Evaluation of Retinal Function and Pathology After Intravitreal Injection of Povidone-Iodine and Polyvinyl Alcohol-Iodine in Rabbits.
This study compared intraocular toxicity of intravitreally injected povidone-iodine (PI) and polyvinyl alcohol-iodine (PAI) in rabbits. In each rabbit, 0.1 mL of PI or PAI solution was injected intravitreally into one eye and saline was injected into the other. PI was tested at available iodine concentrations of 0.05%, 0.1%, 0.2%, and 0.5%, and PAI at 0.05%, 0.1%, and 0.2% (n = 6 each). Electroretinograms were recorded before injection and 1, 7, and 14 days after injection. Pathological examinations of eyeballs were performed on day 15. Mean b-/a-wave ratios of the electroretinograms did not change in eyes injected with 0.05%, 0.1%, or 0.2% PI (PI-0.05, PI-0.1, and PI-0.2, respectively) or in eyes injected with 0.05% or 0.1% PAI (PAI-0.05 and PAI-0.1, respectively) compared to saline-injected eyes, but was transiently impaired on day 1 in PAI-0.2 eyes. Histopathologically, no retinal abnormalities were observed in PI-0.05, PAI-0.05, or PAI-0.1 eyes. One PI-0.1 eye first showed localized inflammatory cell infiltration in the inferior retinal region. Two PI-0.2 eyes and one PAI-0.2 eye had retinal degeneration and inflammatory cell infiltration. In the PI-0.5 group, extensive inflammatory cell infiltration was observed in six eyes and inferior retinal detachment in five eyes. PI and PAI have equivalent retinal toxicity profiles, and retinal toxicity first affects the inner retinal layer in the inferior region. The highest non-retinotoxic vitreous concentration is 0.0033% available iodine from intravitreal injection of PI or PAI containing 0.05% available iodine. Low concentrations of PI or PAI can be used to wash the ocular surface during surgery or intravitreal injection to prevent endophthalmitis.


Weight loss and senile dementia in an institutionalized elderly population.
The purpose of this study was to determine whether patients with Alzheimer's disease or senile dementia have a higher incidence of underweight and weight loss than non-demented patients. In a retrospective study, the admission weight and height and the current weight of 36 patients with Alzheimer's disease and senile dementia of the Alzheimer's type were compared with those of 31 non-demented patients. Patients with Alzheimer's disease or senile dementia were significantly (p less than .05) further below minimum acceptable body weight on admission and were significantly (p less than .05) further below minimum acceptable body weight after an average of 17 months in the institution in comparison with the control group. Additional research is needed to determine whether the weight loss seen in patients with Alzheimer's disease or senile dementia is due to a metabolic aberration inherent in the disease or to management issues in feeding those patients.


The perimeter technique for lentigo maligna: an alternative to Mohs micrographic surgery.
Lentigo maligna (LM) presents a challenge for complete surgical excision because of its extensive subclinical spread and predilection for the face. To report our experience using the staged perimeter technique as an alternative to Mohs micrographic surgery for treatment of LM. The perimeter procedure was performed on 11 patients with LM between March 2003 and June 2004. Data on patient and lesion characteristics, number of stages required to obtain clear margins, and follow-up was obtained by chart review. A mean of 1.9 stages were required to achieve clear margins. A mean of 7 tissue specimens were sent to pathology per patient for evaluation. After a mean follow-up of 4.7 months, all patients were free of recurrence. The perimeter technique is a simple method of margin-controlled excision of LM. The main advantage is that all margins are examined with permanent sections. The main drawback is that multiple operative sessions are required to complete the procedure. This technique does not require specific Mohs training and is therefore applicable to non-Mohs surgeons.


Current standards of care and future directions for "high-risk" pediatric renal tumors: Anaplastic Wilms tumor and Rhabdoid tumor.
'High risk' renal tumors of childhood generally includes anaplastic Wilms tumor, rhabdoid tumor, and metastatic renal sarcomas and carcinomas. In this review, the epidemiology, biology, treatment and prognosis of anaplastic Wilms tumor and rhabdoid tumor are presented. Future directions related to management of such cancers are discussed, with insights provided into possible clinical trials in development that consider integration of novel targeted therapies.


A surgically recovered case of spontaneous rupture of the esophagus--the significance of preoperative esophagoscopy for direct suture.
A 65-year-old man with spontaneous rupture of the esophagus survived with a direct suture of the esophagus 15 hours after the onset of symptoms. Endoscopic examination of the esophagus was especially of great help in determining the surgical procedure in this patient, and we want to stress the importance of prompt diagnosis and immediate surgery for this disease.


Preparation of rutin-loaded mesoporous silica nanoparticles and evaluation of its physicochemical, anticancer, and antibacterial properties.
The studies have shown that rutin has great potential as an anticancer and antimicrobial plant base agent; nevertheless, poor bioavailability and low aqueous solubility of rutin limit its application. One of the beneficial routes to increase the solubility and bioavailability of rutin is the development of nanoparticulate material. This study aimed to assess the anticancer and antibacterial effects of rutin-loaded mesoporous silica nanoparticles (RUT-MSNs). RUT-MSNs were prepared and physicochemically characterized. The cytotoxicity of RUT-MSNs on the HN5 cells as head and neck cancer cells was evaluated. The expression level of apoptosis-related genes such as Bcl-2 and Bax genes were evaluated. In addition, ROS production of RUT-MSNs treated cells was assessed. In addition, minimum inhibitory concentration (MIC), biofilm, and attachment inhibitory effects of RUT-MSNs compared with free rutin were assessed against different bacterial strains. Transmission electron microscopy (TEM) showed mesoporous rod-shaped nanoparticles with an average particle size of less than 100 nm. RUT-MSNs displayed the cytotoxic effect with IC50 of 20.23 µM in 48 h of incubation time (p < 0.05). The elevation in the ratio of Bax/Bcl-2 was displayed within the IC50 concentration of RUT-MSNs in 48 h (p < 0.05). The antibacterial action of rutin was improved by loading rutin in MSNs to the nano-sized range in the MIC test. The anticancer and antibacterial effects of RUT-MSNs were considerably more than rutin. RUT-MSNs inhibited the growth of HN5 cells by inducing apoptosis and producing ROS. These results suggest that RUT-MSNs may be useful in the treatment of cancers and infections.


Synthesis of Conserved Odor Object Representations in a Random, Divergent-Convergent Network.
Animals are capable of recognizing mixtures and groups of odors as a unitary object. However, how odor object representations are generated in the brain remains elusive. Here, we investigate sensory transformation between the primary olfactory center and its downstream region, the mushroom body (MB), in Drosophila and show that clustered representations for mixtures and groups of odors emerge in the MB at the population and single-cell levels. Decoding analyses demonstrate that neurons selective for mixtures and groups enhance odor generalization. Responses of these neurons and those selective for individual odors all emerge in an experimentally well-constrained model implementing divergent-convergent, random connectivity between the primary center and the MB. Furthermore, we found that relative odor representations are conserved across animals despite this random connectivity. Our results show that the generation of distinct representations for individual odors and groups and mixtures of odors in the MB can be understood in a unified computational and mechanistic framework.


O-methyltransferases selectively modify anthraquinone natural products.
In this issue of Structure, Huber et al. identify five O-methyltransferases, and three of them catalyze the sequential methylation of the Gram-negative bacterium-derived aromatic polyketide anthraquinone AQ-256. They present co-crystal structures with bound AQ-256 and its methylated derivatives, which explains the specificities of these O-methyltransferases.


Comparative effects of fast- and slow-ion channel blocking agents on reperfusion-induced arrhythmias in the isolated perfused rat heart.
The effects of bepridil (1-4 microM), a new antianginal agent which reduces the intensity of both the fast and slow inward ionic currents in myocardium, on reperfusion-induced arrhythmias (RA) in the isolated perfused rat heart were compared with those of tetrodotoxin (0.16-1.57 microM), verapamil (0.5-2 microM), diltiazem (1-2 microM), nifedipine (0.02-0.2 microM), and nitrendipine (0.02-0.2 microM). In comparable negative inotropic concentrations, neither nifedipine nor nitrendipine reduced the incidence of RA, whereas the other four agents did. Protection against RA does not appear to be related to coronary vasodilatation or to a reduction in the degree of ischaemia as assessed by lactate dehydrogenase release. However, negative chronotropism appears to be relevant in the mechanism of action of the calcium antagonists. Substantial protection against RA by all active drugs was associated with PR prolongation and/or atrioventricular block or suppression of sinus rhythm. It is concluded that bradycardia may play an important role in the antiarrhythmic action of bepridil, but the relative contributions made by inhibition of the inward calcium and/or sodium currents remain unclear.


Prosthetic management with a scleral prosthesis: an 'eye on an eye'.
Eyes are an essential organ not only in terms of vision but also being an important component of facial expression. The loss of an eye has a crippling effect on the psychology of the patient. A natural eye is surgically removed by enucleation, evisceration or exenteration because of trauma, pathology or tumor. Treatment of such rehabilitation cases includes implant-retained and acrylic eye prostheses by a maxillofacial prosthodontist to restore the patient's quality of life. For economic reasons, a removable acrylic prosthesis is preferred over an implant-retained prosthesis. Here, we describe a case of a customized acrylic scleral shell prosthesis which showed excellent retention and esthetics.


Personality characteristics associated with satisfaction with healthcare and the wish to complain.
There is increasing evidence that satisfaction with healthcare and complaint rates vary with patients' socio-demographic characteristics. Likewise, patient personality might influence the perception of health care; however, empirical research has been scarce. The aim of this study was to investigate associations between health care user personality and satisfaction with care and urge to complain. This study is a randomized survey among Danish men aged 45 to 70 years (N = 6,756; 30% response rate) with hypothetical vignettes illustrating different courses of healthcare. Assuming they received the care described in vignettes, participants rated their satisfaction and wish to complain on a five-point Likert scale. Information on personality characteristics was obtained through self-reports using the standardized Big Five Inventory-10 (BFI-10). In multivariate analyses, we found respondents with higher scores on the agreeableness dimension expressing greater satisfaction with care (Likert difference 0.06, 95% CI 0.04 to 0.07; p < 0.001) and decreased wish to complain (-0.07, 95% CI -0.08 to -0.05; p < 0.001) while high neuroticism scores were associated with less satisfaction (-0.02, 95% CI -0.03 to -0.00, p = 0.012) and an increased wish to complain about healthcare (0.04, 95% CI 0.03 to 0.06, p < 0.001). Interaction analyses could demonstrate no statistically significant interaction between the level of patient involvement in decision making in the scenarios and the effect of personality on respondents' satisfaction and wish to complain. Generally, however, when adjusting for personality, respondents' satisfaction increased (P < 0.001) with greater patient involvement illustrated in case scenarios while the wish to complain decreased (P < 0.001). Our findings suggest low agreeableness and high neuroticism scores are associated with lower patient satisfaction with healthcare and increased wish to complain. Irrespective of personality, however, the wish to complain seems responsive to changes in patient involvement, underscoring the importance of inclusive healthcare communication.


