Pyripyropenes, novel ACAT inhibitors produced by Aspergillus fumigatus. IV. Structure elucidation of pyripyropenes M to R.
Six new pyripyropenes, M to R, were isolated from the ethyl acetate extracts of the jar fermentation broth of Aspergillus fumigatus FO-1289-2501. Structural elucidation indicated that all the pyripyropenes have the same pyridino-alpha-pyrone sesquiterpene core as pyripyropenes A to L. Among them pyripyropene M showed the most potent inhibition against acyl-CoA : cholesterol acyltransferase activity with an IC50 value of 3.80 microM in rat liver microsomes, but pyripyropenes N to R showed moderate inhibitory activity (IC50 11.0 approximately 78.0 microM).


OsAUX1 controls lateral root initiation in rice (Oryza sativa L.).
Polar auxin transport, mediated by influx and efflux transporters, controls many aspects of plant growth and development. The auxin influx carriers in Arabidopsis have been shown to control lateral root development and gravitropism, but little is known about these proteins in rice. This paper reports on the functional characterization of OsAUX1. Three OsAUX1 T-DNA insertion mutants and RNAi knockdown transgenic plants reduced lateral root initiation compared with wild-type (WT) plants. OsAUX1 overexpression plants exhibited increased lateral root initiation and OsAUX1 was highly expressed in lateral roots and lateral root primordia. Similarly, the auxin reporter, DR5-GUS, was expressed at lower levels in osaux1 than in the WT plants, which indicated that the auxin levels in the mutant roots had decreased. Exogenous 1-naphthylacetic acid (NAA) treatment rescued the defective phenotype in osaux1-1 plants, whereas indole-3-acetic acid (IAA) and 2,4-D could not, which suggested that OsAUX1 was a putative auxin influx carrier. The transcript levels of several auxin signalling genes and cell cycle genes significantly declined in osaux1, hinting that the regulatory role of OsAUX1 may be mediated by auxin signalling and cell cycle genes. Overall, our results indicated that OsAUX1 was involved in polar auxin transport and functioned to control auxin-mediated lateral root initiation in rice.


Leptospirosis-induced meningitis and acute renal failure in a 19-month-old male child.
An unusual case of leptospirosis is described in a 19-month-old male child presenting with meningitis and acute renal failure without jaundice. Some aspects concerning the pathogenesis and treatment of this potentially life-threatening disease are also discussed. Leptospirosis was diagnosed on the basis of history and serological tests.


19F/29Si rotational-echo double-resonance and heteronuclear spin counting under fast magic-angle spinning in fluoride-containing octadecasil.
19F/29Si rotational-echo double-resonance (REDOR) and theta-REDOR NMR techniques have been applied under fast magic-angle spinning to a powder sample of fluoride-containing octadecasil. Efficient dipolar recoupling was observed and the effect of finite pulse lengths was found to be negligible using standard radiofrequency field strengths. Moreover, the determined internuclear distance of the 19F-29Si spin pairs formed by the silicons in the D4R units (T-1 site) and the fluoride anions is in very good agreement with previous REDOR and Hartmann-Hahn cross-polarization measurements. Numerical simulation of the REDOR dephasing curves at both the T-1 and T-2 sites considering all fluoride anions in the infinite solid lattice clearly confirm the X-ray crystal structure of octadecasil. Heteronuclear spin-counting theta-REDOR experiments are found to be very useful to obtain direct insight into the local network of dipolar interactions. Indeed, while 19F-29Si pair-like behavior is confirmed at the T-1 site, multiple dipolar interactions are clearly evidenced at the T-2 site.


Dairy in a sustainable diet: a question of balance.
The demand for dairy products is growing rapidly, especially in emerging markets. Dairy products are nutrient rich and, therefore, an important food group for ensuring nutrient security in the future. In many countries, dairy contributes significantly to nutrient intake. Meta-analyses have shown that consumption of dairy may reduce the risk of chronic diseases and thereby lower healthcare costs. Milk production and processing contribute to greenhouse gas emissions, estimated at 2.7% (cradle-to-retail) of the world's total. Evaluating the position of dairy in the diet should take into account the impact of both nutritional and environmental factors. Local conditions are also important; in many parts of the world, the cow is an efficient converter of human-inedible resources into nutrient-dense food. Increased productivity of cows is a decisive factor in realizing sufficient milk production with optimal resource efficiency and minimal greenhouse gas emission. Models that optimize total diets, rather than individual food products, for their nutritional and environmental impact are the preferred approach for developing realistic alternative consumption strategies.


FBG Interrogation Method with High Resolution and Response Speed Based on a Reflective-Matched FBG Scheme.
In this paper, a high resolution and response speed interrogation method based on a reflective-matched Fiber Bragg Grating (FBG) scheme is investigated in detail. The nonlinear problem of the reflective-matched FBG sensing interrogation scheme is solved by establishing and optimizing the mathematical model. A mechanical adjustment to optimize the interrogation method by tuning the central wavelength of the reference FBG to improve the stability and anti-temperature perturbation performance is investigated. To satisfy the measurement requirements of optical and electric signal processing, a well- designed acquisition circuit board is prepared, and experiments on the performance of the interrogation method are carried out. The experimental results indicate that the optical power resolution of the acquisition circuit border is better than 8 pW, and the stability of the interrogation method with the mechanical adjustment can reach 0.06%. Moreover, the nonlinearity of the interrogation method is 3.3% in the measurable range of 60 pm; the influence of temperature is significantly reduced to 9.5%; the wavelength resolution and response speed can achieve values of 0.3 pm and 500 kHz, respectively.


Assessment of adult stereopsis using the Lang 1 Stereotest: a pilot study.
To assess the use of the Lang 1 Stereotest as a vision-screening test for adults, for which little is known or reported. The Lang 1 Stereotest was administered to 292 consecutive participants of the Visual Impairment Project (VIP) five year followup study, which is a population based study of eye disease in Melbourne, Australia. 56.9% were female. The mean age was 59.4 years, range 44-90 years. A "positive" stereoscopic response was recorded where the stereoscopic target image was correctly named; a "partial positive" response where depth was appreciated but the shape could not be named; and a "negative" response where there was no appreciation of a stereo effect. The responses were further categorized so that the test was either "passed" or "failed". A "pass" score was 3/3 positive responses; 3/3 partial positive responses or 2/3 positive and/or partial positive responses where the negative response was at the 550" of arc stereoacuity level. "Failure" was 3/3 negative responses and 2/3 negative responses where the positive or partial positive response as at the 1200" level. Of the 292 participants tested, 19 (6.5%) participants "failed" the test. In addition to strabismus and anisometropia, failure was associated significantly (p<0.001) with reduced distance visual acuity (<6/12) irrespective of the ocular morbidity. The Lang 1 Stereotest correctly identified people with vision defects associated with reduced stereopsis. This suggests the Lang 1 Stereotest is an appropriate for the vision screening of adults as it is for children.


Circular RNAs signature predicts the early recurrence of stage III gastric cancer after radical surgery.
Tumor recurrence is usually detected within one year after radical resection of stage III gastric cancer. This study aimed to establish the expression profile and determine potential circular RNAs (circRNAs) and predict the early recurrence of stage III gastric cancer. We identified 46 differently expressed circRNAs between cancer and adjacent normal tissues through circRNA microarray. We further screened eight indicators related to early recurrence. We subsequently divided the remaining cases into two cohorts. qRT-PCR results demonstrated a significantly different outcome between low and high expressed groups of four circRNAs in the training cohort. We then constructed a four-circRNA-based classifier to evaluate the risk of early recurrence and distinguished patients with a high risk from those with a low risk. The areas under the receiver operator characteristic curve (ROC) of this classifier were 0.763 and 0.711 in the two cohorts, respectively. A new formula could be established by combined the circRNA classifier with TNM stages. The areas under the ROC curve were 0.866 and 0.818 of the two cohorts, respectively. Our study suggested that this four-circRNA-based classifier yielded a predictive ability to the early recurrence of stage III gastric cancer after radical surgery.


Overexpression of LINC00852 promotes prostate cancer cell proliferation and metastasis.
Long noncoding RNAs play a key role in the development and progression of various human cancers. Recently, LINC00852 has been reported to be associated with spinal metastasis lung adenocarcinoma. However, the role and potential mechanisms of LINC00852 in prostate cancer cells remain largely unknown. LINC00852 expression in prostate cancer cells was examined by quantitative real-time polymerase chain reaction. Western blotting was used to detect protein expressions in prostate cancer cells. Cell cycle was analyzed by flow cytometric analysis. Cell proliferation was measured by cck-8 assay. The migration and invasion capabilities were determined using transwell assays. In this study, we found that LINC00852 was highly expressed in prostate cancer tissues based on the TCGA database. Overexpression of LINC00852 mediated by lentivirus significantly reinforced the proliferation and colony formation abilities of prostate cancer cell linePC3. The migration and invasion capabilities were also augmented by overexpression of LINC00852. Flow cytometric analysis revealed that LINC00852 overexpression resulted in a decrease of cells in G0/G1 phase. Moreover, overexpression of LINC00852 affected the expression of epithelial-mesenchymal transition-related proteins. Our data collectively demonstrate that LINC00852 contributes to prostate cancer proliferation and metastasis, indicating that LINC00852is a new promising diagnostic and therapeutic target for treatment of prostate cancer.


Stevens-Johnson syndrome associated with cytomegalovirus infection in a child with ependymoma.
Stevens-Johnson syndrome is an uncommon, acute life-threatening disease characterized by extensive epidermal sloughing and mucositis. In childhood, as in adulthood, this condition is mostly related to drugs, in particular antibiotics. Only a few cases reported were firmly attributed to infectious agents, mainly Mycoplasma pneumonia but the causative role of infectious microorganisms seems particularly relevant in pediatric patients. The seriousness of this condition imposes a prompt recognition and the early withdrawal of the potential causative drugs or the institution of directed measures against infectious agents (depending on the suspected etiology), as well as a supportive and more specific therapy. Some treatments claim to halt the progression of skin detachment, but remain of unproven benefit due to the lack of prospective, well controlled, randomized clinical trials. We report a case of a 2-year-old boy admitted in our hospital for the treatment of an ependymoma of the posterior fossa, who developed a Stevens-Johnson syndrome associated most probably with a cytomegalovirus infection. He was successfully treated with high dose intravenous immunoglobulin and gancyclovir. To the best of our knowledge, this is the first case of SJS associated with CMV infection.


