Differentiation and numerical analysis of oral yeasts based on SDS-Page profiles. Influence of the culture media on the whole-cell protein extracts.
The application of gel electrophoresis and numerical analysis of yeast soluble proteins analysis to the investigation of 12 oral yeast strains belonging to five species is described. It involves one-dimensional electrophoresis of SDS-solubilized whole-cell proteins using different culture media for the cultivation of the cells, integration densitometries in the areas of the gels and percentages of the proteins extraction. These extracts were prepared from four isolates of Candida albicans, two of C. tropicalis, C. guilliermondii, C. parapsilosis and C. krusei. The extracts from whole-cells proteins using different culture media for the cultivation of the cells were fractionated by slab electrophoresis using a discontinuous buffer system. The corresponding patterns showed at least 36 polypeptides in the range of 14.4-200 kDa. Different isolates of each species were clearly different in each of the five species. The data obtained suggest that different nutritional compositions led to the expression of different proteins derived from alternatives metabolic pathways expressed by the electrophoretic profiles. The construction of a database of protein fingerprints and numerical analysis based on such data, may have some implications in the classification and identification of such species with epidemiological, ecological and taxonomic purposes. A well defined or synthetic culture media seems to be much properly.


[Landscape pattern and its functioning after ecological reconstruction in black soil of northern China].
Taken Baiquan County in Heilongjiang Province as a case, this paper studied the effects of regional ecological reconstruction on agricultural landscape pattern and its functioning in soil and water conservation, with the spatial expression and quantity identification investigated based on Geographic Information System (GIS) and field data. The landscape pattern index in class scale, transition matrix of landscape elements, macrostructure of shelter-belt networks, and spatial distribution and hydrological characteristic of reservoirs and ponds in 1989 and 2002, as well as the effects of landscape pattern and its spatial configuration change on soil and water loss were compared. The results showed that artificial ecological reconstruction changed the quantity and spatial configuration of landscape patterns in regional scale, and exerted a significant effect on soil and water conservation. From 1989 to 2002, farmland area reduced 24 731.01 hm2, while forest land, grassland and water area increased 11 728.56, 1838.97 and 1190.97 hm2, respectively. The controlled eroded land increased by 55%, and the shelterbelt-protected farmland increased by 82.2%. The number and storage capacity of reservoirs and ponds added up to 1 490 and 2.4 x 10(8) m3, respectively, and 43.7% of intercepted surface runoff of whole landscape was collected.


Correlation between the urinary dihydrouracil-uracil ratio and the 5-FU plasma concentration in patients treated with oral 5-FU analogs.
The determination of dihydropyrimidine dehydrogenase (DPD) deficiency is important in avoiding severe 5-fluorouracil (FU) toxicity. The dihydrouracil (UH2)-uracil (Ura) ratio (UH2/Ura) in plasma might be an important indicator of the risk of 5-FU catabolic deficiency. In order to clarify this possibility, the pyrimidine metabolites and the UH2/Ura were measured in urine and the plasma level of 5-FU was evaluated in patients with gastric and colorectal cancer. Patients with primary gastric (n=14) and colorectal (n=8) cancer who had undergone surgery were recruited in this study. These patients were divided into the S-1 treatment group, which drug is a novel oral formulation of tegafur, oxonic acid and 5-chloro-2, 4-dihydroxypyridine (CDHP) (n=14) and a group receiving other drugs which include UFT (Uracil/Tegafur) or oral doxifluridine (n=8). The urinary levels of UH2 and Ura were measured by high-performance liquid chromatography (HPLC) using column swiching. The plasma level of 5-FU was assessed by gas chromatography-mass spectrometry (GC-MS). The UH2/Ura or UH2/Ura (treated/no treated) in the S-1 group significantly decreased in comparison to that in the other-drug group and the plasma 5-FU concentration in the S-1 group significantly increased compared to that in the group treated with other drugs. The plasma 5-FU concentration levels significantly indicated a positive correlation with urinary Ura. Moreover, UH2/Ura treated with 5-FU analogs or UH2/Ura (treated/no treated) significantly showed a negative correlation with the plasma 5-FU concentration levels. Our findings indicate that either urinary Ura, the UH2/Ura or UH2/Ura (treated/no treated) can predict the plasma 5-FU concentration levels or DPD deficiencies.


[Decrease in bacterial translocation in burned children treated with controlled nutritional support].
Alteration in epithelial enteric cells are the main cause of bacteria translocation and local and systemic infections. Our aim is to evaluate these infections in burned children treated with enteral nutrition and compare the results with our previous observations. Material and methods. We designed a prospective study including 50 patients (0-14 years) with TBSA > 10% (total body surface area). Bacteriological cultures were performed at their admittance and weekly until the discharge. Nutritional necessities were evaluated using calorimetry. Nutritional support was supplied by nasoduodenal tube at continuous rates. Three (6%) patients with enteral nutrition (Group 1) showed positive blood cultures (two of them by enteric bacteriae). 14 patients (28%) showed local infections (five by enterococci). We performed a retrospective study in a homogenous group of 44 patients (Group 2), previously treated in our Department without controlling nutrition. We found five (11.3%) positive blood cultures (four by enteric bacteriae) and 22 (50%) local infections (eleven by enteric bacteriae). The improvement of systemic and local infection rates and the decrease in infections caused by enteric bacteriae were statistically significative (p < 0.05). A controlled nutritional support is a main cause of the improvement in infection rates and decrease in bacterial translocation in pediatric burned patients.


Removal of para-nitrochlorobenzene from aqueous solution on surfactant-modified nanoscale zero-valent iron/graphene nanocomposites.
This study demonstrated a remarkably simple and efficient method for the synthesis of nanoscale zero-valent iron (NZVI)/graphene (GN) nanocomposites. In order to prevent the agglomeration and restack of nanocomposites, chemical functionalization of nanocomposites with cetyltrimethylammonium bromide was proposed. The adsorption performance of surfactant-modified NZVI/GN nanocomposites was evaluated for the removal of para-nitrochlorobenzene (p-NCB) from aqueous solutions. The characteristics of nanocomposites were characterized by X-ray diffraction, BET surface area, Fourier transform infrared spectrum, thermogravimetric analysis and scanning electron microscopy. The effect factors including initial solution pH, contact time, reaction temperature, dosage, initial concentration of humic acid (HA) on the adsorption property of p-NCB onto surfactant-modified nanocomposites were investigated. The adsorption kinetics fitted well with pseudo-second-order model. The adsorption capacity of p-NCB on surfactant-modified nanocomposites inferred from the Langmuir model was 105.15 mg/g at 293 K. The thermodynamic parameters indicated that the adsorption of p-NCB onto surfactant-modified nanocomposites was an exothermic and spontaneous process. HA had a strong suppression effect on p-NCB uptake in the adsorption experiment.


The Identity of Human Tissue-Emigrant CD8+ T Cells.
Lymphocyte migration is essential for adaptive immune surveillance. However, our current understanding of this process is rudimentary, because most human studies have been restricted to immunological analyses of blood and various tissues. To address this knowledge gap, we used an integrated approach to characterize tissue-emigrant lineages in thoracic duct lymph (TDL). The most prevalent immune cells in human and non-human primate efferent lymph were T cells. Cytolytic CD8+ T cell subsets with effector-like epigenetic and transcriptional signatures were clonotypically skewed and selectively confined to the intravascular circulation, whereas non-cytolytic CD8+ T cell subsets with stem-like epigenetic and transcriptional signatures predominated in tissues and TDL. Moreover, these anatomically distinct gene expression profiles were recapitulated within individual clonotypes, suggesting parallel differentiation programs independent of the expressed antigen receptor. Our collective dataset provides an atlas of the migratory immune system and defines the nature of tissue-emigrant CD8+ T cells that recirculate via TDL.


Carbon and hydrogen isotope fractionation of benzene during biodegradation under sulfate-reducing conditions: a laboratory to field site approach.
The microbial carbon and hydrogen isotope fractionation of benzene under sulfate-reducing conditions was investigated within systems of increasing complexity: (i) batch laboratory microcosms, (ii) a groundwater-percolated column system, and (iii) an aquifer transect. Recent molecular biological studies indicate that, at least in the laboratory microcosms and the column system, benzene is degraded by similar bacterial communities. Carbon and hydrogen enrichment factors (epsilon(C), epsilon(H)) obtained from laboratory microcosms and from the column study varied significantly although experiments were performed under similar redox and temperature conditions. Thus, enrichment factors for only a single element could not be used to distinguish benzene degradation under sulfate-reducing conditions from other redox conditions. In contrast, using correlation of changes of hydrogen vs. carbon isotope ratios (Lambda = Delta delta(2)H/Delta delta(13)C), similar Lambda-values were derived for the benzene biodegradation under sulfate-reducing conditions in all three experimental systems (Lambda(laboratory microcosms) = 23 +/- 5, Lambda(column) = 28 +/- 3, Lambda(aquifer) = 24 +/- 2), showing the robustness of the two-dimensional compound-specific stable isotope analysis (2D-CSIA) for elucidating distinct biodegradation pathways. Comparing carbon and hydrogen isotope fractionation data from recent studies, an overlap in Lambda-values was observed for benzene biodegradation under sulfate-reducing (Lambda = 23 +/- 5 to Lambda = 29 +/- 3) and methanogenic (Lambda = 28 +/- 1 to Lambda = 39 +/- 5) conditions, indicating a similar initial benzene reaction mechanism for both electron-acceptor conditions.


Modification of the Hörmann technique of hyoid suspension in obstructive sleep apnoea.
Hyoid suspension is a procedure to stabilise the retrolingual space in obstructive sleep apnoea. Using the Hörmann technique, a steel wire is slung around the body of the hyoid and fixed to the upper rim of the thyroid cartilage. It was observed, however, that the steel wire may lie very superficially to the pharyngeal mucosa. Evaluation of computed tomography (CT) scans showed a mean distance between the hyoid and the pharynx of only 3 mm. A modification is presented by threading a steel wire through a hole that is drilled through the hyoid bone. Thus pharyngeal exposure of the steel ligature and possible perforation of the mucosa is avoided.


Value of albumin dialysis therapy in severe liver insufficiency.
A blood purification system, molecular adsorbents re-circulating system (MARS), is based on the removal of both protein-bound and water-soluble substances and toxins in the liver. We treated a total of 88 patients within 2 years. Of these patients, 45 had acute liver failure (ALF), 31 had acute decompensation of chronic liver disease, eight had graft failure and four had miscellaneous conditions. Of the patients with ALF, 80% survived; in 23 patients their own liver recovered and 13 patients underwent successful transplantation. Only 23% of patients with acute-on-chronic liver failure survived. Most of them were not considered for transplantation due to their having liver failure from alcoholism and from not abstaining from drinking. MARS is a promising therapy for ALF, allowing the patient's own liver to recover or allowing enough time to find a liver graft. Best results were achieved in patients who had been intoxicated with a lethal dose of toxin. On the other hand, we did not observe much benefit in patients with severe acute-on-chronic liver failure (AcoChr) who did not undergo liver transplantation.


