Proteolytically activated, recombinant anti-mullerian hormone inhibits androgen secretion, proliferation, and differentiation of spermatogonia in adult zebrafish testis organ cultures.
Anti-Müllerian hormone (Amh) is in mammals known as a TGFβ type of glycoprotein processed to yield a bioactive C-terminal homodimer that directs regression of Müllerian ducts in the male fetus and regulates steroidogenesis and early stages of folliculogenesis. Here, we report on the zebrafish Amh homologue. Zebrafish, as all teleost fish, do not have Müllerian ducts. Antibodies raised against the N- and C-terminal part of Amh were used to study the processing of endogenous and recombinant Amh. The N-terminally directed antibody detected a 27-kDa protein, whereas the C-terminally directed one recognized a 32-kDa protein in testes extracts, both apparently not glycosylated. The C-terminal fragment was present as a monomeric protein, because reducing conditions did not change its apparent molecular mass. Recombinant zebrafish Amh was cleaved with plasmin to N- and C-terminal fragments that after deglycosylation were similar in size to endogenous Amh fragments. Mass spectrometry and N-terminal sequencing revealed a 21-residue N-terminal leader sequence and a plasmin cleavage site after Lys or Arg within Lys-Arg-His at position 263-265, which produce theoretical fragments in accordance with the experimental results. Experiments using adult zebrafish testes tissue cultures showed that plasmin-cleaved, but not uncleaved, Amh inhibited gonadotropin-stimulated androgen production. However, androgens did not modulate amh expression that was, on the other hand, down-regulated by Fsh. Moreover, plasmin-cleaved Amh inhibited androgen-stimulated proliferation as well as differentiation of type A spermatogonia. In conclusion, zebrafish Amh is processed to become bioactive and has independent functions in inhibiting both steroidogenesis and spermatogenesis.


Nano-lipoidal carriers of isotretinoin with anti-aging potential: formulation, characterization and biochemical evaluation.
Treatment of photoaging includes non-prescription cosmeceuticals and prescription products, retinoids. Isotretinoin, an established anti-acne retinoid, is also reported to delay the aging process. However, the drug is reported to be an irritant on skin. The present study endeavors to explore the potential of a novel set of biocompatible nano-structured systems of isotretinoin in the treatment of photoaging. Nano-lipoidal carriers (NLCs) of isotretinoin were developed, characterized and investigated in vivo for anti-aging potential in Laca mice vis-à-vis the marketed products of retinoids. The anti-aging efficacy of NLCs was measured in terms of visual and redox-biochemical parameters in ultraviolet (UV)-irradiated mice. Visual observations revealed that there was no significant change (p < 0.05) w.r.t. erythema, skin sagging and wrinkles in the skin of the animals treated with NLCs formulation compared to the marketed product(s). The malondialdehyde levels were found to be significantly reduced, whereas glutathione levels were increased with the application of NLCs vis-à-vis control and test formulations. The NLCs were able to maintain the normal redox-balance of UV-irradiated skin, and were better tolerated by the animals. The study ratifies enhancement in the efficacy of isotretinoin against photoaging and improved skin biocompatibility after its encasement in novel topical dosage forms.


Crystal structures of two cyclic pseudopentapeptides containing psi[CH2S] and psi[CH2SO] backbone surrogates.
The solid state conformations of cyclo [Gly-Pro psi[CH2S] Gly-D-Phe-Pro] and cyclo [Gly-Pro psi[CH2-(S)-SO]Gly-D-Phe-Pro] have been characterized by X-ray diffraction analysis. Crystals of the sulfide trihydrate are orthorhombic, P2(1)2(1)2(1), with a = 10.156(3) A, b = 11.704(3) A, c = 21.913(4) A, and Z = 4. Crystals of the sulfoxide are monoclinic, P2(1) with a = 10.662(1) A, b = 8.552(3) A, c = 12.947(2) A, beta = 94.28(2), and Z = 2. Unlike their all-amide parent, which adopts an all-trans backbone conformation and a type II beta-turn encompassing Gly-Pro-Gly-D-Phe, both of these peptides contain a cis Gly1-Pro2 bond and form a novel turn structure, i.e., a type II' beta-turn consisting of Gly-D-Phe-Pro-Gly. The turn structure in each of these peptides is stabilized by an intramolecular H bond between the carbonyl oxygen of Gly1 and the amide proton of D-Phe4. In the cyclic sulfoxide, the sulfinyl group is not involved in H bonding despite its strong potential as a hydrogen-bond acceptor. The crystal structure made it possible to establish the absolute configuration of the sulfinyl group in this peptide. The two crystal structures also helped identify a type II' beta-turn in the DMSO-d6 solution conformers of these peptides.


Tea and health: the underlying mechanisms.
Detailed multidisciplinary research on the effect of tea and the associated tea polyphenols has led to major advances on the underlying mechanisms. In most studies, green and black tea have similar effects, four of which are reviewed in this paper. 1) Tea polyphenols are powerful antioxidants that may play a role in lowering the oxidation of LDL-cholesterol, with a consequent decreased risk of heart disease, and also diminish the formation of oxidized metabolites of DNA, with an associated lower risk of specific types of cancer. 2) Tea and tea polyphenols selectively induce Phase I and Phase II metabolic enzymes that increase the formation and excretion of detoxified metabolites of carcinogens. 3) Tea lowers the rate of cell replication and thus the growth and development of neoplasms. 4) Tea modifies the intestinal microflora, reducing undesirable bacteria and increasing beneficial bacteria. The accumulated knowledge suggests that regular tea intake by humans might provide an approach to decrease the incidence of and mortality from major chronic diseases.


Arginine supplementation prevents necrotizing enterocolitis in the premature infant.
To determine whether supplementation with L -arginine reduces the incidence of all stages of necrotizing enterocolitis (NEC) in premature infants with birth weight < or =1250 g and gestational age < or =32 weeks. In a randomized, double-blind, placebo-controlled study, 152 premature infants were prospectively, randomly assigned to receive either supplemental L -arginine (1.5 mmol/kg per day; n =75 [group A]) or placebo (control group; n = 77 [group B]) with oral feeds/parenteral nutrition during the first 28 days of life. Nutrient intake, plasma ammonia, arginine, and amino acid concentrations were measured in all infants at days 3, 14, and 28 and at the time of diagnosis of NEC. NEC developed in 5 infants in group A compared with 21 infants in group B (P <.001). Arginine intake and plasma arginine concentrations were similar in both groups at study entry and (as expected) increased in group A at days 14 and 28. Plasma arginine concentrations were lower in both groups at time of diagnosis of NEC. No significant differences in maternal and neonatal demographics, nutrient intake, plasma ammonia and total and essential amino acid concentrations were present between the two groups. Arginine supplementation (1.5 mmol/kg per day) in premature infants reduces the incidence of all stages of NEC.


[A case of invasive bladder cancer with Pagetoid skin lesion of the vulva and anogenital Paget's disease].
A 70-year-old female was admitted to our hospital with a complaint of gross hematuria for two months. She had a 5 years history of eczematous vulvar skin eruption. With the diagnosis of T3N0M0 bladder cancer and anogenital Paget's disease, she underwent pelvic exenteration, vulvectomy and reconstruction of the vulva. Histopathological examinations and mucin stains revealed anogenital Paget's disease and invasive bladder cancer which extended to the clitoral skin and formed Pagetoid skin lesion. CEA and cyokeratin staining demonstrated identical expression pattern in bladder cancer cells and Paget's cells, which suggested both neoplastic cells originated from one progenitor cell.


Predisposing factors and outcomes of malignant skin tumors in children.
Although benign and metastatic tumors occur in children, primary malignant skin tumors are uncommon in the pediatric population. In this study, the authors aimed to determine the incidence, risk factors, treatment, reconstruction details, and outcome of malignant skin tumors occurring in pediatric patients at the Hospital for Sick Children. The electronic database (CoPath) of the pathology department was searched for all cases of malignant skin tumors treated surgically between January of 2000 and September of 2008. Eighteen patients had been diagnosed and treated surgically for malignant skin tumors. The mean age was 10.4 years. Diagnosis of malignant melanoma was made in 14 patients, diagnosis of basal cell carcinoma was made in four patients, and diagnosis of squamous cell carcinoma was made in one patient. The most common sites of occurrence were lower limbs (33 percent) and face (28 percent). Gorlin syndrome was an underlying predisposing condition in three patients with basal cell carcinoma. All cases of basal cell carcinoma and squamous cell carcinoma underwent surgical resection and primary closure or skin graft. Of the patients with malignant melanoma, seven underwent surgical excision and primary closure and five had excision and skin graft. Eleven patients underwent sentinel node biopsy (Breslow thickness > or = 0.75 mm). Interferon was used as an adjuvant therapy in patients with positive regional lymph nodes. One patient with melanoma suffered a recurrence. Malignant skin tumors are rare in children. In accordance with previously published data, malignant melanoma was the most frequent tumor in our study. Epithelial tumors were less common and were all associated with an underlying predisposing condition.


A comparative study of rural athletes of four states of India.
In the present study 22 rural athletes of four different states of India have been studied for 23 anthropometric parameters--weight, height, sitting height, six diameters, six circumferences and eight skin and subcutaneous tissue folds. Rural athletes of Punjab and Haryana have been found to be comparable pertaining to all the anthropometric variables. Athletes of Madhya Pradesh show minimum values for most of the variables. The order of best anthropometry is athletes of Punjab and Haryana followed by Assam and Madhya Pradesh. Athletes of Madhya Pradesh are lacking behind in all the parameters except skin and subcutaneous tissue folds as compared to athletes of Assam.


A deep convolutional neural network for bleeding detection in Wireless Capsule Endoscopy images.
Wireless Capsule Endoscopy (WCE) is a standard non-invasive modality for small bowel examination. Recently, the development of computer-aided diagnosis (CAD) systems for gastrointestinal (GI) bleeding detection in WCE image videos has become an active research area with the goal of relieving the workload of physicians. Existing methods based primarily on handcrafted features usually give insufficient accuracy for bleeding detection, due to their limited capability of feature representation. In this paper, we present a new automatic bleeding detection strategy based on a deep convolutional neural network and evaluate our method on an expanded dataset of 10,000 WCE images. Experimental results with an increase of around 2 percentage points in the Fi score demonstrate that our method outperforms the state-of-the-art approaches in WCE bleeding detection. The achieved Fi score is of up to 0.9955.