Resident foreign patients receive adequate dialysis but fewer preemptive transplantations: data from the Italian pediatric dialysis registry.
Sociocultural issues play a key role in children needing kidney replacement therapy (KRT). Data of incident patients < 18 years treated with chronic dialysis or preemptive kidney transplantation (pTx) between 2007 and 2016 were retrospectively collected from the Italian Pediatric Dialysis Registry; KRT modality and outcome were compared between patients with at least one non-Italian parent ("resident foreign patients," RFPs) and those from native parents ("domestic patients," DPs) and between the quinquennium 2007-2011 (period 1) and 2012-2016 (period 2). We included 448 children (26.8% RFPs). The percentage of RFPs increased from 23 to 30.3% (p = 0.08) from periods 1 to 2. They were younger (6.7 vs. 9.4 years, p = 0.025) and less often treated with pTx (3.3 vs. 13.4%, p = 0.009) than DPs. The percentage of pTx increased from period 1 to 2 in RFPs only (8.4-18.6%, p = 0.006). Independent predictors of a lower probability of pTx were lower age, belonging to RFPs group, starting KRT in period 1 and focal segmental glomerulosclerosis or glomerulopathy as primary kidney disease. Peritoneal dialysis was the preferred dialysis modality in both groups. Age, primary kidney disease, and center size were independently associated with dialysis modality choice. Patient survival, waiting time to Tx, and dialysis modality survival were not different between the two groups. The proportion of patients receiving KRT born from immigrant families increased in recent years in Italy. They were younger and less often treated with pTx than domestic patients. In case of dialysis, the outcome was not different between the two groups. Graphical abstract.


Primary follicular lymphoma arising in the ampulla of Vater.
Primary gastrointestinal lymphomas constitute more than one-third of all extranodal lymphomas, but among them follicular lymphomas (FL) are infrequent, accounting for only 1-4%. We report the case of a 55-year-old man diagnosed with a FL of the ampulla of Vater. He complained of dyspepsia. An upper gastroendoscopic study 1 year before showed a slight enlargement of the papilla with the biopsy initially interpreted as atypical follicular hyperplasia. The study performed because of persistence of the symptoms again showed an enlarged papilla, and the histological examination was diagnostic of FL (CD10+, bcl-2+). The full staging study did not show other FL involvement. The patient was treated with six courses of cyclophosphamide, hydroxydaunomycin, vincristine, and prednisone (CHOP), and the endoscopy as well as the biopsies revealed no abnormalities since the third course of chemotherapy. After 2 years of follow-up he remains asymptomatic and the gastroendoscopic study is normal.


Possible role of oxidative stress and brain derived neurotrophic factor in triazophos induced cognitive impairment in rats.
Triazophos, O,O-diethyl-1-H-1,2,4-triazol-3-yl phosphorothioate, (TZ) is an organophosphate pesticide widely used as an insecticide in agriculture fields, however, its adverse effects on cognitive function remain unknown till date. The present study was designed to identify the effect of TZ on cognitive function in order to gain an insight into the molecular mechanism(s) probably involved in TZ induced toxicity. Wistar male albino rats were orally administered with TZ at 8.2 mg/kg bw daily for 30 days. Cognitive function was assessed by evaluating step down latency (SDL) in passive avoidance apparatus, transfer latency (TL) on elevated plus maze and escape latency (EL) using morris water maze. The biochemical changes, in terms of malondialdehyde (MDA), reduced glutathione (GSH) and brain derived neurotrophic factor (BDNF) levels were evaluated in hippocampi regions. Relative mRNA expression and protein expression of BDNF were also evaluated. The results demonstrated that rats treated with TZ showed significantly (p < 0.01) reduced SDL and prolonged TL and EL as compared to control group rats. Moreover, significantly low (p < 0.01) mRNA expression and protein levels (p < 0.001) of BDNF, increased MDA and reduced GSH levels were observed in TZ treated rats. The study concludes that chronic exposure to TZ significantly impairs the learning and memory which may be attributed to the significantly reduced mRNA and protein expression of BDNF in hippocampus. Moreover, BDNF is negatively correlated to MDA levels and positively correlated to GSH levels. Hence, it can be suggested that interplay between BDNF and oxidative stress plays an important role in mediating the toxic effects of TZ.


Metabolic products of microorganisms. 170. On the antibiotic activity of cladosporin.
Cladosporin was isolated from the cultures of three species of the genus Eurotium. Cladosporin inhibited the growth of several fungi and at very low concentrations the growth of Bacillus brevis and Clostridium pasteurianum. Bacillus subtilis and most other Gram-positive bacteria were not sensitive. Gram-negative bacteria and yeasts were not affected by concentrations up to 100 microgram/ml. Dimethyl cladosporin showed only week activity against Bacillus brevis with the minimal inhibitory concentrations being a 100 times higher than of cladosporin. The incorporation of leucine and uracil into acid insoluble material in Bacillus brevis cells was completely inhibited by concentration of 0.5 microgram/ml cladosporin. The incorporation of thymidine was not affected at this concentration.


[Results of a cytogenetic study of populations with different radiation risks in the Semipalatinsk region].
A cytogenetic study was conducted for the first time on human populations neighboring the Semipalatinsk nuclear test site (STS) and exposed to ionizing radiation for a long period of time. In populations with the extreme and maximum radiation risks, high frequencies of radiation-induced chromosomal markers, including acentric fragments (1.99 +/- 0.10 per 100 cells), dicentrics (0.23 +/- 0.01), ring chromosomes (0.38 +/- 0.14), and stable chromosomal aberrations (1.17 +/- 0.02), were found. These frequencies significantly exceeded those in control populations. The spectrum of chromosomal aberrations and the frequencies of the aberrations of different types in persons living in the areas with the highest radionuclide contamination confirmed the mutagenic effect of radiation on chromosomes in the human populations studied.


Knowledge and perceptions of breast health among free clinic patients.
Breast cancer is a significant women's health problem in the United States. However, critical information on specific populations is still lacking. In particular, it is not well known how free clinic patients perceive breast health. The purpose of this study was to assess knowledge and perceptions of breast health among uninsured women utilizing a free clinic that serves as a safety net for the underserved. A self-administrated survey that included knowledge and perceptions of breast health was conducted for female free clinic patients aged 40 or older in fall 2012. There were 146 participants. The participants were classified into three groups for comparison; U.S. citizen English speakers, non-U.S. citizen English speakers, and Spanish speakers. Spanish speakers had the highest average score on the knowledge of breast health, whereas the non-U.S. citizen English speakers had the lowest average score. Free clinic patients may consider breast health screening if recommended by health care providers. The non-U.S. citizen English speakers and Spanish speakers were more likely to have negative perceptions of breast health compared with the U.S. citizen English speakers. Promoting knowledge about breast health is important for free clinics. Recommendation by a health care provider is a key to increasing attendance at health education programs and breast health screening. Non-U.S. citizens and non-English speakers would need culturally competent interventions. Free clinics have limited human and financial resources. Such characteristics of free clinics should be considered for practice implementations.


[Visual acuity in automobile transport drivers under changed light conditions].
Visual acuity in healthy drivers depends directly on illumination of test objects. This acuity increases with better light conditions in 20-30 years of age, whereas in 35-50 year-olds no significant increase is seen. Lower visual acuity is expected with worse light conditions and vice versa - maximal visual acuity with better illumination.


[The advantages of histological samples in sarcoidosis. Retrospective multicenter analysis of 618 biopsies performed on 416 patients].
The diagnosis of sarcoidosis is based on the finding of an epithelioid granuloma at histological examination. A retrospective study of 618 biopsies obtained from 416 patients with sarcoid disease showed an average sensitivity of 69 p. 100. The sensitivity of guided biopsies, especially skin and lymph node biopsies, was almost 90 p. 100, whereas that of blind biopsies tended to increase with the degree of hazard involved, ranging from 49 p. 100 in proximal bronchial biopsy to 70 p. 100 in liver needle biopsy. When treatment is not urgently required, the Kveim test is safe, cheap and fairly sensitive (65 p. 100 positive results).


Food Residue During Esophagogastroduodenoscopy Is Commonly Encountered and Is Not Pathognomonic of Delayed Gastric Emptying.
Retained gastric food (RGF) identified during esophagogastroduodenoscopy (EGD) is often attributed to gastroparesis. This retrospective study evaluated the prevalence of RGF, risk factors for RGF, and the association between RGF and delayed gastric emptying (GE). The prevalence and odds ratios for RGF in patients with structural foregut abnormalities or medical risk factors for delayed GE were determined from 85,116 EGDs performed between 2012 and 2018. The associations between RGF, delayed GE, and medical comorbidities were evaluated in 2991 patients without structural abnormalities who had undergone EGD and gastric emptying scintigraphy. The relationship between medication use and RGF was evaluated in 249 patients without structural or medical risk factors for RGF. RGF was identified during 3% of EGDs. The odds of RGF were increased in patients with type 1 diabetes (12%, OR 1.7, P ≤ 0.001), type 2 diabetes (6%, OR 1.4, P ≤ 0.001), gastroparesis (14%, OR 4.8, P ≤ 0.001), amyloidosis (5%, OR 1.7, P ≤ 0.001), and structural foregut abnormalities (6%, OR 2.6, P ≤ 0.001). Overall, the PPV of RGF for delayed GE was 55%. However, the PPV varied from 32% in patients without risk factors to 79% in patients with type 1 diabetes. Opioids, cardiovascular medications, and acid suppressants were associated with RGF. RGF is common during EGD. The PPV of RGF for delayed GE varies depending on underlying risk factors (type 1 diabetes, type 2 diabetes, gastroparesis, and amyloidosis). Acid suppressants or antacids, cardiovascular medications, and opioids are associated with RGF independent of delayed GE.