The reproduction number of seasonal influenza epidemics in Brazil, 1996-2006.
The transmission dynamics of influenza in tropical regions are poorly understood. Here we explore geographical variations in the reproduction number of influenza across equatorial, tropical and subtropical areas of Brazil, based on the analysis of weekly pneumonia and influenza (P&I) mortality time series in 27 states. The reproduction number (R) was low on average in Brazil (mean = 1.03 (95% CI 1.02-1.04), assuming a serial interval of 3 days). Estimates of the reproduction number were slightly lower for Brazil than for the USA or France (difference in mean R = 0.08, p < 0.01) and displayed less between-year variation (p < 0.001). Our findings suggest a weak gradient in the reproduction number with population size, where R increases from low population in the North to high population in the South of Brazil. Our low estimates of the reproduction number suggest that influenza population immunity could be high on average in Brazil, potentially resulting in increased viral genetic diversity and rate of emergence of new variants. Additional epidemiological and genetic studies are warranted to further characterize the dynamics of influenza in the tropics and refine our understanding of the global circulation of influenza viruses.


Dermatoses in parkinsonism: the importance of multidisciplinary follow-up.
Parkinsonism is characterized by bradykinesia with rigidity and/or resting tremor, in addition to non-motor symptoms, which include dermatological manifestations. The objective of this study is to evaluate the main dermatoses in patients with parkinsonism found at the Philanthropic Association of Curitiba - PR. A cross-sectional descriptive study was carried out with the application of a questionnaire and dermatological evaluation of the patients. The sample consisted of 386 patients and was composed mainly by men (55.4%), between 60-74 years old (51.6%), with complete primary education (45.3%), disease diagnosis time between 5-10 years (35%) and in use of medication (96.6%). The most prevalent dermatoses were pigmented nevus (36.3%), warts (25.1%), actinic keratosis (22%), seborrheic keratosis (21.5%), seborrheic dermatitis (20.5%), and rosacea (19.2%). Among the 13 cases (3.4%) of malignant cutaneous neoplasms confirmed by biopsy, 2 were melanomas. Regarding patients' sex, there was a higher prevalence of inflammatory dermatoses (OR 1.64, 95% CI 1.08-2.51, p = 0.025) and benign cutaneous neoplasms (OR 1.77, 95% CI 1.16-2.69, p = 0.01) in men. As to age, patients aged between 60-74 years had more pre-malignant skin lesions (OR 2.60, 95% CI 1.05-6.44, p <0.001) and seborrheic keratosis (OR 2.52, 95% CI 1.02-6.25, p = 0.001) and, in those older than 75 years, actinic keratosis was more frequent (OR 5.43, 95% CI 2.17-13.6, p <0.001). The results of the study show that it is fundamental to dermatologically evaluate and monitor these patients, aiming at diagnosis and early treatment of lesions, especially of skin cancer.


Aseptic Technology for Cryoprotectant-Free Vitrification of Human Spermatozoa by Direct Dropping into Clean Liquid Air: Apoptosis, Necrosis, Motility, and Viability.
This study aimed to compare the quality of human spermatozoa vitrified by direct plunging into liquid nitrogen vs. liquid air. Spermatozoa were divided into three groups: fresh spermatozoa (Group F) were used as a control. Spermatozoa suspension (20 μl) was vitrified in open granules by direct dropping into liquid nitrogen (Group LN) or clean liquid air (Group LA). After warming at 37°C, the progressive motility rate of Group F was reduced from 65.9 ± 2.5% to 34.0 ± 1.9% (Group LN) and 38.1 ± 2.3% (Group LA), respectively (P1-2,3 < 0.05). The reductions in viability were 65.6 ± 2.2%, 29.0 ± 1.8%, and 36.6 ± 2.6% for Groups F, LN, and LA, respectively (P1-2,3 < 0.05). Comparing spermatozoa vitrified in liquid nitrogen vs. liquid air, no significant differences were detected in motility (34.0 ± 1.9% vs. 38.1 ± 2.3%), viability (29.0 ± 1.8% vs. 36.6 ± 2.6%), early apoptosis (13.8 ± 1.5% vs. 14.3 ± 1.8%), late apoptosis (45.5 ± 1.8% vs. 43.7 ± 2.2%), and necrosis (19.5 ± 2.0% vs. 15.0 ± 1.8%; p > 0.01 for all respective differences). There was a statistical tendency for increasing rates of "progressive motility" and "viability" and decreasing rates of "apoptosis" and "necrosis" when comparing spermatozoa vitrified in liquid air vs. liquid nitrogen. It is concluded that cryoprotectant-free vitrification by the direct dropping of human spermatozoa in a clean cooling agent (liquid air) is a good alternative to the use of nonsterile liquid nitrogen and can be used to cool cells while minimising the risk of microbial contamination.


Electron microscopic assessment of cervical punch biopsies in women followed-up for human papillomavirus (HPV) lesions.
Cervical punch biopsies from 102 women prospectively followed-up for HPV (Human papillomavirus) lesions (flat, inverted and papillomatous condylomas) were assessed on transmission electron microscopy (TEM) for the presence of HPV particles. The virus discovery rate was correlated with the other characteristics of significance to the clinical behaviour (natural history) of these lesions, i.e. the colposcopic pattern, expression of papillomavirus genus specific structural antigens (demonstrated by an indirect immunoperoxidase, IP-PAP technique), as well as the degree of HPV-associated cervical intraepithelial neoplasia (CIN). Virus particles were disclosed with equal frequency in all three types of HPV lesions. Noteworthy, and so far unreported, was the discovery of HPV particles in 56 and 64% of the biopsies derived from the epithelium without colposcopic or histological evidence (cytopathic effects) of HPV lesions, respectively. The degree of CIN was without influence on the virus discovery rates. Viral particles were present with equal frequency (57 and 60%, respectively) in the lesions expressing HPV antigens and in those which did not. The highest frequency (89%) of viral particles was found in lesions presented with warty or mosaicism pattern in colposcopy. The implications of these findings to understanding the biology of HPV infections in the uterine cervix is discussed, and the importance of TEM in the follow-up of these lesions is emphasized.


Insertion/deletion polymorphism in the gene for angiotensin converting enzyme (ACE) in panic disorder: A gender-specific effect?
Family, twin, and segregation analytic studies indicate a complex genetic contribution to panic disorder with an estimated heritability of 48%. Angiotensin-converting enzyme (ACE) degrades substance P, which has been implicated in anxiety-related behaviour. ACE has been suggested as a potential risk factor in the pathogenesis of panic attacks. A functional insertion deletion (I/D) polymorphism in the ACE gene was suggested to be associated with panic disorder in a potentially gender-specific way ( Olsson et al. 2004 ). The present study aimed to replicate this finding and thereby to further elucidate the role of ACE gene variation in the pathomechanism of panic disorder. The ACE I/D polymorphism was genotyped in a sample of 102 German patients with panic disorder with or without agoraphobia as well as a healthy German control group matched with regard to age and sex (n = 102). In the male subgroup (n = 43) of panic patients a significant association of the ACE I allele (P = 0.0474) and genotypes containing the I allele (P = 0.0195), respectively, was observed. The present results provide further support for a potentially male-specific role of the less active ACE I allele in the pathogenesis of panic disorder, possibly by altering substance P levels.


The Chemical and Physical Properties of Poly(ε-caprolactone) Scaffolds Functionalised with Poly(vinyl phosphonic acid-co-acrylic acid).
There is a clinical need for a synthetic alternative to bone graft substitute (BGS) derived from demineralised bone matrix. We report the electrospinning of Poly(ε-caprolactone) (PCL) to form a 3-dimensional scaffold for use as a synthetic BGS. Additionally, we have used Poly(vinyl phosphonic acid-co-acrylic acid) (PVPA) to improve bone formation. Fibres were formed using a 10% w/v PCL/acetone solution. Infrared spectroscopy confirmed that the electrospinning process had no effect on the functional groups present in the resulting structure. The electrospun scaffolds were coated with PVPA (PCL/PVPA), and characterised. The stability of the PVPA coating after immersion in culture medium was assessed over 21 days. There was rapid release of the coating until day 2, after which the coating became stable. The wettability of the PCL scaffolds improved significantly, from 123.3 ± 10.8° to 43.3 ± 1.2° after functionalisation with PVPA. The compressive strength of the PCL/PVPA scaffolds (72 MPa) was significantly higher to that of the PCL scaffold (14 MPa), and an intermediate between trabecular and cortical bone (7 MPa and 170 MPa, resp.). The study has demonstrated that the PCL/PVPA scaffold has the desired chemical and biomechanical characteristics required for a material designed to be used as a BGS.


Sarcoplasmic reticulum function in smooth muscle.
The sarcoplasmic reticulum (SR) of smooth muscles presents many intriguing facets and questions concerning its roles, especially as these change with development, disease, and modulation of physiological activity. The SR's function was originally perceived to be synthetic and then that of a Ca store for the contractile proteins, acting as a Ca amplification mechanism as it does in striated muscles. Gradually, as investigators have struggled to find a convincing role for Ca-induced Ca release in many smooth muscles, a role in controlling excitability has emerged. This is the Ca spark/spontaneous transient outward current coupling mechanism which reduces excitability and limits contraction. Release of SR Ca occurs in response to inositol 1,4,5-trisphosphate, Ca, and nicotinic acid adenine dinucleotide phosphate, and depletion of SR Ca can initiate Ca entry, the mechanism of which is being investigated but seems to involve Stim and Orai as found in nonexcitable cells. The contribution of the elemental Ca signals from the SR, sparks and puffs, to global Ca signals, i.e., Ca waves and oscillations, is becoming clearer but is far from established. The dynamics of SR Ca release and uptake mechanisms are reviewed along with the control of luminal Ca. We review the growing list of the SR's functions that still includes Ca storage, contraction, and relaxation but has been expanded to encompass Ca homeostasis, generating local and global Ca signals, and contributing to cellular microdomains and signaling in other organelles, including mitochondria, lysosomes, and the nucleus. For an integrated approach, a review of aspects of the SR in health and disease and during development and aging are also included. While the sheer versatility of smooth muscle makes it foolish to have a "one model fits all" approach to this subject, we have tried to synthesize conclusions wherever possible.