Alkaline Salt Inhibits Seed Germination and Seedling Growth of Canola More Than Neutral Salt.
Salinity is a major constraint to crop growth and productivity, limiting sustainable agriculture production. Planting canola (Brassica napus L.) variety with salinity-alkalinity tolerance as a green manure on the large area of salinity-affected land in Xinjiang could alleviate feed shortage. To investigate the differential effects of neutral and alkaline salt stress on seed germination and seedling growth of canola, we used two salts at varying concentrations, i.e., NaCl (neutral salt at 100, 150, and 200 mM) and Na2CO3 (alkaline salt at 20, 30, and 40 mM). To further explore the effects of Na+ and pH on seed germination, we included combined of NaCl (0, 100, 150, and 200 mM) and pH (7.1, 8.0, 9.0, 10.0, and 11.0). Shoot growth was promoted by low concentrations of NaCl and Na2CO3 but inhibited at high salt concentrations. Given the same Na+ concentration, Na2CO3 inhibited seed germination and seedling growth more than NaCl. The results showed that the main factor affecting seed germination and seedling growth is not pH alone, but the interaction between pH and salt ions. Under NaCl stress, canola increased the absorption of K+, Ca2+, and Mg2+ in roots and K+ in leaves. However, under Na2CO3 stress, canola maintained a high K+ concentration and K+/Na+ ratio in leaves and increased Ca2+ and Mg2+ in roots. Our study showed that alkaline salts inhibit canola seed germination and seedling growth more significantly than neutral salts and salt species, salt concentration, and pH significantly affected on seed germination and seedling growth. However, pH affected seed germination and seedling growth mainly through an interaction with salt ions.


[Effects of clinical application of free anterolateral thigh perforator lobulated flap in repair of electrical burn wounds on head based on the concept of donor site protection].
Objective: To explore the effects of clinical application of free anterolateral thigh perforator lobulated flap in repair of electrical burn wounds on head based on the concept of donor site protection. Methods: A retrospective observational study was conducted. Eight patients with electrical burns with huge scalp defects and exposed skulls were admitted to the First Affiliated Hospital of Zhengzhou University, from May 2017 to December 2019, who were all males, aged 21-57 (39±13) years, sustaining multiple deep partial thickness to full-thickness electrical burns to 5%-14% total body surface area. Among the scalp burn sites of the patients, 1 case was posterior occipital, 2 cases were parietal occipital, 4 cases were parietal temporal, and 1 case was frontotemporal. After debridement, the defect area was 10 cm×9 cm-16 cm×14 cm. The incision area of the free anterolateral thigh perforator lobulated flap was 22 cm×6 cm-30 cm×9 cm. The artery and vein of flap were anastomosed with superficial temporal artery and vein or facial artery and vein, and the other vein of skin flap was anastomosed with superficial vein of recipient area. The donor site of skin flap was closed by layer interrupted tension-reducing suture. After the operation, the survival of flop, donor site wound healing and complications were observed. The flap appearance, wound healing of donor sites, long-term complications and functional recovery of donor sites were observed on follow-up. Results: After the operation, the flaps of 8 patients survived completely without vascular crisis. The donor sites of flaps in all the patients healed well with no osteofascial compartment syndrome. Seven patients were followed up for 3 to 12 months, and 1 case was lost to follow up. During follow-up, the flaps of the patients' heads were in good appearance but with alopecia. The donor sites showed linear scars, which were well hidden. There were no significant differences in sensory and motor functions between the two sides, and no complications were found such as muscle hernia. Conclusions: Free anterolateral thigh perforator lobulated flap has a good clinical effect in the early repair of electrical burn wounds with huge scalp defect and skull exposure on head, and the donor wounds can be directly closed and sutured, greatly reducing the damage to the donor area.


Empagliflozin Protects HK-2 Cells from High Glucose-Mediated Injuries via a Mitochondrial Mechanism.
Empagliflozin is known to retard the progression of kidney disease in diabetic patients. However, the underlying mechanism is incompletely understood. High glucose induces oxidative stress in renal tubules, eventually leading to mitochondrial damage. Here, we investigated whether empagliflozin exhibits protective functions in renal tubules via a mitochondrial mechanism. We used human proximal tubular cell (PTC) line HK-2 and employed western blotting, terminal deoxynucleotidyl transferase dUTP nick end labelling assay, fluorescence staining, flow cytometry, and enzyme-linked immunosorbent assay to investigate the impact of high glucose and empagliflozin on cellular apoptosis, mitochondrial morphology, and functions including mitochondrial membrane potential (MMP), reactive oxygen species (ROS) production, and adenosine triphosphate (ATP) generation. We found that PTCs were susceptible to high glucose-induced mitochondrial fragmentation, and empagliflozin ameliorated this effect via the regulation of mitochondrial fission (FIS1 and DRP1) and fusion (MFN1 and MFN2) proteins. Empagliflozin reduced the high glucose-induced cellular apoptosis and improved mitochondrial functions by restoring mitochondrial ROS production, MMP, and ATP generation. Our results suggest that empagliflozin may protect renal PTCs from high glucose-mediated injuries through a mitochondrial mechanism. This could be one of the novel mechanisms explaining the benefits demonstrated in EMPA-REG OUTCOME trial.


Genetic variants for personalised management of very low carbohydrate ketogenic diets.
The ketogenic diet (KD) is a low-carbohydrate, high-fat, adequate-protein diet proven to be effective for the reversal of obesity, metabolic syndrome and type 2 diabetes, and holding therapeutic potential for the prevention and treatment of other chronic diseases. Genetic and dynamic markers of KD response may help to identify individuals most likely to benefit from KD and point to individuals at higher risk for adverse health outcomes. Here, we provide a clinician-friendly review of state-of-the-art research on biomarkers of KD response for a variety of outcomes including weight loss, body composition and cognitive performance drawing data from both intervention trials and case reports of rare inborn errors of metabolism. We also present a selection of the most promising candidate genes to evaluate in future studies and discuss key aspects of study design and variant interpretation that may help accelerate the implementation of these biomarkers in clinical practice.


Safety and efficacy of high-dose infusions of a preformed amphotericin B fat emulsion for treatment of Indian visceral leishmaniasis.
Amphotericin B deoxycholate is used as a first-line drug for visceral leishmaniasis (VL) in India. Its major drawbacks are prolonged hospitalization of treated patients and toxicity. An open label phase II study with pre-formed amphotericin B lipid emulsion (ABLE) was conducted to evaluate safety and efficacy of four regimens of 15 mg/kg each administered in 1-2 doses. Regimen 1 was 7.5 mg/kg/day on day 1 and day 3, and regimen 4 was a single bolus infusion of 15 mg/kg. The safety profile was excellent with mild infusion reactions seen in 38% of the patients. Definitive cure was achieved in 100% of the patients treated with regimen 4. The overall cure rate was 87% (95% confidence interval = 75-94%). In this study, ABLE was safe and had excellent efficacy when given as a bolus of 15 mg/kg. More studies with larger number of patients and higher doses are needed to establish acceptable, safe and efficacious regimen.


Factors Associated with Nutritional Risk in Patients with Pulmonary Tuberculosis and Structural Lung Disease: A Hospital-Based Cross-Sectional Study.
Patients with tuberculosis have a high nutritional risk, and patients with tuberculosis and structural lung disease have a poor quality of life. However, few studies have investigated the nutritional risk of patients with tuberculosis and structural lung disease. This study aimed to evaluate nutritional risk in patients with pulmonary tuberculosis and structural lung disease and to identify factors associated with nutritional risk in this population. We performed a cross-sectional study of patients diagnosed with pulmonary tuberculosis and structural lung disease admitted to The Third People's Hospital of Shenzhen, China between January 1, 2019 and December 31, 2021. We assessed participants' nutritional risk using the Nutritional Risk Screening 2002 tool, and analyzed the relationship between nutritional risk and sociodemographic factors, disease status, and laboratory test results. Of the 415 participants, 53.5% were at nutritional risk on admission to the hospital. Nutritional risk was significantly associated with being unmarried, destroyed lung, and red blood cell (RBC) and lymphocyte counts. Patients with tuberculosis and structural lung disease had a high prevalence of nutritional risk. The main factors associated with nutritional risk were being unmarried, lung cavitation, and low RBC and lymphocyte counts. Patients hospitalized with pulmonary TB should be evaluated for nutritional risk. Moreover, unmarried patients and patients with lung cavitation or low RBC or lymphocyte counts should be closely monitored.


Regional accumulation of calcium in postischemic rat brain.
The regional concentrations of intravenously injected 45Ca and total calcium were measured in rat brain during recovery from transient occlusion of the four major arteries to the brain. 45Ca was injected at intervals after ischemia, and the regional distribution of 45Ca was estimated by autoradiography. The 45Ca appeared to enter the brain via the choroid plexus, labeling the paraventricular tissue at 1 h after the injection. Control brains had more 45Ca in the gray matter compared to fiber-rich areas at 5 and 24 h, but within these regions the optical density was nearly uniform. The accumulation and retention of 45Ca in postischemic brain were selective and time-dependent. The regional pattern of 45Ca uptake correlated with the temporal progression of ischemic cell change. Infarction and preischemic hyperglycemia increased morphological damage, and increased the extent and distribution of 45Ca accumulation. The rise in total calcium concentration appeared to be biphasic in irreversibly damaged tissue.


Peptidergic inputs to sympathetic preganglionic neurons.
This paper presents data showing that the sympathetic autonomic areas of the cat thoracolumbar spinal cord contain nerve terminals and fibres with immunoreactivity for at least seven neuropeptides. The distribution in the intermediolateral cell column of the terminals and fibres which contain enkephalin-, neuropeptide Y-, neurotensin-, substance P-, and neurophysin II-like immunoreactivity (ENK, NPY, NT, SP, and NP2, respectively) suggests that these peptides are involved in more generalized functions of the autonomic nervous system. On the other hand, peaks in density of immunoreactivity at certain levels suggest that different levels of influence of sympathetic preganglionic neurons by the various peptides may occur along the length of the thoracolumbar cord. The distribution of terminals and fibres containing somatostatin- and oxytocin-like immunoreactivity (SS and OXY) suggests that these peptides may be part of specific pathways to particular sympathetic preganglionic neurons. The possible sources of the terminals and fibres containing ENK, NPY, NT, SS, and SP include the spinal cord and supraspinal areas, whereas the source of these structures with OXY and NP2 is most likely supraspinal. The data suggest that coexistence of peptides and interactions between structures containing different neuropeptides occur in the spinal autonomic areas. It is speculated that neuropeptides have an important role to play in the regulation of the cardiovascular division of the autonomic nervous system.