Muscle echo intensity of abdominal wall in Parkinson's disease and healthy controls: a cross sectional study.
The aim of this study was to describe the differences between abdominal wall muscles echo intensity (EI) in PD patients and healthy controls. Forty-three consecutive PD patients (25 males and 18 females, age 73.7 ± 7.1, and 42 controls without neurological diseases (22 males, 20 females, age 69.8 ± 6.0) participated in this cross-sectional study. The clinical assessment included the following: IPAQ (International Physical Activity Questionnaire), Hoehn Yahr score, plumb line distance from the spinous process of C7, kyphosis apex, and spinous process of L3 and S1. A real-time ultrasound B-scanner (system MyLab40 by Esaote, Genoa, Italy) was used to obtain muscle images of the right and left biceps brachii (BB), external (EO), and internal oblique (IO) and rectus abdomen (RA). Heckmatt scale and measure of EI through ImageJ software were used to assess muscle quality. When considering the Heckmatt score, the RA and BB did not significantly differ between PD and control patients, while there was a significant difference for right (p < 0.01) and left (p = 0.02) IO muscles. There was no difference among EI values of the RA, IO, and BB between PD and control patients. Echo intensity of abdominal wall muscles (rectus abdominis, internal oblique) and biceps brachii did not differ between Parkinsonian patients and healthy subjects. We did not found ultrasound useful in disease evolution assessment or in early diagnosis of postural disorders.


Imperfect information on physical activity and caloric intake.
Using the National Health and Nutrition Examination Survey Data, I find that individuals who overestimate their activity level by one standard deviation consume 40-60 extra calories per day, or enough to gain five pounds per year. These extra calories are composed mainly of sugar and carbohydrate, and are concentrated among individuals in the 75th and 90th percentiles of caloric intake. The link between overeating and inaccurate estimation of physical activity is strongest among less educated individuals and individuals with high variance in their physical activity, suggesting that imperfect recall or information gaps explain at least part of the relationship of interest. These results imply the existence of a necessary condition for physical activity-based information treatments to be effective in changing health behaviors and obesity rates.


Increased proliferation of a human breast carcinoma cell line by recombinant interleukin-2.
Two adenocarcinoma cell lines, Breast M25-SF and Breast M, were established from tumor tissue resected surgically from a patient with breast cancer. One, Breast M25-SF, expresses interleukin-2 receptor (IL-2R) on the cell surface and the other, Breast M does not. The effects of recombinant interleukin-2 (rIL-2) on the proliferation of these cell lines were investigated. The growth of Breast M25-SF was significantly promoted by rIL-2 ranging from 1.25 U/ml to 640 U/ml. Anti-CD25 (Tac) antibody significantly blocked the growth enhancement of Breast M25-SF by rIL-2. Breast M, however, did not respond to rIL-2. To confirm more directly the promotion of Breast M25-SF growth by rIL-2, cloning of IL-2 responders from parent Breast M25-SF cells was carried out by limiting dilution without feeder cells in 96-well microplates. No colony formation was found in 24 wells without rIL-2. Eleven, 13 and 6 clones were established from groups of 24 wells containing rIL-2 at 200, 20 and 2 U/ml respectively. All of the clones expressed IL-2R and respond to rIL-2. By using a sensitive polymerase chain reaction technique, we demonstrated that Breast M25-SF but not Breast M expressed IL-2 mRNA, and IL-2 secretion from Breast M25-SF but not Breast M was also confirmed by radioimmunoassay. These findings suggest a role for IL-2 in autocrine support of Breast M25-SF growth. IL-2 may play an important role in the growth control of breast carcinoma cells.


Novel compact hard x-ray spectrometer with MCps counting rate capabilities for runaway electron measurements on DIII-D.
A novel compact spectrometer optimized for the measurement of hard x rays generated by runaway electrons is presented. The detector is designed to be installed in the fan-shaped collimator of the gamma-ray imager diagnostic at the DIII-D tokamak. The spectrometer is based on a 1 × 1 cm2 cerium doped yttrium aluminum perovskite scintillator crystal coupled with a silicon photomultiplier. The detector dynamic energy range is in excess of 10 MeV, with an energy resolution of ∼10% at 661.7 keV. The fast detector signal (≈70 ns full width at half maximum) allows for operation at counting rates in excess of 1 MCps. The gain stability of the system can be monitored in real time using a light-emitting diode embedded in the instrument. The detector is expected to be deployed in the forthcoming DIII-D runaway electron experimental campaign.


Step-economical synthesis of the marine ascidian antibiotics cadiolide A, B, and D.
A concise, modular and efficient synthesis of the title natural products is reported. Prominent steps include (i) one-pot assembly of a key β-aryl-α-benzoylbutenolide building block by regiocontrolled "click-unclick" oxazole-ynone Diels-Alder cycloaddition/cycloreversion and ensuing 2-alkoxyfuran hydrolysis and (ii) a protecting group-free vinylogous Knoevenagel condensation enabling rapid access to cadiolides A, B, and D from a common precursor.


Detection and treatment of early cancer in high-risk populations.
In this paper we describe how to more efficiently detect and treat early gastric cancer (EGC) in high-risk populations. For detection, we first assess the value of known risk factors from the viewpoint of availability for cancer screening. Serum pepsinogen appears to be the most useful and realistic of the factors examined, although its adequacy needs to be assessed in high-risk populations other than those in Japan. Helicobacter pylori infection is known to be a universal risk factor (or gastric carcinogen), and several interventional studies have recently shown positive results. However, H. pylori infection can be eradicated from at-risk populations, thereby decreasing its availability for cancer screening. Smokers are thought to be at risk epidemiologically, but the efficacy of screening in this population has yet to be elucidated, and further studies are warranted. Gender and aging can be risk factors in Japanese populations; male gender and old age are predominant in the intestinal type of carcinoma which is dominant in Japan, although this is not the case in the West. As for early diagnosis of cancer, only endoscopy can be commonly used for the detection of gastritis-like EGC, seen as a faint mucosal irregularity or discoloration. To make early diagnosis more accurate, it is indispensable to carry out detailed endoscopy together with careful scrutiny of the mucosa using dye-spraying techniques. The remarkable progress of early diagnosis in Japan prompted the endoscopic treatment for less invasive EGCs. The first success was with endoscopic mucosal resection (EMR). Although convenient, its therapeutic efficacy is inadequate, particularly for larger lesions. Endoscopic submucosal dissection (ESD) has no limitation on resection size and is expected to replace surgery, although it needs a high level of skill and there are several technical problems to be solved.


Effects of omeprazole or cola beverage on the pharmacokinetics of oral DA-8159, a new erectogenic, in rats.
The changes in pharmacokinetics of DA-8159 by omeprazole with respect to inhibition of CYP3A1/2 in rats were evaluated. After oral administration of DA-8159 at dose of 30 mg/kg to rats pretreated with oral omeprazole at 30 mg/kg for 1 week, the total area under the plasma concentration-time curve from time zero to time infinity (AUC) of DA-8159 was significantly greater (37.5% increase) than that in control rats. This could be due to inhibition of metabolism of DA-8159 by inhibition of CYP3A1/2 by omeprazole. The AUC(DA-8164 (a metabolite of DA-8159))/AUC(DA-8159) ratio was also smaller (32.4% decrease) with omeprazole. After oral administration of DA-8159 at a dose of 30 mg/kg to rats without or with cola beverage, the pharmacokinetic parameters of DA-8159 and DA-8164 were not significantly different between two groups of rats. This suggested that cola beverage did not have any considerable effects on CYP3A1/2 in rats.


5-hydroxymethylcytosine-mediated DNA demethylation in stem cells and development.
The pursuit of DNA demethylation has a colorful history, but it was not until 2009 that the stars of this story, the Ten-eleven-translocation (Tet) family of proteins, were really identified. Tet proteins convert 5-methylcytosine to 5-hydroxymethylcytosine (5hmC), which can be further oxidized to 5-formylcytosine and 5-cyboxycytosine by Tet proteins to achieve DNA demethylation. Recent studies have revealed that 5hmC-mediated DNA demethylation can play essential roles in diverse biological processes, including development and diseases. Here, we review recent discoveries in 5hmC-mediated DNA demethylation in the context of stem cells and development.


Integrating Virtual Teaching in a New Era of Medical Education: Lessons from a Neurology Course.
The COVID-19 pandemic has led to a sudden shift toward virtual learning in neurology education, which presents challenges for educators. However, virtual learning is here to stay for three key reasons: demand among students, ease of dissemination, and potential to improve educational quality. Despite challenges, educators can teach effectively using appropriate virtual tools and methods, with innovative approaches that will ultimately lead to sustained improvements in neurology education. Here, we aim to help educators effectively incorporate virtual instruction into their "new normal" by offering practical, evidence-based tips for balancing in-person and virtual learning, selecting the appropriate tools and methods for virtual teaching, and creating a supportive virtual learning environment. Using a systematic approach, educators can identify specific, achievable goals, determine the content's scope, appropriate assessments, select appropriate teaching methods, and create the session schedule and materials. Here we described evidence-based strategies for best practices, developing virtual material, and creating the appropriate virtual learning environment.


Biochemical changes in Hyalomma (Hyalomma) dromedarii (Acari: Ixodidae) embryos and effect of 20-hydroxyecdysone applied to the mother.
Changes in DNA, RNA, total lipids, phospholipids, and proteins and the activity of certain enzymes and pattern of their isozymes were studied in Hyalomma dromedarii Koch during embryogenesis. Total proteins fluctuated with a net increase (P less than 0.05) on day 20. Total lipids increased during the first half of embryogenesis and then declined with a net decrease to about 60% of the original level. Total phospholipids decreased to half this original level. DNA content increased greatly during cleavage, gastrulation, and organogeny and RNA increased during cleavage and blastula formation. Glucose-6-phosphate dehydrogenase (G6PDH) activity decreased (P less than 0.05), reaching 20% of its original level on day 12. Malic acid dehydrogenase (MDH) activity remained nearly unchanged throughout embryogenesis. Lactic acid dehydrogenase (LDH) activity increased greatly, with the highest level on day 14 with no further change. Acetylcholinesterase (AchE) activity increased greatly during the first 12 d, with no significant change thereafter. Acid (ACP) and alkaline (ALP) phosphatase activity increased during the first 12 d and declined returning to the original level on day 20. Seven AchE and 5 LDH isozymes were detected during different embryogenesis stages. Two MDH, 2 ACP, 1 ALP, and 2 G6PDH isozymes were detected throughout embryogenesis. Treating the mother with 20-hydroxyecdysone was associated with increases in protein and RNA contents and G6PDH and AchE activity and with decreases in ACP and ALP activity in the embryos.