The impact of thyroid nodule size on the risk of malignancy and accuracy of fine-needle aspiration: a 10-year study from a single institution.
False-negative rates for thyroid fine-needle aspiration (FNA) vary from 0.4% to 13%, but the effect of nodule size on the accuracy of thyroid FNA remains controversial. We hypothesized that large thyroid nodule size does not contribute to the risk of malignancy or the risk of a false-negative FNA. All thyroid FNAs performed at the Walter Reed Army Medical Center during September 2001-August 2011 were reviewed. A strict correlation between the biopsy site, location, and size of nodule on ultrasound (US) and pathology report was ensured. FNA results were classified as benign, atypical, follicular neoplasm/suspicious for follicular neoplasm (FN/SFN), suspicious for malignancy (SM), or malignant, and the pathology result was categorized as either benign or malignant. Nodules were analyzed by size: 0.5-0.9 cm (group A), 1.0-3.9 cm (group B), and ≥ 4 cm (group C). Incidental thyroid cancer was not included. Of 3013 patients undergoing FNA, 667 (22.1%) had surgery. Patients were excluded for nodules <0.5 cm, nondiagnostic FNA, or no preoperative US, leaving 540 patients with 695 nodules. Among patients referred for surgery, FNA results were benign in 417 nodules (60%), atypical in 22 (3.2%), FN/SFN in 122 (17.6%), SM in 77 (11.1%), and malignant in 57 (8.2%). Postoperative malignancy rates by FNA result were 7% if benign, 4.5% if atypical, 23% if FN/SFN, 33.8% if SM, and 78.9% if malignant. FNA accuracy was 60% in group A, 68.5% in group B, and 80.3% in group C (p=0.01). False-negative rates for FNA were 7.0% overall, 15.8% in group A, 6.3% in group B, and 7.1% in group C (p=0.25). Sensitivity and negative predictive value were highest in group B at 81.6% and 93.7%, respectively. The prevalence of malignancy was not different between groups. Our results show that the thyroid nodule size ≥ 4 cm increases neither the risk of false-negative FNA results, nor the overall risk of malignancy. We also show a tendency toward a higher false-negative rate in subcentimeter nodules. We conclude that a large nodule size should not prompt automatic referral for thyroidectomy. An increased awareness of potential sampling error in subcentimeter nodules is warranted.


[Role of magnetic resonance imaging (MRI) in evaluation of the extension of endometrial carcinoma].
The extent of endometrial carcinoma in Magnetic Resonance Imaging (MRI) was compared with that of histopathological findings. There was a significant positive correlation between the MRI values and the measured tissue specimen values for the minimum thickness of the residual myometrium (r = 0.8608; p less than 0.001). Twenty patients in the present study were divided into two groups according to myometrial invasion. Six patients (Group A) met the following criteria: (1) the area occupied by a high intensity lesion in the uterine body in the sagittal image is 50% or less, (2) the area occupied by a high intensity lesion in the uterine body in the transverse image is 50% or less, (3) the minimum thickness of the myometrium is 0.5 cm or more, and (4) the maximum-minimum ratio of myometrial thickness is 0.5 or more. Fourteen patients (Group B) did not meet these conditions. Myometrial invasion of carcinoma exceeding 1/3 of the myometrial thickness was not observed in any patient in Group A. A significantly greater percentage (86%) of Group B patients had myometrial invasion. Vessel permeation of carcinoma and metastasis was detected in 5 and 2 patients in Group B, respectively, but no patient in Group A had either vessel permeation or metastasis. A junctional zone was seen in 10 of 20 patients, and the carcinomatous lesions were limited to the endometrium in 2 patients, in which the junctional zone was not disrupted. In the other 8 patients, the localization of disruption of this zone corresponded to that of myometrial invasion. The sensitivity, specificity, and accuracy of MRI evaluation in the presence or absence of cervical involvement were 0.71, 0.92 and 0.85, respectively.


In vivo measurement of the longitudinal relaxation time of arterial blood (T1a) in the mouse using a pulsed arterial spin labeling approach.
A novel method for measuring the longitudinal relaxation time of arterial blood (T1a) is presented. Knowledge of T1a is essential for accurately quantifying cerebral perfusion using arterial spin labeling (ASL) techniques. The method is based on the flow-sensitive alternating inversion recovery (FAIR) pulsed ASL (PASL) approach. We modified the standard FAIR acquisition scheme by incorporating a global saturation pulse at the beginning of the recovery period. With this approach the FAIR tissue signal difference has a simple monoexponential dependence on the recovery time, with T1a as the time constant. Therefore, FAIR measurements performed over a range of recovery times can be fitted to a monoexponential recovery curve and T1a can be calculated directly. This eliminates many of the difficulties associated with the measurement of T1a. Experiments performed in vivo in the mouse at 2.35T produced a mean value of 1.51 s for T1a, consistent with previously published values.


Direct, rapid, facile photochemical method for preparing copper nanoparticles and copper patterns.
We develop a facile method for preparing copper nanoparticles and patterned surfaces with copper stripes by ultraviolet (UV) irradiation of a mixture solution containing a photoinitiator and a copper-amine coordination compound. The copper-amine compound is formed by adding diethanol amine to an ethanol solution of copper chloride. Under UV irradiation, free radicals are generated by photoinitiator decomposition. Meanwhile, the copper-amine coordination compound is rapidly reduced to copper particles because the formation of the copper-amine coordination compound prevents the production of insoluble cuprous chloride. Poly(vinylpyrrolidone) is used as a capping agent to prevent the aggregation of the as-prepared copper nanoparticles. The capping agent increases the dispersion of copper nanoparticles in the ethanol solution and affects their size and morphology. Increasing the concentration of the copper-amine coordination compound to 0.1 M directly forms a patterned surface with copper stripes on the transparent substrate. This patterned surface is formed through the combination of the heterogeneous nucleation of copper nanoparticles and photolithography. We also investigate the mechanism of photoreduction by UV-vis spectroscopy and gas chromatography-mass spectrometry.


Antioxidant, Anti-Obesity, Nutritional and Other Beneficial Effects of Different Chili Pepper: A Review.
Fruits and vegetables are important components of a healthy diet. They are rich sources of vitamins and minerals, dietary fibre and a host of beneficial non-nutrient substances including plant sterols, flavonoids and other antioxidants. It has been reported that reduced intake of fruits and vegetables may increase the risk of non-communicable diseases (NCDs). Chili pepper, is a common and important spice used to enhance taste and nutrition. Over the years, reports have shown its potential as antioxidant and an anti-obesity agent. Obesity is a serious health concern as it may initiate other common chronic diseases. Due to the side effects of synthetic antioxidants and anti-obesity drugs, scientists are now focusing on natural products which produce similar effects to synthetic chemicals. This up-to-date review addresses this research gap and presents, in an accessible format, the nutritional, antioxidant and anti-obesity properties of different chili peppers. This review article serves as a reference guide for use of chili peppers as anti-obesity agents.


Sympathetic innervation of the mouse kidney and liver arising from prevertebral ganglia.
The sympathetic nervous system (SNS) plays a crucial role in the regulation of renal and hepatic functions. Although sympathetic nerves to the kidney and liver have been identified in many species, specific details are lacking in the mouse. In the absence of detailed information of sympathetic prevertebral innervation of specific organs, selective manipulation of a specific function will remain challenging. Despite providing major postganglionic inputs to abdominal organs, limited data are available about the mouse celiac-superior mesenteric complex. We used tyrosine hydroxylase (TH) and dopamine β-hydroxylase (DbH) reporter mice to visualize abdominal prevertebral ganglia. We found that both the TH and DbH reporter mice are useful models for identification of ganglia and nerve bundles. We further tested if the celiac-superior mesenteric complex provides differential inputs to the mouse kidney and liver. The retrograde viral tracer, pseudorabies virus (PRV)-152 was injected into the cortex of the left kidney or the main lobe of the liver to identify kidney-projecting and liver-projecting neurons in the celiac-superior mesenteric complex. iDISCO immunostaining and tissue clearing were used to visualize unprecedented anatomical detail of kidney-related and liver-related postganglionic neurons in the celiac-superior mesenteric complex and aorticorenal and suprarenal ganglia compared with TH-positive neurons. Kidney-projecting neurons were restricted to the suprarenal and aorticorenal ganglia, whereas only sparse labeling was observed in the celiac-superior mesenteric complex. In contrast, liver-projecting postganglionic neurons were observed in the celiac-superior mesenteric complex and aorticorenal and suprarenal ganglia, suggesting spatial separation between the sympathetic innervation of the mouse kidney and liver.


Evidence that orexin-containing neurones provide direct input to gonadotropin-releasing hormone neurones in the ovine hypothalamus.
Orexins A and B (ORX) have been added recently to the growing list of neuropeptides implicated in feeding and drinking behaviour as well as neuroendocrine function. In the present study, we have used single and dual labelling immunohistochemistry and a rabbit polyclonal anti-orexin-A antibody, which recognizes both ORX A and B, to examine ORX pathways in the sheep hypothalamus. ORX immunoreactive cells were distributed in the dorsomedial hypothalamic nucleus, lateral hypothalamic area, zona incerta and perifornical area; a few cells were also observed in the anterior hypothalamic area. In contrast to distribution in the rat brain, most of the ORX immunoreactive cells are localized to the dorsomedial hypothalamic nucleus and perifornical area; scattered cells are found in lateral hypothalamic area. ORX immunoreactive fibres were widely distributed throughout the hypothalamus and preoptic area with dense innervation of the medial preoptic area and bed nucleus of stria terminalis. Dual labelling demonstrated widespread expression of the long form of the leptin receptor within all ORX cells that were examined. Thirty percent of the gonadotropin releasing hormone (GnRH) cells that were examined had ORX immunoreactive terminals in close contact with no regional or sex differences. FluoroGold injections into the preoptic area retrogradely labelled a subpopulation of ORX cells in the lateral hypothalamic/perifornical area, showing ORX cells of this region project to the preoptic and could potentially provide input to GnRH cells. These findings suggest an integral role for ORX in the regulation of GnRH cells in the sheep and thus provide evidence of a novel mechanism whereby leptin can influence reproductive neuroendocrine function.


Continuous source outbreak of campylobacteriosis traced to chicken.
Poultry is a source of human campylobacteriosis, but a large continuous source outbreak, heretofore, has not been attributed to both a single source of poultry and single serotype of Campylobacter. Here we report an outbreak of C. jejuni affecting 6 catering college trainees and 13 patrons of a restaurant in southern England. An epidemiological investigation successfully tracked the outbreak source to the farm of origin. Frequency of occurrence of campylobacters and outbreak serotype distribution were determined in index cases, the local population, and local chicken suppliers. The source farm was investigated and the effect of interventions assessed. A single outbreak serotype of C. jejuni was isolated from trainee chefs, patrons, and chicken supplied to the college by Wholesaler A. The Campylobacter isolation rate for Wholesaler A was 89% (98% outbreak serotype), compared to 40% for non-Wholesaler A (10% outbreak serotype). The isolation rate for 14 months averaged 85% (99% outbreak serotype) in chickens grown on two farms (X and Y) supplying Wholesaler A, contributing approximately 40% to all local cases. In the research reported here, a specific strain and hygiene practice were found to be important for understanding transmission of Campylobacter from poultry to humans in this outbreak.