IL-17E, a proinflammatory cytokine, has antitumor efficacy against several tumor types in vivo.
Interleukin-17E (IL-17E) belongs to a novel family of cytokines that possess significant homology to IL-17. IL-17E has potent inflammatory effects in vitro and in vivo. Overexpression of IL-17E in mice results in a T helper-2 (Th2)-type immune response, which includes the expansion of eosinophils through the production of IL-5, and elevated gene expression of IL-4 and IL-13 in multiple tissues. In this study, we show that IL-17E has antitumor activity in vivo, a previously unrecognized function of IL-17E. Antitumor efficacy of IL-17E was examined in a variety of human tumor xenograft models, including melanoma, breast, lung, colon, and pancreatic cancers. Injection of recombinant IL-17E every other day resulted in significant antitumor activity in these tumor models. In addition, the combination of IL-17E with chemotherapy or immunotherapy agents showed an enhanced antitumor efficacy in human tumor xenograft models in mice as compared to either agent alone. Antitumor activity was demonstrated using different routes of administration, including intraperitoneal, intravenous, and subcutaneous injection. Anticancer activity was shown for both mouse and human forms of IL-17E, which have a high degree of sequence identity. Tumor-bearing mice treated with IL-17E showed a significant increase in serum levels of IL-5 and increased numbers of eosinophils in peripheral blood compared to the control group. Spleens isolated from IL-17E-treated mice showed a significant increase in eosinophils that correlated with antitumor activity of IL-17E in a dose-response manner. Finally, we demonstrate that B cells are necessary for IL-17E-mediated antitumor activity and that IL-17E was found to activate signaling pathways in B cells in vitro. Taken together, these data demonstrate that IL-17E has antitumor activity in vivo, and support further investigation of the potential clinical use of IL-17E as an anticancer agent.


Serum and salivary antigliadin antibodies and serum IgA anti-endomysium antibodies as a screening test for coeliac disease.
Serum and salivary IgA and IgG antigliadin antibodies were determined by an enzyme-linked immunosorbent assay in 18 children with villous atrophy and 30 children on a gluten-free diet for coeliac disease in whom normal intestinal mucosa was found. Serum IgA anti-endomysium antibodies were also determined by an immunofluorescence method in these children. Serum IgG antigliadin and IgA anti-endomysium antibodies had the highest sensitivity (100 and 94.4%, respectively), followed by serum IgA antibodies to gliadin (72.2%), salivary IgA antigliadin (61.2%) and IgG antigliadin (50%) antibodies. The highest specificity was found for serum IgA anti-endomysium (100%) and IgA antigliadin (96.6%) antibodies and salivary IgA and IgG antigliadin antibodies (93.3%), while serum IgG antigliadin antibodies were found to be least specific (63.3%).


Heart transplantation candidates: psychological evaluation.
Most medical centers that perform heart transplantation have established medical review boards that consider medical, psychosocial, and financial factors in choosing appropriate candidates. The psychological evaluation described here can furnish clinically useful baseline data regarding the patient's emotional and cognitive functioning, and identify other individual and family variables that may affect patient compliance and the outcome of transplantation.


Wall paintings facies and their possible genetic correlates in the ancient Pompeii: A bio-anthropologic message from the past?
The figurative arts and precisely the ancient Pompeian wall paintings portraits can provide an additional source of information in supplementing bio-anthropological studies. There are several genetic diseases with a wide spectrum of congenital bone stigmata in association to distinctive facial features. Gorlin-Goltz syndrome, also named nevoid basal cell carcinoma syndrome, is an autosomal dominant syndrome characterized by unusual skeletal changes, such as macrocephaly, facial asymmetry, hypertelorism, frontal and parietal bossing caused by germline mutations of the gene PTCH1. The Gorlin syndrome, clinically defined in 1963, existed during Dynastic Egyptian times, as revealed by a spectrum of skeletal findings compatible with the syndrome in mummies dating back to three thousand years ago and, most likely, in the ancient population of Pompeii. In the present research, we discuss the potential relationship between Pompeian wall paintings portrait and the cranio-metric bone changes revealed among the Pompeian skull collections assuming that the ancient portraits can constitute an important tool that should be strictly integrated with osteologic and biomolecular data in order to argue a syndromic diagnosis in ancient population.


Systematic review and meta-analysis of the effects of high protein oral nutritional supplements.
Disease-related malnutrition is common, detrimentally affecting the patient and healthcare economy. Although use of high protein oral nutritional supplements (ONS) has been recommended to counteract the catabolic effects of disease and to facilitate recovery from illness, there is a lack of systematically obtained evidence to support these recommendations. This systematic review involving 36 randomised controlled trials (RCT) (n=3790) (mean age 74 years; 83% of trials in patients >65 years) and a series of meta-analyses of high protein ONS (>20% energy from protein) demonstrated a range of effects across settings and patient groups in favour of the high protein ONS group. These included reduced complications (odds ratio (OR) 0.68 (95%CI 0.55-0.83), p<0.001, 10 RCT, n=1830); reduced readmissions to hospital (OR 0.59 (95%CI 0.41-0.84), p=0.004, 2 RCT, n=546); improved grip strength (1.76 kg (95%CI 0.36-3.17), p<0.014, 4 RCT, n=219); increased intake of protein (p<0.001) and energy (p<0.001) with little reduction in normal food intake and improvements in weight (p<0.001). There was inadequate information to compare standard ONS (<20% energy from protein) with high protein ONS (>20% energy from protein). The systematic review and meta-analysis provides evidence that high protein supplements produce clinical benefits, with economic implications.


Detection of Colonic Polyps During Colonoscopy in a Tertiary Care Center of Nepal.
Colorectal cancer is the third leading cause of cancer death in the world. Most colon cancer develop from the polyps. Data on the prevalence of colorectal polyps in Nepal is lacking. The objective was to determine the prevalence of colorectal polyps, site of occurrence and adenomas among various age groups. All polyps after removal by polypectomy was sent for histopathological examination. Study was done in 1027 consecutive patients who underwent colonoscopy in the pre-specified time after excluding patients with colorectal cancer, Inflammatory Bowel Disease and polyposis syndromes. Among 1027 patients, the mean age was 45 years. 292 (28.43%) were below 40 years, whereas, 735 (71.57%) were above 40 years. Polyps were detected in 12.95% of overall patients and in 9.73% of patients over age 40. The most common location of polyps was rectum (46.62%). 43.61% were adenomatous polyps, 11.28% were hyperplastic polyps, 18.05% were juvenile polyps, 22.56% were inflammatory polyps and 1.50% were malignant adenocarcinoma. Polyp detection rate was 12.95%, whereas adenoma detection rate was 5.84%. 46.55% had advanced adenomas. A positive correlation between the size of polyp and adenomatous variety was found [Chi-square value ?2 = 8.42 (>3.841), p value <0.05]. Prevalence of adenomatous polyps was significantly higher above the age of 40 [Chi-square value ?2 = 11.53 (>3.841), p value<0.05]. Conclusions: The prevalence of polyp increases with age. With increasing age and size of polyp, the prevalence of adenomatous polyp increases significantly. One out of every eight people over 40 years had a colonic polyp.


Different strokes for different folks: Examining additive and complimentary effects of the advisory working alliance and research team cohesion on trainees' research outcomes.
A primary task of scientific and scientist-practitioner training programs is to assist graduate students in acquiring research skills and, ultimately, developing research and scientific acumen. Informed by Gelso's (1979) model of effective research training environments (RTEs), we assessed the effect of the advisory working alliance and research team cohesion on trainees' research self-efficacy and research activity. With a sample of 76 counseling psychology doctoral trainees nested within 34 advisors, we examined the association between the advisory working alliance and research team cohesion and trainees' research self-efficacy and research activity. Next, we used polynomial regression and response surface analysis to test the additive and complementary effects between the advisory working alliance and research team cohesion on trainees' research self-efficacy and research activity. Univariate analyses indicated that the advisory working alliance and research team cohesion were positively associated with trainees' research self-efficacy and research activity. Moreover, polynomial regression models and response surface analyses indicated an additive effect between the advisory working alliance and research team cohesion on trainees' research self-efficacy and research activity, such that trainees' research self-efficacy and research activity were highest when the advisory working alliance and research team cohesion were consistent and high. Lastly, we found a complementary effect between the advisory working alliance and research team cohesion for trainees' research self-efficacy, meaning research self-efficacy was highest when students perceived either (a) high advisory working alliance and low research team cohesion or (b) low advisory working alliance and high research team cohesion. Training implications and future directions are discussed. (PsycINFO Database Record (c) 2019 APA, all rights reserved).


1-Aryl-3-(1-acylpiperidin-4-yl)urea inhibitors of human and murine soluble epoxide hydrolase: structure-activity relationships, pharmacokinetics, and reduction of inflammatory pain.
1,3-Disubstituted ureas possessing a piperidyl moiety have been synthesized to investigate their structure-activity relationships as inhibitors of the human and murine soluble epoxide hydrolase (sEH). Oral administration of 13 1-aryl-3-(1-acylpiperidin-4-yl)urea inhibitors in mice revealed substantial improvements in pharmacokinetic parameters over previously reported 1-adamantylurea based inhibitors. For example, 1-(1-(cyclopropanecarbonyl)piperidin-4-yl)-3-(4-(trifluoromethoxy)phenyl)urea (52) showed a 7-fold increase in potency, a 65-fold increase in C(max), and a 3300-fold increase in AUC over its adamantane analogue 1-(1-adamantyl)-3-(1-propionylpiperidin-4-yl)urea (2). This novel sEH inhibitor showed a 1000-fold increase in potency when compared to morphine by reducing hyperalgesia as measured by mechanical withdrawal threshold using the in vivo carrageenan induced inflammatory pain model.


Clinical characteristics, therapeutic management, and prognostic factors of adult COVID-19 inpatients with hematological malignancies.
Patients with hematological malignancies with immunodeficiency are at high risk for SARS-CoV-2 infection. We retrospective summarized clinical characteristics of coronavirus disease 2019 (COVID-19) inpatients with hematological malignancies, shared treatment experiences, and analysis prognostic factors. Fourteen patients were enrolled. The median duration of viral shedding was 27.5 days in survivors. The median duration of time to death was 13 days in non-survivors. Non-survivors tend to present lower neutrophil count, more imaging finding of bilateral diffuse patch opacities, more undergoing intensive chemotherapy or immunosuppression. Laboratory and image findings were atypical and diverse. COVID-19 inpatients undergoing intensive chemotherapy or immunosuppression might have increased risk of death. The diagnostic value of specific antibody detection is limited. Therefore, adult COVID-19 inpatients with hematological malignancies present atypical, severe symptoms, decreased virus clearance ability, abnormal antibody response and poor outcome. During the epidemic, the pros and cons need to be carefully weighed while selecting the treatment methods.