Maturation of rat visual cortex. I. A quantitative study of Golgi-impregnated pyramidal neurons.
The early postnatal maturation of pyramidal neurons in layers II/III and V of the rat visual cortex has been examined in an attempt to elucidate some determinants of their mature morphology. Three indices have been quantified using Golgi-impregnated pyramidal cells; densities of spines along apical dendrites, numbers of primary based dendrites and volumes of cell bodies. The mean density of spines on the apical dendrites of all pyramidal neurones increases in a stepwise fashion. The first significant increase occurs between days 6 and 9 and the second, between days 12 and 15; these increases may correlate with the arrival of geniculate afferents and with the opening of the eyes, respectively. In younger animals, the distribution of spines along the apical shafts is relatively even, whereas in older animals, spine density increases significantly over the proximal 125 micrometers portion and is relatively constant over the remaining distal portion. By day 21, layer V pyramidal cells have acquired more primary basal dendrites and larger somatic volumes than layer II/III cells. Furthermore, as the cells mature the rate of change in these characteristics are significantly different for neurons in layer II/III and in layer V. For both cell populations, the mean number of primary basal dendrites increases to a maximum before falling to a steady level, but for neurons in layer V, the maximum is higher and attained three days earlier than for layer II/III cells. Moreover, the increase in volume of cell bodies of layer V neurons begins three days before that of layer II/III cells. This three day phase difference in maturation may reflect the cell birth dates, since autoradiographic evidence indicates that layer V pyramidal neurons reach the cortical plate about three days prior to those which occupy layer II/III in the adult visual cortex.


Estrogen effects on the urethra: beneficial effects in women with genuine stress incontinence.
The urethra, which originates from the urogenital sinus, is under the influence of estrogen just like the vagina. The concentration of estrogen receptors in the urethral mucosa is similar to that of the vaginal mucosa. Estrogen deprivation will result in atrophic urethritis and sometimes urinary incontinence, and estrogen replacement therapy may reverse this trend. Estrogens have been shown to increase urethral pressure in up to 30 per cent of women and to significantly improve or cure stress urinary incontinence in many cases. Adding alpha-sympathomimetic drugs to estrogens may further improve symptoms in women with stress incontinence. It seems that vaginal estrogens have more beneficial effect on the urethra, compared with the oral medication, although prospective control studies have not always supported these findings. Overall, it seems that estrogens have beneficial effects on urethral function in women with postmenopausal stress incontinence, although more prospective randomized control studies are needed to assess the effect of estrogens on the lower urinary tract.


Efficacy of Granisetron versus Sufentanil on Reducing Myoclonic Movements Following Etomidate: Double-blind, randomised clinical trial.
This study aimed to reduce the intensity of myoclonus movements by comparing the effectiveness of granisetron and sufentanil in reducing the intensity of etomidate-induced myoclonic movements. Etomidate-induced myoclonus occurs in up to 85% of patients under general anaesthesia. This type of myoclonus can induce significant clinical and economic problems in patients with special conditions. This double-blind randomised clinical trial study consisted of 96 adult patients recruited between January and July 2021 from Mashhad University of Medical Sciences, Mashhad, Iran. Using block randomisation, subjects were divided into three groups of 32 patients: the group receiving granisetron 40 μg/kg (group G), the group receiving sufentanil 0.2 μg/kg (group S) and the control group who did not receive the pretreatment (group C). Patients received these medications as pretreatments 120 seconds before induction with etomidate. After the injection of etomidate with a dose of 0.3 mg/kg, the incidence of myoclonus was evaluated. After evaluating the myoclonus, the full dose of narcotics (fentanyl 1 μg/kg) and muscle relaxants (atracurium 0.5 mg/kg) were administered to patients and a suitable airway was established for them. The findings indicated that granisetron reduced the intensity and incidence of myoclonic movements more than sufentanil. In addition, myoclonic movements were observed at a significantly higher intensity in the control group (P = 0.001). The results obtained from the current study indicate that granisetron and sufentanil as pretreatments are effective for reducing myoclonus in patients.


Visualized thermal history sensor based on the rare-earth-doped zirconia.
Temperature is one of the most fundamental parameters, and its accurate measurement is critically important for thermal systems. Despite substantial progress in temperature measuring techniques, design and fabrication of a reliable thermal history sensor, which can remember thermal events, still remain a significant challenge. In this Letter, we propose and experimentally demonstrate a new thermal history sensor based on the rare-earth-activated and yttria-stabilized zirconia (YSZ). This material candidate exhibits strong heat-treatment-dependent upconversion emission color. The structure and optical characterizations indicate that the phenomenon originates from the cooperative effects of multiple physical parameters, including crystallinity, crystal size, and the quantity of residual OH. This allows us to achieve excellent linear relationship between the heat-treatment temperature and the intensity ratio of the green and red emission band over a wide temperature range from 800°C to 1350°C. Thus, the thermal history information can be directly judged based on the emission color. These results provide a major step forward in expanding the scope of thermal history sensor materials.


Pathways for Neuroimaging of Neonatal Stroke.
To provide consensus-based, suggested imaging protocols to facilitate the accurate and timely diagnosis of a neonate with symptoms concerning for stroke. The Writing Group, an international collaboration of pediatric neurologists and neuroradiologists with expertise in perinatal and childhood stroke, participated in a series of pediatric stroke neuroimaging symposia. These discussions, in conjunction with extensive literature review, led to a consensus for imaging protocols to guide practitioners in the diagnosis of neonatal stroke subtypes as defined by the National Institute of Neurological Disorders and Stroke Common Data Elements. The epidemiology, clinical presentation, and associated risk factors for arterial ischemic stroke, cerebral sinovenous thrombosis, and hemorrhagic stroke are reviewed, with a focused discussion regarding the role of neuroimaging for each subtype. In a neonate with suspected stroke, magnetic resonance imaging is the preferred modality, given the lack of X-irradiation, superior anatomic resolution, and sensitivity for acute ischemia. Core recommended sequences include diffusion-weighted imaging and apparent diffusion coefficient mapping to diagnose acute ischemia, gradient-recalled echo or susceptibility-weighted imaging to detect intracranial blood and its breakdown products, and T1- and T2-weighted imaging to assess for myelination, extra-axial blood, and edema. Magnetic resonance angiography of the brain may be useful to detect vascular abnormalities, with venography if venous sinus thrombosis is suspected. The application of more novel sequences, as well as the utility of follow up-imaging, is also discussed.


Safety of non‑peptide thrombopoietin receptor agonists in patients with immune thrombocytopenia: A systematic review and meta‑analysis of short‑term double‑blind randomized clinical trials.
The aim of the present study was to analyze the safety of non-peptide thrombopoietin receptor agonists (TPO-RAs) for immune thrombocytopenia (ITP) treatment. All studies reporting adverse events (AEs) in relation to ITP treatment with eltrombopag, avatrombopag, and hetrombopag were retrieved from PubMed, Web of Science, and Embase databases. RevMan 5.4.1 was used for meta-analysis, heterogeneity and bias analyses. A total of 1,078 patients from seven eligible studies were enrolled. In the enrolled clinical trials, the double-blind period was between 6 weeks and 6 months. The results revealed that the chances of any AEs [relative risk (RR)=1.16; 95% confidence interval (CI), 0.90-1.51; I2=78%; P=0.26], grade 3/4 AEs (RR=1.07; 95% CI, 0.63-1.80; I2=0%; P=0.81), elevated transaminase levels (RR=1.09; 95% CI, 0.68-1.74; I2=0%; P=0.72), thrombosis (RR=1.92; 95% CI, 0.55-6.66; I2=0%; P=0.31) and cataracts (RR=0.83; 95% CI, 0.38-1.83; I2=0%; P=0.65) were not significantly higher in patients with ITP that received non-peptide TPO-RAs compared with patients with ITP treated with a placebo. The present study indicated that non-peptide TPO-RAs were relatively safe for patients with ITP, at least within 6 months of administration.


Faecal fat and faecal weight: reproducibility and diagnostic efficiency of various regimens.
The reproducibility of measuring 3-day faecal fat and weight in outpatients, in inpatients served a fixed diet, and in intake-excretion studies was estimated from 64 duplicate measurements. Qualitatively, no significant difference between the results of the three regimens was found. Quantitatively, however, the more controlled the regimen, the better the reproducibility. The diagnostic efficiency of measuring faecal fat was estimated from comparison with the other clinical findings. No significant difference between the three regimes was found, the overall diagnostic efficiency being 83% (95% confidence limits, 71-91%). The inconvenience, the uncontrollable sources of error, and the difficulties in obtaining quantitative information still make measurement of faecal fat and weight inexpedient as a clinical test.


Hepatotoxicity and molecular aspects of hepatocyte function in primary culture.
1. The application of primary cultures of hepatocytes in testing for hepatotoxicity of drugs is reviewed. 2. Hepatotoxicity results principally from the biotransformation of toxic agents. This process is very complex and specific and involves a powerful system of multigenic isozyme families for both phase I and phase II drug metabolizing reactions. Many of the isozymes are specifically expressed in the liver in relation to the maturation or differentiation state, and are specifically induced, possibly through a complex temporally programmed gene regulation. 3. This highly specific, coordinated, molecular regulation is difficult to maintain in vitro. Isolation of hepatocytes induces a prompt differential decline of liver-specific gene transcription, which leads to preferential loss of the most specific functions, including those of the drug metabolizing isozymes, whereas repair of cell damage remains active. 4. The use of serum-free, hormonally defined media stabilizes specific hepatic functions, but not transcriptional activity, for 4-5 days. Defined media retain active DNA replication but do not permit clonal growth of hepatocytes. Co-culturing hepatocytes with primitive biliary cells prolongs cell survival and their functional capacities for several weeks, including some of the transcriptional activity.


[Surgical treatment of a pregnant female with AVM hemorrhage].
Hemorrhages from arteriovenous malformations (AVMs) in pregnant females are rare, but they are known to lead to high maternal and infant mortality. There are no standards for AVM treatment in pregnant females. Many authors believe that AVM resection before delivery improves the prognosis for life and health of the mother and fetus. In this paper, we present a case of successful surgical treatment of a female patient with AVM hemorrhage at 20 weeks and address management issues of these patients.


