The authors advocate that there is a role for the recently developed serotonin-mediated anorectic compounds in the treatment of obesity, particularly in those individuals with abnormal glucose tolerance or who are hypertensive.


Depression in children and adolescents.
Among children and adolescents, the prevalence of depressive symptoms is about 15%. Clinically significant depression occurs in 5%. Depression in children overlaps with other childhood emotional and behavioural disorders. Depression in children is multifactorial and includes biological, psychological and social factors. Tricyclic antidepressants such as imipramine are ineffective in children and have limited effect in adolescents. SSRIs are also of limited value. For total health benefit in the treatment of depression, cognitive behaviour therapy (CBT) is found to be more beneficial than SSRIs.


Effect of Endolift laser on upper eyelid and eyebrow ptosis treatment.
Drooping of the upper eyelid and eyebrow (ptosis) is common among people and cause the patients dissatisfaction. Various methods have been developed to treatment of the upper eyelid and eyebrow ptosis. However, the current methods focus on surgery to improve the disorder. But patients are worried about the risks of the procedure, and seeking for a non-invasive alternative method. Therefore, non-invasive methods with consistent efficient improvement are needed, especially for middle-aged patients. This study was conducted of 9 patients who underwent the upper eyelid and eyebrow ptosis. Endolift laser method was used to treat the patients' upper eyelid and eyebrow ptosis. The biometric assessment was used to evaluate the efficiency of the technique. Also the results were evaluated by 3 board-certified dermatologists (blind). Additionally, patients' satisfaction was evaluated at the end of the treatment. The biometric results showed that Endolift laser can increase the thickness, density, and elasticity of the skin in the eyelid area. The patient's satisfaction results showed excellent improvement in the 90% of patients. The results by the dermatologist displayed improvement in about 90% of patient. Endolift laser has been proved efficient and consistent for upper eyelid and eyebrow ptosis rejuvenation and treatment.


Kinetic properties of NMDA receptors in embryonic Xenopus spinal neurons.
1. The kinetic properties of embryonic Xenopus spinal cord neuron N-methyl-D-aspartate (NMDA)-activated receptors (NMDAR) were examined at the single-channel level. These receptors have a main conductance state of 50 pS and make occasional sojourns to a subconductance level of approximately 40 pS. The open channel lifetime is 1.3 ms at -80 mV and in 1 mM Ca(2+)-, Mg(2+)-free solution. Extracellular Mg2+ blocks the channel at a rate of 2.9 x 10(8) M-1 s-1 and with a Kd of approximately 20 microM at -80 mV. In patches with only one channel active, the closed interval duration distribution requires at least four exponentials to be fit. The time constant of one closed interval component decreases with increasing NMDA concentration. Kinetic modeling indicates that these NMDA receptors open at a rate of 230 s-1 and close at a rate of 167 s-1, that in the absence of desensitization the maximum probability of being open is approximately 0.5, and that this probability is half-maximal at approximately 150 microM NMDA.


Integrating Gemcitabine-Based Therapy With AdipoRon Enhances Growth Inhibition in Human PDAC Cell Lines.
Pancreatic ductal adenocarcinoma (PDAC) accounts for 90% of all pancreatic cancers. Albeit its incidence does not score among the highest in cancer, PDAC prognosis is tremendously fatal. As a result of either aggressiveness or metastatic stage at diagnosis, chemotherapy constitutes the only marginally effective therapeutic approach. As gemcitabine (Gem) is still the cornerstone for PDAC management, the low response rate and the onset of resistant mechanisms claim for additional therapeutic strategies. The first synthetic orally active adiponectin receptor agonist AdipoRon (AdipoR) has recently been proposed as an anticancer agent in several tumors, including PDAC. To further address the AdipoR therapeutic potential, herein we investigated its pharmacodynamic interaction with Gem in human PDAC cell lines. Surprisingly, their simultaneous administration revealed a more effective action in contrasting PDAC cell growth and limiting clonogenic potential than single ones. Moreover, the combination AdipoR plus Gem persisted in being effective even in Gem-resistant MIA PaCa-2 cells. While a different ability in braking cell cycle progression between AdipoR and Gem supported their cooperating features in PDAC, mechanistically, PD98059-mediated p44/42 MAPK ablation hindered combination effectiveness. Taken together, our findings propose AdipoR as a suitable partner in Gem-based therapy and recognize the p44/42 MAPK pathway as potentially involved in combination outcomes.