Portable Heating System Based on a Liquid Metal Bath for Rapid PCR.
With the outbreak of COVID-19 around the world, rapid and accurate detection of new coronaviruses is the key to stop the transmission of the disease and prevent and control the novel coronavirus, among which polymerase chain reaction (PCR) is the mainstream nucleic acid detection method. A temperature cycling device is the core of the PCR amplification micro-device. The precision of the temperature control and temperature change rate directly affect the efficiency of PCR amplification. This study proposes a new PCR method based on rapid PCR chip optimization of a liquid metal bath, which realizes precise and rapid temperature rise and fall control. We systematically explored the feasibility of using liquid metals with different melting points in the system and proposed a 47 °C bismuth-based liquid metal bath as the heat conduction medium of the system to optimize the system. The heat conduction properties of the thermally conductive silicone oil bath were compared. Compared with the thermally conductive silicone oil bath, thermal cycle efficiency is improved nearly 3 times. The average heating rate of the liquid metal bath is fast, and the temperature control stability is good, which can significantly reduce the hysteresis, and the temperature change curve is more gentle, which can greatly improve the efficiency of PCR amplification. The results of gene amplification using rat DNA as the template and SEC61A as the target also indicate that the system can be successfully used in PCR devices, and the types of PCR containers can be not limited to PCR tubes. Based on the experiment, we proved that the PCR method optimized by the liquid metal bath multi-gene rapid PCR chip can further improve the temperature response speed. It has the advantages of accurate data, fast response speed, low price, safety, and environmental protection and can effectively reduce the time of PCR and improve the application efficiency. As far as we know, this is the first international report on using a liquid metal bath to do rapid-cooling PCR.


Age-related distribution of elastic fibers in the rabbit knee.
The distribution and histochemical properties of elastic fibers in the knee of newborn, young, adult, and old New Zealand White rabbits were studied. In the growing rabbit, elastic fibers, especially oxytalan fibers, are abundant in the perichondrium and the fibrous layer of the periosteum. They are homogeneously distributed in tendons, ligaments, and menisci, and are absent in the epiphyseal cartilage and growth plate and at the enthesis. In mature rabbits, the articular capsule, the synovial membrane, the peritenon, the periosteum, the perimysium, and the perivascular connective tissue are rich with elastic fibers. They are rarer in the tendon and are absent at the enthesis, in bone and articular cartilage. In the meniscus, the fibers are distributed centripetally. The distribution of elastic fibers is probably related to the different functional role and biomechanical behavior of each tissue. Finally, the type of elastic fiber in the various tissues changes with age; younger animals have more oxytalan fibers than adult animals. A gradual process of maturation and specialization of the network of elastic fibers takes place with age.


Diversity in the structural chemistry of (phosphine)gold(I) 1,3,4-thiadiazole-2,5-dithiolates (bismuthiolates I).
A series of dinuclear (phosphine)gold(I) complexes of the ambidentate 1,3,4-thiadiazoledithiolate ligand (SSS) were prepared in high yield from the corresponding (phosphine)gold(I) chlorides and K(2)(SSS) in methanol. While mononuclear components (R(3)P)AuCl with R(3) = Ph(3), Ph(2)Py, or Me(3) (1-3) gave open-chain complexes, the dinuclear components ClAu(Ph(2)P-E-PPh(2))AuCl with E = (CH(2))(6), (C(5)H(4))Fe(C(5)H(4)), or 1,4-CH(2)C(6)H(4)CH(2) afforded cyclic complexes (4-6). The products have been characterized by analytical and spectroscopic methods, and the crystal structures of 1-4 have been determined by single-crystal X-ray techniques. Crystals of 1 [(CH(2)Cl(2))(2)] and 2 (CH(2)Cl(2)) contain the molecules aggregated in strings with long and probably very weak intermolecular Au.S contacts. The P-Au-S groups are aligned parallel head-to-tail and shifted in opposite directions to reduce steric conflicts, thus ruling out aurophilic Au...Au bonding. By contrast, in crystals of 3 (CH(2)Cl(2)) with smaller tertiary phosphine ligands, the molecules are aggregated via short [3.0089(3) and 3.1048(5) A] and probably strong aurophilic bonding to give a two-dimensional network with tetranuclear units formed from four (Me(3)P)AuS moieties of four different molecules as the connecting elements. In these tetranuclear units [(Me(3)P)AuS-](4), the P-Au-S axes are rotated against each other ("crossed swords") by 108.5 degrees (P2-Au2...Au2'-P2') or 116.9 degrees (P2-Au2...Au1'-P1'), respectively, to minimize steric conflicts. There is also significant bending of the P-Au-S axes to bring the metal atoms closer together: P1-Au1-S1 = 171.88(8) degrees and P2-Au2-S2 = 165.52(8) degrees. In the crystals of the cyclic complex 4 which contain no solvent molecules, the molecular units are aggregated in strings with short closed-shell interactions between the gold atoms of neighboring molecules [3.1898(3) A]. Because of the metallocyclic structure, the shielding of the gold atoms is reduced to allow aurophilic bonding as the P-Au-S groups are rotated against each other (crossed) by a dihedral angle P-Au...Au-P of 74.6 degrees.


Beneficial effects of a higher starting dose of gonadotrophins in some poor responders.
We performed a prospective study to examine the benefits of higher starting dose in poor responders to gonadotrophins. One hundred eighty-seven normal responders (group 1), 40 poor responders (group 2), and 25 poor responders from group 2 (group 3) were included in the study. Groups 1 and 2 received 300 IU of metrodin HP for 5 days followed by 150 IU of recombinant human follicle-stimulating hormone (rhFSH) until the day before hCG. Group 3 received 450 IU of metrodin followed by rhFSH as in groups 1 and 2. Number of oocytes retrieved, rates of fertilization, implantation, pregnancy, and miscarriage rates were compared between the groups. There were no differences between the three groups in the fertilization rate. The higher dose of metrodin (450 IU) for 5 days increased the number of oocytes retrieved in some patients belonging to group 3 and significantly increased (P < 0.01) the implantation and pregnancy rates compared with group 2 patients. However, the higher dose of metrodin also increased miscarriage rates significantly in group 3 compared with groups 1 and 2 (P < 0.04). In some poor responders, a higher starting dose of gonadotrophin resulted in more oocytes retrieved and led to higher implantation and pregnancy rates and a higher miscarriage rate.


ONYCHOMYCOSIS: A Review of New and Emerging Topical and Device-based Treatments.
Onychomycosis is a challenging nail condition to treat. The gold standard treatment relies on long-term systemic therapy, which carries risks of potential side effects and drug interactions. Topical alternatives exist; however, treatment outcomes remain disappointing. In this article, we review newer topical formulations that are approved by the United States Food and Drug Administration, as well as other topical drugs that are still undergoing clinical trials. Lasers and energy-based devices have also been used for the treatment of onychomycosis; however, standardized parameters and clear treatment endpoints have yet to be specified. Currently, device-based therapies are considered as options for improving the cosmetic appearance of nails. The use of lasers to improve the penetration of topical antifungal treatments as possible combination treatments is also reviewed.


The Axenfeld syndrome and the Rieger syndrome.
A family is reported in which both the syndrome of Axenfeld and the eye malformations of the syndrome of Rieger occur, indicating that both may be expressions of the same gene. We also review the associated anomalies already reported, emphasise their high incidence, suggest that these are not accidental associations, and propose some possible explanations for the high incidence.


Foxtail mosaic virus-induced flowering assays in monocot crops.
Virus-induced flowering (VIF) exploits RNA or DNA viruses to express flowering time genes to induce flowering in plants. Such plant virus-based tools have recently attracted widespread attention for their fundamental and applied uses in flowering physiology and in accelerating breeding in dicotyledonous crops and woody fruit-trees. We now extend this technology to a monocot grass and a cereal crop. Using a Foxtail mosaic virus (FoMV)-based VIF system, dubbed FoMViF, we showed that expression of florigenic Flowering Locus T (FT) genes can promote early flowering and spikelet development in proso millet, a C4 grass species with potential as a nutritional food and biofuel resource, and in non-vernalized C3 wheat, a major food crop worldwide. Floral and spikelet/grain induction in the two monocot plants was caused by the virally expressed untagged or FLAG-tagged FT orthologs, and the florigenic activity of rice Hd3a was more pronounced than its dicotyledonous counterparts in proso millet. The FoMViF system is easy to use and its efficacy to induce flowering and early spikelet/grain production is high. In addition to proso millet and wheat, we envisage that FoMViF will be also applicable to many economically important monocotyledonous food and biofuel crops.


Metal-Free Boron/Phosphorus Co-Doped Nanoporous Carbon for Highly Efficient Benzyl Alcohol Oxidation.
An in-depth understanding of the electronic structures of catalytically active centers and their surrounding vicinity is key to clarifying the structure-activity relationship, and thus enabling the design and development of novel metal-free carbon-based materials with desired catalytic performance. In this study, boron atoms are introduced into phosphorus-doped nanoporous carbon via an efficient strategy, so that the resulting material delivers better catalytic performance. The doped B atoms alter the electronic structures of active sites and cause the adjacent C atoms to act as additional active sites that catalyze the reaction. The B/P co-doped nanoporous carbon shows remarkable catalytic performance for benzyl alcohol oxidation, achieving high yield (over 91% within 2 h) and selectivity (95%), as well as low activation energy (32.2 kJ mol-1 ). Moreover, both the conversion and selectivity remain above 90% after five reaction cycles. Density functional theory calculations indicate that the introduction of B to P-doped nanoporous carbon significantly increases the electron density at the Fermi level and that the oxidation of benzyl alcohol occurs via a different reaction pathway with a very low energy barrier. These findings provide important insights into the relationship between catalytic performance and electronic structure for the design of dual-doped metal-free carbon catalysts.