An Overview of Antimicrobial Activity of Lysozyme and Its Functionality in Cheese.
Due to the concern of consumers about the presence of synthetic preservatives, researchers and food manufacturers have recently conducted extensive research on the limited use of these preservatives and the introduction and use of natural preservatives, such as herbal extracts and essential oils, bacteriocins, and antimicrobial enzymes. Lysozyme is a natural enzyme with antimicrobial activity that has attracted considerable attention to be potentially utilized in various industries. Since lysozyme is an intrinsic component of the human immune system and has low toxicity; it could be considered as a natural antimicrobial agent for use in food and pharmaceutical industries. Lysozyme exerts antimicrobial activity against microorganisms, especially Gram-positive bacteria, by hydrolyzing 1,4-beta-linkages between N-acetylmuramic acid and N-acetylglucosamine in the cell wall. In addition, increased antimicrobial activity of lysozyme against Gram-negative bacteria could be achieved by the modification of lysozyme through physical or chemical interactions. Lysozyme is presented as a natural preservative in mammalian milk and can be utilized as a bio-preservative in dairy products, such as cheese. Both bacteria and fungi can contaminate and spoil the cheese; especially the one that is made traditionally by raw milk. Furthermore, uncontrolled and improper processes and post-pasteurization contamination can participate in the cheese contamination. Therefore, besides common preservative strategies applied in cheese production, lysozyme could be utilized alone or in combination with other preservative strategies to improve the safety of cheese. Hence, this study aimed to review the antimicrobial properties of lysozyme as natural antimicrobial enzyme and its functionality in cheese.


THE EFFECTIVE SIZE OF A HIERARCHICALLY STRUCTURED POPULATION.
A knowledge of the effective size of a population (Ne ) is important in understanding its current and future evolutionary potential. Unfortunately, the effective size of a hierarchically structured population is not, in general, equal to the sum of its parts. In particular, the inbreeding structure has a major influence on Ne . Here I link Ne to Wright's hierarchical measures of inbreeding, FIS and FST , for an island-structured population (or metapopulation) of size NT . The influence of FST depends strongly on the degree to which island productivity is regulated. In the absence of local regulation (the interdemic model), interdemic genetic drift reduces Ne . When such drift is combined with local inbreeding under otherwise ideal conditions, the effects of FIS and FST are identical: increasing inbreeding either within or between islands reduces Ne , with Ne = NT /[(1 + FIS )(1 + FST ) - 2FIS FST ]. However, if islands are all equally productive because of local density regulation (the traditional island model), then Ne = NT /[(1 + FIS )(1 -FST )] and the effect of FST is reversed. Under the interdemic model, random variation in the habitat quality (and hence productivity) of islands act to markedly decrease Ne . This variation has no effect under the island model because, by definition, all islands are equally productive. Even when no permanent island structure exists, spatial differences in habitat quality can significantly increase the overall variance in reproductive success of both males and females and hence lower Ne . Each of these basic results holds when other nonideal factors are added to the model. These factors, deviations from a 1:1 sex ratio, greater than Poisson variance in female reproductive success, and variation in male mating success due to polygynous mating systems, all act to lower Ne . The effects of male and female variance on Ne have important differences because only females affect island productivity. Finally, it is noted that to use these relationships, FIS and FST must be estimated according to Wright's definition (and corrected to have a zero expectation under the null model). A commonly used partitioning (θ, θg ) can be biased if either island size or the number of islands is small.


Hwangdonia seohaensis gen. nov., sp. nov., a member of the family Flavobacteriaceae isolated from a tidal flat sediment.
A Gram-staining-negative, aerobic, non-flagellated, non-gliding and rod-shaped bacterial strain, HD-3(T), was isolated from a tidal flat sediment of Hwangdo in the Yellow Sea, South Korea. Strain HD-3(T) grew optimally at pH 7.0-8.0, at 30 °C and in the presence of 2-3% (w/v) NaCl. Phylogenetic trees based on 16S rRNA gene sequences revealed that strain HD-3(T) joined the cluster comprising the type strains of Jejuia pallidilutea and Hyunsoonleella jejuensis. Strain HD-3(T) exhibited 16S rRNA gene sequence similarity values of 93.8% to each of the type strains of J. pallidilutea and Hyunsoonleella jejuensis. Strain HD-3(T) contained MK-6 as the only menaquinone and iso-C(15:0), iso-C(15:1) G, iso-C(17:0) 3-OH and iso-C(15:0) 3-OH as the major fatty acids. The polar lipid profile of strain HD-3(T), which contained phosphatidylethanolamine and one unidentified lipid as major components and one unidentified phospholipid as a significant component, differed slightly from those of the type strains of J. pallidilutea and Hyunsoonleella jejuensis. The DNA G+C content of strain HD-3(T) was 42.3 mol%. Differential phenotypic and chemotaxonomic properties and phylogenetic data of strain HD-3(T) demonstrated that this strain is distinguishable from J. pallidilutea and Hyunsoonleella jejuensis. On the basis of the data presented, strain HD-3(T) is considered to represent a novel genus and species, for which the name Hwangdonia seohaensis gen. nov., sp. nov. is proposed. The type strain is HD-3(T) ( =KCTC 32177(T) =CCUG 63246(T)).


Nomograms for clinically localized prostate cancer. Part I: radical prostatectomy.
Many nomograms are currently available for patients' and physicians' use for prediction of pathologic stage based on preoperative parameters, such as prostate-specific antigen (PSA) level, clinical stage (tumor, node, metastasis), and Gleason score from prostate biopsy specimen. Based on the probability of final pathologic stage as well as patient comorbidity and life expectancy, patients and physicians can decide whether definitive local therapy, systemic therapy, or palliative therapy would be most appropriate. Nomograms have also been developed based on preoperative parameters for prediction of biochemical recurrence-free survival outcome following surgery. These nomograms can help patients understand the long-term cancer cure rates after radical prostatectomy.


[Cytogenetic effects on blood lymphocytes of cosmonauts after low doses of space radiation].
Cytogenetic changes in cultures of blood lymphocytes from 37 cosmonauts returned from space flights of varying duration were analyzed. Prolonged stay in space was shown to increase numbers of stable and unstable chromosomal aberrations. Frequency of dicentric and centric rings depends on flight duration, as well as values of accumulated dose from and dose rate of space radiation. Egress into open space leads to an additional growth in the number of chromosomal aberrations. It was found that frequency of chromosomal aberrations in blood lymphocytes remains altered even after several years of cosmonaut's return from space flight. Based on the counts of symmetric translocations obtained with the FISH-technique, mean dose from space radiation following the maiden prolonged space flight amounted to 110 mGy which is in agreement with the biodosimetric data about frequency of dicentric and centric rings (140 mGy).


Effect of Calcination Temperatures on Surface Properties of Spinel ZnAl2O4 Prepared via the Polymeric Citrate Complex Method-Catalytic Performance in Glycerolysis of Urea.
In this study, we investigated urea glycerolysis over ZnAl2O4 catalysts that were prepared by using a citrate complex method and the influence of calcination temperatures on the surface properties of the prepared catalysts by varying the calcination temperature from 550 °C to 850 °C. As the reciprocal substitution between Al3+ and Zn2+ cations led to the formation of a disordered bulk ZnAl2O4 phase, different calcination temperatures strongly influenced the surface properties of the ZnAl2O4 catalysts, including oxygen vacancy. The increase in the calcination temperature from 550 °C to 650 °C decreased the inversion parameter of the ZnAl2O4 structure (from 0.365 to 0.222 for AlO4 and 0.409 to 0.358 for ZnO6). The disordered ZnAl2O4 structure led to a decrease in the surface acidity. The ZnAl2O4-550 catalyst had a large specific surface area, along with highly disordered surface sites, which increased surface acidity, resulting in a stronger interaction of the Zn NCO complex on its surface and an improvement in catalytic performance. Fourier transform infrared and thermogravimetric analysis results of the spent catalysts demonstrated the formation of a greater amount of a solid Zn NCO complex over ZnAl2O4-550 than ZnAl2O4-650. Consequently, the ZnAl2O4-550 catalyst outperformed the ZnAl2O4-650 catalyst in terms of glycerol conversion (72%), glycerol carbonate yield (33%), and byproduct formation.


Dedifferentiated Liposarcoma in a Giant Esophageal Polyp: A Case Report and Review of the Literature.
Soft tissue sarcomas represent an extremely rare cause of esophageal masses, and undifferentiated sarcomas are rarer. The proportion of dedifferentiated liposarcomas (DDL) is even lower. The case of a 58-year-old male who complained of dysphagia and was found to have an 18-centimeter long esophageal mass/polyp on esophagogastroduodenoscopy is presented. The lesion was resected endoscopically and a diagnosis of DDL was confirmed by fluorescence in situ hybridization. Due to its rarity, the treatment experience with esophageal DDLs is limited. However, based on our experience, endoscopic resection of the lesion can be considered as the treatment of choice when feasible. We performed a review of the literature to identify and analyze similar reported cases.


Chronic Treatment with Morphine Disrupts Acute Kinase-Dependent Desensitization of GPCRs.
Based on studies using mutations of the µ-opioid receptor (MOR), phosphorylation of multiple sites on the C-terminus has been recognized as a critical step underlying acute desensitization and the development of cellular tolerance. The aim of this study is to explore which kinases mediate desensitization of MOR in brain slices from drug-naïve and morphine-treated animals. Whole-cell recordings from locus coeruleus neurons were made, and the agonist-induced increase in potassium conductance was measured. In slices from naïve animals, pharmacological inhibition of G-protein receptor kinase (GRK2/3) with compound 101 blocked acute desensitization. Following chronic treatment with morphine, compound 101 was less effective at blocking acute desensitization. Compound 101 blocked receptor internalization in tissue from both naïve and morphine-treated animals, suggesting that GRK2/3 remained active. Kinase inhibitors aimed at blocking protein kinase C and c-Jun N-terminal kinase had no effect on desensitization in tissue taken from naïve animals. However, in slices taken from morphine-treated animals, the combination of these blockers along with compound 101 was required to block acute desensitization. Acute desensitization of the potassium conductance induced by the somatostatin receptor was also blocked by compound 101 in slices from naïve but not morphine-treated animals. As was observed with MOR, it was necessary to use the combination of kinase inhibitors to block desensitization of the somatostatin receptor in slices from morphine-treated animals. The results show that chronic treatment with morphine results in a surprising and heterologous adaptation in kinase-dependent desensitization. SIGNIFICANCE STATEMENT: The results show that chronic treatment with morphine induced heterologous adaptations in kinase regulation of G protein coupled receptor (GPCR) desensitization. Although the canonical mechanism for acute desensitization through phosphorylation by G protein-coupled receptor kinase is supported in tissue taken from naïve animals, following chronic treatment with morphine, the acute kinase-dependent desensitization of GPCRs is disrupted such that additional kinases, including protein kinase C and c-Jun N-terminal kinase, contribute to desensitization.