Involvement of growth-associated protein-43 with irreversible neurite outgrowth by dibutyryl cyclic AMP and phorbol ester in NG108-15 cells.
Simultaneous treatment with 12-O-tetradecanoylphorbol 13-acetate (TPA) and dibutyryl cyclic AMP (diBu-cAMP) for 72 h induced neurites in NG108-15 cells significantly longer than treatment with each alone. Treatment for 72 h with both drugs induced irreversible neurite extension and a decline in protein kinase C activity, although neurites extended by diBu-cAMP alone disappeared after the withdrawal of the drug. The expression of growth-associated protein-43 (GAP-43) mRNA was also observed by a combined application of TPA and diBu-cAMP. The increased level of GAP-43 mRNA induced by treatment with both drugs for 72 h was maintained at least 24 h after withdrawal of the drugs. In cells transfected with GAP-43 cDNA, neurites induced by treatment with diBu-cAMP alone for 72 h were maintained at least 48 h after removal of the drugs. These results suggest that GAP-43 could be involved in the maintenance of elongated neurites and that a decline in protein kinase C activity may be involved in the accumulation of GAP-43.


Cutting Corners: Provider Perceptions of Interpretation Services and Factors Related to Use of an Ad Hoc Interpreter.
This study assessed health providers' perceptions of factors related to professional interpretation services and the association between these factors and the potential use of ad hoc interpreters. Data were collected from a convenience sample of 150 health services providers at a large, regional health system in South Carolina. Providers rated "ability to communicate effectively during a clinical encounter" as paramount regarding the use of interpretation services. The most important factors related to the likely use of ad hoc interpreters (cutting corners) included locating a qualified interpreter, having to wait for a qualified interpreter, and technical difficulties regarding phone and video technology. Health care organizations may benefit from increasing staff awareness about patient safety and legal and regulatory risks involved with the use of ad hoc interpreters.


Morphological Analysis of the Respiratory Tract of Rats after Parenteral Administration of Silicon Dioxide Nanoparticles.
Morphological analysis of the respiratory tract of Wistar rats was performed after a single parenteral administration of 12-nm silicon dioxide nanoparticles (1 ml, 2 mg/ml, intravenously) was performed. On day 21 and in 2, 4, and 6 months after the administration of nanoparticles, the development of macrophage infiltration in the interstitium of the respiratory tract was demonstrated by histological and immunohistochemical methods. The pool of alveolar macrophages increased in 4 months after administration (p=0.004) and returned to the control values in 6 months. The number of mast cells did not significantly change at all stages of the experiment. Connective tissue remodeling in the interstitium of the respiratory tract was not observed throughout the observation period.


Ambulatory monitoring of blood pressure (AMBP) in patients with primary hyperparathyroidism.
The purpose of our study was to evaluate the behaviour of blood pressure (BP) by ambulatory monitoring of blood pressure (AMBP) in 53 patients with primary hyperparathyroidism (PHPT) compared to 100 essential hypertensive (EH) and 31 healthy subjects (HS). The correlations between calcium-phosphorus metabolism and haemodynamic parameters in all groups are included in the study. AMBP was performed using the oscillometric technique (Space-Labs, 90207, Redmond, WA, USA) and the following AMBP parameters were evaluated: average day time systolic (S) and diastolic (D) blood pressure (BP) and heart rate (HR) (when awake), average night time SBP, DBP and HR (when asleep) and average 24-h-SBP, DBP and HR. The definition of 'dipper' or 'non-dipper' subjects was established if night time SBP and DBP fall was >10% and <10%, respectively. In total, 25 PHPT patients (47.2%) were hypertensive (HT-PHPT) and 28 PHPT (52.8%) were normotensive (NT-PHPT). Mean 24-h-SBP and DBP obtained by AMBP was higher in HT-PHPT (P < 0.05) and EH (P < 0.05) than in NT-PHPT and HS. The multiple linear regression has shown that in PHPT-HT patients ionized calcium is an independent factor for the rise of 24-h-DBP values (r: 0.497; P < 0.05) and daytime DBP values (r: 0.497; P < 0.05). In 56% of HT-PHPT patients there is an absence of physiological BP nocturnal fall ('non-dipper'), which is statistically significant (P < 0.05) compared with 'non-dipper' EH patients (30%). In conclusion, in our study the prevalence of hypertension in PHPT was 47%. AMBP revealed that the 'non-dipping 'pattern was much higher in HT-PHPT patients in respect to EH patients.


Effect of premenopausal castration and incremental dosages of conjugated equine estrogens on plasma follicle-stimulating hormone, luteinizing hormone, and estradiol.
Plasma levels of follicle-stimulating hormone (FSH), luteinizing hormone (LH), and estradiol (E2) were measured serially in 11 premenopausal patients before and after hysterectomy with bilateral salpingo-oophorectomy. One week after operation an incremental dosage regimen of conjugated estrogens (CEE) in tablet form was commenced on a basis of two weeks with therapy (0.3, 0.625, 1.25, and finally 2.5 mg.), with each dose interspersed by two weeks without therapy. FSH, LH and E2 levels were measured at the end of each period with and without therapy. E2 levels fell within 24 hours of operation while FSH and LH levels rose gradually. CEE therapy produced an elevation of E2, but circulating concentrations comparable to the premenopausal values were only maintained during the dosage periods of 0.625 and 1.25 mg. of CEE. In only one instance did CEE succeed in reducing FSH to premenopausal levels, and that was at a dosage of 2.5 mg., in which instance the E2 level was higher than the premenopausal value. LH was never reduced to a premenopausal level. Thus, the data indicate that CEE alone in dosages up to 2.5 mg. per day was unable to reproduce in postmenopausal women the gonadotropin and E2 blood serum levels shown to exist prior to oophorectomy. Usual CEE treatment after menopause, therefore, in itself does not represent physiologic "hormone replacement therapy," if defined as the dosage required to maintain premenopausal circulating concentrations of reproductive hormones.


Analysis on Enrichment and Mass of Uranium Materials With Time-Correlated Measurement.
Effective determination for enrichment of the uranium materials in heavy shielding is technically difficult to solve. Various technical methods so far have been proposed to deal with this problem. With the time-correlated coincidence measurement method, 14 MeV neutrons and fission spectrum neutrons are chosen to interrogate the uranium samples with different masses and enrichments. The fission spectrum neutrons are obtained by slowing down the 14 MeV neutrons. Results have shown that a good linear relationship exists between masses of the uranium materials (≤10% enriched U) that possess the same enrichment. A linear relationship also exists between enrichments of the uranium materials that possess the same mass.


Continuous co-production of ethanol and xylitol from rice straw hydrolysate in a membrane bioreactor.
The present study was set to develop a robust and economic biorefinery process for continuous co-production of ethanol and xylitol from rice straw in a membrane bioreactor. Acid pretreatment, enzymatic hydrolysis, detoxification, yeast strains selection, single and co-culture batch fermentation, and finally continuous co-fermentation were optimized. The combination of diluted acid pretreatment (3.5 %) and enzymatic conversion (1:10 enzyme (63 floating-point unit (FPU)/mL)/biomass ratio) resulted in the maximum sugar yield (81 % conversion). By concentrating the hydrolysates, sugars level increased by threefold while that of furfural reduced by 50 % (0.56 to 0.28 g/L). Combined application of active carbon and resin led to complete removal of furfural, hydroxyl methyl furfural, and acetic acid. The strains Saccharomyces cerevisiae NCIM 3090 with 66.4 g/L ethanol production and Candida tropicalis NCIM 3119 with 9.9 g/L xylitol production were selected. The maximum concentrations of ethanol and xylitol in the single cultures were recorded at 31.5 g/L (0.42 g/g yield) and 26.5 g/L (0.58 g/g yield), respectively. In the batch co-culture system, the ethanol and xylitol productions were 33.4 g/L (0.44 g/g yield) and 25.1 g/L (0.55 g/g yield), respectively. The maximum ethanol and xylitol volumetric productivity values in the batch co-culture system were 65 and 58 % after 25 and 60 h, but were improved in the continuous co-culture mode and reached 80 % (55 g/L) and 68 % (31 g/L) at the dilution rate of 0.03 L per hour, respectively. Hence, the continuous co-production strategy developed in this study could be recommended for producing value-added products from this hugely generated lignocellulosic waste.


Socioeconomic status and multiple myeloma among US blacks and whites.
This study examined the relation between socioeconomic status (SES) and risk of multiple myeloma among Blacks and Whites in the United States. This population-based case-control study included 573 cases (206 Blacks and 367 Whites) with new diagnoses of multiple myeloma identified between August 1, 1986, and April 30, 1989, and 2131 controls (967 Blacks and 1164 Whites) from 3 US geographic areas. Information on occupation, income, and education was obtained by personal interview. Inverse gradients in risk were associated with occupation-based SES, income, and education. Risks were significantly elevated for subjects in the lowest categories of occupation-based SES (odds ratio [OR] = 1.71, 95% confidence interval [CI] = 1.16, 2.53), education (OR = 1.36, 95% CI = 1.06, 1.75), and income (OR = 1.43, 95% CI = 1.05, 1.93). Occupation-based low SES accounted for 37% of multiple myeloma in Blacks and 17% in Whites, as well as 49% of the excess incidence in Blacks. Low education and low income accounted for 17% and 28% of the excess incidence in Blacks, respectively. Our results indicate that the measured SES-related factors account for a substantial amount of the Black-White differential in multiple myeloma incidence.


Ocular aberrations and contrast sensitivity after cataract surgery with AcrySof IQ intraocular lens implantation Clinical comparative study.
To determine whether implantation of an intraocular lens (IOL) with a modified posterior aspherical surface (AcrySof IQ, Alcon Surgical Laboratories) results in reduced ocular aberrations (spherical aberration) and improved contrast sensitivity after cataract surgery. Brasilia Ophthalmologic Hospital, Brasilia, and Sao Geraldo Eye Hospital, Federal University of Minas Gerais, Belo Horizonte, Brazil. In an intraindividual randomized prospective study of 25 patients with bilateral cataract, an IOL with a modified posterior surface (AcrySof IQ) was compared with a biconvex IOL with spherical surfaces (AcrySof Natural, Alcon). Ocular aberrations with a 5.0 mm and 6.0 mm pupil were measured with a Hartmann-Shack aberrometer. Quality of vision was measured by visual acuity and contrast sensitivity under mesopic and photopic conditions. All patients were followed for 3 months. There were no statistically significant differences between eyes in postoperative uncorrected and best corrected distance visual acuities after a follow-up of 1 month and 3 months. Postoperatively, there was a statistically significant between-group difference in contrast sensitivity under photopic conditions without glare at 18 cycles per degree (cpd) (P = .04) and under mesopic conditions without glare at all spatial frequencies (3 cpd, 6 cpd, 12 cpd, and 18 cpd; P = .03, P = .009, P = .003, and P = .003, respectively) and with glare at 3 cpd and 6 cpd (P = .001 and P = .02, respectively). The difference in higher-order aberration (HOA) values between groups was statistically significant with a 5.0 mm and 6.0 mm pupil, with the AcrySof IQ IOL inducing less HOA than the AcrySof Natural IOL. Eyes with an AcrySof IQ IOL also had statistically significant less spherical aberration than eyes with an AcrySof Natural IOL with both pupil diameters (P<.001). The AcrySof IQ IOL with a modified posterior surface induced significantly less HOA and spherical aberration than the AcrySof Natural IOL. Contrast sensitivity was better under mesopic conditions with the AcrySof IQ IOL.