Clinical measures of dysarthria in Friedreich Ataxia.
Dysarthria in Friedreich Ataxia (FA) is difficult to quantify. This study evaluated a series of performance measures for speech in 22 patients with genetically confirmed FA and 16 age-matched controls. Tests included the PATA examination, the PATAKA examination, the Oral Motor component of the Boston Aphasia examination, the Boston Cookie Theft description task, and the Assessment of Intelligibility of Dysarthric Speech. All measures, except the Cookie theft description task, demonstrated significantly lower scores for patients with FA when compared with controls and correlated with measures of disease progression. Thus, four of five measures capture speech dysfunction in FA and may provide feasible, inexpensive, quantitative testing for therapeutic monitoring in FA.


Effects of Long-Term Regular Continuous and Intermittent Walking on Oxidative Stress, Metabolic Profile, Heart Rate Variability, and Blood Pressure in Older Adults with Hypertension.
It is documented that regular exercise is beneficial for improving the antioxidant system, metabolic system, cardiac autonomic function, and blood pressure in those with hypertension. In this regard, low-intensity exercise is recommended for older adults, particularly those with chronic diseases. This study aimed to compare the effects of long-term regular continuous walking with intermittent walking on oxidative stress, metabolic profile, heart rate variability, and blood pressure in older adults with hypertension. Forty-three participants with hypertension aged 60-80 years were randomly divided into the continuous or intermittent walking (CON or INT) groups. Participants in the CON group walked for 30 min, 3 days/week for 12 weeks. Participants in the INT group split 30 min walking into 3 identical sessions punctuated by a 1 min rest after each session, 3 days/week for 12 weeks. Antioxidant and oxidative stress markers, metabolic markers, heart rate variability, and blood pressure were evaluated before and after the exercise program. Glutathione (GSH), GSH to GSH disulfide (GSSG) ratio, and total GSH increased significantly, and GSSG and malondialdehyde decreased significantly in both groups (p < 0.05) without significant differences between groups. Triglycerides, ratio of total cholesterol to high-density lipoprotein cholesterol, and atherosclerogenic index were significantly lower in the CON group than those in the INT group (p < 0.05). The standard deviation of the NN intervals and root mean square of the successive differences were significantly higher, and low-frequency power was significantly lower in the INT group than that in the CON group (p < 0.05). No significant changes in blood pressure were noted in both groups, and nor were there any significant differences between groups. Long-term regular continuous and intermittent walking may comparably increase antioxidants, reduce oxidative stress, and be beneficial for improving important blood pressure-related outcomes, including metabolic profile or cardiac autonomic function in older adults with hypertension.


Impact of Socioeconomic Status on Breast Reconstruction Outcomes.
Minority patients and those from low socioeconomic backgrounds are faced with barriers to care regarding breast reconstruction. With this study, we seek to elucidate variances in demographics to determine predictors of complications in implant-based breast reconstruction. Patients who underwent breast reconstruction with either direct to implant or immediate expander reconstruction by 1 surgeon were identified using the preoperative Breast-Q.Current income statistics available from the US Census Bureau by self-reported zip code were used to determine the median household income (MHI) to stratify differing socioeconomic backgrounds. Demographics were compared with body mass index, comorbidities, overall rate of postoperative complications, rate of implant infection, and type of reconstruction. Two hundred ninety-five patients met inclusion criteria. Overall rate of complications and rate of breast implant infection was higher for MHI of less than $50,000 compared with greater than $50,000 (P = 0.043 overall complications 40.20% vs 28.8%) (P = 0.04 implant infection 14.4% vs 7.1%). African American patients had higher body mass index (P = <0.001), rates of HTN (P = <0.001), and diabetes (P = 0.001), and were more likely to have a lower income (P = <0.001). There was, however, no difference in overall complications (P = 0.26), implant infection rate (P = 0.994), or capsular contracture (0.367) based on race. There was no difference in rate of comorbidities between low and high socioeconomic areas. This cohort demonstrates a higher rate of overall complications and infection in patients with a lower MHI and no difference based on race despite having higher risk factors for complications.Socioeconomic status is a multifaceted barrier to care that must be addressed in the perioperative period to decrease breast implant associated complications.


Evidence of lipid peroxidation and protein phosphorylation in cells upon oxidative stress photo-generated by fullerols.
An oxidative stress (OS) state is characterized by the generation of Reactive Oxygen Species (ROS) in a biological system above its capacity to counterbalance them [1]. Exposure to OS induces the accumulation of intracellular ROS, which in turn causes cell damage in the form of protein, lipid, and/or DNA oxidations. Such conditions are believed to be linked to numerous diseases or simply to the ageing of tissues. However, the controlled generation of ROS via photosensitizing drugs or photosensitizers (PS) is now widely used to treat various tumors and other infections [2,3]. Here we present a method to track the chemical changes in a cell after exposure to oxidative stress. OS is induced via fullerols, a custom made water soluble derivative of fullerene (C(60)), under visible light illumination. Synchrotron-based Fourier Transform InfraRed Microspectroscopy (S-FTIRM) was used to assess the chemical makeup of single cells after OS exposure. Consequently, a chemical fingerprint of oxidative stress was probed in this study through an increase in the bands linked with lipid peroxidation (carbonyl ester group at 1740 cm(-1)) and protein phosphorylation (asymmetric phosphate stretching at 1240 cm(-1)).


Meiotic behavior of rye heterozygous for ditelocentric substitutions.
Meiotic behavior has been investigated in rye plants carrying a heterozygous ditelocentric substitution for chromosomes 1R and 3R. Such a chromosomal rearrangement replaces a biarmed chromosome with two telocentrics, a situation karyotypically comparable to a Robertsonian translocation. As in Robertsonian translocation heterozygotes, delayed pairing characterizes the centromeric region in the rye pachytene heteromorphic trivalents. In addition, telocentric axes appear to be frequently engaged in nonhomologous synapsis (e.g., fold-back loops and two-by-two heterosynapsis) at their centromeric ends. Unlike those in Robertsonian translocation heterozygotes, the synaptic abnormalities detected here cannot be due to lack of partner homology. Rather, the chromosomal rearrangement itself appears to interfere with normal synaptonemal complex (SC) progression. The synaptic irregularities, which often result in complex pachytene multivalents, seem to have no effect on chiasma formation, since the rearranged pairs behave properly at metaphase I. Finally, differences in both SC length and progression patterns between plants and animals could explain the trans configurations of telocentric centromeres in plants, whereas only cis configurations of acrocentric kinetochores have been described in animals.


Hydrophobic ice-binding sites confer hyperactivity of an antifreeze protein from a snow mold fungus.
Snow mold fungus, Typhula ishikariensis, secretes seven antifreeze protein isoforms (denoted TisAFPs) that assist in the survival of the mold under snow cover. Here, the X-ray crystal structure of a hyperactive isoform, TisAFP8, at 1.0 Å resolution is presented. TisAFP8 folds into a right-handed β-helix accompanied with a long α-helix insertion. TisAFP8 exhibited significantly high antifreeze activity that is comparable with other hyperactive AFPs, despite its close structural and sequence similarity with the moderately active isoform TisAFP6. A series of mutations introduced into the putative ice-binding sites (IBSs) in the β-sheet and adjacent loop region reduced antifreeze activity. A double-mutant A20T/A212S, which comprises a hydrophobic patch between the β-sheet and loop region, caused the greatest depression of antifreeze activity of 75%, when compared with that of the wild-type protein. This shows that the loop region is involved in ice binding and hydrophobic residues play crucial functional roles. Additionally, bound waters around the β-sheet and loop region IBSs were organized into an ice-like network and can be divided into two groups that appear to mediate separately TisAFP and ice. The docking model of TisAFP8 with the basal plane via its loop region IBS reveals a better shape complementarity than that of TisAFP6. In conclusion, we present new insights into the ice-binding mechanism of TisAFP8 by showing that a higher hydrophobicity and better shape complementarity of its IBSs, especially the loop region, may render TisAFP8 hyperactive to ice binding.


Controlled growth of triblock polyelectrolyte brushes.
We have achieved a significant breakthrough in the synthesis of polyelectrolyte brushes of controlled thickness and density, which has been demonstrated by the synthesis of triblock copolymer brushes composed of cationic, neutral, and anionic segments.


Series of screening compounds with high hit rates for the exploration of multi-target activities and assay interference.
Generation of a database of analog series (ASs) with high assay hit rates for the exploration of assay interference and multi-target activities of compounds. ASs were computationally extracted from extensively tested screening compounds with high hit rates. A total of 6941 ASs were assembled comprising 14,646 unique compounds that were tested in a total of 1241 different assays covering 426 specified targets. These ASs were organized and prioritized on the basis of different activity and assay frequency criteria. All ASs and associated information are made available in an open access deposition. The large set of ASs will be further analyzed computationally and from a chemical perspective to identify assay interference compounds and candidates for exploring target promiscuity.


Low molecular weight GTP-binding proteins are altered in platelet hyperaggregation in IDDM.
We examined the hypothesis that hyperaggregating platelets from patients with insulin dependent diabetes mellitus (IDDM) have an alteration in location and function of the guanine nucleotide (GTP)-binding proteins. Platelets from 10 IDDM and 12 age-matched healthy control subjects were collected and washed. Thrombin-induced platelet aggregation (0.025 and 0.05 units for 60 seconds) was increased in IDDM (8.3 +/- 1.8% vs 22.3 +/- 4.4%, P < .05 and 49.9 +/- 7.3% vs 70.9 +/- 7.0%, P < .05). Four small molecular weight GTP-binding proteins were identified by binding of [32P]-GTP on sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) in the cytosol and membranes of these platelets. Each showed specificity for binding [32P]-GTP by competitive inhibition with unlabeled GTP. The total of the 27/28 kDa proteins was decreased in the membrane fraction (414 +/- 30 vs 252 +/- 40 dpm micrograms-1 protein x min, P < .05) and increased in the cytosolic fraction (62 +/- 8 vs 129 +/- 21 dpm unit-1 LDH x min, P < .05) in IDDM. The 21 kDa protein (60.3 +/- 3.5 vs 45.4 +/- 2.9 dpm micrograms-1 protein x min, P < .05) was decreased in platelet membrane in persons with IDDM. In conclusion, increased platelet aggregation in IDDM is accompanied by an altered cellular distribution of a 27/28 kDa GTP-binding protein. These data suggest that the low molecular weight GTP-binding proteins of the 27/28 kDa range may play an important regulatory role in the hyperaggregatory platelets in diabetes.