Melatonin Decreases Pulmonary Vascular Remodeling and Oxygen Sensitivity in Pulmonary Hypertensive Newborn Lambs.
Background: Chronic hypoxia and oxidative stress during gestation lead to pulmonary hypertension of the neonate (PHN), a condition characterized by abnormal pulmonary arterial reactivity and remodeling. Melatonin has strong antioxidant properties and improves pulmonary vascular function. Here, we aimed to study the effects of melatonin on the function and structure of pulmonary arteries from PHN lambs. Methods: Twelve lambs (Ovis aries) gestated and born at highlands (3,600 m) were instrumented with systemic and pulmonary catheters. Six of them were assigned to the control group (CN, oral vehicle) and 6 were treated with melatonin (MN, 1 mg.kg-1.d-1) during 10 days. At the end of treatment, we performed a graded oxygenation protocol to assess cardiopulmonary responses to inspired oxygen variations. Further, we obtained lung and pulmonary trunk samples for histology, molecular biology, and immunohistochemistry determinations. Results: Melatonin reduced the in vivo pulmonary pressor response to oxygenation changes. In addition, melatonin decreased cellular density of the media and diminished the proliferation marker KI67 in resistance vessels and pulmonary trunk (p < 0.05). This was associated with a decreased in the remodeling markers α-actin (CN 1.28 ± 0.18 vs. MN 0.77 ± 0.04, p < 0.05) and smoothelin-B (CN 2.13 ± 0.31 vs. MN 0.88 ± 0.27, p < 0.05). Further, melatonin increased vascular density by 134% and vascular luminal surface by 173% (p < 0.05). Finally, melatonin decreased nitrotyrosine, an oxidative stress marker, in small pulmonary vessels (CN 5.12 ± 0.84 vs. MN 1.14 ± 0.34, p < 0.05). Conclusion: Postnatal administration of melatonin blunts the cardiopulmonary response to hypoxia, reduces the pathological vascular remodeling, and increases angiogenesis in pulmonary hypertensive neonatal lambs.These effects improve the pulmonary vascular structure and function in the neonatal period under chronic hypoxia.


Quality of medical service, patient satisfaction and loyalty with a focus on interpersonal-based medical service encounters and treatment effectiveness: a cross-sectional multicenter study of complementary and alternative medicine (CAM) hospitals.
Treatment effectiveness holds considerable importance in the association between service quality and satisfaction in medical service studies. While complementary and alternative medicine (CAM) use grows more prominent, comprehensive evaluations of the quality of medical service at CAM-oriented hospitals are scarce. This study assesses the quality of medical services provided at a CAM-oriented hospital of Korean medicine using the service encounter system approach and analyzes the influence of treatment effectiveness on patient loyalty. A survey study using one-on-one interviews was conducted using a cross-sectional design in outpatients visiting one of fifteen Korean medicine facilities located throughout Korea. A total of 880 surveys were completed from June to July, 2014, and 728 surveys were included in the final analysis after excluding incomplete or incorrect questionnaires. The reliability and validity of the surveys was confirmed using Cronbach's alpha coefficient and confirmatory factor analysis, and a structural equation modeling analysis was performed to verify causality and association between factors (quality of medical service, treatment effectiveness, patient satisfaction, and intent to revisit). The measured factors of physician performance and quality of service procedures had a positive effect on treatment effectiveness. The impression of the facilities and environment directly impacted satisfaction rates for interpersonal-based medical service encounters, while treatment effectiveness positively affected satisfaction regarding quality of medical service. However, treatment effectiveness had a more significant effect on satisfaction compared to facilities and environment, and it indirectly affected satisfaction and directly influenced intent to revisit. Treatment effectiveness and satisfaction both positively influenced intent to revisit. The importance of treatment effectiveness should be recognized when examining quality of medical services, and we hope that these findings may contribute to future studies.


The development of the notochord in the chick embryo, studied by scanning and transmission electron microscopy.
The notochord of the chick embryo between stages 5 and 23 inclusive has been studied by scanning electron microscopy, supplemented by transmission electron microscopy. Three main phases of development are described, and these have been designated: bilaminar; rod-like, unvacuolated; rod-like and vacuolated. The changes in shape of the organ from bilaminar to rod-like is accompanied by changes in the shape, orientation and position of the cells, an increase in the complexity of the cell contacts, and the laying down of a basal lamina. The change from the unvacuolated to the vacuolated phase is accompanied by increasing complexity within the cytoplasm. Most of the vacuoles are intracellular and appear empty though some contain a granular material. The notochordal sheath appears to be secreted by the notochordal cells and fine fibrillar material has been seen in the intercellular spaces. By stage 23, most of the notochordal cells have become so highly vacuolated that the cytoplasm has become closely packed around the nucleus.


Comparison of sub mucosal diathermy and partial resection of Inferior turbinate in the treatment of symptomatic nasal valve blockage.
to evaluate the efficacy of sub mucosal diathermy (SMD) and partial resection of inferior turbinate (PRIT) in the treatment of symptomatic enlarged inferior turbinates. prospective. Forty patients of age group 18 -56 yrs with symptomatic enlarged inferior turbinates had given choices for SMD and PRIT. All the patients had history of failed medical treatment. Each twenty patients underwent SMD (group I), PRIT (group II), five pt of gr. I had to have anterior nasal packing after surgery for bleeding. Three pt complained of excessive rhinorrhoea for first 2 weeks while 3 pt of Group 1 complained of nasal blockage for 1 week even after intervention. In group 2, 5 pt had to have re-anterior nasal packing after pack removal. Both groups followed up for 6 months. Nine patients were lost in follow up, so excluded from the study. Following 6 months of follow up, 6 patient of gr. I had recurrence with nasal blockage and in gr. II none had recurrence. PRIT is better than SMD in long course; nevertheless it should be reserved for failed SMD, not as a primary option.


Convection-enhanced delivery to achieve widespread distribution of viral vectors: Predicting clinical implementation.
Convection-enhanced delivery (CED) has been introduced to overcome the inability of many pharmacological agents to cross the blood-brain barrier, making these agents potentially effective in situ and suitable for the treatment of brain disorders. To achieve CED, drugs are pumped continuously through stereotactically placed catheters directly into the brain, or into or within the vicinity of a tumor mass. This medical technology has been applied to the local delivery of small-molecule drugs, including standard chemotherapeutics, and novel experimental targeted drugs, including targeted cytotoxins. When administered by an experienced clinician, the CED of a molecularly targeted cytotoxin has resulted in a significantly better outcome in patients with recurrent glioblastoma multiforme (GBM). More recent gene therapy clinical trials have also demonstrated that such treatments impact on the course of the disease when administered using CED. The use of CED to administer gene therapy for brain neoplasms may improve the efficacy of this treatment. However, CED is under development, and issues such as the type of catheters to use and their placement, as well as the pharmacological formulation and stability of drugs or vectors, are being studied to achieve efficacious delivery into the desired regions of the diseased brain. This review discusses the use of CED to deliver gene therapy for brain tumors, particularly gliomas, such as GBM.


Precision Medicine in Acute Brain Injury: A Narrative Review.
Over the past few years, the concept of personalized medicine has percolated into the management of different neurological conditions. Improving outcomes after acute brain injury (ABI) continues to be a major challenge. Unrecognized individual multiomic variations in addition to multiple interacting processes may explain why we fail to observe comprehensive improvements in ABI outcomes even when applied treatments appear to be beneficial logically. The provision of clinical care based on a multiomic approach may revolutionize the management of traumatic brain injury, delayed cerebral ischemia after subarachnoid hemorrhage, acute ischemic stroke, and several other neurological diseases. The challenge is to incorporate all the information obtained from genomic studies, other omic data, and individual variability into a practical tool that can be used to assist clinical decision-making. The effective execution of such strategies, which is still far away, requires the development of protocols on the basis of these complex interactions and strict adherence to management protocols. In this review, we will discuss various omics and physiological targets to guide individualized patient management after ABI.


Association between polymorphisms in interleukins and oral lichen planus: A meta-analysis.
More and more studies have suggested that single-nucleotide polymorphisms (SNPs) in interleukin (IL) genes are correlated with an increased risk of developing oral lichen planus (OLP). However, these results were inconsistent. Therefore, the aim of this meta-analysis is to retrieve and comprehensively analyze all related clinical studies to investigate the association of ILs gene polymorphisms with the OLP risk. PubMed, Embase, and the Cochrane Library were searched for eligible studies to evaluate the association between IL polymorphisms and the OLP. The odds ratios (ORs) and 95% confidence intervals (CIs) from each study were pooled to estimate the strength of the association. Statistical analyses were performed by using STATA software. In all 6 studies, including 4 SNPs (IL6-174G/C, IL10-592C/A, IL10-819C/T, and IL10-1082G/A), 362 OLP patients and 622 non-OLP control subjects from five different countries were investigated. As for the IL6-174G/C, IL10-819C/T, and IL10-1082G/A, no evidence was found to support the association between SNP and OLP susceptibility in any genetic models. However, as for IL10-592C/A, a significant relationship between them was identified in all of comparison models (C vs A: OR = 0.724, 95% CI = 0.585-0.897, P = 0.003; CC vs AA: OR = 0.447, 95% CI = 0.276-0.722, P = 0.001; AC vs AA: OR = 0.585, 95% CI = 0.387-0.883, P = 0.011; CC+AC vs AA: OR = 0.544, 95% CI = 0.365-0.809, P = 0.003; CC vs AA+AC: OR = 0.715, 95% CI = 0.515-0.994, P = 0.046). With the presently available evidence, this meta-analysis fails to show the statistical associations between IL6-174G/C, IL10-819C/T, and IL10-1082G/A and OLP susceptibility in any genetic models. However, the A allele and AA genotype in IL10-592C/A polymorphism may increase the risk of OLP. In the future, more well-designed studies with larger sample sizes are needed.