Effects of mindfulness-based stress reduction on adults with sleep disturbance: an updated systematic review and meta-analysis.
Mindfulness-based stress reduction (MBSR) is a meditation-based therapy originally recommended for stress management. However, it is currently used to alleviate sleep disturbances. Therefore, this contemporary systematic review aimed to elucidate the clinical effects of MBSR on sleep quality and sleep-related daytime impairment in adults with sleep disturbances, including chronic insomnia disorders. Systematic review and meta-analysis of randomised controlled trials (RCTs). A comprehensive search was conducted using the following databases: Ovid MEDLINE, AMED, Ovidembase, PsycINFO, Cochrane Library, CINAHL, and four domestic databases: KoreaMed, KISS, KMbase and NDSL. The final search update was performed in June 2022. Two researchers independently selected relevant studies, assessed the risk of bias and extracted the data. Of the 7516 records searched, 20 RCTs and 21 reports were included. In the subgroup analysis, MBSR did not improve objective or subjective sleep quality in chronic insomnia and cancers. However, MBSR versus waitlist control might have been effective in improving subjective sleep quality, but with substantial heterogeneity (standardised mean difference=-0.32; 95% CI: -0.56 to -0.08; I2=71%). In addition, MBSR compared with active control did not improve the sleep-related daytime impairments including depression, anxiety, stress, fatigue and quality of life. The overall risk of bias included in this review was a concern because of performance and detection bias. MBSR might be ineffective for improving sleep quality in patients with chronic insomnia and cancers. In addition, more than half of the RCTs included in this review had small sample sizes and were vulnerable to performance and detection biases. Therefore, well-designed RCTs with larger sample sizes are required to confirm the clinical effects of MBSR in adults with sleep disturbances. CRD42015027963.


Serum 7-alpha-hydroxy-4-cholesten-3-one as a marker for bile acid loss in children.
To establish age-related reference values for 7-alpha-hydroxy-4-cholesten-3-one (C4) in a pediatric population and to investigate bile acid malabsorption in children with short bowel syndrome (SBS). Serum was obtained between 8:00 a.m. and 11:00 a.m. from 100 healthy children (52% males, 9 months to 18 years of age) after 10 hours of fasting. Pediatric patients with SBS served as disease controls (n = 12). Following solid-phase extraction and purification, C4 was determined by high-performance liquid chromatography using a ultraviolet detector at a wavelength of 241 nm. The upper limit of normal for C4 concentrations was defined as the mean plus 2 SD of the log-normal distribution. The mean concentration and SD of C4 in healthy children was 22.8 ± 15.8 ng/mL with no relation to age or sex and an upper limit of normal of 66.5 ng/mL. Normal C4 values were found in 97 of 100 healthy children, and all 12 patients with SBS had C4 concentrations above 100 ng/mL (mean 299.6 ± 167.8 ng/mL; range 105.7-562.1 ng/mL, P < .0001 compared with controls). The determined upper limit of normal for C4 concentration in healthy children corresponds to previously published levels in healthy adults and is independent of age and sex. The consistently elevated C4 concentrations in our patients with SBS confirm the reliability of this noninvasive, nonisotopic method to assess bile acid malabsorption in children.


Male-male interactions and mating kinetics in Drosophila.
Male-male interaction (K) has been estimated from data on the attrition rate of virgin females per minute in a study of the mating kinetics in Drosophila. K is expressed as the time males expend on other males relative to that expended while searching for, courting, and copulating with females. The value of K in these studies ranged from 0 (approximately) to .695; it was affected both by strain (sepia or ebony D. melanogaster and wild-type D. simulans) and by size of the mating chamber. Host-parasitoid models of ecologists appear to be appropriate for examining mating kinetics in Drosophila.


A false lesion in the center of the pons on magnetic resonance images.
Three-hundred pediatric patients were evaluated for pontine signal abnormalities with special reference to small nodular, central pontine lesions. The ages of the patients ranged from 1 year to 17 years (mean = 7.3 years). There were 157 males and 143 females. The magnetic resonance (MR) imaging examinations were performed at 0.5 Tesla. There were 26 cases out of the 300 patients with pontine involvement due to a variety of clinically proved disorders. Except for these, we noted four patients with nodular, central pontine changes in the remaining 274 cases (four out of 274 = approximately 1.5%). These appeared as hyperintense foci on T2-weighted images, and hypointense on T1-weighted images. They were approximately 2-3 mm in diameter, and confined exactly to the middle of the pons. There was no clinical correspondence for these. The condition was attributed to an artefact created by a relatively deep interpedincular cistern leading to a volume-averaging effect.


Ten-year survival outcomes after radical nephroureterectomy with a risk-stratified approach using prior diagnostic ureteroscopy: a single-institution observational retrospective cohort study.
To evaluate the long-term oncological outcomes of patients with upper tract urothelial carcinoma (UTUC) undergoing radical nephroureterectomy (RNU) and the impact of diagnostic ureteroscopy (URS) on survival outcomes. A retrospective analysis of all consecutive patients undergoing RNU for suspected UTUC at a UK tertiary referral centre from a prospectively maintained database was conducted. The primary outcome measures were 5- and 10-year cancer-specific survival (CSS). The secondary outcomes were: overall survival (OS), recurrence-free survival (RFS), impact of prior diagnostic URS on OS, CSS and intravesical RFS (intravesical-RFS), and predictors of intravesical recurrence. Statistical analysis was performed in R using the 'survminer' and 'survival' packages. The Kaplan-Meier method was used to calculate survival functions and these were expressed in graphical form. Uni-/multivariate survival analyses were performed using the Cox proportional hazard regression model. Statistical significance in this study was set at P < 0.05. A total of 422 patients underwent RNU with confirmed UTUC. The median (interquartile range) follow-up of patients with confirmed UTUC was 9.2 (5.6-12.7) years. The 5- and 10-year CSS rates were 70.5% (95% confidence interval [CI] 65.9-74.9) and 67.1% (95% CI 62.4-71.6), respectively. OS (HR 1.04 [95% CI 0.78-1.38]; P = 0.46) and CSS (HR 0.96 [95% CI 0.68-1.34]; P = 0.81) were similar in the diagnostic URS and the direct RNU cohorts. intravesical RFS was superior for the direct RNU cohort (HR 1.94 [95% CI 1.19-3.17]; P = 0.008). In multivariate analysis, prior URS, T2 stage, proximal ureter tumour and bladder cancer history were predictors of metachronous bladder recurrence. This single-centre retrospective cohort study reports the long-term oncological outcomes of RNU with a median follow-up of 9.2 years, serving as a reference standard in counselling patients undergoing RNU. Stage and grade of the RNU specimen were the only two studied factors that appeared to adversely impact long-term CSS and OS. Our results suggest that the risk of intravesical recurrence is increased nearly twofold in patients who have undergone diagnostic URS prior to RNU. Prior URS, however, does not appear to adversely impact long-term CSS and OS. The authors suggest that a risk-stratified approach be adopted, wherein diagnostic URS is offered only in equivocal cases.


Prospective evaluation of occlusive hydrocolloid dressing versus conventional gauze dressing regarding the healing effect after abdominal operations: randomized controlled trial.
To compare occlusive hydrocolloid dressing (OHD; Karayahesive) and gauze dressing (GD) with regard to the cost and incidence of wound infection after abdominal surgery. A total of 134 patients who underwent incisions were randomized to have their wounds dressed with either OHD or GD. OHD was left on until the sutures were removed, and GD was changed everyday postoperatively. The cost calculations represent the number of dressings required for each treatment group as determined by the frequency of required dressing changes and cost per dressing. There were no differences between the groups regarding the need for dressings to be changed or the incidence of infection. OHD was less expensive and complicated than GD, which needed to be changed everyday (p < 0.0001). The results suggest that OHD is less expensive to use than GD, and the risk of wound infection is not increased compared to GD.


Update of the current role of ultrasound in asymptomatic hyperuricemia. A systematic literature review.
Ultrasound (US) is a recognized imaging modality for the assessment of gout. Recently it is being explored for its potential role in the evaluation of subjects with asymptomatic hyperuricemia (AH). Preliminary reports demonstrated the presence of monosodium urate (MSU)-crystal deposits including aggregates, double contour sign and/or tophi in both intra-articular and periarticular tissues of AH individuals. Although these results are exciting, the value and potential application of US in AH remain to be clearly delineated. In this systematic literature review, we aim to summarise the recent publications regarding the role of US in the assessment of AH. We analyzed possible application of US in the daily clinical practice and its future clinical and research potential in the evaluation of AH individuals.


Immunohistological profiling confirms salivary gland-like nature of the tubarial glands and suggests closest resemblance to the palatal salivary glands.
High label uptake in 68 Ga-PSMA-11 PET/CT recently identified a bilateral nasopharyngeal structure as a salivary gland (SG)-like additional 'area of interest', to be considered in conditions affecting SGs. These structures were termed 'tubarial glands'. We aimed to further characterize their histological and immunohistochemical position compared to established SGs. Tubarial gland tissue was compared with parotid, submandibular, sublingual, palatal and labial SGs tissue using immunohistological techniques. Expression of acinar cell-associated aquaporin-5 (AQP5) was detected in tubarial glands, in an apical location associated in control, established SGs with polarized, secretory acinar cells. Keratin14 (KRT14) expression in cells peripheral to AQP5+ clusters also suggested presence of myoepithelial cells. α-amylase, prolactin-induced protein, proline rich protein Haelll subfamily 2, and Muc5B expression suggests mucous acinar cell presence, and presence of muco-serous acinar cells peripheral to putative mucous acinar cells. Expression of adrenergic receptor-β1 by acinar-like cells of the tubarial gland suggests ability to transduce sympathetic neuronal signaling. In terms of ductal architecture, tubarial glands contained large excretory-like ducts (similar to all other SGs), and squamous ducts, comprised of intermingled KRT14+ and KRT7+ cells. These squamous ducts were also observed in palatal, sublingual and labial SGs. No striated or intercalated ducts were observed, similar to palatal SGs. Based on histological and immunohistochemical analyses, the tubarial glands resemble SGs. They most convincingly echo characteristics of the palatal SGs in terms of ductal cells, and both the palatal and labial SGs when considering acinar cells.