Insights From the Geographic Spread of the Lyme Disease Epidemic.
Lyme disease is the most common reportable zoonotic infection in the United States. Recent data suggest spread of the Ixodes tick vector and increasing incidence of Lyme disease in several states, including Pennsylvania. We sought to determine the clinical presentation and healthcare use patterns for pediatric Lyme disease in western Pennsylvania. The electronic medical records of all patients with an International Classification of Disease, Ninth Revision, diagnosis of Lyme disease between 2003 and 2013 at Children's Hospital of Pittsburgh were individually reviewed to identify confirmed cases of Lyme disease. The records of 773 patients meeting these criteria were retrospectively analyzed for patient demographics, disease manifestations, and healthcare use. An Lyme disease increased exponentially in the pediatric population of western Pennsylvania. There was a southwestward migration of Lyme disease cases, with a shift from rural to nonrural zip codes. Healthcare provider involvement evolved from subspecialists to primary care pediatricians and emergency departments (EDs). Patients from nonrural zip codes more commonly presented to the ED, while patients from rural zip codes used primary care pediatricians and EDs equally. The current study details the conversion of western Pennsylvania from a Lyme-naive to a Lyme-epidemic area, highlighting changes in clinical presentation and healthcare use over time. Presenting symptoms and provider type differed between those from rural and nonrural zip codes. By elucidating the temporospatial epidemiology and healthcare use for pediatric Lyme disease, the current study may inform public health measures regionally while serving as an archetype for other areas at-risk for Lyme disease epidemics.


Corn oil supplementation to steers grazing endophyte-free tall fescue. II. Effects on longissimus muscle and subcutaneous adipose fatty acid composition and stearoyl-CoA desaturase activity and expression.
Eighteen steers were used to evaluate the effect of supplemental corn oil level to steers grazing endophyte-free tall fescue on fatty acid composition of LM, stearoyl CoA desaturase (SCD) activity and expression as well as cellularity in s.c. adipose. Corn oil was supplemented (g/kg of BW) at 0 (none), 0.75 (medium), and 1.5 (high). Cottonseed hulls were used as a carrier for the corn oil and were supplemented according to pasture availability (0.7 to 1% of BW). Steers were finished on a rotationally grazed, tall fescue pasture for 116 d. Fatty acid composition of LM, s.c. adipose, and diet was determined by GLC. Total linoleic acid intake increased linearly (P < 0.01) with corn oil supplementation (90.7, 265.1, and 406.7 g in none, medium, and high, respectively). Oil supplementation linearly reduced (P < 0.05) myristic, palmitic, and linolenic acid percentage in LM and s.c. adipose. Vaccenic acid (C18:1 t11; VA) percentage was 46 and 32% greater (linear, P = 0.02; quadratic, P = 0.01) for medium and high, respectively, than none, regardless of tissue. Effect of oil supplementation on CLA cis-9, trans-11 was affected by type of adipose tissue (P < 0.01). In the LM, CLA cis-9, trans-11 isomer was 25% greater for medium than for none and intermediate for high, whereas CLA cis-9, trans-11 CLA isomer was 48 and 33% greater in s.c. adipose tissue for medium and high than for none, respectively. Corn oil linearly increased (P </= 0.01) trans-10 octadecenoic acid and CLA trans-10, cis-12; however, values were low (<0.35 and <0.035% of total fatty acids, respectively). Oil supplementation did not change (P > 0.05) the percentage of total SFA, MUFA, or PUFA but linearly increased (P = 0.03) n-6:n-3 ratio from 2.4 to 2.9 in none and high, respectively. Among tissues, total SFA and MUFA were greater in s.c. adipose than LM, whereas total PUFA, n-6, and n-3 fatty acids and the n-6:n-3 ratio were lower. Trans-10 octadecenoic acid, VA, and CLA trans-10, cis-12 were greater (P < 0.01) in s.c. adipose than in LM. Oil supplementation did not alter (P > 0.05) stearoyl CoA desaturase activity or mRNA expression. Corn oil supplementation to grazing steers reduced the percentages of highly atherogenic fatty acids (myristic and palmitic acids) and increased the percentages of antiatherogenic and anticarcinogenic fatty acids (VA and cis-9, trans-11 CLA).


Electrical forces determine glomerular permeability.
There is ongoing controversy about the mechanisms that determine the characteristics of the glomerular filter. Here, we tested whether flow across the glomerular filter generates extracellular electrical potential differences, which could be an important determinant of glomerular filtration. In micropuncture experiments in Necturus maculosus, we measured a potential difference across the glomerular filtration barrier that was proportional to filtration pressure (-0.045 mV/10 cm H₂O). The filtration-dependent potential was generated without temporal delay and was negative within Bowman's space. Perfusion with the cationic polymer protamine abolished the potential difference. We propose a mathematical model that considers the relative contributions of diffusion, convection, and electrophoretic effects on the total flux of albumin across the filter. According to this model, potential differences of -0.02 to -0.05 mV can induce electrophoretic effects that significantly influence the glomerular sieving coefficient of albumin. This model of glomerular filtration has the potential to provide a mechanistic theory, based on experimental data, about the filtration characteristics of the glomerular filtration barrier. It provides a unique approach to the microanatomy of the glomerulus, renal autoregulation, and the pathogenesis of proteinuria.


Poroid Hidradenoma: A Two-Case Report and Literature Review.
Poroid hidradenoma (PH) is a rare benign tumor that shows differentiation of the eccrine sweat gland. It occurs mainly in adults, presenting as a 0.5 to 2 cm-sized intradermal nodule, mostly on the head, extremities, trunk and neck. We report two rare cases of PH, one on the face and the other on the heel. The first patient was a 50-year-old male who had a solitary, skin-colored nodule on his right temple for 6 months. The second patient was a 67-year-old female who presented with a solitary, bean-sized, tender nodule on her left heel for 1 year. The common histological examination finding was a well-circumscribed tumor composed of solid portions and large cystic spaces in the center. The tumor cells consisted of small, monomorphic poroid cells and large cuticular cells in both cases. To our knowledge, only few cases of PH have been reported. Herein, we report two rare cases of PHs with literature review.


Active methanotrophs in two contrasting North American peatland ecosystems revealed using DNA-SIP.
The active methanotroph community was investigated in two contrasting North American peatlands, a nutrient-rich sedge fen and nutrient-poor Sphagnum bog using in vitro incubations and (13)C-DNA stable-isotope probing (SIP) to measure methane (CH(4)) oxidation rates and label active microbes followed by fingerprinting and sequencing of bacterial and archaeal 16S rDNA and methane monooxygenase (pmoA and mmoX) genes. Rates of CH(4) oxidation were slightly, but significantly, faster in the bog and methanotrophs belonged to the class Alphaproteobacteria and were similar to other methanotrophs of the genera Methylocystis, Methylosinus, and Methylocapsa or Methylocella detected in, or isolated from, European bogs. The fen had a greater phylogenetic diversity of organisms that had assimilated (13)C, including methanotrophs from both the Alpha- and Gammaproteobacteria classes and other potentially non-methanotrophic organisms that were similar to bacteria detected in a UK and Finnish fen. Based on similarities between bacteria in our sites and those in Europe, including Russia, we conclude that site physicochemical characteristics rather than biogeography controlled the phylogenetic diversity of active methanotrophs and that differences in phylogenetic diversity between the bog and fen did not relate to measured CH(4) oxidation rates. A single crenarchaeon in the bog site appeared to be assimilating (13)C in 16S rDNA; however, its phylogenetic similarity to other CO(2)-utilizing archaea probably indicates that this organism is not directly involved in CH(4) oxidation in peat.


Ethical approaches to triage in public health emergencies.
General concepts and about medical disasters, public health and triage are outlined. Ethical values at stake are summarized. A special attention is given to conflicts between protection of individual interests (typical of clinical ethics) and collective interests (typical of public health and triage). Hippocratic ethics is compared to utilitarian ethics and to perspectives that emphasize the principle of justice. Three attitudes are suggested: protection of human dignity, precaution, solidarity. A personalistic perspective is suggested to deepen solidarity as a pillar both of clinical and public health ethics.


Development of Screening Assays for Pathogen Virulence and Resistance to Phytophthora Root Rot and Wilting Complex in Raspberry.
Phytophthora root rot and wilting complex (PRRW) of red raspberry, caused primarily by Phytophthora rubi, is an economically important disease in British Columbia (BC) and in raspberry producing regions globally. Reliable, rapid, and efficient screening methods are lacking for evaluating germplasm for potential disease resistance in raspberry breeding programs as well as for screening pathogen isolates for virulence. The objective of this study was to compare various screening methods for efficiency and rapidity in inducing symptoms of disease to identify the most suitable approach. We compared several intact plant root inoculation (IPRI) assays, detached stem assays, and an intact plant stem inoculation (IPSI) assay. A virulent isolate of P. rubi was inoculated in two commercial cultivars: 'Chemainus' (susceptible to PRRW) and 'Cascade Bounty' (moderately resistant to PRRW). For IPRI assays, days to first symptom development, plant wilt progression, and root assessment were recorded. For detached stem tissue and IPSI assays, days to first visible lesions and lesion size were assessed. Experiments were arranged in a completely randomized design with three replications in each experiment. Three IPRI assays produced reliable symptoms in both cultivars. Among the detached stem assays, a node inoculation method performed better than other methods. Detached stem assays are useful for rapid pathogenicity testing of P. rubi, whereas IPRI assays are better for screening germplasm for disease resistance. Overall, this study identified several assays that can be used for conducting studies on pathogen phenotypic diversity (pathogenicity and virulence tests) and screening raspberry cultivars, germplasm, and breeding materials for response to PRRW.


The feet of the measles virus polymerase bind the viral nucleocapsid protein at a single site.
Measles virus has a single-stranded RNA genome that is organized into a helical complex by the viral N protein. The resulting structure is termed the nucleocapsid and is traversed by the viral polymerase during RNA synthesis. The P protein, the noncatalytic subunit of the polymerase, provides the "legs and feet" that allow the polymerase to walk along its protein-RNA template. The polymerase feet are very simple three-helix bundles, only 50 amino acids in size. Previously, we have shown that these feet grasp the viral N protein during movement by attaching to a short sequence (amino acids 487-503) within the disordered and surface-exposed tail of N, causing it to fold into a helix. The result is a weak-affinity complex with a short lifetime, which would allow the polymerase to take rapid steps forward. The structure of the complex was determined using X-ray crystallography. This simple model of binding was challenged by a paper in this journal, claiming that a downstream sequence in the tail of N (amino acids 517-525) was also critical for the association. Its presence was reported to enhance the overall affinity of the polymerase feet for N by three orders of magnitude. We have, therefore, examined binding of the polymerase foot domain to amino acids 477-525 of N using quantitative biophysical techniques, and compared the results to our previous binding studies, performed using amino acids 477-505 of N. We find no evidence that the sequence downstream of amino acid 505 influences binding, validating the original single-site binding model.