[Analysis of gene expression profiles in heart tissues from two breeds of pigs].
To study the expression profiles in the heart tissues of domestic pigs,five un-normalized cDNA libraries from Danish adult female Landrace heart, biceps femoris, aorta, left ventricle tissues and Chinese adult female Erhualian heart tissue were constructed. Totally 35 180 expressed sequence tags (ESTs) were randomly sequenced. Using functional clustering and statistic methods, three gene clusters and 47 genes highly expressed in Landrace heart tissue were found. These genes are corresponding to the chaperone activity, motor activity and physiology process, implying the functional importance of the protection and movement process in heart. Between the two pig breeds, most of the differentially expressed genes are related with energy metabolism and catalytic activity, of which the majority are highly expressed in Landrace. The results indicate that the physiological activities of Landrace heart are more active and effective than Erhualian heart.


L-arginine stimulation of glucose-induced insulin secretion through membrane depolarization and independent of nitric oxide.
The mechanism of L-arginine stimulation of glucose-induced insulin secretion from mouse pancreatic islets was studied. At 16.7 mmol/l glucose, L-arginine (10 mmol/l) potentiated both phases 1 and 2 of glucose-induced insulin secretion. This potentiation of glucose-induced insulin secretion was mimicked by the membrane depolarizing agents tetraethylammonium (TEA, 20 mmol/l) and K+ (60 mmol/l), which at 16.7 mmol/l glucose obliterated L-arginine (10 mmol/l) modulation of insulin secretion. Thus L-arginine may potentiate glucose-induced insulin secretion by stimulation of membrane depolarization. At 3.3 mmol/l glucose, L-arginine (10 mmol/l) failed to stimulate insulin secretion. In accordance with membrane depolarization by the electrogenic transport of L-arginine, however, L-arginine (10 mmol/l) stimulation of insulin secretion was enabled by the K+ channel inhibitor TEA (20 mmol/l), which potentiates membrane depolarization by L-arginine. Furthermore, L-arginine (10 mmol/l) stimulation of insulin secretion was permitted by forskolin (10 micromol/l) or tetradecanoylphorbol 13-acetate (0.16 micromol/l), which, by activation of protein kinases A and C respectively sensitize the exocytotic machinery to L-arginine-induced Ca2+ influx. Thus glucose may sensitize L-arginine stimulation of insulin secretion by potentiation of membrane depolarization and by activation of protein kinase A or protein kinase C. Finally, L-arginine stimulation of glucose-induced insulin secretion was mimicked by NG-nitro-L-arginine methyl ester (10 mmol/l), which stimulates membrane depolarization but inhibits nitric oxide synthase, suggesting that L-arginine-derived nitric oxide neither inhibits nor stimulates insulin secretion. In conclusion, it is suggested that L-arginine potentiation of glucose-induced insulin secretion occurs independently of nitric oxide, but is mediated by membrane depolarization, which stimulates insulin secretion through protein kinase A- and C-sensitive mechanisms.


The beryllium lymphocyte proliferation test: Relevant issues in beryllium health surveillance.
The beryllium lymphocyte proliferation test (Be-LPT) measures beryllium-specific cellular immune response, and is useful in medical surveillance of beryllium sensitivity and chronic beryllium disease (CBD). Current and former employees (n = 12,194) of 18 United States Department of Energy (DOE) sites were tested for beryllium sensitization at four laboratories with Be-LPT expertise. Beryllium sensitized individuals were offered evaluations for CBD. The sensitivity, specificity, and positive predictive value (PPV) of the Be-LPT were determined, as was inter- and intra-laboratory agreement. False positives were calculated to be 1.09%, with a laboratory range of 0.00-3.35% for the 10-year investigation. Be-LPTs performed on inter-laboratory split blood specimens from sensitized individuals showed a false negative rate of 31.7%. The intra-laboratory repeatability of abnormal Be-LPT results ranged from 80.4-91.9%. The sensitivity of the Be-LPT was determined to be 0.683, with a specificity of 0.969. The PPV of one abnormal Be-LPT was 0.253. The Be-LPT is efficacious in medical surveillance of beryllium-exposed individuals. The PPV of the Be-LPT is comparable to other widely accepted medical tests. Confirmation of an abnormal result is recommended to assure appropriate referral for CBD medical evaluation.