High performance H2 sensor based on ZnSnO3 cubic crystallites synthesized by a hydrothermal method.
Zinc stannate (ZnSnO3) cubic crystallites have been successfully synthesized by hydrothermal reaction at 140°C. X-ray diffraction (XRD), field emission scanning electron microscopy (FESEM) and transmission electron microscopy (TEM) have been employed to characterize the crystal structure and morphology of the as-synthesized ZnSnO3. The ZnSnO3 cubic crystallites exhibited selective sensing performance towards H2 in terms of higher gas response, rapid response-recovery, repeatability and relatively lower operating temperature. This experimental result demonstrates that the synthesized ZnSnO3 cubic crystallites have noteworthy H2 sensing characteristics which make them a promising material for the fabrication of high performance H2 sensor.


DNA makes GFP shine.
An oligomerization-dependent system comprising two fragments of green fluorescent protein (GFP) fused to engineered zinc fingers could be a means to detect virtually any double-stranded DNA sequence.


Microcantilever-Based Label-Free Characterization of Temperature-Dependent Biomolecular Affinity Binding.
This paper presents label-free characterization of temperature-dependent biomolecular affinity binding on solid surfaces using a microcantilever-based device. The device consists of a Parylene cantilever one side of which is coated with a gold film and functionalized with molecules as an affinity receptor to a target analyte. The cantilever is located in a poly(dimethylsiloxane) (PDMS) microfluidic chamber that is integrated with a transparent indium tin oxide (ITO) resistive temperature sensor on the underlying substrate. The ITO sensor allows for real-time measurements of the chamber temperature, as well as unobstructed optical access for reflection-based optical detection of the cantilever deflection. To test the temperature-dependent binding between the target and receptor, the temperature of the chamber is maintained at a constant setpoint, while a solution of unlabeled analyte molecules is continuously infused through the chamber. The measured cantilever deflection is used to determine the target-receptor binding characteristics. We demonstrate label-free characterization of temperature-dependent binding kinetics of the platelet-derived growth factor (PDGF) protein with an aptamer receptor. Affinity binding properties including the association and dissociation rate constants as well as equilibrium dissociation constant are obtained, and shown to exhibit significant dependencies on temperature.


Microwave staining of enteric neurons using cuprolinic blue (Quinolinic phthalocyanin) combined with enzyme histochemistry and peroxidase immunohistochemistry.
Methods that visualize subsets as well as the entire enteric neuron population are not readily available or have proved to be unreliable. Therefore, we attempted to combine NADPH-d histochemistry, AChE histochemistry, and CGRP immunohistochemistry, techniques that mark subsets of enteric neurons, with a technique that appeared to visualize the entire enteric neuron population, the cuprolinic blue staining method. To guarantee representative staining results, the individual staining methods were modified by using microwaves. In addition, this preserved the characteristics of each of the individual techniques. The distribution of NADPH-d, AChE, and CGRP corresponded well with previous morphological and physiological reports. Consequently, the different combinations gave rise to rapid, useful, and ready-to-use double labeling techniques. Their main advantage is that they simultaneously visualize the total population as well as subsets of enteric neurons.


Recovery Kinetics After Speed-Endurance Training in Male Soccer Players.
To determine the recovery kinetics of performance, muscle damage, and neuromuscular fatigue following 2 speed-endurance production training (SEPT) protocols in soccer. Ten well-trained, male soccer athletes randomly completed 3 trials: work-to-rest ratio (SEPT) 1:5, SEPT/1:8, and a control trial. Training load during SEPT was monitored using global positioning system and heart-rate monitors. Performance (isokinetic strength of knee extensors and flexors, speed, and countermovement jump) and muscle damage (delayed-onset muscle soreness [DOMS] and creatine kinase) were evaluated at baseline and at 0, 24, 48 and 72 h posttraining. Maximal voluntary contraction (fatigue index) of knee extensors and flexors was additionally assessed at 1, 2, and 3 h posttraining. Fatigue increased (P < .05) in SEPT/1:5 (∼4-30%) for 3 h and in SEPT/1:8 (∼8-17%) for 2 h. Strength performance declined (P < .05) in both SEPT trials (∼5-20%) for 48 h. Speed decreased (∼4-18%; P < .05) for 72 h in SEPT/1:5 and for 48 h in SEPT/1:8. Countermovement-jump performance decreased (∼7-12%; P < .05) in both SEPT trials for 24 h. DOMS increased (P < .05) in SEPT/1:5 (∼2-fold) for 72 and in SEPT/1:8 (∼1- to 2-fold) for 48 h. Creatine kinase increased (∼1- to 2-fold, P < .05) in both SEPT trials for 72 h. SEPT induces short-term neuromuscular fatigue; provokes a prolonged deterioration of strength (48 h), speed (72 h), and jump performance (24 h); and is associated with a prolonged (72-h) rise of DOMS and creatine kinase. Time for recovery is reduced when longer work-to-rest ratios are applied. Fitness status may affect quality of SEPT and recovery kinetics.


Potential effects of Cladophora oligoclora Decomposition: Microhabitat variation and Microcystis aeruginosa growth response.
Excessive proliferation of filamentous green algae (FGA) is a new ecological problem in lake systems that have not yet reached a steady state. However, knowledge on how FGA decomposition affects the physical and chemical properties of microhabitats, and whether FGA decomposition stimulates the growth of harmful microalgae in the same niche and promotes the formation of harmful algal blooms remains unclear. In this study, we investigated the decomposing effect of a typical FGA, Cladophora oligoclora, on the density and photosynthetic capacity of Microcystis aeruginosa. C. oligoclora decomposition was characterized under different conditions, namely, unshaded and aerobic, unshaded and anoxic, shaded and anaerobic, and shaded and anoxic, which represented different environmental states in the sedimentation process of decaying C. oligoclora mats from water surface to sediment. The shaded and anaerobic treatment significantly decreased the dissolved oxygen and pH of the culture medium by 66.48 % and 7.21 %, respectively, whereas the conductivity and total organic carbon increased by 71.17 and 70.19 times compared with the control group, respectively. This indicated that the decomposing C. oligoclora deposited at the bottom under dark and anaerobic conditions in natural waters had the greatest impact on the lake environment. Further, the cell density of M. aeruginosa was higher than that in the control group with low concentration (10 % of decomposing solution), whereas the cell density and photosynthetic activity decreased significantly at high concentration of the decomposing solution. Fatty acids and phenolic acids were identified as the main Cyanobacteria-inhibiting active substances in the organic acid components of the decomposing solution. Furthermore, phenol, 4-methyl- and indole compounds were active organic lipophilic compounds in the residue and solution of decomposing C. oligoclora were difficult to degrade. Our findings will be valuable for understanding the succession relationships between FGA and cyanobacteria, which have the same niche in lake ecosystems.


Scale of dispersal in varying environments and its implications for life histories of marine invertebrates.
We present several models concerning the short term consequences of spreading offspring in varying environments. Our goal is to determine what patterns of spatial and temporal variation yield an advantage to increasing scale of dispersal. Of necessity, the models are somewhat artificial but we feel they are a reasonable approximation of and hence generalizable to natural systems. With these models we examine consequences of dispersal arising from environmental variation: increased environmental variance, different degrees of spatial and temporal correlation, some arbitrary spatial patterns of favorability and finally some patterns derived from long-term, large-scale weather data collected along a contiguous stretch of coastline from southern Oregon to northern Washington (USA). We examine the costs and benefits of increasing sclae of dispersal in both density dependent and density independent models.Several conclusions may be drawn from the results of these models. In the absence of any spatial or temporal order to favorability (where favorability is directly proportional to either fitness or carrying capacity) increasing scale of spread produces a higher tate of population increase. At larger scales, though, an asymptote of maximum relative advantage is approached, so each added increment of spread has a smaller contribution to fitness. This asymptote is higher and the approach to it relatively slower with increasing environmental variance. For a given environmental variance, increasing spatial correlation results in a slower approach to the same asymptote. In density independent models, increasing temporal correlation of fitness selects against increased dispersal if expected differences between sites are sufficiently great relative to variation within sites; but in this instance, density dependence yields a somewhat different result: dispersers have a refuge at sites of low carrying capacity or sites lacking non-dispersers. Finally, optimum intermediate scales of dispersal can occur where differences in expected fitness increase with increasing distance from the parental site, such as in a gradient, but where the environmental variation at a given site is fairly large relative to differences in expected fitness between adjacent sites.The foregoing results are extended for the following predictions. When greater longevity in a resistant phase of the life cycle reduces temporal variation in survival and fecundity, increased generation time should decrease the benefits of spreading offspring in an environment that would otherwise favor spread and could either increase or decrease the costs of spreading offspring in an environment selecting against spread. We speculate that if large scale patterns of varying survival and fecundity are similar to the variation in the physical environment which we examined with weather data, there should be little or no short term advantage to large scale spread of offspring (on the order of 50 kilometers or more) because expected differences increase and seldom if ever decrease with increasing distance between sites.This suggests that feeding larvae of benthic invertebrates with their concomitant long planktonic period, receive little if any advantage from increased scale of dispersal, and consequently that the advantages to planktotrophy over lecithotrophy must lie in other life history aspects, such as the ability to produce a greater number of smaller eggs.


Leveraging ecological momentary assessment to understand variability in food parenting practices within a low-income racially/ethnically diverse sample of parents of preschoolers.
Children's eating behaviors are shaped significantly by their home food environment, including exposure to food parenting practices. The current study leveraged ecological momentary assessment (EMA) to describe how food parenting practices used to feed preschoolers (n = 116) differed across contextual factors around eating, including type of eating occasion (i.e., meals vs. snacks), day of the week (i.e., weekend vs. weekday), who initiated the meal (parent vs. child), emotional climate of the eating occasion. Parent perceptions of how well the eating occasion went, including how well the child ate and whether the food parenting practices worked as intended were also explored. Parent use of specific food parenting practices, situated within four higher-order domains (i.e., structure, autonomy support, coercive control, indulgent), was found to differ by type of eating occasion; parents engaged in a higher proportion of structure practices at meals than at snacks. Use of specific food parenting practices differed by mealtime emotional climate; parent use of structure and autonomy support was associated with eating occasions described as relaxed, enjoyable, neutral, and fun. Finally, parent perception of how well the child ate differed by use of specific food parenting practices; during eating occasions when parent's felt their child ate "not enough", they used less autonomy support and more coercive control compared to eating occasions where the child ate "enough and a good balance." Leveraging EMA allowed for increased understanding of the variability in food parenting practices and contextual factors. Findings may be utilized to inform the development of larger-scale studies seeking to understand why parents choose specific approaches to feeding their children, as well as the impact of various approaches to child feeding on child health outcomes.