Molecular modulation of estrogen-induced apoptosis by synthetic progestins in hormone replacement therapy: an insight into the women's health initiative study.
Hormone replacement therapy (HRT) is widely used to manage menopausal symptoms in women and can be comprised of an estrogen alone or an estrogen combined with a progestin. The Women's Health Initiative demonstrated in their randomized trials that estrogen alone HRT decreases the risk of breast cancer in postmenopausal women, whereas combined estrogen plus a progestin (medroxyprogesterone acetate, MPA) HRT increases this risk. Long-term estrogen-deprived MCF-7:5C cells were used to model the postmenopausal breast cancer cell environment. MPA is able to modify E2-induced apoptosis in MCF-7:5C cells. MPA, similar to dexamethasone, increases glucocorticoid receptor (GR) transcriptional activity, increases SGK1, a GR target gene, and can be blocked by RU486 (an antiglucocorticoid), suggesting that it functions through the GR. Norethindrone acetate (NETA), another progestin used in HRT, acts like an estrogen at high doses, upregulating estrogen receptor target genes and generating apoptosis in MCF-7:5C cells. The data suggest that women taking HRT comprising an estrogen plus MPA may have an increased risk of breast cancer due to MPA acting as a glucocorticoid and blunting E2-induced apoptosis in this environment. Therefore, perhaps other approved progestins (e.g., NETA) should be considered as alternatives to MPA.


[I.M. Sechenov's creative development of ideas in aviation and space medicine].
Research carried outby the great Russian scholar I. M. Sechenov has significantly contributed to development of aviation physiology, medicine and psychology. His fundamental works consisted of discovery of the constancy of alveolar air composition theory, study of interactions of analyzers systems in solving the problem of human spatial orientation under flight conditions, development of a nervous theory of fatigue. Creative development of ideas by I. M. Sechenov allowed enhancing the efficiency of performing and safety of aviation and space flights.


Primidone/phenobarbital-induced periodic alternating nystagmus.
A 37-year-old man with a history of seizures developed periodic alternating nystagmus (PAN) along with other signs of primidone/phenobarbital toxicity. The PAN gradually diminished in cycle length and intensity, finally resolving with gradual discontinuation of the drugs.


Tagging Functional Polymorphism in 3' Untranslated Region of Methylene Tetrahydrofolate Reductase and Risk of Ischemic Stroke.
The association between genetic polymorphisms in the exon or untranslated region of the methylenetetrahydrofolate reductase gene (MTHFR) and the risk of human ischemic stroke (IS) has been well-documented. In this study, we focused on a polymorphism previously screened by high-throughput analysis and on its potential function in patients with IS Methods: This hospital-based case-control study was conducted in 400 patients and 400 healthy volunteers. Genotyping was conducted using TaqMan probes. Potential interactions were predicted by multiple bioinformatics analysis. Relative expression levels of MTHFR were detected confirmed by dual-luciferase assay. The MTHFR polymorphism rs142884651 was significantly associated with a decreased risk of IS compared with the wild-type GA genotype (P = 0.02) and AA genotype (P = 0.001). According to bioinformatics analysis and luciferase assay, this polymorphism could attenuate the binding of let-7f and miR-196a (P = 0.021 and 0.019, respectively) leading to the accumulation of MTHFR and degradation of serum homocysteine, and resulting in a better IS outcome. This study demonstrated that the MTHFR rs142884651 polymorphism is associated with a decreased risk of IS and may act as a biomarker of short-term outcome in patients with IS.


Matrices for capillary gel electrophoresis--a brief overview of uncommon gels.
This article gives an overview of uncommon replaceable matrices (gels) for capillary gel electrophoresis. This electrophoretic technique is useful mainly for the separation and analysis of biopolymers-nucleic acids and their fragments, and proteins/peptides. Commonly used gels are not reviewed. Those mentioned and discussed here are gels containing saccharides, newly developed acrylamide-based gels and thermoadjustable viscosity polymers, namely triblock copolymers and grafted polyacrylamide.


Optical imaging of the adoptive transfer of human endothelial cells in mice using anti-human CD31 monoclonal antibody.
The development of endothelium-specific imaging agents capable of specific binding to human cells under the conditions of flow for the needs of regenerative medicine and cancer research. The goal of the study was testing the feasibility of optical imaging of human endothelial cells implanted in mice. Mouse model of adoptive human endothelial cell transfer was obtained by implanting cells in Matrigel matrix in subcutaneous space (Kang, Torres, Wald, Weissleder, and Bogdanov, Jr., Targeted imaging of human endothelial-specific marker in a model of adoptive cell transfer. Lab. Invest. 86: 599-609, 2006). Several endothelium-specific proteins were labeled with near-infrared fluorochrome (Cy5.5) and tested in vitro. Fluorescence imaging using anti-human CD31 antibody was performed in vivo. The obtained results were corroborated by using fluorescence microscopy of tissue sections. We determined that monoclonal anti-human CD31 antibodies labeled with Cy5.5 were efficiently binding to human endothelial cells and were not subject to rapid endocytosis. We further demonstrated that specific near-infrared optical imaging signal was present only in Matrigel implants seeded with human endothelium cells and was absent from control Matrigel implants. Histology showed staining of cells lining vessels and revealed the formation of branched networks of CD31-positive cells. Anti-human CD31 antibodies tagged with near-infrared fluorochromes can be used for detection of perfused blood vessels harboring human endothelial cells in animal models of adoptive transfer.


Infection of B lymphocytes by a human herpesvirus, Epstein-Barr virus, is blocked by calmodulin antagonists.
Epstein-Barr virus (EBV) is a human herpesvirus that selectively binds to and infects human B lymphocytes (B cells). In the studies presented here, we found that several phenothiazines, including trifluoperazine, chlorpromazine, prochlorpromazine, and promethazine, blocked EBV infectivity of isolated adult human B cells as measured either by outgrowth of transformed cell colonies or by [3H]thymidine incorporation. Trifluoperazine, chlorpromazine, and prochlorpromazine were equally effective with 20 microM fully inhibiting infectivity, whereas 100 microM promethazine was required for a comparable effect. Inhibition by trifluoperazine was partially reversible. Studies with radiolabeled EBV demonstrated that the inhibitors did not impair virus binding to B cells. Electron microscopic examination of B lymphocytes revealed that trifluoperazine reduced the number of large uncoated cell vacuoles and the number of membrane microvilli, indicating that this agent interfered with cell pinocytosis. This process was accompanied by inhibition of EBV endocytosis into B cells. Phenothiazines bind to and inhibit calmodulin, an intracellular calcium-binding protein that regulates several key enzymes, some of which directly affect cytoskeletal elements, although they also may interact nonspecifically with other cellular constituents. In this regard, haloperidol, a non-phenothiazine calmodulin antagonist, and R24571, a derivative of the antimycotic miconazole, which is a potent and highly specific calmodulin inhibitor, also blocked EBV infection. These studies suggest that calmodulin or a calmodulin-regulated cellular enzyme(s) is involved in normal cellular endocytic processes in B lymphocytes and thereby in the early stages of EBV infection.


Behavioral Activation System and Early Life Parental Abuse Are Associated with Antisocial Behaviors in Mexican Adolescents.
Antisocial behavior (AB) is a complex phenomenon, predicted by a wide range of biological, environmental, and personality factors. These have high human and economic costs especially in adolescents, highlighting the importance of investigating factors that may be associated with these behaviors. Among the most potent predictors of AB are early life experiences and personality. To this end, the present study sought to investigate the association between early life parental abuse and behavioral activation system (BAS) personality traits assessed within the reinforcement sensitivity theory (RST) framework and antisocial behaviors in Mexican adolescents. Our sample consisted of 342 adolescents (Mage = 17, SD = 2.47) from northwestern Mexico. Participants, after parental consent and participant consent/assent (if minors), self-reported early life parental abuse, current BAS personality traits, and antisocial behaviors. Through structural equation models, our results suggest there is a positive association between early life parental abuse and antisocial behaviors, as well as a negative association with BAS personality traits (R2 = 37%). These results contribute to the current literature by suggesting that personality and environmental variables can predict adolescent antisocial behaviors. Future studies should explore the interplay between these variables longitudinally and investigate both risk and protective factors, as well as negative and positive outcomes.


Sericin protects against diabetes-induced injuries in sciatic nerve and related nerve cells.
Sericin from discarded silkworm cocoons of silk reeling has been used in different fields, such as cosmetology, skin care, nutrition, and oncology. The present study established a rat model of type 2 diabetes by consecutive intraperitoneal injections of low-dose (25 mg/kg) streptozotocin. After intragastrical perfusion of sericin for 35 days, blood glucose levels significantly declined, and the expression of neurofilament protein in the sciatic nerve and nerve growth factor in L4-6 spinal ganglion and anterior horn cells significantly increased. However, the expression of neuropeptide Y in spinal ganglion and anterior horn cells significantly decreased in model rats. These findings indicate that sericin protected the sciatic nerve and related nerve cells against injury in a rat type 2 diabetic model by upregulating the expression of neurofilament protein in the sciatic nerve and nerve growth factor in spinal ganglion and anterior horn cells, and downregulating the expression of neuropeptide Y in spinal ganglion and anterior horn cells.


Synthesis and Electrochemical Performance of KVO/GO Composites as Anodes for Aqueous Rechargeable Lithium-Ion Batteries.
K0.25V2O5 (KVO) and K0.25V2O5/graphene oxide (KVO/GO) have been successfully synthesized by a chemical coprecipitation method and a subsequent calcination process. The structure and morphology of KVO and KVO/GO were characterized by X-ray diffraction, scanning electron microscopy, transmission electron microscopy, and X-ray photoelectron spectroscopy. The as-obtained vanadate and vanadate modified by GO materials were used as anodes with LiMn2O4 as a cathode and saturated LiNO3 as an electrolyte to assemble an aqueous rechargeable lithium-ion battery (ARLB). The cyclic voltammogram curves of both KVO and KVO/GO electrodes exhibited three pairs of redox peaks corresponding to charge/discharge platforms. We found that a small amount of graphene oxide added improved the electrochemical performance more significantly than excess graphene oxide. The as-prepared KVO/GO//LiMn2O4 could not only improve the initial discharge capacity but could also reduce the attenuation at a high current density. Furthermore, the ARLB with a KVO/GO anode exhibited an excellent rate performance and super long cycle life. These good electrochemical properties of this new ARLB system actually provided feasibility for application in large-scale power sources and energy storage devices.