Differences in children and adolescents with SARS-CoV-2 infection: a cohort study in a Brazilian tertiary referral hospital.
To compare demographic/clinical/laboratory/treatments and outcomes among children and adolescents with laboratory-confirmed coronavirus disease 2019 (COVID-19). This was a cross-sectional study that included patients diagnosed with pediatric COVID-19 (aged <18 years) between April 11, 2020 and April 22, 2021. During this period, 102/5,951 (1.7%) of all admissions occurred in neonates, children, and adolescents. Furthermore, 3,962 severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) detection samples were processed in patients aged <18 years, and laboratory-confirmed COVID-19 occurred in 155 (4%) inpatients and outpatients. Six/155 pediatric patients were excluded from the study. Therefore, the final group included 149 children and adolescents (n=97 inpatients and 52 outpatients) with positive SARS-CoV-2 results. The frequencies of sore throat, anosmia, dysgeusia, headache, myalgia, nausea, lymphopenia, pre-existing chronic conditions, immunosuppressive conditions, and autoimmune diseases were significantly reduced in children and adolescents (p<0.05). Likewise, the frequencies of enoxaparin use (p=0.037), current immunosuppressant use (p=0.008), vasoactive agents (p=0.045), arterial hypotension (p<0.001), and shock (p=0.024) were significantly lower in children than in adolescents. Logistic regression analysis showed that adolescents with laboratory-confirmed COVID-19 had increased odds ratios (ORs) for sore throat (OR 13.054; 95% confidence interval [CI] 2.750-61.977; p=0.001), nausea (OR 8.875; 95% CI 1.660-47.446; p=0.011), and lymphopenia (OR 3.575; 95% CI 1.355-9.430; p=0.010), but also had less hospitalizations (OR 0.355; 95% CI 0.138-0.916; p=0.032). The additional logistic regression analysis on patients with preexisting chronic conditions (n=108) showed that death as an outcome was significantly associated with pediatric severe acute respiratory syndrome (SARS) (OR 22.300; 95% CI 2.341-212.421; p=0.007) and multisystem inflammatory syndrome in children (MIS-C) (OR 11.261; 95% CI 1.189-106. 581; p=0.035). Half of the laboratory-confirmed COVID-19 cases occurred in adolescents. Individuals belonging to this age group had an acute systemic involvement of SARS-CoV-2 infection. Pediatric SARS and MIS-C were the most important factors associated with the mortality rate in pediatric chronic conditions with COVID-19.


Leptin interacts with heart rate but not sympathetic nerve traffic in healthy male subjects.
Administration of leptin to animals increases sympathetic nerve activity and heart rate. We therefore tested the hypothesis that plasma leptin is linked independently to muscle sympathetic nerve activity (MSNA) and heart rate in healthy humans. We measured plasma leptin, plasma insulin, body mass index (BMI), percent body fat, waist: hip ratio, MSNA, heart rate and blood pressure in 88 healthy individuals (50 men and 38 women). In men, plasma leptin concentration correlated significantly with BMI (r = 0.75, P < 0.001), percent body fat (r = 0.70, P< 0.001), waist: hip ratio (r = 0.69, P < 0.001), insulin (r = 0.37, P = 0.009), and age (r = 0.38, P = 0.006). Only BMI and waist: hip ratio were linked independently to plasma leptin concentration (r = 0.78, P < 0.001). Plasma leptin concentrations also correlated with heart rate (r = 0.39, P = 0.006) and mean arterial pressure (MAP; r = 0.38, P = 0.007), but not with MSNA (r = 0.17, P = 0.24). After adjustment for BMI and waist: hip ratio, plasma leptin concentration correlated significantly only with heart rate (r = 0.29, P = 0.04), and not with MAP (r = 0.21, P = 0.14). Individuals were divided into high-leptin and low-leptin subgroups on the basis of plasma leptin concentrations adjusted for BMI and waist: hip ratio. Those with high leptin concentrations had significantly faster heart rates than those with low leptin. MAP and MSNA were similar in both subgroups. No relationship between leptin and either heart rate or MSNA was evident in women. In normal men, heart rate, but not MSNA, is linked to plasma leptin concentration. This sex-specific relationship between heart rate and plasma leptin is independent of plasma insulin, BMI, waist:hip ratio and percentage body fat.