A multicellular systems biology model predicts epidermal morphology, kinetics and Ca2+ flow.
Systems biology is currently focused on integrating intracellular networks, although clinically, diseases are largely defined by their histological features. For example, no computational model can simulate today the formation of a horizontally layered epidermis. Since the epidermis is the most complex structured epithelial tissue, systems biology models could yield important insights in epithelial tissue, in which most of all human cancers arise. We describe the algorithms of a system, capable of simulating the tissue homeostasis in human epidermis leading to a horizontally layered tissue with cells of different differentiation stages. The system predicts epidermal morphology, tissue kinetics and 2D flow of Ca2+ ions. Predicted properties of an epidermis with a healthy and a disturbed barrier are compared with the literature. The system closely mimics the respecting physiological situations. Additional information and films of the simulation are available at the website. Source code is available on request. http://www.zbh.uni-hamburg.de/research/ESB/index.php email@example.com


Membrane adhesion in photosynthetic bacterial membranes. Light harvesting complex I (LHI) appears to be the main adhesion factor.
We have reconstituted pigment-protein complexes isolated from Rhodopseudomonas palustris photosynthetic membranes into phospholipid liposomes. The various complexes were tested for their ability to promote adhesion of the liposome membrane in the presence and absence of Mg2+ ions. Samples containing a reaction center (RC)/light-harvesting I (LHI) complex appeared to stack in a manner resembling control thylakoids in 2 and 5 mM Mg2+. We also tested for the effects of Mg2+ on detergent extractability of pigment-protein complexes from intact membranes. Mg2+ sharply reduced the amount of LHI solubilized from membranes, while having little effect on the extractability of the light harvesting II complex (LHII) and the RC. Based on these results we suggest that LHI is the principal adhesion factor of R. palustris thylakoids.


Postnatal development and cell death in the sciatic motor nucleus of the mouse.
Motoneurons of the sciatic nerve were studied in the lumbar cord of the mouse, at various postnatal stages, 1-3 days, 6-7 days, three weeks, and 2-3 months. Horseradish peroxidase (HRP) was applied at the cut end of the distal sciatic nerve, and, after retrograde transport, transversal and longitudinal histological sections of the cord were made in order to compare various features of the motor pool such as cell grouping, position in gray matter, cell number, cell size, and gross dendritic patterns. As early as birth, sciatic nerve motoneurons were grouped in a longitudinal column in the homolateral gray matter. No labelled cells were found outside the column either ipsilaterally or contralaterally. The location of the column was constant throughout postnatal development, encompassing the same spinal root levels and occupying the same position in the gray matter, the lateral portion of the ventral horn. Cell volume showed a 4-5 fold increase. Dendrites were not visible at the early stages and became labelled at 2-3 months. The neuropil also displayed a 4-5 fold increase, causing considerable spacing of the motoneurons. Histograms of cell body volume showed the progressive differentiation of the initially uniform motoneuronal pool in different sub-populations. In each experimental animal, labelled cells were counted in all histological sections and, for statistical comparison, the value was corrected for mean cell size. A 31% decrease in the number of labelled cells was observed between birth and 2-3 months. The rate of cell death was not constant, since 17% disappeared during the first week and 14% thereafter. The 31% decrease was lower than that observed in previous studies in the rat, 50-80%. The difference in species may explain this discrepancy, however, technical differences must also be invoked. In these studies, HRP was injected into the biceps brachii muscle. An overestimation of cell death is possible with this technique because postnatal changes of the axonal endings permit easier HRP uptake in immature muscles than in mature muscles. The cut nerve technique however by-passes the axonal endings.


Central olfactory processing in patients with disorders of consciousness.
Previous studies have demonstrated that individuals suffering from disorder of consciousness (DOC) maintain some minor neural processing of percepts mediated by senses that early in their pathway intersect the thalamus, a key dysfunctional area in DOC patients. Here the degree of sensory preservation within the olfactory system, a system that lacks an obligatory thalamic relay, and its relationship to the consciousness level in DOC patients of various etiologies was assessed. Clinical Coma Recovery Scale - Revised (CRS-R) as well as cerebral responses to odors by means of functional magnetic resonance were obtained in a group of vegetative state/unresponsive wakefulness syndrome (n = 26) patients, minimally conscious state (n = 7) patients and healthy controls (n = 25). A majority of vegetative state/unresponsive wakefulness syndrome patients (58%) and 100% of minimally conscious state patients demonstrated a significant preservation of olfactory neural processing, manifested by activation within the piriform cortex, an area considered as a primary olfactory region. Degree of preservation of olfactory processing differed linearly in line with the patients' etiologies where groups demonstrating greater conscious awareness demonstrated more significant processing. Viewed over all DOC patients, there was a significant negative association between odor-related activity in the orbitofrontal cortex and CRS-R scores. It is demonstrated that DOC patients exhibit a significant preservation of olfactory neural processing with a clear relationship to etiopathologies and clinical measures even years after of chronification of DOC.


Induced Pluripotent Stem Cell-Derived Endothelial Networks Accelerate Vascularization But Not Bone Regeneration.
Vascularization is critical for engineering mineralized tissues. It has been previously shown that biomaterials containing preformed endothelial networks anastomose to host vasculature following implantation. However, the networks alone may not increase regeneration. In addition, a clinically applicable source of cells for vascularization is needed. In this study, vascular networks were generated from endothelial cells (ECs) derived from human induced pluripotent stem cells (iPSCs). Network formation by iPSC-ECs within fibrin gels was investigated in a mesenchymal stem cells (MSCs) coculture spheroid model. Statistical design of experiments technique was evaluated for its predicting capability during the optimization of experimental parameters. The prevascularized units were combined with hydroxyapatite nanoparticles to develop a vascularized composite hydrogel that was implanted in a rodent critical-sized cranial defect model. Immunohistological staining for human-specific CD31 at week 1 indicated the presence and maintenance of the implanted vessels. At 8 weeks, the prevascularized systems resulted in higher vessel density over MSC-only scaffolds. The implanted vessels appeared to establish flow with host vasculature. While there was a slight increase in bone volume in the prevascularized bone construct compared to MSC-only bone constructs, there was not a profound increase in bone regeneration. These results show that scaffolds with network structures can be generated from ECs derived from iPSC and that the networks survive and inosculate with the host postimplantation in a bone model. Impact statement Vascularization is critical for engineering bone. Prevascularized scaffolds have been shown to improve postimplantation vascularization. Herein, vascularized networks were generated from induced pluripotent cells derived from endothelial cells. These vascularized units were combined with a fibrin/hydroxyapatite scaffold to develop a prevascularized construct for bone regeneration. Implantation of these scaffolds in a small animal cranial defect model resulted in network inosculation and increased vascularization, but exhibited only a limited effect on bone formation. This study provides insight into the challenges of generating vascularized bone.


Dexmedetomidine alleviates insulin resistance in hepatocytes by reducing endoplasmic reticulum stress.
Dexmedetomidine (DEX) stabilizes intraoperative blood glucose levels and reduces insulin resistance (IR), a common perioperative complication. However, the molecular mechanisms underlying these effects remain unclear. Since endoplasmic reticulum stress (ERS) is a mechanism of IR, this study sought to examine whether DEX can effectively alleviate IR by reducing ERS. HepG2 and LO2 cells were treated with different concentrations of insulin. The glucose content assay and Cell Counting Kit-8 (CCK-8) were then employed to determine the optimal insulin concentration capable of inducing IR without affecting cell viability. Insulin-resistant hepatocytes were cultured with different concentrations of DEX for 24 h, and the glucose concentration in the supernatant was measured. ERS was assessed by qPCR and western blotting. The latter was also used to quantify the expression of phosphorylated protein kinase B (p-AKT), phosphoenolpyruvate carboxykinase (PEPCK), and glucose 6 phosphatase (G6Pase), which are key proteins involved in the action of insulin. After 48-h of culturing with 10 μg/mL insulin, glucose consumption in hepatocytes was found to be reduced. IR hepatocytes cultured with 10, 100, or 1000 ng/ml DEX for 24 h showed a concentration-dependent increase in glucose consumption. Elevated mRNA and protein levels of ERS markers binding immunoglobulin protein (BIP) and ER protein 29 (ERp29), were reversed by DEX treatment. Moreover, reduced p-AKT and increased PEPCK and G6Pase protein levels in IR hepatocytes were also restored following DEX treatment. DEX may alleviate IR in hepatocytes by reducing ERS serving to restore insulin action via the IRS-1/PI3K/AKT pathway.


N-WASP plays a critical role in fibroblast adhesion and spreading.
N-WASP (Neural Wiskott Aldrich Syndrome Protein) regulates actin polymerization by activating the Arp2/3 complex and promotes the formation of actin-rich structures such as filopodia. Such actin-rich structures play critical roles in cell adhesion and cell motility. Analysis of the adhesion properties of N-WASP+/+ and N-WASP-/- mouse embryonic fibroblasts to extracellular matrix proteins revealed that N-WASP is critical for cell adhesion to fibronectin. There was no significant difference in the localization of paxillin in the two cell lines, however the vinculin patches in WASP+/+ cells were thicker and more prominent than those in N-WASP-/- cells. The beta1 integrins in N-WASP+/+ cells were found in large clusters, while beta1 integrins were more dispersed in N-WASP-/- cells. The N-WASP-/- cells migrated more rapidly than N-WASP+/+ cells in a scratch migration assay. Thus, our data suggest that N-WASP deficiency leads to reduced adhesion to fibronectin and increased cell motility.


Prevalence of Candida in the oral cavity of diabetic subjects.
Estimation of prevalence of Candida in the oral cavity of diabetic and non-diabetic subjects. One hundred and three subjects of diabetes mellitus (49 Type 1 diabetes mellitus and 54 Type 2 diabetes mellitus) and one hundred non-diabetic subjects (control) were studied. 41(83.67%) out of 49 Type 1 diabetes mellitus, 37(68.52%) out of 54 Type 2 diabetes mellitus and 27(27%) out of 100 in non-diabetic subjects were found to carry Candida in their oral cavity. Colony Forming Unit (CFU) of Candida in the oral cavity ranking in groups was Type 1 diabetes mellitus > Type 2 diabetes mellitus > non-diabetic subjects. Colonization and carriage of Candida in the oral cavity was found to be higher in diabetic subjects than in non-diabetic subjects. However anti-diabetic therapy and glycaemic control in diabetes were found to bear no relation with carriage of Candida in the oral cavity.