The influence of the initial stretch and the agonist-induced tone on the effect of basal and stimulated release of EDRF.
1. The effects of initial stretch and degree of agonist-induced tone on acetylcholine-induced relaxations were examined in rings of rat isolated aorta. The relaxation to acetylcholine was antagonized by atropine and almost completely abolished by haemoglobin. Relaxation to sodium nitroprusside was similar in rings with an intact or disrupted endothelium but that to isoprenaline was greater in intact preparations. 2. In preparations with either an intact or disrupted endothelium there was a similar length-dependent increase in the resting tension of the aortic rings. The size of the contractile response to phenylephrine (1 microM) was dependent on the initial length (and hence degree of stretch) of the preparation in both rubbed and unrubbed tissues. The absolute difference in contractile response between rubbed and unrubbed was greatest at 1.8 mm and less at the other lengths tested, including the optimum degree of stretch for contraction i.e. 2.4 mm. 3. The absolute acetylcholine-induced relaxation (only seen in rings with an intact endothelium) was dependent on the initial length (and hence degree of stretch) of the preparation and was maximum at 2.4 mm. The proportionate relaxation (i.e. expressed as a percentage of induced tone) was also length-dependent being optimal at 1.5 mm. 4. The sensitivity of the vessels to acetylcholine varied depending on the level of agonist-induced tone. When tone was low, acetylcholine sensitivity was high (at [NA] 0.03 microM: pIC50 = 7.36 +/- 0.07), when the concentration of noradrenaline was increased the tone increased and the acetylcholine sensitivity was low (at [NA] 0.3 microM: pIC50 = 6.57 +/- 0.07). 5. The absolute sensitivities and maximum relaxations induced by acetylcholine are discussed in relation to the initial degree of stretch (and hence length of the preparation) or the degree of agonist-induced tone.


Highly efficient visible light-induced photocatalytic oxidation of arsenite with nanosized WO3 particles in the presence of Cu2+ and CuO.
Although WO3 appears to be one of the extensively studied photocatalysts, the low response of pure WO3 in aqueous solution under visible light limits its application remarkably. In this work, the enhancement of the efficiency of WO3 for the visible light-driven photocatalytic oxidation of arsenite was explored using Cu2+ ion and CuO as a co-catalyst. While the addition of Cu2+ was found effective for the suppression of dissolution of WO3, the efficiency of CuO appeared to be slightly lower. Significant improvement of the efficiency for the photocatalytic oxidation of As(III) with WO3 was noted when Cu2+ ions and CuO were added. The optimized conditions were WO3 in the presence of 10 mg L-1 Cu2+ ion and 1 wt% CuO coupled with WO3, respectively. The As(III) concentration of 10 mg L-1 could be lowered to less than 0.1 mg L-1 by the photocatalytic treatment. Acidic pH favours the oxidation of arsenite in the presence of Cu2+ whereas basic pH is suitable with CuO. Characterization techniques such as TEM, XPS, XRD and UV-DRS were used to characterize photocatalysts. The reactive species scavenger tests revealed that the photo-induced holes (h+) play a key role in the photocatalytic oxidation process while the effect of •OH is negligible. It was found that As(III) oxidation rate was remarkably suppressed in the nitrogen atmosphere. A mechanism for enhanced photocatalytic oxidation has been proposed based on the results of the reactive species scavenger tests. This research may contribute to the large-scale As(III) oxidation treatment in the groundwater.


Delayed high-dose intravesical epirubicin therapy of superficial bladder cancer. A way to reduce the side effects and increase the efficacy--a phase 2 trial.
Intravesical epirubicin is a widely used agent for the treatment of superficial bladder cancer. A direct relationship between dose and activity has been reported: unfortunately the dose increase also increased the frequency and the intensity of treatment-related side effects. A phase 2 trial was designed to evaluate the toxicity and the activity of a delayed (biweekly) high-dose (80 mg) epirubicin therapy of superficial bladder cancer. Thirty patients with intermediate risk superficial bladder cancer (stage mTa, G2) have been treated with transurethral resection and epirubicin intravesical therapy: the patients were given 80 mg epirubicin in 50 ml sterile saline every 2 weeks for 6 times (delayed regimen). The follow-up ranged from 3 to 26 months. Eleven of 30 (37%) patients experienced a local adverse reaction to intravesical epirubicin requiring specific medication (grade > or = 2 according to NCI-CTC v.2.0, 1999). No systemic toxicity related to the treatment was observed. Out of the 29 evaluable patients, 22 (76%) were free of disease after the induction course, 6 (21%) had superficial bladder cancer recurrences and 1 (3%) experienced tumor progression. A delayed (biweekly instillation) high-dose (80 mg) intravesical epirubicin regimen was acceptable in terms of side effects and showed a worthwhile therapeutical impact in patients with intermediate risk superficial bladder cancer.


lon-1 regulates Caenorhabditis elegans body size downstream of the dbl-1 TGF beta signaling pathway.
In Caenorhabditis elegans, two well-characterized TGF beta signaling cascades have been identified: the Small/Male tail abnormal (Sma/Mab) and Dauer formation (Daf) pathways. The Sma/Mab pathway regulates body size morphogenesis and male tail development. The ligand of the pathway, dbl-1, transmits its signal through two receptor serine threonine kinases, daf-4 and sma-6, which in turn regulate the activity of the Smads, sma-2, sma-3, and sma-4. In general, Smads have been shown to both positively and negatively regulate the transcriptional activity of downstream target genes in various organisms. In C. elegans, however, target genes have remained elusive. We have cloned and characterized lon-1, a gene with homology to the cysteine-rich secretory protein (CRISP) family of proteins. lon-1 regulates body size morphogenesis, but does not affect male tail development. lon-1 is expressed in hypodermal tissues, which is the focus of body size determination, similar to sma-2, sma-4, and sma-6. Using genetic methods, we show that lon-1 lies downstream of the Sma/Mab signaling cascade and demonstrate that lon-1 mRNA levels are up-regulated in sma-6-null mutant animals. This provides evidence that lon-1 is negatively regulated by Sma/Mab pathway signaling. Taken together, these data identify lon-1 as a novel downstream target gene of the dbl-1 TGF beta-like signaling pathway.


Socioeconomic status and childhood leukaemia: a review.
A long-held view links higher socioeconomic status (SES) to higher rates of childhood leukaemia. Some recent studies exhibit associations in the opposite direction. We reviewed journal literature through August 2002 for associations between childhood leukaemia and socioeconomic measures. We determined the direction of each association and its P-value. We described the results with regard to study design, calendar period, geographic locale, and level of the socioeconomic measures (individual or ecological). For measures with sufficient number of results, we computed summary P-values across studies. Case-control studies conducted in North America since 1980 have involved subject interviews or self-administered questionnaires and have consistently reported inverse (negative) associations of childhood leukaemia with individual-level measures of family income, mother's education, and father's education. In contrast, associations have been consistently positive with father's occupational class in record-based case-control studies and with average occupational class in ecological studies. Connections of SES measures to childhood leukaemia are likely to vary with place and time. Validation studies are needed to estimate SES-related selection and participation in case-control studies. Because different socioeconomic measures (such as income and education) and individual-level and ecological-level measures may represent different risk factors, we advise researchers to report these measures separately rather than in summary indices of social class.


Rosacea and exposure to tandoor heat: Is there an association?
Particularly in eastern and southeastern regions of Turkey, women use tandoor ovens to bake bread and as a result are exposed to excessive heat. Exposure to heat for long periods may lead to the initiation or exacerbation of rosacea. The aim of this study was to investigate whether there is a relationship between exposure to heat from a tandoor and rosacea. A total of 350 female patients with various dermatological diseases were included in this study. These patients were divided into two groups comprising a control group and a group of tandoor users. Subjects in both the control and tandoor-user groups were screened to identify clinical and other characteristics, and symptoms and findings of rosacea and other dermatological disorders. The frequency of rosacea was significantly (P < 0.001) higher and that of acne markedly (P < 0.001) lower in the tandoor-user group than in the control group. Incidences of temporary and persistent types of erythema and telangiectasia, which are considered to be among the symptoms and findings of rosacea, were also significantly (P < 0.001) higher in the tandoor-user group than the control group. Frequencies of asthma and ex-smoker status differed significantly (P < 0.001 and P < 0.002, respectively) between the tandoor-user and control groups. Furthermore, the period of exposure to tandoor heat was positively correlated with the frequency of telangiectasia (r = 0.321, P < 0.01). Our study revealed a strong association between exposure to tandoor heat and rosacea. Further studies including higher numbers of patients are required to confirm our results.


Nitrate Reductases from Wild-Type and nr(1)-Mutant Soybean (Glycine max [L.] Merr.) Leaves : I. Purification, Kinetics, and Physical Properties.
NADH:nitrate reductase (EC 18.104.22.168) and NAD(P)H:nitrate reductase (EC 126.96.36.199) were purified from wild-type soybean (Glycine max [L.] Merr., cv Williams) and nr(1)-mutant soybean plants. Purification included Blue Sepharose- and hydroxylapatite-column chromatography using acetone powders from fully expanded unifoliolate leaves as the enzyme source.Two forms of constitutive nitrate reductase were sequentially eluted with NADPH and NADH from Blue Sepharose loaded with extract from wild-type plants grown on urea as sole nitrogen source. The form eluted with NADPH was designated c(1)NR, and the form eluted with NADH was designated c(2)NR. Nitrate-grown nr(1) mutant soybean plants yielded a NADH:nitrate reductase (designated iNR) when Blue Sepharose columns were eluted with NADH; NADPH failed to elute any NR form from Blue Sepharose loaded with this extract. Both c(1)NR and c(2)NR had similar pH optima of 6.5, sedimentation behavior (s(20,w) of 5.5-6.0), and electrophoretic mobility. However, c(1)NR was more active with NADPH than with NADH, while c(2)NR preferred NADH as electron donor. Apparent Michaelis constants for nitrate were 5 millimolar (c(1)NR) and 0.19 millimolar (c(2)NR). The iNR from the mutant had a pH optimum of 7.5, s(20,w) of 7.6, and was less mobile on polyacrylamide gels than c(1)NR and c(2)NR. The iNR preferred NADH over NADPH and had an apparent Michaelis constant of 0.13 millimolar for nitrate.Thus, wild-type soybean contains two forms of constitutive nitrate reductase, both differing in their physical properties from nitrate reductases common in higher plants. The inducible nitrate reductase form present in soybeans, however, appears to be similar to most substrateinduced nitrate reductases found in higher plants.


