Regional hyperperfusion in older adults with objectively-defined subtle cognitive decline.
Although cerebral blood flow (CBF) alterations are associated with Alzheimer's disease (AD), CBF patterns across prodromal stages of AD remain unclear. Therefore, we investigated patterns of regional CBF in 162 Alzheimer's Disease Neuroimaging Initiative participants characterized as cognitively unimpaired (CU; n = 80), objectively-defined subtle cognitive decline (Obj-SCD; n = 31), or mild cognitive impairment (MCI; n = 51). Arterial spin labeling MRI quantified regional CBF in a priori regions of interest: hippocampus, inferior temporal gyrus, inferior parietal lobe, medial orbitofrontal cortex, and rostral middle frontal gyrus. Obj-SCD participants had increased hippocampal and inferior parietal CBF relative to CU and MCI participants and increased inferior temporal CBF relative to MCI participants. CU and MCI groups did not differ in hippocampal or inferior parietal CBF, but CU participants had increased inferior temporal CBF relative to MCI participants. There were no CBF group differences in the two frontal regions. Thus, we found an inverted-U pattern of CBF signal across prodromal AD stages in regions susceptible to early AD pathology. Hippocampal and inferior parietal hyperperfusion in Obj-SCD may reflect early neurovascular dysregulation, whereby higher CBF is needed to maintain cognitive functioning relative to MCI participants, yet is also reflective of early cognitive inefficiencies that distinguish Obj-SCD from CU participants.


Cortical sensory suppression during arousal is due to the activity-dependent depression of thalamocortical synapses.
The thalamus serves as a gate that regulates the flow of sensory inputs to the neocortex, and this gate is controlled by neuromodulators from the brainstem reticular formation that are released during arousal. Here we show in rats that sensory-evoked responses were suppressed in the neocortex by activating the brainstem reticular formation and during natural arousal. Sensory suppression occurred at the thalamocortical connection and was a consequence of the activity-dependent depression of thalamocortical synapses caused by increased thalamocortical tonic firing during arousal. Thalamocortical suppression may serve as a mechanism to focus sensory inputs to their appropriate representations in neocortex, which is helpful for the spatial processing of sensory information.


Vascular injury biomarkers and stroke risk: A population-based study.
Because little is known about associations between biomarkers of vascular injury and stroke risk, we evaluated associations between plasma concentrations of 6 novel biomarkers of vascular injury and stroke risk in a population-based study. A case-cohort subset of EPIC-Heidelberg (European Prospective Investigation for Cancer and Nutrition-Heidelberg) including incident stroke cases (n = 335) and a random subcohort (n = 2,418) was selected. Concentrations of intercellular adhesion molecule 3 (ICAM3), soluble E-selectin and P-selectin, soluble thrombomodulin (sTM), thrombopoietin, and glycoprotein IIb/IIIa were measured in baseline plasma samples. Weighted Cox regression analyses were used to assess associations between biomarker levels and stroke risk. Median follow-up in the subcohort and among cases was 9.8 (range, 0.1-12.5) years and 6.2 (range, 0.01-12.1) years, respectively. ICAM3 levels were associated with increased risk of incident stroke after multivariable adjustment (hazard ratio, highest vs lowest quartile: 1.64 [95% confidence interval, 1.15-2.32]; p linear trend < 0.001). This association was more apparent for ischemic (1.65 [1.12-2.45]; p linear trend < 0.01) than for hemorrhagic stroke (1.29 [0.60-2.78]; p linear trend = 0.3). We further observed a borderline significant trend for a positive association between sTM and overall stroke risk (1.47 [0.99-2.19]; p linear trend = 0.05). In this population-based study, circulating levels of ICAM3, an adhesion molecule shed by leukocytes, were associated with increased risk of incident stroke. Further mechanistic studies are needed to elucidate the pathophysiology underlying this association. This study provides Class II evidence that plasma levels of ICAM3 are associated with increased stroke risk.