Household Crowding During Childhood and Long-Term Education Outcomes.
Household crowding, or having more household members than rooms in one's residence, could potentially affect a child's educational attainment directly through a number of mechanisms. We use U.S. longitudinal data from the Panel Study of Income Dynamics to derive new measures of childhood crowding and estimate negative associations between crowding during one's high school years and, respectively, high school graduation by age 19 and maximum education at age 25. These negative relationships persist in multivariate models in which we control for the influence of a variety of factors, including socioeconomic status and housing-cost burden. Given the importance of educational attainment for a range of midlife and later-life outcomes, this study suggests that household crowding during one's high school years is an engine of cumulative inequality over the life course.


Incorporation of UDPGlucose into Cell Wall Glucans and Lipids by Intact Cotton Fibers.
The [(14)C] moiety from [(3)H]UDP[(14)C]glucose was incorporated by intact cotton fibers into hot water soluble, acetic-nitric reagent soluble and insoluble components, and chloroform-methanol soluble lipids; the [(3)H] UDP moiety was not incorporated. The (3)H-label can be exchanged rapidly with unlabeled substrate in a chase experiment. The cell wall apparent free space of cotton fibers was in the order of 30 picomoles per milligram of dry fibers; 25 picomoles per milligram easily exchanged and about 5 picomoles per milligram more tightly adsorbed. At 50 micromolar UDPglucose, 70% of the [(14)C]glucose was found in the lipid fraction after both a short labeling period and chase. The percent of [(14)C]glucose incorporated into total glucan increased slightly with chase, but the fraction of total glucans incorporated into insoluble acetic-nitric reagent (cellulose) did increase within a 30-minute chase period. The data supports the concept that glucan synthesis, including cellulose, as well as the synthesis of steryl glucosides, acetylated steryl glucosides, and glucosyl-phosphoryl-polyprenol from externally supplied UDPglucose occurs at the plasma membrane-cell wall interface. The synthase enzymes for such synthesis must be part of this interfacial membrane system.


[Dynamic changes of heme oxygenase-1 protein and mRNA in the brains of rats with experimental allergic encephalomyelitis].
In order to investigate the role of heme oxygenase-1 (HO-1) in the molecular mechanism of experimental allergic encephalomyelitis (EAE), which was induced by guinea pig spinal cord homogenate + complete freund adjuvant on Wistar rats, we observed the gene of HO-1 and its protein expression with reverse transcriptase polymerase chain reaction(RT-PCR) and immunohistochemistry 1, 7, 14, and 21 d after EAE induction in rats. The relationship between HO-1 and the symptoms of EAE was also observed. The results showed that the levels of HO-1 mRNA and its protein expression were very low in the brains of the control group, whereas they were enhanced gradually with pathological course in the brain and onsets of symptoms, signs of EAE. On day 7, the level of HO-1 mRNA reached the peak, but the expression level of HO-1 protein in the brains reached the peak on day 14. The immunoreactive cells of HO-1 were mainly located at the choroid plexuses and subfornical organ (SFO), as well as in regions around the "sleeve-like" lesion foci, all of which were coincident with the locations of lesions of EAE. The levels of HO-1 mRNA and its protein expression were lowered gradually on day 21, which were in parallel with the severities of symptoms and signs of EAE. After a specific inhibitor of HO-1, Snpp-9, was applied, both of the symptoms and pathological lesions of EAE in the rat brains were mitigated markedly. Therefore, these results may suggest that the dynamic changes of HO-1 mRNA and its protein expression are in parallel with the changes of symptoms and pathological lesions of EAE in the brain. In conclusion, the levels of HO-1 mRNA and its protein expression in brains may play an important role in the pathogenesis of EAE, and application of inhibitors of HO-1 may be one of the potential therapeutic ways for the prevention and treatment of EAE.