Mouse dispatched mutants fail to distribute hedgehog proteins and are defective in hedgehog signaling.
Hedgehog (Hh) signaling plays a major role in multiple aspects of embryonic development, which involves both short- and long-range signaling from localized Hh sources. One unusual aspect of Hh signaling is the autoproteolytic processing of Hh followed by lipid modification. As a consequence, the N-terminal fragment of Hh becomes membrane anchored on the cell surface of Hh-producing cells. A key issue in Hh signaling is to understand the molecular mechanisms by which lipid-modified Hh protein is transported from its sites of synthesis and subsequently moves through the morphogenetic field. The dispatched gene, which encodes a putative multipass membrane protein, was initially identified in Drosophila and is required in Hh-producing cells, where it facilitates the transport of cholesterol-modified Hh. We report the identification of the mouse dispatched (Disp) gene and a phenotypic analysis of Disp mutant mice. Disp-null mice phenocopy mice deficient in the smoothened gene, an essential component for Hh reception, suggesting that Disp is essential for Hh signaling. This conclusion was further supported by a detailed molecular analysis of Disp knockout mice, which exhibit defects characteristic of loss of Hh signaling. We also provide evidence that Disp is not required for Hh protein synthesis or processing, but rather for the movement of Hh protein from its sites of synthesis in mice. Taken together, our results reveal a conserved mechanism of Hh protein movement in Hh-producing cells that is essential for proper Hh signaling.


Pathomechanism of Triangular Fibrocartilage Complex Injuries in Patients with Distal-Radius Fractures: A Magnetic-Resonance Imaging Study.
Injury to the triangular fibrocartilage complex (TFCC) is one of the most common complications following a fracture of the distal radius. In this study, an examination of TFCC injuries in patients with distal-radius fractures was conducted using magnetic-resonance imaging (MRI); the aim of the study was to analyze the prevalence of TFCC injury as well as to suggest acceptable radiologic parameters for use in prediction of the injury pattern. Fifty-eight patients with distal-radius fractures who underwent MRI prior to undergoing open-reduction surgery between April 2020 and July 2021 were included in this study. An analysis of various radiologic parameters, the fracture type, and the MRI classification of TFCC injuries was performed. Radiologic parameters were used in the evaluation of distal radioulnar joint (DRUJ), radial shortening, and the dorsal angularity of the fracture. All of the patients in this study had definite traumatic TFCC injuries. A statistical relationship was observed between the radial length gap between the intact wrist and the injured wrist, which represents relative radial shortening, and the pattern of TFCC injury. In conclusion, the shortening of the distal radius, causing peripheral soft tissue of the ulnar side to become tauter, is highly relevant with regard to the pattern of TFCC injury. However, because no data on the clinical outcome were utilized in this study, it is lacking in clinical perspective. The conduct of further studies on patients' clinical outcome will be necessary.


Gene conversion in human immunoglobulin gamma locus shown by unusual location of IgG allotypes.
The constant region of the gamma 1, gamma 2 and gamma 3 heavy chains of the human IgG1, IgG2 and IgG3 immunoglobulins carries antigenic determinants or G1m, G2m and G3m allotypes, which are genetic markers of these subclasses. The exceptional presence on gamma 1 and gamma 2 chains of Gm allotypes usually located on the CH3 domain of gamma 3 shows an unexpected clustering of base changes and subsequent identity of short DNA sequences in the CH3 exon of the non-allelic gamma 1, gamma 2 and gamma 3 genes. Such clusters of substitutions are not easily explained on the classical basis of point mutations. A gene conversion, which substituted a segment of the gamma 1 or gamma 2 gene with the homologous region of the non-allelic gamma 3 gene, is more likely. Other examples of possible conversion involving the gamma genes are described. The conservation or the restoration of short sequences produced by the conversion events might be related to the biological properties of the constant region of the heavy chains.


Metacognition for spelling in higher education students with dyslexia: is there evidence for the dual burden hypothesis?
We examined whether academic and professional bachelor students with dyslexia are able to compensate for their spelling deficits with metacognitive experience. Previous research suggested that students with dyslexia may suffer from a dual burden. Not only do they perform worse on spelling but in addition they are not as fully aware of their difficulties as their peers without dyslexia. According to some authors, this is the result of a worse feeling of confidence, which can be considered as a form of metacognition (metacognitive experience). We tried to isolate this metacognitive experience by asking 100 students with dyslexia and 100 matched control students to rate their feeling of confidence in a word spelling task and a proofreading task. Next, we used Signal Detection Analysis to disentangle the effects of proficiency and criterion setting. We found that students with dyslexia showed lower proficiencies but not suboptimal response biases. They were as good at deciding when they could be confident or not as their peers without dyslexia. They just had more cases in which their spelling was wrong. We conclude that the feeling of confidence in our students with dyslexia is as good as in their peers without dyslexia. These findings go against the Dual Burden theory (Krüger & Dunning, 1999), which assumes that people with a skills problem suffer twice as a result of insufficiently developed metacognitive competence. As a result, there is no gain to be expected from extra training of this metacognitive experience in higher education students with dyslexia.


Assessing quality of life in patients with chronic leg ulceration using the Medical Outcomes Short Form-36 questionnaire.
Clinician awareness of the importance of recognizing, assessing, and ultimately addressing the negative impact of chronic wounds on patient quality of life is increasing. One hundred, eighteen (118) patients (average age 78 years) participated in a study to evaluate the use of the Medical Outcomes Short Form-36 for assessing the health-related quality of life of patients with chronic leg ulceration. Most patients (104, 88%) were treated at home by community nurses. A medical history was obtained and patients completed the Short Form-36 questionnaire at baseline and after 12 weeks of receiving standard ulcer care. Published normative data were used to ascertain the effect of leg ulcers on health-related quality of life. Short Form-36 responsiveness was determined by comparing baseline and 12-week scores. Results suggest that the questionnaire is reliable for five of eight Short Form-36 domains (alpha > 0.8), with the remainder alpha > 0.7. Compared to age-sex adjusted published normative scores, patients with leg ulcers had significantly lower mean scores in the following domains: role-emotional (d = 28.6, P <0.001), social functioning (d = 22.8, P <0.001), role-functioning (d = 20.8, P <0.001), role-physical (d = 20.7, P <0.001), and bodily pain (d = 12.3, P <0.001). Short Form-36 scores barely changed between baseline and the 12-week assessment, but bodily pain improved in the 31 patients whose ulcers healed during that time (d = 14.6, P = 0.006; SRM = 0.60). Pain did not improve in patients whose ulcers remained open (d = -2.1, P = 0.45). Compared to patients whose ulcers did not heal, patients with healed ulcers experienced greater improvements in the following domains: body pain (d = 16.8, P = 0.003), mental health (d = 9.4, P = 0.013), role-physical (d = 19.7, P = 0.06), role-emotional (d = 17.2, P = 0.12), and vitality (d = 9.0, P = 0.052). The results of this study suggest that leg ulcers reduce patient quality of life and that the Short Form-36 can be used to ascertain their impact


Volitional disability and physician attitudes toward noncompliance.
We develop the concept of a volitional disability as an aid in understanding those patients who behave in ways that are harmful to themselves in spite of their desire to do otherwise. Using this concept enables us to describe their behavior as intentional but 'involuntary'. We demonstrate the clinical reality of such behavior by giving clinical examples of the behavior of those with phobic, compulsive, and addictive disorders. We then attempt to show how some kinds of self-harming behavior of noncompliant patients are similar to phobic and compulsive behavior. We propose use of the concept of volitional disability to make it easier for physicians to work with these noncompliant patients and thus to improve their ability to provide better care for them.


Endohedral Cluster Superconductors in the Mo-Ga-Sn System Explored by the Joint Flux Technique.
Endohedral Ga cluster compounds feature nontrivial superconducting states including the two-gap superconductivity similar in nature to MgB2. We use the joint flux synthetic technique to introduce Sn into the Ga matrix and tune the valence electron count in the two new endohedral cluster superconductors Mo8Ga41-xSnx and Mo4Ga21-x-δSnx with critical temperatures of Tc = 8.7 and 5.85 K, respectively. While the former compound is a derivative of the previously known Mo8Ga41 superconductor, where Sn atoms are enclosed inside the Sn@Ga6 octahedral clusters, the latter is a new architecture built upon Mo@Ga9Sn clusters, Ga@Ga12 cuboctahedra, and Sn4 squares. We show that this novel Mo4Ga21-x-δSnx superconductor features strong electron-phonon coupling with the large ratio of 2Δ(0)/(kBTc) = 4.1 similar to that of the Mo8Ga41 superconductor with the closely related crystal structure.


Characterization of diffusion MRI using the mean apparent propagator model in hemodialysis patients: A pilot study.
To better understand documented cognitive decline in hemodialysis (HD) patients, diffusion MRI (dMRI) has been used to characterize brain anatomical deficits relative to controls. Studies to this point have primarily used diffusion tensor imaging (DTI) to model the three-dimensional diffusion of water in HD patients, with DTI parameters reflecting underlying microstructural changes of brain tissue. Since DTI has some limitations in characterizing tissue microstructure, some of which may be complicated by HD, we explored the use of the mean apparent propagator (MAP) model to describe diffusion in HD patients. We collected anatomical T1 and T2 FLAIR MRIs as well as multi-shell dMRI in ten HD participants and ten age-matched controls. The T1 and T2 FLAIR MRIs were used for tissue segmentation and identification of white matter hyperintensity, respectively. Multi-shell dMRI data were used to estimate MAP and DTI diffusion models. Each model was then used to characterize the differences between the HD cohort and the age-matched controls in normal appearing white matter, subcortical gray matter, corpus callosum (CC) and bilateral radiata (Rad). As expected, parameters of both DTI and MAP models of dMRI were significantly different in HD participants compared to controls. However, some MAP parameters suggested additional tissue microstructural changes in HD participants, such as increased axonal diameter. Measurements of non-Gaussianity indicated that MAP provided better a diffusion estimate than DTI, and MAP appeared to provide a more accurate measure of anisotropy in Rad, based on measures of the Rad/CC ratio. In conclusion, parameters of the MAP and DTI models were both sensitive to changes in diffusivity in HD participants compared to controls; however, the MAP model appeared to provide additional detailed information about changes in brain tissue microstructure.


Temporal regulation of rapamycin on memory CTL programming by IL-12.
Mammalian target of rapamycin (mTOR) is a master regulator of cell growth. Recent reports have defined its important role in memory cytotoxic T lymphocyte (CTL) differentiation in infections and memory programming. We report that rapamycin regulated memory CTL programming by IL-12 to a similar level in a wide range of concentrations, and the enhanced memory CTLs by rapamycin were functional and provided similar protection against Listeria Monocytogenes challenge compared to the control. In addition, rapamycin-experienced CTLs went through substantially enhanced proliferation after transfer into recipients. Furthermore, the regulatory function of rapamycin on CD62L expression in memory CTLs was mainly contributed by the presence of rapamycin in the first 24-hr of stimulation in vitro, whereas the effective window of rapamycin on the size of memory CTLs was determined between 24 to 72 hrs. In conclusion, rapamycin regulates IL-12-driven programming of CTLs to a similar level in a wide range of concentrations, and regulates the phenotype and the size of memory CTLs in different temporal windows.