Vinblastine resets tumor-associated macrophages toward M1 phenotype and promotes antitumor immune response.
Massive tumor-associated macrophage (TAM) infiltration is observed in many tumors, which usually display the immune-suppressive M2-like phenotype but can also be converted to an M1-like antitumor phenotype due to their high degree of plasticity. The macrophage polarization state is associated with changes in cell shape, macrophage morphology is associated with activation status. M1 macrophages appeared large and rounded, while M2 macrophages were stretched and elongated cells. Manipulating cell morphology has been shown to affect the polarization state of macrophages. The shape of the cell is largely dependent on cytoskeletal proteins, especially, microtubules. As a microtubule-targetting drug, vinblastine (VBL) has been used in chemotherapy. However, no study to date has explored the effect of VBL on TAM shape changes and its role in tumor immune response. We used fluorescent staining of the cytoskeleton and quantitative analysis to reveal the morphological differences between M0, M1, M2, TAM and VBL-treated TAM. Flow cytometry was used to confirm the polarization states of these macrophages using a cell surface marker-based classification. In vivo antibody depletion experiments in tumor mouse models were performed to test whether macrophages and CD8+ T cell populations were required for the antitumor effect of VBL. VBL and anti-PD-1 combination therapy was then investigated in comparison with monotherapy. RNA-seq of TAM of treated and untreated with VBL was performed to explore the changes in pathway activities. siRNA mediated knockdown experiments were performed to verify the target pathway that was affected by VBL treatment. Here, we showed that VBL, an antineoplastic agent that destabilizes microtubule, drove macrophage polarization into the M1-like phenotype both in vitro and in tumor models. The antitumor effect of VBL was attenuated in the absence of macrophages or CD8+ T cells. Mechanistically, VBL induces the activation of NF-κB and Cyba-dependent reactive oxygen species generation, thus polarizing TAMs to the M1 phenotype. In parallel, VBL promotes the nuclear translocation of transcription factor EB, inducing lysosome biogenesis and a dramatic increase in phagocytic activity in macrophages. This study explored whether manipulating cellular morphology affects macrophage polarization and consequently induces an antitumor response. Our data reveal a previously unrecognized antitumor mechanism of VBL and suggest a drug repurposing strategy combining VBL with immune checkpoint inhibitors to improve malignant tumor immunotherapy.


Regulation of c-MYC protein expression in the developing rat cerebellum by phosphoinositide turnover.
Using developing rat cerebellum, we examined the correlation between the turnover of phosphoinositide (PI) and c-myc expression. The 32P incorporation into polyphosphoinositides changed remarkably with advancing age. It reached a maximum value on PND 7, and then decreased gradually until PND 14. Immunostaining by anti-PIP2 antibody changed in parallel. The expression of c-myc mRNA was also changed developmentally, showing a peak on PND 7; whereas c-MYC protein expression showed a peak on PND 10. Together, these results suggest that c-myc expression is regulated by PI turnover during the early developing stage of rat cerebellum.


[Effect of transforming growth factor-beta1 on proliferation and apoptosis of mononuclear cells of cord blood].
To explore the mechanism of transforming growth factor-beta1 (TGF-beta1) effect on umbilical cord blood mononuclear cells proliferation and apoptosis, 5-bromo-2'-deoxyurine (BrdU) incorporation assay was adopted to detect effect of TGF-beta1 on synthesis of DNA in cells. Western blot method was used to examine effect of TGF-beta1 on expression of cyclin A, Cyclin D1, CDK2 and CDK4 in G1 phase of cell cycle. Giemsa staining and flow cytometry (FCM) were performed to detected effect of TGF-beta1 on cell apoptosis. The results showed that (1) after culture of cells with IMDM containing 10% FBS, 10% FBS + 1 ng/ml TGF-beta1, 10% FBS + 2 ng/ml TGF-beta1 or 10% FBS + 5 ng/ml TGF-beta1 for 12 hours the OD values of TGF-beta1 group were significantly lower than control group (P <0.01); after culture for 24 hours the OD values of 1 ng/ml TGF-beta1 group had no significant difference compared with control group (P >0.05), but the OD values of 2 ng/ml and 5 ng/ml TGF-beta1 groups were significantly lower than control group (P <0.05). (2) 2 ng/ml TGF-beta1 could significantly inhibit the production of cyclin A, cyclin D1, CDK2 and CDK4, the protein levels were significantly lower than control group. (3) when the cells were co-cultured with 2 ng/ml TGF-beta1 for 12 and 24 hours, Giemsa staining and FCM detection could display typical apoptosis, the apoptosis rates were 14.42% and 31.98%, while apoptosis rate in control were 4.71% and 5.76%. It is concluded that TGF-beta1 can inhibit production of G1 cyclins and CDKs of umbilical cord blood mononuclear cells, arrest cells in the G1 phase of cell cycle and induce cell apoptosis. Thus, TGF-beta1 may be an important negative modulator in hematopoiesis.


Gorlin syndrome: a case report.
Gorlin syndrome is an autosomal dominant inherited condition that exhibits high penetrance and variable expressivity. It is characterized mainly by Basal cell carcinomas, Odontogenic keratocysts and skeletal anomalies. However, medical literature documents both common and lesser known manifestations of the disorder involving the skin, central nervous system, skeletal system etc. Diagnosis of the syndrome in childhood is basically through oral abnormalities. A case of Gorlin syndrome has been reported here, with review of literature.


A reassessment of the molecular origin of cold denaturation.
The existence of cold denaturation is now firmly demonstrated by its direct observation for several globular proteins in aqueous solution. But the physico-chemical explanation of this intriguing phenomenon is still unsatisfactory. In this paper we deepen our understanding of cold denaturation by taking advantage of the theoretical model developed by Ikegami and using thermodynamic data on the transfer to water of liquid N-alkyl amides. The analysis leads to the conclusion that the presence of water is fundamental to determine the existence of cold denaturation due to its strong energetic interaction with the amino acid residues previously buried in the protein's interior.


Primary chondrosarcoma of the lung. A report of two cases.
This report describes two cases of primary chondrosarcoma arising in the lung. In both cases, the treatment was palliative due to unresectable primary tumours. One patient's tumour appears to have originated in a persistent hamartoma; the other, from lung parenchyma. Primary chondrosarcoma of the lung tends to remain localized. Wide local excision is the treatment of choice when possible. Palliation can be accomplished with radiation and/or systemic chemotherapy.


Effects of glycopyrrolate and atropine on heart rate variability.
Analysis of heart rate variability, combined with physiological tests (deep breathing and tilt tests) was used to characterise the effects of atropine and glycopyrrolate on the parasympathetic nervous tone of the heart in healthy male volunteers. The low dose of atropine (120 micrograms) administered as a continuous infusion in 15 min was associated with parasympatomimetic effects estimated by the slowing of the heart rate and an increase of the mean and beat-to-beat heart rate variability. The bradycardia and increase of heart rate variability following infusion of glycopyrrolate (50 micrograms) was less marked and did not differ significantly from that of placebo. The higher doses of atropine (720 micrograms) and glycopyrrolate (300 micrograms) administered as a continuous infusion in 15 min produced an equal vagal cardiac blockade characterised by significant tachycardia and a decrease in overall and beat-to-beat heart rate variability. It is concluded that at low doses the parasympatomimetic action of glycopyrrolate is less marked than that of atropine; and at higher doses only small differences exist between these two muscarinic antagonists in their effects on cardiac vagal outflow, assessed by heart rate and heart rate variability.


Penetrating craniocerebral injuries in civilians.
During a 6-year period (1984-89), 31 patients were treated at Rambam Medical Center with penetrating craniocerebral injuries (PCCI) not associated with military action. Eighteen (58%) patients died during their initial hospitalization; only two of them had admission Glasgow Coma Scale (GCS) above five. The admission GCS coupled with the mode of injury (type of missile and motivation of shooting) were valuable for early accurate prognosis assessment. Patients with admission GCS of 3 and 4 invariably died despite rapid treatment and attempted haematoma evacuation. The neurological status, CT appearance, as well as the motivation of shooting should be considered in order to assess accurately the possible outcome. Compared with our military series of 113 patients with PCCI, there were more extensive injuries, although the mean period until neurosurgical treatment was the same. Long-term complications connected to dural tears remote from the entrance wound occurred in three of the survivors.


Effect of diethyldithiocarbamate on Cryptosporidium parvum infection in immunosuppressed rats.
Diethyldithiocarbamate was the only immune modulator of 7 evaluated to show activity against Cryptosporidium parvum in immunosuppressed rats. The model was then used to assess the drug's activity further. When administered prophylactically, oral doses > or = 75 mg/kg/day significantly (P < or = 0.05) reduced the severity of ileal infection and doses > or = 300 mg/kg/day significantly (P < or = 0.05) inhibited infection of the biliary tract. When administered to rats with established infection, the drug significantly (P < or = 0.05) reduced the parasite burden in the ileum but was ineffective against biliary tract infection. The data suggest that diethyldithiocarbamate is effective for treating cryptosporidiosis of the small intestine but is probably ineffective against chronic cryptosporidiosis involving the large intestine or biliary tract.


Homocrystallization and Stereocomplex Crystallization Behaviors of As-Spun and Hot-Drawn Poly(l-lactide)/Poly(d-lactide) Blended Fibers During Heating.
A series of poly(l-lactide)/poly(d-lactide) blended chips (LDC), as-spun LD fibers (LDA) and hot-drawn LD fibers (LDH) were prepared for investigating the homocrystallization and stereocomplex crystallization behaviors of LDA and LDH fibers during heating. Modulated differential scanning calorimetry (MDSC), hot stage polarized microscopy (HSPM), and real-time wide-angle X-ray diffraction (WAXD) were used for studying the crystallization and melting behaviors, fiber morphology, and crystalline structure evolution of the LDA and LDH fibers' homocrystals and stereocomplex crystals during heating. The molecular chain orientations of the LDA and LDH fibers were obtained through spinning and improved through the hot drawing processes. When the molecular chain was oriented on the fiber axis, the homocrystals and stereocomplex crystals of the fibers began to form in turn as the heating temperature exceeded the glass transition temperature of the fiber. The side-by-side packing of the molecular chains was promoted by mixing the molecular chains with the extrusion screw during the spinning process, facilitating stereocomplex crystallization. When the LDA fiber was heated above the glass transition temperature of the fiber, movement of the fiber molecular chain-including molecular chain orientation and relaxation, as well as crystallization, melting, and recrystallization of homocrystals and stereocomplex crystals-were investigated through HSPM. MDSC and real-time WAXD were used to observe the molecular chains of the melted poly(l-lactide) and poly(d-lactide) homocrystals of the fibers rearranging and transiting to form stereocomplex crystals during heating.


The chlamydial organism Simkania negevensis forms ER vacuole contact sites and inhibits ER-stress.
Most intracellular bacterial pathogens reside within membrane-surrounded host-derived vacuoles. Few of these bacteria exploit membranes from the host's endoplasmic reticulum (ER) to form a replicative vacuole. Here, we describe the formation of ER-vacuole contact sites as part of the replicative niche of the chlamydial organism Simkania negevensis. Formation of ER-vacuole contact sites is evolutionary conserved in the distantly related protozoan host Acanthamoeba castellanii. Simkania growth is accompanied by mitochondria associating with the Simkania-containing vacuole (SCV). Super-resolution microscopy as well as 3D reconstruction from electron micrographs of serial ultra-thin sections revealed a single vacuolar system forming extensive ER-SCV contact sites on the Simkania vacuolar surface. Simkania infection induced an ER-stress response, which was later downregulated. Induction of ER-stress with Thapsigargin or Tunicamycin was strongly inhibited in cells infected with Simkania. Inhibition of ER-stress was required for inclusion formation and efficient growth, demonstrating a role of ER-stress in the control of Simkania infection. Thus, Simkania forms extensive ER-SCV contact sites in host species evolutionary as diverse as human and amoeba. Moreover, Simkania is the first bacterial pathogen described to interfere with ER-stress induced signalling to promote infection.