Comprehensive presurgical functional MRI language evaluation in adult patients with epilepsy.
Functional magnetic resonance imaging (fMRI) has the potential to replace the intracarotid amobarbital procedure (IAP) in presurgical evaluation of patients with epilepsy. In this study, we compared fMRI verb generation (VG) and semantic decision/tone decision (SDTD) tasks and the IAP in their ability to localize language functions in patients with epilepsy undergoing presurgical evaluation. We enrolled 50 healthy controls to establish normal language activation patterns for VG and SDTD tasks at 3 or 4 T, and to design language regions of interest (ROIs) that were later applied to 38 patients with epilepsy (28 of 38 also underwent the IAP). We calculated laterality indices (LIs) for each task for each subject based on the ROIs, and we used general linear modeling to analyze the fMRI data. All healthy and epileptic subjects activated language areas with both fMRI tasks. We found significant correlations in language lateralization between the fMRI tasks (r=0.495, P<0.001) and between VG and IAP (r=0.652, P<0.001) and SDTD and IAP (r=0.735, P<0.001). The differences in LIs between SDTD and VG tasks were small and not affected by age, gender, epilepsy status, handedness, or performance. SDTD and VG tasks combined explained approximately 58.4% in the variability of the IAP/language. In the general linear modeling, only the SDTD task significantly contributed to the determination of language lateralization in patients with epilepsy undergoing presurgical evaluation. Results indicate a moderate convergent validity between both fMRI language tasks and between IAP and fMRI tasks. The results of this study indicate that either of these fMRI tasks can be used for language lateralization in patients with epilepsy undergoing presurgical evaluation, but that the SDTD task is likely to provide more information regarding language lateralization than the VG task.


Does participation in standardized aerobic fitness training during inpatient stroke rehabilitation promote engagement in aerobic exercise after discharge? A cohort study.
To determine whether attending an aerobic fitness program during inpatient stroke rehabilitation is associated with increased participation in physical activity after discharge. This was a prospective cohort study. Patients who received inpatient stroke rehabilitation and were discharged into the community (n = 61; mean age, 65 years) were recruited. Thirty-five participants attended a standardized aerobic fitness program during inpatient rehabilitation, whereas 26 did not. The Physical Activity Scale for Individuals with Physical Disabilities (PASIPD) and adherence to the American College of Sports Medicine (ACSM) guidelines were assessed up to 6 months after discharge. Participants in the fitness group had PASIPD scores and adherence to ACSM guidelines similar to those of participants in the nonfitness group up to 6 months after discharge. There was no significant correlation between volume of exercise performed during the inpatient program and amount of physical activity after discharge. Participation in an inpatient fitness program did not increase participation in physical activity after discharge in individuals with stroke. A new model of care that encourages patients to pursue physical activity after discharge and reduces the potential barriers to participation should be developed.


Smooth-muscle endoplasmic reticulum contains a cardiac-like form of calsequestrin.
It is proposed that smooth-muscle endoplasmic reticulum contains calsequestrin and that this protein in smooth muscle resembles cardiac calsequestrin more than the skeletal-muscle form. This proposal is based on seven similarities between the smooth-muscle protein and cardiac calsequestrin. Proteins with an Mr of 55,000 can be extracted from the membranes of smooth muscle and of cardiac muscle using 100 mM Na2CO3. The protein from smooth muscle binds to phenyl-Sepharose in the absence of Ca2+ and is released by 10 mM CaCl2, as has been observed for cardiac calsequestrin. The protein from smooth muscle comigrates with the cardiac calsequestrin on Laemmli-type SDS-polyacrylamide gel electrophoresis. The protein of Mr 55,000 from smooth muscle and cardiac calsequestrin both strain blue with the carbocyanine dye Stains-all. Both proteins present similar one-dimensional Cleveland peptide maps although minor differences might exist. From an analysis of subcellular membranes separated by sucrose gradient centrifugation it is concluded that the protein with Mr 55,000 from the smooth muscle is confined to the endoplasmic reticulum, the same subcellular structure from which, in heart muscle, calsequestrin can be isolated. Antibodies raised against canine cardiac calsequestrin bind to a protein of similar Mr in smooth-muscle endoplasmic reticulum. In addition to the calsequestrin, three other extrinsic proteins with an Mr of 130,000, 100,000 and 63,000, stain blue with Stains-all and occur in the endoplasmic reticulum of smooth muscle.


Tubeless versus standard percutaneous nephrolithotomy in pediatric patients: a systematic review and meta-analysis.
This systematic review and meta-analysis was designed to evaluate the post-operative outcomes between tubeless and standard percutaneous nephrolithotomy (PCNL) among children. Literature searches were performed following the Cochrane guidelines. We conducted a systematic review and meta-analysis that included three trials investigating the outcomes including the length of hospital stay, operation time, hemoglobin decrease, blood transfusion rate, perirenal fluid presence, post-operative fever, stone clearance rate, and the need for a second operation. The patients who underwent tubeless PCNL had shorter length of hospitalization compared to standard PCNLs (mean difference -1.57, 95% confidence interval -3.2 to 0.07, p = 0.06). No significant decrease was detected in hemoglobin after tubeless PCNL compared to standard PCNL (mean difference 0.05, 95% confidence interval -0.03 to 0.13, p = 0.21). There were no significant differences in operation time (p = 0.7), perirenal fluid presence (p = 0.15), post-operative fever (p = 0.72), stone clearance (p = 0.68), and the need for a second operation (p = 0.90). This study showed no significant difference between tubeless and standard PCNLs in children. However, due to the lack of data, the results should be mentioned prudently. Future randomized trials with more sample sizes and longer follow-ups are warranted.


Morale of vocational dental practitioners in the United Kingdom.
This study was undertaken to devise a suitable survey instrument to measure morale, and to undertake an assessment of morale amongst vocational dental practitioners (VDPs) in the UK. Postal questionnaire survey. Dental vocational training schemes in the UK. Vocational dental practitioners. A confidential postal questionnaire was used to measure levels of morale among all VDPs in the UK in 2007. A response rate of 76.7% was achieved. The mean morale score for Scottish VDPs was significantly higher than that of the Northern Irish VDPs, which in turn was significantly higher than those of the VDPs in England or Wales. In England and Wales females recorded higher morale scores than males. Lowest morale scores were associated with statements referring to concerns about future changes to NHS dentistry, and the limits on treatment within the NHS system. The highest scores were associated with good working relationships. The use of an appropriately tested questionnaire has provided a convenient objective measure of morale. The morale of VDPs in the United Kingdom was lower than expected. Scottish VDPs recorded higher morale scores than other VDPs and responded more positively in the survey instrument. The most negative responses from all VDPs were regarding the effect of the NHS system on treatment and concerns about future changes to the NHS.


Clinical effectiveness of one ultrasound guided intra-articular corticosteroid and local anaesthetic injection in addition to advice and education for hip osteoarthritis (HIT trial): single blind, parallel group, three arm, randomised controlled trial.
To compare the clinical effectiveness of adding a single ultrasound guided intra-articular hip injection of corticosteroid and local anaesthetic to advice and education in adults with hip osteoarthritis. Pragmatic, three arm, parallel group, single blind, randomised controlled trial. Two community musculoskeletal services in England. 199 adults aged ≥40 years with hip osteoarthritis and at least moderate pain: 67 were randomly assigned to receive advice and education (best current treatment (BCT)), 66 to BCT plus ultrasound guided injection of triamcinolone and lidocaine, and 66 to BCT plus ultrasound guided injection of lidocaine. BCT alone, BCT plus ultrasound guided intra-articular hip injection of 40 mg triamcinolone acetonide and 4 mL 1% lidocaine hydrochloride, or BCT plus ultrasound guided intra-articular hip injection of 5 mL 1% lidocaine. Participants in the ultrasound guided arms were masked to the injection they received. The primary outcome was self-reported current intensity of hip pain (0-10 Numerical Rating Scale) over six months. Outcomes were self-reported at two weeks and at two, four, and six months. Mean age of the study sample was 62.8 years (standard deviation 10.0) and 113 (57%) were women. Average weighted follow-up rate across time points was 93%. Greater mean improvement in hip pain intensity over six months was reported with BCT plus ultrasound-triamcinolone-lidocaine compared with BCT: mean difference -1.43 (95% confidence interval -2.15 to -0.72), P<0.001; standardised mean difference -0.55 (-0.82 to -0.27). No difference in hip pain intensity over six months was reported between BCT plus ultrasound-triamcinolone-lidocaine compared with BCT plus ultrasound-lidocaine (-0.52 (-1.21 to 0.18)). The presence of ultrasound confirmed synovitis or effusion was associated with a significant interaction effect favouring BCT plus ultrasound-triamcinolone-lidocaine (-1.70 (-3.10 to -0.30)). One participant in the BCT plus ultrasound-triamcinolone-lidocaine group with a bioprosthetic aortic valve died from subacute bacterial endocarditis four months after the intervention, deemed possibly related to the trial treatment. Ultrasound guided intra-articular hip injection of triamcinolone is a treatment option to add to BCT for people with hip osteoarthritis. EudraCT 2014-003412-37; ISRCTN50550256.


Mathematical modeling of movement on fitness landscapes.
Movement of populations on fitness landscapes has been a problem of interest for a long time. While the subject has been extensively developed theoretically, reconciliation of the theoretical work with recent experimental data has not yet happened. In this work, we develop a computational framework and study evolution of the simplest transcription network between a single regulator, R and a single target protein, T. Through our simulations, we track evolution of this transcription network and comment on its dynamics and statistics of this movement. Significantly, we report that there exists a critical parameter which controls the ability of a network to reach the global fitness peak on the landscape. This parameter is the fraction of all permissible values of a biochemical parameter that can be accessed from its current value via a single mutation. Overall, through this work, we aim to present a general framework for analysis of movement of populations (and particularly regulatory networks) on landscapes.


The Stability of Comorbid Psychiatric Disorders: A 7 Year Follow Up of Children with Pervasive Developmental Disorder-Not Otherwise Specified.
The current study was a 7-year follow-up of 74 6-12 year old children with Pervasive Developmental Disorder-Not Otherwise Specified. We examined the rates and 7 year stability of comorbid psychiatric diagnoses as ascertained with the Diagnostic Interview Schedule for Children: Parent version at ages 6-12 and again at ages 12-20. Also, we examined childhood factors that predicted the stability of comorbid psychiatric disorders. The rate of comorbid psychiatric disorders dropped significantly from childhood (81 %) to adolescence (61 %). Higher levels of parent reported stereotyped behaviors and reduced social interest in childhood significantly predicted the stability of psychiatric comorbidity. Re-evaluation of psychiatric comorbidity should be considered in clinical practice, since several individuals shifted in comorbid diagnoses.