Fruit and Vegetable Preferences and Identification by Kindergarteners through 2nd-Graders With or Without the US Department of Agriculture Fresh Fruit and Vegetable Program.
The US Department of Agriculture Fresh Fruit and Vegetable Program (FFVP) allows schools to increase fruit and vegetable (FV) exposure by distributing FV as snacks. The objective of this study was to compare kindergarten through second (K-2nd)-graders who were exposed or not to FFVP for preferences and identification. The FV Preference Survey for K-2nd-graders contained 12 fruits and 12 vegetables, a 3-Likert scale (liked it, okay, don't like it), and an I don't know option. Data were collected from K-2nd-graders at 2 elementary schools near Chicago, IL (n = 435, FFVP school, n = 235 with 12 teachers; non-FFVP school, n = 200 with 10 teachers). Mean preference scores. Chi-square, Mann-Whitney U, and multiple linear regression analyses compared school data (P < .05). There were significant differences in mean preference scores, with higher fruit scores at the FFVP school (1.8 ± 0.6) than at the non-FFVP school (1.7 ± 0.6). In contrast, there was a higher vegetable score for the non-FFVP school (1.3 ± 0.9) than for the FFVP school (1.2 ± 0.9). The school variable had weak impact on fruit ranking (multivariate coefficient = 0.01; P < .05). For fruits and vegetables and combined, there were fewer I don't know responses in the FFVP (χ2 = 149.080; P < .01). At the FFVP school, fewer I don't know responses suggested better FV identification. Non-FFVP students had higher vegetable preferences than did FFVP students. Tasting a variety of FV may help with identifying FV, but more research is needed to determine the impact on preferences.


A review: The formation, prevention, and remediation of acid mine drainage.
In abandoned open-pit coal mines, surface water and groundwater form acidic waters with high concentrations of metal ions due to chemical interactions with ores such as pyrite, and the formation of acid mine drainage (AMD) is one of the major sources of pollution of world concern. For this reason, this paper reviews the formation mechanisms and influencing factors of AMD. It also describes the prediction, prevention, and remediation techniques for AMD, identifying key research gaps. It also discusses the current challenges and shortcomings faced globally in the management of AMD. The formation of AMD is mainly caused by the oxidation of pyrite in mines, but it is mainly influenced by history, climate, topography, and hydrogeology, making the formation mechanism of AMD extremely complex. Currently, the remediation technologies for AMD mainly include active treatment and passive treatment, which can effectively neutralize acidic wastewater. However, the prediction technology for AMD is blank, and the source treatment technology such as passivation and microencapsulation only stays in the experimental stage. This leads to the high cost of treatment technologies at this stage and the inability to identify potential risks in mines. Overall, this review provides remediation tools for AMD from predicting root causes to treatment. Geophysical technology is an effective method for predicting the motion path and pollution surface of AMD in the future, and resource recovery for AMD is a key point that must be paid attention to in the future. Finally, integrated treatment technologies that deserve further exploration need to be emphasized.


Ultrasound-targeted microbubble destruction for chemotherapeutic drug delivery to solid tumors.
Ultrasound-targeted microbubble destruction (UTMD) is a promising technique for non-invasive, targeted drug delivery, and its applications in chemotherapeutic drug delivery to solid tumors have attracted growing interest. Ultrasound, which has been conventionally used for diagnostic imaging, has evolved as a promising tool for therapeutic applications mainly because of its ability to be focused deep inside the human body, providing a modality for targeted delivery. Although originally being introduced into clinics as ultrasound contrast agents, microbubbles (MBs) have been developed as a diagnostic and therapeutic agent that can both be tracked through non-invasive imaging and deliver therapeutic agents selectively at ultrasound-targeted locations. Whereas free drugs often possess harmful side effects, their encapsulation in MBs and subsequent local release at the targeted tissue by ultrasound triggering may help improve the margin of safety. In the past 10 years, the feasibility and safety of UTMD have been extensively tested using normal animal models. Most recently, a growing number of preclinical studies have been reported on the therapeutic benefits of UTMD in the delivery of chemotherapeutic drugs to various malignant tumors, such as brain, liver, eyelid, pancreas, and breast tumors. Increased drug concentration in tumors and reduced tumor sizes were achieved in those tumors treated with UTMD in combination with chemotherapeutic drugs, when compared to tumors treated with chemotherapy drugs alone. This review presents an overview of current preclinical applications of UTMD in chemotherapeutic drug delivery for the treatment of cancers along with a discussion of its future developments.


Inhibition of 5 alpha-reductase and aromatase by the ellagitannins oenothein A and oenothein B from Epilobium species.
Species of the genus Epilobium (Onagraceae) have been investigated for their activity against 5 alpha-reductase and aromatase, two enzymes which are involved in the aetiology of benign prostatic hyperplasia (BPH). Activity-guided fractionation has led to the identification of two macrocyclic ellagitannins, oenothein A (1) and oenothein B (2), as the main constituents responsible for the inhibition of the two enzymes. Quantitation of oenothein B in 10 different species of Epilobium has shown that amounts of up to 14% in the crude plant extracts are possible.


Intercondylar notch width and inner angle of lateral femoral condyle as the risk factors for anterior cruciate ligament injury in female handball players in Herzegovina.
The principal purpose of this prospective study was to examine intercondylar notch size and the value of inner angle of lateral femoral condyle as the risk factors for noncontact anterior cruciate ligament ACL injury and than to correlate them to the physical values of the athletes such as body mass index (BMI), hight, wight, etc. There are indentified two type of risk factors, external include shoes-surface interaction, type of playing surface, weather conditions and internal include anatomic, neuromuscular, biomechanical and hormonal factors that may predispose female athlets to noncontact injury of ACL. Among anatomic factors, intercondylar notch stenosis and larger inner angle of lateral condyle of femur as the factors which can cause impigement of ACL, were related to an increased risk of injury of ACL. In this study were included 51 female athlete. In the study group there were 24 female handball players with ACL tear and in control group there were 27 female handball players without any type of injury of the knee, who are practicing handball on a daily basis for at least for two years. In the first step, were gathered clinical data performed by orthopaedic surgeon. In the second step, the femoral notch width and the inner angle of lateral condyle of femur were measured on coronal MR-images. Study has shown that value of inner angle of lateral condyle of femur was significantly higher in athletes with ACL tear compared to those without. Value of width of intercondylar notch was statisticaly smaller in athletes with ACL tear, compared to those without. In the conclusion the inner angle of lateral femoral condyle is better predicting factor for ACL tear in young female handball players compared to intercondylar notch width.


Where is mTOR and what is it doing there?
Target of rapamycin (TOR) forms two conserved, structurally distinct kinase complexes termed TOR complex 1 (TORC1) and TORC2. Each complex phosphorylates a different set of substrates to regulate cell growth. In mammals, mTOR is stimulated by nutrients and growth factors and inhibited by stress to ensure that cells grow only during favorable conditions. Studies in different organisms have reported localization of TOR to several distinct subcellular compartments. Notably, the finding that mTORC1 is localized to the lysosome has significantly enhanced our understanding of mTORC1 regulation. Subcellular localization may be a general principle used by TOR to enact precise spatial and temporal control of cell growth.


Physical activity and postmenopausal breast cancer: effect modification by breast cancer subtypes and effective periods in life.
Physical activity (PA) has been inversely associated with postmenopausal breast cancer risk. However, it is unclear how and in which life periods PA may be effective to reduce breast cancer risk. Moreover, the evidence is still not judged as 'convincing' as there is some heterogeneity among study results. Most studies regarded breast cancer as a single disease, at best separated by menopausal status. Yet, breast cancers are heterogeneous and likely have different etiologies. Therefore, we analyzed the association of PA with different breast cancer subtypes in 3,414 postmenopausal cases and 6,569 controls from a case-control study on breast cancer conducted 2002-2005 in Germany (MARIE study). PA in the age periods 30-49 and 50+ years was assessed, including leisure-time PA (sports, cycling, walking) and non-recreational PA (occupational and household activities). There was a significant protective effect of leisure-time PA for ER+/PR+ carcinomas (adjusted odds ratio = 0.71, 95% confidence interval: 0.60, 0.85; trend P = 0.0001), but no effect for ER-/PR- carcinomas. Moreover, looking at physical activity pattern over time, the effect of PA after menopause on reducing breast cancer risk was more pronounced than the effect of PA before menopause. Overall, effects of PA were independent from adult weight gain, body mass index, and energy intake. These findings suggest that leisure-time PA after menopause may reduce postmenopausal breast cancer risk at least in part via hormonal pathways and not solely by changing body composition. Inactive postmenopausal women should be encouraged to become physically active even later in life.


Reliability of cross-cultural adapted Turkish version of the Pediatric Outcomes Data Collection Instrument (PODCI).
The Pediatric Outcomes Data Collection Instrument (PODCI) has been created to evaluate functional status, to assess therapeutic needs and changes after treatment in 2 to 18 years old children and adolescents who have orthopedic problems. The PODCI has three forms; parent form for children, parent and self report forms for adolescents. Instrument has 86 items assessing `upper extremity and physical function', `transfer and basic mobility', `sports and physical function', `pain/comfort', `happiness', `global functioning' and `expectations from treatment domains'. The PODCI has been validated in multiple languages. The aim of this study was to investigate the reliability of the cross-cultural adapted Turkish version of the PODCI parent forms for children and adolescents in a variety of chronic musculoskeletal disorders. This was a methodological study. The instrument was translated and cross-culturally adapted into Turkish. Turkish version was called Bedensel İşlevsellik Değerlendirme Aracı (BIDA). It was completed by the parents/caregivers of ninety-eight children and adolescents being treated at Marmara University Medical School Department of Physical Medicine and Rehabilitation outpatient clinics at the baseline and 2-4 weeks after between April 2013-October 2013. Internal consistency and test-retest reliability (ICC) were determined. Internal consistency of the subscales and test/retest cronbach alpha values were 0.90-0.91 (r= 0.71, p= 0.000) for ``upper extremity and physical function''; 0.95-0.95 (r= 0.84, p= 0.000) for ``transfer and basic mobility''; 0.93-0.91 (r= 0.78, p= 0.000) for ``sports and physical functioning''; 0.77-0.82 (r= 0.45, p= 0.000) for ``happiness'' and 0.96-0.96 (r= 0.82, p= 0.000) for ``global functioning''. Pain/comfort subscale showed low internal consistency (-0.38-0.49; r= 0.34, p= 0.004). The Turkish version of the PODCI was found to be a reliable instrument to evaluate functionality of children and adolescents with chronic musculoskeletal disorders.