A case report of Basal Ganglia calcification - a rare finding of hypoparathyroidism.
Physiological intracranial calcification occurs in about 0.3-1.5% of cases. It is asymptomatic and detected incidentally by neuroimaging. Pathological basal ganglia calcification is due to various causes, such as: metabolic disorders, infectious and genetic diseases. Hypoparathyroidism and pseudohypoparathyroidism are the most common causes of pathological basal ganglia calcification. Besides tetany and seizures this condition is presented by parkinsonism and dementia. Such parkinsonism does not respond to drugs containing levodopa. Infections (toxoplasmosis, rubella, cytomegalovirus, cysticercosis, AIDS) give multiple and asymmetric intracranial calcification. Inherited and neurodegenerative diseases cause symmetrical, bilateral basal ganglia calcification which is not related to metabolic disorders. Since adequate treatment of hypoparathyroidism may lead to marked clinical improvement, serum concentration of calcium, phosphorus, and parathyroid hormone (PTH) is suggested to be determined in all individuals with calcification of the basal ganglia to rule out hypoparathyroidism.


Synthesis and degranulation-inhibiting activities of the proposed apteniols B, C, and G.
The synthesis of compounds with the structures proposed for the oxyneolignan apteniols B, C, and G is described. The diphenyl ether skeletons of the proposed apteniols were formed via Ullmann ether synthesis. In particular, the spectral data for the synthesized apteniols B, C, and G did not agree with those previously reported for the isolated compounds. Furthermore, the synthesized proposed apteniol B did not show degranulation-inhibiting activity, while the prepared proposed apteniols C and G exhibited activities considerably weaker than that of the methyl ester of proposed apteniol A.


[Opportunities, Challenges and Strategies for Malaria Elimination in the Tibet Autonomous Region of China].
This review summarizes the endemic characteristics and influencing factors of malaria in the Tibet Autonomous Region of China, as well as the opportunities and challenges for malaria elimination in this region. Recommendations on strategies for malaria control are also made.


Transcriptional profiling suggests that multiple metabolic adaptations are required for effective proliferation of Pseudomonas aeruginosa in jet fuel.
Fuel is a harsh environment for microbial growth. However, some bacteria can grow well due to their adaptive mechanisms. Our goal was to characterize the adaptations required for Pseudomonas aeruginosa proliferation in fuel. We have used DNA-microarrays and RT-PCR to characterize the transcriptional response of P. aeruginosa to fuel. Transcriptomics revealed that genes essential for medium- and long-chain n-alkane degradation including alkB1 and alkB2 were transcriptionally induced. Gas chromatography confirmed that P. aeruginosa possesses pathways to degrade different length n-alkanes, favoring the use of n-C11-18. Furthermore, a gamut of synergistic metabolic pathways, including porins, efflux pumps, biofilm formation, and iron transport, were transcriptionally regulated. Bioassays confirmed that efflux pumps and biofilm formation were required for growth in jet fuel. Furthermore, cell homeostasis appeared to be carefully maintained by the regulation of porins and efflux pumps. The Mex RND efflux pumps were required for fuel tolerance; blockage of these pumps precluded growth in fuel. This study provides a global understanding of the multiple metabolic adaptations required by bacteria for survival and proliferation in fuel-containing environments. This information can be applied to improve the fuel bioremediation properties of bacteria.


Short-term consequences of Helicobacter pylori treatment in patients with oral lichen planus: A prospective study.
Oral lichen planus (OLP) is a multifactorial chronic inflammatory condition with unknown etiology. This condition has been associated with Helicobacter pylori. This study aimed to investigate the relationship between the treatment of H. pylori infection and improvements in OLP lesions. In this cohort study, 42 patients with erosive or ulcerative OLP lesions were evaluated in terms of H. pylori infection using the H. pylori stool antigen (HpSA) test. The patients were divided into three groups. The first group consisted of 12 H. pylori-negative patients. The second group consisted of 21 H. pylori-positive patients receiving antibacterial treatment. The third group included nine H. pylori-positive patients not willing to receive treatment. All the three groups underwent the usual OLP treatment. Patients in the second and third groups were re-evaluated by the HpSA test after two months. The efficacy indexes and visual analog scale were used to evaluate clinical improvements. The efficiency index and pain scores were affected by the intervention (P<0.001). The logistic regression analysis showed that the severity index before treatment was significantly effective (OR=0.745 (95% CI: 0.602‒0.923; P=0.007). No statistical significance for factors affecting other variables (P>0.05) was obtained. Pain intensity was higher in patients with H. pylori than in those without H. pylori before treatment. Also, in patients with H. pylori, the treatment affects the complete recovery rate.


Fascin-1 Contributes to Neuropathic Pain by Promoting Inflammation in Rat Spinal Cord.
Neuropathic pain is a complicated clinical syndrome caused by heterogeneous etiology. Despite the fact that the underlying mechanisms remain elusive, it is well accepted that neuroinflammation plays a critical role in the development of neuropathic pain. Fascin-1, an actin-bundling protein, has been proved to be involved in the processing of diverse biological events including cellular development, immunity, and tumor invasion etc. Recent studies have shown that Fascin-1 participates in antigen presentation and the regulation of pro-inflammatory agents. However, whether Fascin-1 is involved in neuropathic pain has not been reported. In the present study we examined the potential role of Fascin-1 by using a rodent model of chronic constriction injury (CCI). Our results showed that Fascin-1 increased rapidly in dorsal root ganglions (DRG) and spinal cord (SC) after CCI. The increased Fascin-1 widely expressed in DRG, however, it localized predominantly in microglia, seldom in neuron, and hardly in astrocyte in the SC. Intrathecal injection of Fascin-1 siRNA not only suppressed the activation of microglia and the release of pro-inflammatory mediators, but also attenuated the mechanical allodynia and thermal hyperalgesia induced by CCI.


EGFR and KRAS mutational profiling in fresh non-small cell lung cancer (NSCLC) cells.
Knowledge of tumor mutational status has become a priority for effective NSCLC-tailored treatment. NSCLC diagnosis is more often reached through biopsy; thus, there is a clear need to implement for routine tumor molecular profiling on small cytological samples. This work aims to screen and compare the EGFR and KRAS mutational prevalence in fresh tumor cells and in corresponding routinely processed samples derived from trans-thoracic fine-needle aspiration. The latter currently represents the most appropriate diagnostic procedure in case of peripheral lesions, such as adenocarcinomas, which account for almost 40% of all NSCLCs and for the highest EGFR mutational rates. Two hundred and forty-four patients carrying peripheral lung masses underwent CT-guided aspiration. The obtained material was split, and a part was addressed to conventional histopathological analysis while the remaining one was stored at -20 °C. In case of confirmation of adenocarcinoma, tumor genomic DNA was extracted from both fresh and fixed material, and EGFR and KRAS sequencing was performed. We identified 136 adenocarcinomas; from 134, we could recover enough material for the study. A full match was demonstrated between EGFR/KRAS mutational prevalences through the two approaches tested. We found EGFR mutations in 13 patients (9.7%); 7 were females and 11 never or former smokers. KRAS mutations occurred in 20 (14.9%) patients. EGFR and KRAS mutations were mutually exclusive. Mutational screening on fresh cancer cells is an achievable, safe and cost-effective procedure which might allow routinely tumor molecular profiling as powerful integration of conventional histopathological analysis.


Cetuximab intensifies the ADCC activity of adoptive NK cells in a nude mouse colorectal cancer xenograft model.
Natural killer (NK) cells, discovered ~40 years ago, are believed to be the most effective cytotoxic lymphocytes to counteract cancer; however, adoptive NK cell therapy in vivo has encountered certain limitations, including a lack of specificity. The drug cetuximab can mediate antibody dependent cell mediated cytotoxicity (ADCC) activity through NK cells in vivo, and has been approved for the first-line treatment of epidermal growth factor receptor (EGFR)-positive metastatic colorectal cancer (CRC). However, the ADCC activity of adoptive NK cells, induced by cetuximab in a nude mouse CRC xenograft model, has not been previously reported. The aim of the present study was to explore the ADCC activity of cetuximab combined with adoptive NK cells in CRC xenograft models with various EGFR expressions. The nude mouse xenograft models were established by subcutaneously injecting LOVO or SW620 cells. The mice were then randomly divided into 6 groups: Phosphate-buffered saline, cetuximab, human immunoglobulin G (hIgG), NK cells, hIgG plus NK cells and cetuximab plus NK cells. The ADCC antitumor activity was evaluated in these CRC models. The results indicated that the cetuximab plus NK cells group showed the greatest tumor inhibition effect compared with the NK cells group in LOVO xenograft tumor models with positive EGFR expression. However, the combination of cetuximab and NK cells did not show a stronger tumor inhibitory effect against the SW620 xenograft tumor models compared with the efficiency of NK cells. In conclusion, cetuximab could intensify the ADCC antitumor activity of adoptive NK cells towards CRC with an increased EGFR expression. The combination of cetuximab and NK cells may be a potential immunotherapy for metastatic CRC patients with positive EGFR expression.