Genomic Analysis of Tumor Microenvironment Immune Types across 14 Solid Cancer Types: Immunotherapeutic Implications.
We performed a comprehensive immuno-genomic analysis of tumor microenvironment immune types (TMITs), which is classified into four groups based on PD-L1+CD8A or PD-L1+cytolytic activity (CYT) expression, across a broad spectrum of solid tumors in order to help identify patients who will benefit from anti- PD-1/PD-L1 therapy. The mRNA sequencing data from The Cancer Genome Atlas (TCGA) of 14 solid cancer types representing 6,685 tumor samples was analyzed. TMIT was classified only for those tumor types that both PD-L1 and CD8A/CYT could prefict mutation and/or neoantigen number. The mutational and neoepitope features of the tumor were compared according to the four TMITs. We found that PD-L1/CD8A/CYT subgroups could not distinguish different mutation and neoantigen numbers in certain tumor types such as glioblastoma multiforme, prostate adenocarcinoma, and head and neck and lung squamous cell carcinoma. For the remaining tumor types, compared with TIMT II (low PD-L1 and CD8A/CYT), TIMT I (high PD-L1 and CD8A/CYT) had a significantly higher number of mutations or neoantigens in bladder urothelial carcinoma, breast and cervical cancer, colorectal, stomach and lung adenocarcinoma, and melanoma. In contrast, TMIT I of kidney clear cell, liver hepatocellular, and thyroid carcinoma were negatively correlated with mutation burden or neoantigen numbers. Our findings show that the TMIT stratification proposed could serve as a favorable approach for tailoring optimal immunotherapeutic strategies in certain tumor types. Going forward, it will be important to test the clinical practicability of TMIT based on quantification of immune infiltrates using mRNA-seq to predict clinical response to these and other immunotherapeutic strategies in more different tumors.


[The estimation of thyroxine, triiodothyronine, thyro-binding-index, and free-thyroxine-index in the newborn (author's transl)].
Because of the importance of early diagnosis of hypothyroidism normal values of thyroxine (T4), thyro-binding-index (TBI), free thyroxine-index (FTI) and triiodothyronine (T3) in the serum of newborns were established. In extremely premature babies as in early fetal life the total thyroxine is relatively low. The lowest serum thyroxine in newborns without hypothyroidism was found in a premature infant with a birth weight of 750 g, i.e. 4.8 mug/100 ml on the 4th day of life. Otherwise the T4 values were quite high during the neonatal period, without signs of hyperthyroidism. Our hypothyroid patients scarcely had higher T4 values (0.8-5.1 mug/100 ml) within the first month of life than older hypothyroid patients. Healthy newborns had a mean T4 value of about 15 mug/100 ml during the first week of life (two standard deviations 6.4-23.6 mug/100 ml). Afterwards the T4 values slowly came down to a mean of about 12 mug/100 ml in the 4th week of life. During the first month of life the FTI of hypothyroid patients was below two standard deviations of normal newborn values, whereas TBI-values showed an overlap. During the first 3 days of life newborns with goiter had T4-values in the lower normal or hypothyroid range without obvious signs of hypothyroidism. FTI was quite low, too, and TBI relatively high (as in hypothyroidism). Within the second week of life all these values normalized mostly after treatment with KI ointment, occasionally without this treatment. Where these values did not normalize, hypohtyroidism was assumed. Triiodothyronine in cord blood was very low (0.47 ng/1.6 ng/ml) during the neonatal period (one to two days after birth almost 2.0 mg/ml). Values in our hypothyroid patients fluctuated widely (zero to slightly elevated values with a mean of 0.78 ng/ml). Therefore, T4 seemed more reliable than T3 for the diagnosis of hypothyroidism (the opposite was true for hyperthyroidism.


SCIRehab Project series: the speech language pathology taxonomy.
Outcomes research for speech language pathology (SLP) interventions for acute traumatic spinal cord injury (SSC) rehabilitation in the US is difficult because of the lack of a treatment classification system (taxonomy). To describe a taxonomy developed by speech language pathologists (SLPs) to examine the effects of SLP interventions on SCI rehabilitation outcomes. The SCIRehab study uses practice-based evidence, a rigorous observational methodology that examines treatment processes without specifying or requiring specific therapeutic interventions. Speech language pathology lead clinicians and researchers at 6 US SCI centers developed a detailed SLP taxonomy documentation process that is comprehensive of SLP interventions for patients with SCI. The SLP taxonomy consists of 7 intervention categories that address deficits (speech production for patients with artificial airway, motor speech and voice, swallowing, cognitive-communication, and communication) and the associated exercises and tasks that patients perform. Time is recorded for each category, and supplementary information focuses on cueing needs and family involvement that helps to describe and guide intervention selection. The SCIRehab project is enrolling 1,500 patients with acute traumatic SCI at 6 inpatient rehabilitation facilities. Speech language pathology taxonomy information is being captured for the SCIRehab patients who are referred for SLP services; this may be the first attempt to document the many details of the SLP rehabilitation process for patients with SCI in the US.


Methods for assessment of short-term coral reef fish movements within an acoustic array.
Arrays of passive receivers are a widely used tool for tracking the movements of acoustically-tagged fish in marine ecosystems; however, the spatial and temporal heterogeneity of coral reef environments pose challenges for the interpretation of tag detection data. To improve this situation for reef fishes, we introduced a novel response variable method that treats signal detections as proportions (i.e., percent transmissions detected or "detection rates") and compared this against prior approaches to examine the influence of array and transmitter performance, signal distance and environmental factors on detection rates. We applied this method to tagged snappers and groupers in the Florida reef ecosystem and controlled range-tests on static targets in Bayboro Harbor, Florida, to provide methodological guidance for the planning and evaluation of passive array studies for coral reef fishes. Logistic regression analysis indicated detection rates were primarily a non-linear function of tag distance from receiver. A 'model-weighted' function was developed to incorporate the non-linear relationship between detection rate and distance to provide robust positioning estimates and allow for easy extension to tags with different ping rates. Optimal acoustic array design requires balancing the interplay between receiver spacing, detection rates, and positioning error. Spacing receivers at twice the distance of the modeled 50% detection rate may be appropriate when quantification of overall space use is a priority, and would provide a minimum of 75% detection rate. However, for research where missing detections within the array is unacceptable or time-at-arrival based fine-scale positioning is needed, tighter receiver spacing may be required to maintain signal detection probability near 100%.


Light and electron microscopic localization of atrial natriuretic peptide in the heart of spontaneously hypertensive rat.
Atrial natriuretic peptide (ANP) is a newly discovered peptide hormone present mainly in the atria. We investigated the occurrence and distribution of ANP immunoreactivity in the myocardiocytes of the ventricles of spontaneously hypertensive rats by use of immunocytochemistry at both light and electron microscopic level. ANP immunoreactivity was found in the specific granules in the cytoplasm of the cardiocytes in the subendocardium and the myocardium of the ventricles, as well as in the atria. The specific granules found in the ventricles of hypertensive rats were similar in size, shape, and ANP immunoreactive content to those in the atria. The abundance of ANP immunoreactivity in the left ventricle is greater than that in the right, and appears to increase with increasing severity of hypertension. Conversely, the overall content of ANP in the atria of hypertensive rats was decreased when compared with that in age-matched normotensive rats. The present findings indicate that ventricles may become a major source for ANP synthesis and release during hypertension, and may play important roles in cardiac endocrine pathology and cardiac hypertrophy.


Disentangling the temporal relationship between parental depressive symptoms and early child behavior problems: a transactional framework.
Despite the considerable amount of research demonstrating the relationship between parental depressive symptoms and child behavior problems, few studies have examined the direction of the relationship between these variables. Therefore, the purpose of this study was to examine transactional effects between parental depressive symptoms and child behavior problems. Participants were 209 parent-child dyads drawn from the Oregon Adolescent Depression Project who completed at least 2 of 4 annual questionnaire assessments between the child's age of 4 and 7 years. Structural equation modeling was used to examine the autoregressive paths from one year to the next year within each construct, as well as cross-lagged paths from one year to the next year between constructs. Findings indicated that parental depressive symptoms at each year predicted child behavior problems at the subsequent year and vice versa. No support was found for differential gender effects. These findings highlight the reciprocal relationship between parental depressive symptoms and child behavior problems and suggest intervention programs for young children should assess for and target parental depression when appropriate. Future research should examine these relationships across a broader developmental spectrum and in more diverse, heterogeneous samples.


Delusional parasitosis of body orifices - a cultural variant?
Predominant or specific involvement of the eyes, ears, nostrils, mouth, anus and urethra (the body orifices) has not previously been reported in the literature on delusional parasitosis. Their involvement in the cases reported here is discussed in the context of the Hindu religio-cultural belief system which attaches special significance to these organs in the personal quest for physical, mental and spiritual purity. The involvement of the ears, in particular, appears to be influenced by native healing methods.


Evidence-based medicine for every day, everyone, and every therapeutic study.
The rapid growth in published medical literature makes it difficult for clinicians to keep up with advances in their fields. This may result in a cursory scan of the abstract and conclusion of a study without critically evaluating study quality. The application of evidence-based medicine (EBM) is the process of converting the abstract task of reading the literature into a practical method of using the literature to inform care in a specific clinical context while simultaneously expanding one's knowledge. EBM involves 4 steps: (1) stating the clinical problem in a defined question; (2) searching the literature for the evidence; (3) critically appraising the evidence for its validity; and (4) applying the evidence in the context of the patient's situation, preferences, and values. In this review, we use the recently published trial of thymectomy in myasthenia gravis as an example and systematically go through the steps of assessing internal validity, precision, and external validity. Muscle Nerve 58: 486-496, 2018.


Synthesis and characterization of a new trifunctional magnetic-photoluminescent-oxygen-sensing nanomaterial.
Magnetic Fe(2)O(3) nanoparticles coated with SiO(2) chemically doped with a Ru(II) complex were prepared using a simple solution based method. Field-emission scanning electron microscopy (FE-SEM) and transmission electron microscopy (TEM) showed that the Fe(2)O(3) nanoparticles with a mean diameter of ∼115 nm were successfully coated with Ru(II) complex-chemically doped SiO(2) shell with a thickness of ∼30 nm. The obtained nanocomposite material showed a strong magnetic response to a varying magnetic field, exhibited the bright red triplet metal-to-ligand charge transfer ((3)MLCT) emission, and its photoluminescent intensity was sensitive to oxygen concentration. Compared with the Ru(II) complex in silica gels, the Ru(II) complex in the magnetic-optical-oxygen-sensing nanocomposite demonstrated improved thermodynamic stability of emissions. These nanocomposites are also nontoxic and easily conjugated with biomolecules. Their magnetic, photoluminescent and oxygen-sensing properties make them promising candidates for cell separation, biomarkers and optical oxygen sensors, which can measure the O(2) concentration in biological bodies.