A socio-geographic perspective of health and economic impacts of COVID-19 on poor households in ghana.
COVID-19 outbreak has had multidimensional effects on human lives. The impacts are expected to be more severe on poor households, especially in resource-constraint economies such as Ghana. The Country has a higher poverty rate [24.2%] and this is likely to upsurge in the coming years due to this pandemic. We aimed to document the pandemic-related health and socioeconomic hazards in Ghana. A content analysis of relevant literature, and a qualitative survey using a socioecological lens were conducted. Based on the Ghana Living Standard Survey report (GLSS 7), twenty interviewees were recruited from 3 most poverty-stricken regions in the country to verify the findings of the content review. The findings indicate a significant health burden and a large-scale socioeconomic negative outcome among the Ghanaian poor households. The disproportionate health access by the poor and the rural inhabitants has and will continue to exacerbate. The social hazards are mainly circumscribed relating to poor economic conditions due to job losses, lack of access to income/savings, food insecurity, and lack of welfare support. At the national level, the economy is particularly vulnerable due to low levels of economic diversification. The ultimate manifestation of the pandemic impacts are higher risk of morbidity and mortality rates, and deteriorating wellbeing and livelihoods. These highlights are beneficial to policymakers, development partners, and human rights advocates to make collaborative efforts in helping the poor households during and the post-pandemic periods.


Prognostic Value of the Apparent Diffusion Coefficient in Newborns with Hypoxic-Ischaemic Encephalopathy Treated with Therapeutic Hypothermia.
Apparent diffusion coefficient (ADC) quantification has been proven to be of prognostic value in term newborns with hypoxic-ischaemic encephalopathy (HIE) who were treated under normothermia. To evaluate the prognostic value of ADC in standardized brain regions in neonates with HIE who were treated with therapeutic hypothermia (TH). This prospective cohort study included 54 term newborns who were admitted with HIE and treated with TH. All magnetic resonance imaging examinations were performed between days 4 and 6 of life, and ADC values were measured in 13 standardized regions of the brain. At 2 years of age we explored whether ADC values were related to composite outcomes (death or survival with abnormal neurodevelopment). The severity of HIE is inversely related to ADC values in different brain regions. We found that lower ADC values in the posterior limb of the internal capsule (PLIC), the thalami, the semioval centre, and frontal and parietal white matter were related to adverse outcomes. ADC values in the PLIC and thalami are good predictors of adverse outcomes (AUC 0.86 and 0.76). Low ADC values in the PLIC, thalamus, semioval centre, and frontal and parietal white matter in full-term infants with HIE treated with TH were associated with a poor outcome.


Some observations on poliomyelitis lameness surveys.
Since 1974, greater than 100 different surveys have been carried out throughout the developing world to estimate the prevalence of lameness due to poliomyelitis. Reported prevalence rates have ranged from less than 1 to a high of 25 per 1,000 children surveyed and have prompted many countries to undertake polio vaccination programs. A review of surveys conducted to date reveals considerable variation in both the choice and use of survey methods and in the assumptions made in the analysis and interpretation of findings. More precise and comparable data about the risk of poliomyelitis could be obtained in future surveys by incorporating a standard case definition, by using house-to-house case-finding methods in representative community-based samples, by analyzing and presenting rates in more clearly defined ways, and by selecting stable populations for study.


Zn(II) mediates vancomycin polymerization and potentiates its antibiotic activity against resistant bacteria.
Vancomycin is known to bind to Zn(II) and can induce a zinc starvation response in bacteria. Here we identify a novel polymerization of vancomycin dimers by structural analysis of vancomycin-Zn(II) crystals and fibre X-ray diffraction. Bioassays indicate that this structure is associated with an increased antibiotic activity against bacterial strains possessing high level vancomycin resistance mediated by the reprogramming of peptidoglycan biosynthesis to use precursors terminating in D-Ala-D-Lac in place of D-Ala-D-Ala. Polymerization occurs via interaction of Zn(II) with the N-terminal methylleucine group of vancomycin, and we show that the activity of other glycopeptide antibiotics with this feature can also be similarly augmented by Zn(II). Construction and analysis of a model strain predominantly using D-Ala-D-Lac precursors for peptidoglycan biosynthesis during normal growth supports the hypothesis that Zn(II) mediated vancomycin polymerization enhances the binding affinity towards these precursors.


Temporal and spatial regulation of phosphoinositide signaling mediates cytokinesis.
Polarity is a prominent feature of both chemotaxis and cytokinesis. In chemotaxis, polarity is established by local accumulation of PI(3,4,5)P3 at the cell's leading edge, achieved through temporal and spatial regulation of PI3 kinases and the tumor suppressor, PTEN. We find that as migrating D. discoideum cells round up to enter cytokinesis, PI(3,4,5)P3 signaling is uniformly suppressed. Then, as the spindle and cell elongate, PI3 kinases and PTEN move to and function at the poles and furrow, respectively. Cell lines lacking both of these enzymatic activities fail to modulate PI(3,4,5)P3 levels, are defective in cytokinesis, and cannot divide in suspension. The cells continue to grow and duplicate their nuclei, generating large multinucleate cells. Furrows that fail to ingress between nuclei are unable to stably accumulate myosin filaments or suppress actin-filled ruffles. We propose that phosphoinositide-linked circuits, similar to those that bring about asymmetry during cell migration, also regulate polarity in cytokinesis.


GRC-Sensing: An Architecture to Measure Acoustic Pollution Based on Crowdsensing.
Noise pollution is an emerging and challenging problem of all large metropolitan areas, affecting the health of citizens in multiple ways. Therefore, obtaining a detailed and real-time map of noise in cities becomes of the utmost importance for authorities to take preventive measures. Until now, these measurements were limited to occasional sampling made by specialized companies, that mainly focus on major roads. In this paper, we propose an alternative approach to this problem based on crowdsensing. Our proposed architecture empowers participating citizens by allowing them to seamlessly, and based on their context, sample the noise in their surrounding environment. This allows us to provide a global and detailed view of noise levels around the city, including places traditionally not monitored due to poor accessibility, even while using their vehicles. In the paper, we detail how the different relevant issues in our architecture, i.e., smartphone calibration, measurement adequacy, server design, and client⁻server interaction, were solved, and we have validated them in real scenarios to illustrate the potential of the solution achieved.


Rescue of morphogenetic defects and of retinoic acid signaling in retinaldehyde dehydrogenase 2 (Raldh2) mouse mutants by chimerism with wild-type cells.
Retinoic acid (RA), the active vitamin A derivative, is an important developmental signaling molecule in vertebrates. In this study, we have assessed whether minimal numbers and/or specific distributions of RA-producing cells can support normal mouse embryonic development. Retinaldehyde dehydrogenase 2 (RALDH2) is the main RA-synthesizing enzyme acting during development. We have generated an embryonic stem (ES) cell line homozygous for an Raldh2 gene disruption, and have analyzed chimeric embryos with various contributions of wild-type cells. Whereas embryos almost completely derived from Raldh2(-/-) cells phenocopy the corresponding germline null mutants, the presence of even small numbers (<10%) of wild-type cells can rescue most of the morphogenetic defects, including embryonic turning and axial elongation, and left-right looping of the heart tube. No consistent bias in the distribution of wild-type cells was observed in the phenotypically rescued Raldh2(-/-) chimeras. Analysis of an RA-sensitive transgene indicates that RA can diffuse from wild-type cells and elicit a widespread transcriptional response in Raldh2-deficient cells. Our results show that few wild-type RA-producing cells, even when present in apparent random distributions, can support early morphogenesis of the mouse embryo. However, the Raldh2(-/-) chimeric fetuses display lung abnormalities, persistent truncus arteriosus, and abnormal myocardial differentiation, showing that subsequent RA-dependent events cannot be fully rescued by the mosaic presence of wild-type cells.


[Modelling pollutant loads and management alternatives in Jiulong River watershed with AnnAGNPS].
The modelling package Annualized Agricultural Nonpoint Source Model (AnnAGNPS) was used to predict pollutant loads, and simulate catchment processes and management practices in Jiulong River watershed, a medium-sized mountainous watershed in southeast of China. Four typical sub-watersheds were primarily chosen to calibrate AnnAGNPS model by data collected from storm events during the period of April to September, 2003. The model was further validated in the two biggest branches of Jiulong River watershed, i.e. West river and North river by the data regarding climate, and land using condition in 2002 - 2003. The simulation results show that annual total nitrogen load was 24.76kg/(hm2 x a) and 10.28kg/(hm2 x a) in the West river and North river, respectively, and annual total phosphorus load was 0.67 kg/(hm2 x a) and 0.40 kg/(hm2 x a) in the West river and North river, respectively. With the support of AnnAGNPS model, several management alternatives were separately simulated in the typical sub-watersheds, West river and North river. In the specific cell with cell-ID of 92 in Tianbao and Xiandu sub-watershed, after reforesting in sloping field, runoff surface, sediment yield, total nitrogen load and total phosphorus load cut down with 21.6%, 25.9%, 96% and 79.2%, respectively. In West river, with the cultivation plant changing from banana into rice, the total nitrogen, dissolved nitrogen, total phosphorus and dissolved phosphorus cut down with 23.83%, 25.44%, 9.08% and 19.84%, respectively. In North river, when removing all the hoggerys, nitrogen and dissolved nitrogen cut down with 63.54% and 76.92% , respectively.


Tapered fiber bundles for combining high-power diode lasers.
Tapered fiber bundles are often used to combine the output power of several semiconductor lasers into a multimode optical fiber for the purpose of pumping fiber lasers and amplifiers. It is generally recognized that the brightness of such combiners does not exceed the brightness of the individual input fibers. We report that the brightness of the tapered fibers (and fiber bundles) depends on both the taper ratio and the mode-filling properties of the beams launched into the individual fibers. Brightness, therefore, can be increased by selection of sources that fill a small fraction of the input fiber's modal capacity. As proof of concept, we present the results of measurements on tapered fiber-bundle combiners having a low-output étendue. Under low mode-filling conditions per input multimode fiber (i.e., fraction of filled modes < or =0.29), we report brightness enhancements of 8.0 dB for 19 x 1 bundles, 6.7 dB for 7 x 1 bundles, and 4.0 dB for 3 x 1 combiners. Our measured coupling efficiency variations of approximately 1%-2% among the various fibers in a given bundle confirm the uniformity and quality of the fabricated devices.