Diverse 3D microarchitectures made by capillary forming of carbon nanotubes.
A new technology called capillary forming enables transformation of vertically aligned nanoscale filaments into complex three-dimensional microarchitectures. We demonstrate capillary forming of carbon nanotubes into diverse forms having intricate bends, twists, and multidirectional textures. In addition to their novel geometries, these structures have mechanical stiffness exceeding that of microfabrication polymers, and can be used as masters for replica molding


Cytological, molecular, and clinical features of noninvasive follicular thyroid neoplasm with papillary-like nuclear features versus invasive forms of follicular variant of papillary thyroid carcinoma.
The noninvasive follicular variant of papillary thyroid carcinoma (PTC) has an indolent clinical behavior in comparison with other PTCs, including the invasive follicular variant of papillary thyroid carcinoma (IFVPTC). Recently, the term noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP) was introduced to emphasize the low biological potential of these tumors. This study compares clinical, cytological, and molecular features of NIFTP and IFVPTC. The study consisted of 97 thyroid fine-needle aspiration biopsy (FNAB) cases with corresponding surgical pathology from the pathology archives of the Massachusetts General Hospital. The collected patient data included the following: age, sex, type of surgery, tumor size, and prior cytological diagnosis with The Bethesda System for Reporting Thyroid Cytopathology. A molecular analysis using anchored multiplex polymerase chain reaction was performed for all cases. Each case was reviewed and subclassified histologically as NIFTP or IFVPTC. Cytology slides were scored semiquantitatively for nuclear atypia. The statistical analysis was performed with the nonparametric Mann-Whitney test. The 97-case cohort consisted of 50 NIFTP cases and 47 IFVPTC cases, including 18 encapsulated IFVPTC cases and 29 nonencapsulated IFVPTC cases. Differences in the type of surgery (P = .0399), molecular features (P = .0141), cytological classification (P = .0266), and nuclear scores (P = .0141) between NIFTP and IFVPTC were observed. There was overlap in the cytological classification of NIFTP and IFVPTC; however, NIFTP was more often classified as atypia of undetermined significance/follicular lesion of undetermined significance or follicular neoplasm/suspicious for follicular neoplasm in comparison with both subsets of IFVPTC. NIFTP was primarily associated with mutations in RAS, whereas an equal number of IFVPTC cases were associated with BRAFV600E or with RAS mutations. Despite differences in the cytological classification and molecular profiles between NIFTP and IFVPTC, the degree of overlap makes it unlikely that most cases of NIFTP and IFVPTC can be accurately distinguished with FNAB. Cancer Cytopathol 2017;125:323-331. © 2017 American Cancer Society.


Neuroendocrine regulation of LHRH and gonadotropin.
Analysis of gonadotropin secretion patterns throughout the menstrual cycle revealed a complex rhythm. Especially at 1-3 hour intervals this was seen, with a frequency that was dependent on the phase of the menstrual cycle. There is little information available concerning the role of plasma luteinizing hormone-releasing hormone (LHRH) in the regulation of donadotropin secretion in amenorrheic and postmenopausal women. In this paper, the authors present the results of a detailed investigation into the secretory pattern of LH, follicle stimulating hormone, and LHRH in normal women with a normal menstrual cycle, amenorrheic women, and postmenopausal women.


Complications of adenotonsillectomy.
Tonsillectomy and adenoidectomy are two of the most commonly performed pediatric surgical procedures. As with all surgical intervention, tonsillectomy and adenoidectomy are associated with a host of potential complications. Fortunately, for most children undergoing adenotonsillectomy (T&A), complications are rare. This review is intended to summarize recent reports, which may lead to prevention and treatment of T&A complications. The presented reports of complications and risk factors for complications in children undergoing T&A highlight perioperative medical management as a means to decrease perioperative complications. Certain tonsillectomy techniques, such as microdebrider intracapsular tonsillectomy, may lead to decreased posttonsillectomy hemorrhage and dehydration. Despite published recommendations, preoperative assessments for bleeding diatheses vary among practitioners. Conversely, guidelines for evaluation of posttonsillectomy hemorrhage are lacking. Some pediatric populations, such as children with coagulopathy, neurologic disease, and obesity, have increased risk of perioperative complications, and recent reports regarding their care are presented. We present recent data pertinent to the contemporary management of medical and surgical complications of T&A, with particular focus on specific at-risk pediatric populations. In the patient groups illustrated in this review, anticipation of complications may decrease complications or lead to improved management of complications when they occur.


Malignant cutaneous melanoma associated with neurofibromatosis in two sisters from a family with familial atypical multiple mole melanoma syndrome. Case reports and review of the literature.
Two cases of malignant melanoma associated with neurofibromatosis in two first-degree female relatives from a family with familial atypical multiple mole melanoma (FAMMM) syndrome are presented. The types of neurofibromatosis and the FAMMM syndrome are discussed in relation to these cases and the family genealogic tree. Although the FAMMM syndrome could probably be seen as the underlying disease in the current cases, review of literature has failed to establish a clear relation. Research into pigmentary disturbance in neurofibromatosis is necessary to give a final explanation. To our knowledge, this is the first report in literature describing the familial occurrence of both diseases and it might present an addition to the tumor spectrum in the FAMMM syndrome.


Coronavirus disease (COVID-19) prevention and treatment methods and effective parameters: A systematic literature review.
The coronavirus disease 2019 (COVID-19) outbreak was first identified in Wuhan in December 2019, which was declared a pandemic virus by the world health organization on March 11 in 2020. COVID-19 is an infectious disease and almost leads to acute respiratory distress syndrome. Therefore, the virus epidemic is a big problem for humanity healthy and can lead die in special people with background diseases such as chronic obstructive pulmonary diseases, chronic heart failure, diabetes mellitus, and kidney failure. Different medical, social, and engineering methods have been proposed to face the disease include treatment, detection, prevention, and prediction approaches. We propose a taxonomy tree to investigate the disease confronting methods and their negative and positive effects. Our work consists of a case study and systematic literature review (SLR) to evaluate the proposed methods against the virus outbreak and disease epidemic. Our experimental results and observations demonstrate the impact of the proposed medical, prevention, detection, prediction, and social methods for facing the spread of COVID-19 from December 2019 to July 2020. Our case study can help people have more information about the disease and its impact on humanity healthy and illustrate effective self-caring methods and therapies.


The C-terminal domain of perfringolysin O is an essential cholesterol-binding unit targeting to cholesterol-rich microdomains.
There is much evidence to indicate that cholesterol forms lateral membrane microdomains (rafts), and to suggest their important role in cellular signaling. However, no probe has been produced to analyze cholesterol behavior, especially cholesterol movement in rafts, in real time. To obtain a potent tool for analyzing cholesterol dynamics in rafts, we prepared and characterized several truncated fragments of theta-toxin (perfringolysin O), a cholesterol-binding cytolysin, whose chemically modified form has been recently shown to bind selectively to rafts. BIAcore and structural analyses demonstrate that the C-terminal domain (domain 4) of the toxin is the smallest functional unit that has the same cholesterol-binding activity as the full-size toxin with structural stability. Cell membrane-bound recombinant domain 4 was detected in the floating low-density fractions and was found to be cofractionated with the raft-associated protein Lck, indicating that recombinant domain 4 also binds selectively to cholesterol-rich rafts. Furthermore, an enhanced green fluorescent protein-domain 4 fusion protein stains membrane surfaces in a cholesterol-dependent manner in living cells. Therefore, domain 4 of theta-toxin is an essential cholesterol-binding unit targeting to cholesterol in membrane rafts, providing a very useful tool for further studies on lipid rafts on cell surfaces and inside cells.


Protective Effect of Melatonin for Renal Ischemia-Reperfusion Injury: A Systematic Review and Meta-Analysis.
Background: Renal ischemia-reperfusion (I/R) injury is one of the major causes related to acute kidney damage. Melatonin has been shown as a powerful antioxidant, with many animal experiments have been designed to evaluate the therapeutic effect of it to renal I/R injury. Objectives: This systematic review aimed to assess the therapeutic effect of melatonin for renal I/R injury in animal models. Methods and Results: The PubMed, Web of Science, Embase, and Science Direct were searched for animal experiments applying melatonin to treat renal I/R injury to February 2021. Thirty-one studies were included. The pooled analysis showed a greater reduction of blood urea nitrogen (BUN) (21 studies, weighted mean difference (WMD) = -30.00 [-42.09 to -17.91], p < 0.00001), and serum creatinine (SCr) (20 studies, WMD = -0.91 [-1.17 to -0.66], p < 0.00001) treated with melatonin. Subgroup analysis suggested that multiple administration could reduce the BUN compared with control. Malondialdehyde and myeloperoxidase were significantly reduced, meanwhile, melatonin significantly improved the activity of glutathione, as well as superoxide dismutase. The possible mechanism for melatonin to treat renal I/R injury is inhibiting endoplasmic reticulum stress, apoptosis, inflammation, autophagy, and fibrillation in AKI to chronic kidney disease. Conclusions: From the available data of small animal studies, this systematic review demonstrated that melatonin could improve renal function and antioxidative effects to cure renal I/R injury through, then multiple administration of melatonin might be more appropriate. Nonetheless, extensive basic experiments are need to study the mechanism of melatonin, then well-designed randomized controlled trials to explore the protective effect of melatonin.


[Determination of nitrogen compounds in catalytic gasolines by gas chromatography-nitrogen chemiluminescence detection].
A method for the separation and determination of nitrogen compounds in catalytic gasolines by gas chromatography-nitrogen chemiluminescence detection (GC-NCD) was established. The effects of the flow rate of carrier gas and the oven temperature on the resolution were studied. More than 20 nitrogen compounds, including amines, pyridine, aniline, 2-methyl aniline, 3-methyl aniline, 4-methyl aniline, quinoline, and indole, in catalytic gasoline were identified based on the retention time of some pure nitrogen compounds and by gas chromatography-mass spectrometry. The relative standard deviations of the peak areas of main nitrogen compounds in a catalytic gasoline sample were less than 2.5% and the detection limits for nitrogen were 1.0 mg/L under the chosen conditions. The linear ranges were 1.0-100 mg/L nitrogen for each nitrogen compound. The correlation coefficients were more than 0.998. The method can be successfully applied for the determination of each nitrogen compound in different catalytic gasolines.


Efficacy of treatment of insomnia in migraineurs with eszopiclone (Lunesta®) and its effect on total sleep time, headache frequency, and daytime functioning: A randomized, double-blind, placebo-controlled, parallel-group, pilot study.
A review on headache and insomnia revealed that insomnia is a risk factor for increased headache frequency and headache intensity in migraineurs. The authors designed a randomized, double blind, placebo-controlled, parallel-group, pilot study in which migraineurs who also had insomnia were enrolled, to test this observation. In the study, the authors treated 79 subjects with IHS-II migraine with and/or without aura and with DSM-IV primary insomnia for 6 weeks with 3 mg eszopiclone (Lunesta(®)) or placebo at bedtime. The treatment was preceded by a 2-week baseline period and followed by a 2-week run-out period. Of the 79 subjects treated, 75 were evaluable, 35 in the eszopiclone group, and 40 in the placebo group. At baseline, the groups were comparable except for sleep latency. Of the three remaining sleep variables, total sleep time, nighttime awakenings, and sleep quality, the number of nighttime awakenings during the 6-week treatment period was significantly lower in the eszopiclone group than in the placebo group (P = 0.03). Of the three daytime variables, alertness, fatigue, and functioning, this was also the case for fatigue (P = 005). The headache variables, frequency, duration, and intensity, did not show a difference from placebo during the 6-week treatment period. The study did not meet primary endpoint, that is, the difference in total sleep time during the 6-week treatment period between eszopiclone and placebo was less than 40 minutes. Therefore, it failed to answer the question as to whether insomnia is, indeed, a risk factor for increased headache frequency and headache intensity in migraineurs.