Brachial artery thrombosis secondary to fixation screw pullout: Case report.
The vascular supply of the shoulder and forearm are principal derivates of the ipsilateral subclavian artery. The trajectory of this arterial supply predisposes it to concomitant injuries in the shoulder and clavicular fractures proximally and elbow dislocation distally. Distal bicep tendon tears often occur most commonly in middle-aged men due to trauma to the elbow, typically in weight-bearing situations [1]. To our knowledge, this is the first case of distal biceps tendon tear repair resulting in distal brachial artery injury from displaced hardware due to postoperative re-injury. We present a case of a 41-year-old male who developed a vaso-occluding hematoma at the distal biceps secondary to a displaced fixation screw. The patient required emergency vascular surgery with embolectomy and arterial bypass. Although this patient fully recovered, the clinical course the patient experienced could have been minimized with appropriate postoperative care. This report aims to alert clinicians to the relevant local anatomy and relate it to the proposed mechanism of injury, thereby bringing attention to the importance of postoperative limb protection in at-risk patients. The timing of the injury, and the protracted rate of thrombus formation suggest that the brachial artery's thrombosis was associated with the screw pullout during reinjury of the area. Screw pullout in orthopedics is a rare phenomenon that can lead to significant complications. The risk of reinjury, screw pullout, and other complications such as thrombosis is evidence to support the careful treatment of the area postoperatively.


Isolation of a reovirus from the snake, Python regius. Brief report.
A reovirus isolated from a moribund snake was not neutralized by antisera against mammalian serotypes, did not agglutinate human O erythrocytes, and produced fusion of IgH 2 cells. The genome contained 10 segments of dsRNA.


Parasites, Zoonoses and War: A Themed Issue in Honor of Emeritus Professor John M. Goldsmid.
This Special Issue of Tropical Medicine and Infectious Disease is dedicated to the life and work of Emeritus Professor John Marsden Goldsmid [...].


Temporal trends in decompensated heart failure and outcomes during COVID-19: a multisite report from heart failure referral centres in London.
Admission rates for acute decompensated heart failure (HF) declined during the COVID-19 pandemic. However, the impact of this reduction on hospital mortality is unknown. We describe temporal trends in the presentation of patients with acute HF and their in-hospital outcomes at two referral centres in London during the COVID-19 pandemic. A total of 1372 patients hospitalized for HF in two referral centres in South London between 7 January and 14 June 2020 were included in the study and their outcomes compared with those of equivalent patients of the same time period in 2019. The primary outcome was all-cause in-hospital mortality. The number of HF hospitalizations was significantly reduced during the COVID-19 pandemic, compared with 2019 (P < 0.001). Specifically, we observed a temporary reduction in hospitalizations during the COVID-19 peak, followed by a return to 2019 levels. Patients admitted during the COVID-19 pandemic had demographic characteristics similar to those admitted during the equivalent period in 2019. However, in-hospital mortality was significantly higher in 2020 than in 2019 (P = 0.015). Hospitalization in 2020 was independently associated with worse in-hospital mortality (hazard ratio 2.23, 95% confidence interval 1.34-3.72; P = 0.002). During the COVID-19 pandemic there was a reduction in HF hospitalization and a higher rate of in-hospital mortality. Hospitalization for HF in 2020 is independently associated with more adverse outcomes. Further studies are required to investigate the predictors of these adverse outcomes to help inform potential changes to the management of HF patients while some constraints to usual care remain.


Influence of housing variables on the development of stress-sensitive behaviors in the rat.
Diverse environments early in mammalian life can have profound influences on the physiology and behavior of developing offspring. Environmental factors can influence offspring development directly or through perturbations in parental care. In the current study, we wished to determine if the influence of a single environmental variable, type of bedding material used in laboratory cages, is capable of altering physiological and behavioral outcomes in offspring. Female rats were housed in cages containing wood pulp or corncob bedding and allowed to mature. These rats, while housed on assigned bedding material, were bred and allowed to give birth. At weaning, male offspring were housed on one of the two bedding conditions and tested later in adulthood on stress-sensitive behavioral measures. Postmortem analysis of glucocorticoid receptor expression and CRH mRNA levels were also measured. Maternal care directed at the pups reared in the two different bedding conditions was also recorded. Rats reared from birth on corncob bedding exhibited decreased anxiety-like behavior, as adults, in both open field and light-dark box tasks compared to wood pulp reared animals. Animals that received similar overall levels of maternal care, regardless of bedding condition, also differed in anxiety-like behaviors as adults, indicating that the bedding condition is capable of altering phenotype independent of maternal care. Despite observed behavioral differences in adult offspring reared in different bedding conditions, no changes in glucocorticoid receptor expression at the level of the hippocampus, frontal cortex, or corticotrophin releasing hormone (CRH) mRNA expression in the hypothalamus were observed between groups. These results highlight the importance of early life housing variables in programming stress-sensitive behaviors in adult offspring.


Identification of a Novel Pathogenic Germline KDR Variant in Melanoma.
The application of pan-cancer next-generation sequencing panels in the clinical setting has facilitated the identification of low frequency somatic mutations and the testing of new therapies in solid tumors using the "basket trial" scheme. However, little consideration has been given to the relevance of nonsynonymous germline variants, which are likely to be uncovered in tumors and germline and which may be relevant to prognostication and prediction of treatment response. We analyzed matched tumor and normal DNA from 34 melanoma patients using an Ion Torrent cancer-associated gene panel. We elected to study the germline variant Q472H in the kinase insert domain receptor (KDR), which was identified in 35% of melanoma patients in both a pilot and an independent 1,223 patient cohort. Using patient-derived melanoma cell lines and human samples, we assessed proliferation, invasion, VEGF levels, and angiogenesis by analyzing tumor microvessel density (MVD) using anti-CD34 antibody. Serum VEGF levels and tumor MVD were significantly higher in Q472H versus KDR wild-type (WD) patients. Primary cultures derived from melanomas harboring the KDR variant were more proliferative and invasive than KDR wild type. Finally, using a VEGFR2 antibody, we showed that KDR Q472H cells were sensitive to targeted inhibition of VEGFR2, an effect that was not observed in KDR WT cells. Our data support the integration of germline analysis into personalized treatment decision-making and suggest that patients with germline KDR variant might benefit from antiangiogenesis treatment. Clin Cancer Res; 22(10); 2377-85. ©2015 AACR.


Combination therapy with radiation, mitomycin C, and 5-fluorouracil in EMT6 tumors.
The primary purpose of these studies was to assess whether concomitant treatment with 5-fluorouracil increased the cytotoxicity of radiation, mitomycin C, or the combination of these two agents to cells in solid tumors. All studies were performed using EMT6 mouse mammary tumor cells. In vitro studies used exponentially-growing monolayers. In vivo studies used solid EMT6 tumors growing in BALB/c Rw mice. The effects of treatment on tumors or cultures were assessed using clonogenic assays which considered both the colony forming abilities of the intact cells and the numbers of cells in the cultures or tumors. EMT6 cells in vitro were killed effectively by 5-fluorouracil. The cytotoxicity increased as the drug concentration increased from 1 microM to 1 mM or as the treatment time increased from 1 to 48 hr. However, 5-fluorouracil was only marginally active against solid EMT6 tumors: treatment with doses of up to 400 micrograms/gm killed less than 50% of the tumor cells, regardless of whether the drug was given as an injection or an infusion over 48 hr and regardless of the time between injection of the drug and assay of cell survival. Treatment with 5-fluorouracil produced only a statistically insignificant increase in the effect of 15 Gy of x-rays, whether the drug was given by injection or infusion over 48 hr. Both injection of 200 micrograms/g 5 FU and infusion of 100 micrograms/g 5-fluorouracil decreased the cytotoxicity of 6 micrograms/g of MC to cells in solid tumors. Injection of 200 micrograms/g of 5-fluorouracil decreased the cytotoxic effects of a regimen combining 6 micrograms/g MC plus 15 Gy of x-rays. In this solid tumor system, a regimen combining single doses of mitomycin C and x-rays was more effective in killing the tumor cells than was the same regimen combined with 5-fluorouracil.


Succinimide formation from aspartyl and asparaginyl peptides as a model for the spontaneous degradation of proteins.
Nonenzymatic intramolecular reactions can result in the deamidation, isomerization, and racemization of protein and peptide asparaginyl and aspartyl residues via succinimide intermediates. To understand the sequence dependence of these reactions, we measured the rate of succinimide formation in a series of synthetic peptides at pH 7.4. These peptides (Val-Tyr-Pro-X-Y-Ala) contained an internal aspartyl, asparaginyl, aspartyl beta-methyl ester, or aspartyl alpha-methyl ester residue (X) followed by a glycyl, seryl, or alanyl residue (Y). The rates of succinimide formation of the asparaginyl peptides were found to be 13.1-35.6 times faster than those of the aspartyl peptides. The rates of succinimide formation for the glycyl peptides were 6.5-17.6 times faster than those of the alanyl peptides, while the rates for the seryl peptides were 1.6-4.5 times faster than those of the alanyl peptides. The overall 232-fold range in these reaction rates for aspartyl and asparaginyl residues suggests that sequence can be an important determinant in their stability in flexible peptides. In proteins, there may be a much larger range in the rates of succinimide formation because specific conformations may greatly enhance or inhibit this reaction.


Prevalence of oncogenic human papillomavirus in pregnant adolescents, association with colpocytological changes, risk factors and obstetric outcomes.
The authors aim to carry out an investigation on the impact of cervical oncogenic Human Papillomavirus (HPV) detection in pregnant adolescents, to clarify the prevalence and risk factors, considering the importance and lack of data on this topic in Brazil. A cross-sectional study was conducted with adolescents receiving prenatal care in a tertiary hospital in São Paulo, Brazil, with routine Pap smear and oncogenic HPV detection test in the uterine cervix. The authors sought to associate the results of these tests with demographic and obstetric variables. A total of 303 pregnant adolescents whose mean age was 15.30 ± 1.22 years comprised the study subjects. The frequency of high-risk HPV cervical detection was 50.50%. Multivariate analysis revealed that a large number of partners in their lifetime (OR = 1.27) and having a religion (OR = 2.05) were risk factors for cervical detection of oncogenic HPV, while schooling appeared as a protective factor (OR = 0.85). There was an association between this detection and colpocytological alterations, reaching almost 30% of patients, but without association with obstetric and neonatal outcomes. The prevalence found is one of the highest in Brazil and worldwide. A greater number of partners during their lifetime and having religion were detected as possible factors associated with cervical HPV detection. Detection of cervical HPV-DNA did not influence obstetric and neonatal outcomes. The findings of this study reinforce the need to implement educational measures capable of modifying the incidence of sexually transmitted infections in this population and capable of promoting adherence to HPV vaccination programs.