Glial A30P alpha-synuclein pathology segregates neurogenesis from anxiety-related behavior in conditional transgenic mice.
In Parkinson's disease (PD) patients, alpha-synuclein (α-syn) pathology advances in form of Lewy bodies and Lewy neurites throughout the brain. Clinically, PD is defined by motor symptoms that are predominantly attributed to the dopaminergic cell loss in the substantia nigra. However, motor deficits are frequently preceded by smell deficiency or neuropsychological symptoms, including increased anxiety and cognitive dysfunction. Accumulating evidence indicates that aggregation of α-syn impairs synaptic function and neurogenic capacity that may be associated with deficits in memory, learning and mood. Whether and how α-syn accumulation contributes to neuropathological events defining these earliest signs of PD is presently poorly understood. We used a tetracycline-suppressive (tet-off) transgenic mouse model that restricts overexpression of human A30P α-syn to neurons owing to usage of the neuron-specific CaMKIIα promoter. Abnormal accumulation of A30P correlated with a decreased survival of newly generated neurons in the hippocampus and olfactory bulb. Furthermore, when A30P α-syn expression was suppressed, we observed reduction of the human protein in neuronal soma. However, residual dox resistant A30P α-syn was detected in glial cells within the hippocampal neurogenic niche, concomitant with the failure to fully restore hippocampal neurogenesis. This finding is indicative to a potential spread of pathology from neuron to glia. In addition, mice expressing A30P α-syn show increased anxiety-related behavior that was reversed after dox treatment. This implies that glial A30P α-synucleinopathy within the dentate gyrus is part of a process leading to impaired hippocampal neuroplasticity, which is, however, not a sole critical event for circuits implicated in anxiety-related behavior.


Replication of echo virus type 25 JV-4 reference strain and wild type strains in MRC5 cells compared with that of poliovirus type 1.
In echo virus type 25/JV-4 the shut off of host cell protein synthesis took significantly longer and the kinetics of the synthesis of viral proteins and viral RNA occurred much later than in the poliovirus. However, these characteristics impaired neither polyprotein processing nor virus production in the JV-4 strain. In contrast the two wild strains M.1262 and Th.222 had a lower virus yield than strain JV-4. The presence of a high Mr protein in the pattern of viral proteins of wild strains suggested that a defect in the polyprotein processing was responsible for the decreased virus yield. The infectious cycle of strain Th.222 differed from that of strains JV-4 and M.1262 in the rapid inhibition of host cell translation and the extent of viral protein synthesis. The sensitivity to actinomycin D was also investigated. Strain M.1262 was found to be insensitive. The virus yield of strains JV-4 and Th.222 was three- and fourfold lower respectively in the presence of actinomycin D. This sensitivity to the antibiotic was observed during viral RNA synthesis in strain JV-4 and during viral protein synthesis in strain Th.222. These results suggest that cellular factors are involved in the replication of echo virus type 25 strains in MRC5 cells.


Novel ophthalmological features in hereditary endotheliopathy with retinopathy, nephropathy and stroke syndrome.
The ophthalmic features are reported of a member of an Australian pedigree with three affected individuals spanning two generations with a hereditary endotheliopathy syndrome resulting in retinopathy, leukoencephalopathy and nephropathy. The index case initially presented with asymptomatic retinopathy, cerebral microvascular disease, nephropathy and raised inflammatory markers. The clinical, neuro-radiological, biochemical and histopathological findings in this patient are consistent with a diagnosis of hereditary endotheliopathy, retinopathy, nephropathy and stroke (HERNS). Linkage analysis has identified a locus for HERNS on chromosome 3p21.1-p21.3. This locus is shared with two other diseases: hereditary vascular retinopathy (HVR) and cerebroretinal vasculopathy (CRV). Although peripheral retinal involvement is a feature of HVR, it has not previously been described in HERNS. This case represents a novel phenotype of HERNS, and serves to blur the distinction between the vasculopathies mapping to chromosome 3p21. Although previously thought to be distinct clinical entities, it is possible that HERNS, HVR and CRV simply represent different phenotypes of the same disease. This will only be clarified with the identification of the gene or genes. This case also raises the question of how best to manage rare forms of vascular retinopathy.


Investigation and Analysis of the Current Status of Rationality and Standardization of Oxygen Therapy in Hospitalized Adult Patients.
To investigate the rationality and standardization of oxygen therapy for hospitalized adult patients, so as to provide a basis for improving the quality of oxygen therapy care. Self-designed "Inpatient Oxygen Therapy Status Questionnaire", using a cross-sectional survey, surveyed 185 oxygen inhalation patients in a tertiary general hospital from August 3-15, 2020, based on the formulation and promulgation of the Chinese Nursing Association The "Nursing care for adult patient with oxygen therapy" standard evaluates the rationality of clinical oxygen therapy implementation and the standardization of nursing measures. The reasonable rate of oxygen therapy for hospitalized adult patients was 19.46%, and the standardized rate of nursing measures was 54.52%. The reasonable and standardized rates of medical wards were higher than those of surgical and specialized wards, and were statistically significant (P<0.05). The incidence of complications of oxygen therapy was positively correlated with the rationality of oxygen therapy and the standardized data of nursing measures. The clinical oxygen therapy nursing practice and the standard of "Nursing care for adult patient with oxygen therapy" are quite inadequate. There are differences in the quality of oxygen therapy in different wards. Nursing managers should strengthen training and management, standardize nursing behaviors, and improve the quality of oxygen therapy and ensure oxygen therapy for patients' safety.


Promotive effect of primary and secondary bile acids on the induction of gamma-glutamyl transpeptidase-positive liver cell foci as a possible endogenous factor for hepatocarcinogenesis in rats.
The promoting effects of 5 bile acids on liver carcinogenesis were investigated in male Fischer rats initially treated with diethylnitrosamine (DEN). Two weeks after a single dose of DEN (200 mg/kg, intraperitoneally), rats were given bile acids for 8 weeks. At 3 weeks following DEN administration, all rats were subjected to partial hepatectomy. Among the bile acids tested, cholic acid (CA) and deoxycholic acid (DCA) exerted promoting activity as evidenced by significantly increased values of gamma-glutamyl transpeptidase-positive (gamma-GT+) foci as compared with the corresponding controls given DEN alone. In contrast, the other 3 bile acids tested, chenodeoxycholic acid (CDCA), lithocholic acid (LCA) and ursodeoxycholic acid (UDCA), did not significantly increase the level of gamma-GT+ foci over that induced by DEN alone. It is noteworthy that only bile acids of the same metabolic pathway, CA as a primary bile acid and DCA as a secondary bile acid, showed promoting effects whereas CDCA and its metabolic derivatives, LCA and UDCA, were inactive. The results indicate that CA and DCA might act as endogenous promoters of hepatocarcinogenesis in pathological conditions with increased levels of serum bile acids.


A Retrospective Chart Review of Lithium Side Effects in a Geriatric Outpatient Population.
The charts of 114 elderly outpatients with mood disorders treated with lithium were reviewed to determine the incidence of side effects. Patients had been treated with lithium for an average of 7.5 years, with an average serum lithium level of 0.5. Overall, 61.4% of patients experienced side effects from lithium at some point in their treatment, but only 0.11 side effects occurred per patient per year. Two (1.8%) patients had to discontinue lithium because of side effects and four (3-5%) required hospitalization. Delirium was the most common side effect noted (19.3%). Side effects occurred both at low ("subtherapeutic") and higher serum lithium levels. Variables significantly associated with experiencing side effects included male sex and higher serum lithium level. Hypothyroidism was significantly associated with longer length of time in years treated with lithium.


Bicistronic Design-Based Continuous and High-Level Membrane Protein Production in Escherichia coli.
Escherichia coli has been widely used as a platform microorganism for both membrane protein production and cell factory engineering. The current methods to produce membrane proteins in this organism require the induction of target gene expression and often result in unstable, low yields. Here, we present a method combining a constitutive promoter with a library of bicistronic design (BCD) elements, which enables inducer-free, tuned translation initiation for optimal protein production. Our system mediates stable, constitutive production of bacterial membrane proteins at yields that outperform those obtained with E. coli Lemo21(DE3), the current gold standard for bacterial membrane protein production. We envisage that the continuous, fine-tunable, and high-level production of membrane proteins by our method will greatly facilitate their study and their utilization in engineering cell factories.


A study of trade-specific occupational ergonomics considerations in the U.S. construction industry.
The aim of this survey study was to identify trade-specific ergonomic issues, and discuss practical solutions to reduce work-related musculoskeletal disorders (WMSDs) and injuries in the construction industry. Thirty-two construction firms in the Midwestern United States completed the final survey questionnaire. Twelve different construction skilled trades participated included: general contractor, road, heavy and highway, concrete, electrical, carpentry, landscaping, plumbing, roofing, steel erection, street lighting/traffic signal, and utility construction. Total workforce of the participating companies numbered 11,118 employees. More than 90% of the participants in the survey had a written safety program; however, the majority of the firms did not have a trade-specific ergonomic intervention. The survey revealed that construction constructors perceived safety (worker well-being) as a high priority in their company. This study suggested that construction skilled-trade jobs the construction worker to employ trade-specific hand tools and working body positions that may contribute to different types of WMSD risks, body parts injured, and injury sources. Possible practical construction trade-specific ergonomic solutions might be considered includinge: selection of ergonomic hand tools, reduction of weight of construction materials, and promotion of wellness exercises. This paper may imply that need for more trade-specific ergonomics program elements to help alleviate the work-related musculoskeletal problems in the construction field.


Synergistic effects of antiviral agents and humoral antibodies in experimental Herpesvirus hominis encephalitis.
Experimental Herpesvirus hominis encephalitis in 3-week-old Swiss mice was utilized to evaluate the antiviral effects of adenine arabinoside (ara-A), phosphonacetic acid (PAA), and humoral antibodies to H. hominis (HIG). Administration of ara-A, PAA, or HIG during the early phase of infection reduced the mortality rate of H. hominis encephalitis in mice. Combined administration of humoral antibodies with an antiviral agent (ara-A or PAA) resulted in an enhanced protection, accompanied by a decreased virus concentration in the brain tissues and a diminished tissue injury. The generality of this enhancing effect of humoral antibodies on the action of antiviral agents and its possible use in therapy of viral infections warrant further investigation.


Microresonators in CMOS compatible substrate.
We report our recent progress in designing and developing traveling-wave microresonators on CMOS compatible substrate, with a focus on ultra-compact Si-based microring and microdisk resonators in the visible and near infrared wavelengths with ultra-high Q and small mode volume, suitable for strong light-matter interaction. The performance of these resonators is discussed, and the design and fabrication challenges and solutions to achieve efficient coupling from the bus-waveguide to the resonator is mentioned. Coupled-resonator architectures for the design of filters are analyzed and theoretical and experimental results for the flat-band filters with wide bandwidth and large free spectral range are presented. Furthermore, by using a detailed thermal model we demonstrate optimized microresonator structures on semiconductor substrates with improved thermal conductivity that can sustain a high circulating optical intensity at the resonance wavelength, which is particularly useful for nonlinear optics and optical signal processing applications. Finally, we address some of the applications and future prospects of such microresonators in CMOS-compatible substrate technology, including portable multi-purpose bio/chemical sensing systems, reconfigurable optical signal processing modules and chip-scale optical amplifiers and lasers.