Plaque pH response to snack foods in children with different levels of mutans streptococci.
This study aimed to investigate the effects of some snack foods on plaque pH in children with different levels of mutans streptococci (MS). Six children, aged 9-12 years, with low (<10(4)) and 6 children, aged 10-12 years, with high (>106) numbers of MS/ml saliva participated in the study. Dental plaque pH changes, after the consumption of milk chocolate, sweet biscuit, instant noodle, sticky rice with banana and a 10% sucrose positive control were measured using pH-electrode. The measurements of plaque pH were made on forty-eight-hour accumulated plaque, at baseline to determine the resting pH of the fasted plaque and at time intervals of 2, 5, 10, 20 and 30 minutes after food consumption. The plaque pH curves, delta pH values and area under curve for pH 6.0 for each test food were determined. Plaque acidogenicity was more pronounced for the high-MS group at almost all test periods compared to the low-MS group with all test foods. The test foods were ranked according to maximum pH drop in about the same order in both groups as follows: 10% sucrose > milk chocolate > sweet biscuit > sticky rice with banana > instant noodle. The plaque pH also stayed below pH 6.00 for a longer period in the high-MS group with sweet biscuit, milk chocolate, and sticky rice with banana. Findings suggest that pH responses were more acidic in high-MS group than low-MS group.


Pore Geometry Optimization of Titanium (Ti6Al4V) Alloy, for Its Application in the Fabrication of Customized Hip Implants.
The present study investigates the mechanical response of representative volume elements of porous Ti-6Al-4V alloy, to arrive at a desired range of pore geometries that would optimize the reduction in stiffness necessary for biocompatibility with the stress concentration arising around the pore periphery, under physiological loading conditions with respect to orthopedic hip implants. A comparative study of the two is performed with the aid of a newly defined optimizing parameter called pore efficiency that takes into consideration both the stiffness quantity and the stress localization around pores. To perform a detailed analysis of the response of the porous structure over the entire spectrum of loading conditions that a hip implant is subjected to in vivo, the mechanical responses of 3D finite element models of cubic and rectangular parallelepiped geometries, with porosities varying over a range of 10% to 60%, are simulated under representative compressive, flexural as well as combined loading conditions. The results that are obtained are used to suggest a range of pore diameters that lower the effective stiffness and modulus of the implant to around 60% of the stiffness and modulus of dense solid implants while keeping the stress levels within permissible limits.


Proline utilization system is required for infection by the pathogenic α-proteobacterium Brucella abortus.
Proline utilization (Put) systems have been described in a number of bacteria; however, the importance and functionality of the Put system in the intracellular pathogen Brucellaabortus has not been explored. Generally, bacterial Put systems are composed of the bifunctional enzyme proline dehydrogenase PutA and its transcriptional activator PutR. Here, we demonstrate that the genes putA (bab2_0518) and putR (bab2_0517) are critical for the chronic infection of mice by B. abortus, but putA and putR are not required for the survival and replication of the bacteria in naive macrophages. Additionally, in vitro experiments revealed that putR is necessary for the ability of the bacteria to withstand oxidative stress, as a ΔputR deletion strain is hypersensitive to hydrogen peroxide exposure. Quantitative reverse transcription-PCR and putA-lacZ transcriptional reporter studies revealed that PutR acts as a transcriptional activator of putA in Brucella, and electrophoretic mobility shift assays confirmed that PutR binds directly to the putA promoter region. Biochemical analyses demonstrated that a purified recombinant B. abortus PutA protein possesses quintessential proline dehydrogenase activity, as PutA is capable of catalysing the conversion of proline to glutamate. Altogether, these data are the first to reveal that the Put system plays a significant role in the ability of B. abortus to replicate and survive within its host, as well as to describe the genetic regulation and biochemical activity of the Put system in Brucella.


Cryptosporidium muris-like infection in stomach of cynomolgus monkeys (Macaca fascicularis).
Abstract. Protozoa were present in routine sections of the gastric fundus of 15 cynomolgus monkeys (Macaca fascicularis) that were being studied in three toxicity studies with novel immunosuppressive agents. Upon detailed light microscopic and ultrastructural evaluation, all stages of parasite development (trophozoites, schizonts, gamonts, and oocysts) were seen and they structurally resembled Cryptosporidium muris, which normally is found in stomachs of rodents. Cryptosporidia were primarily present in the upper one third of fundic glands that were often concurrently colonized by a Helicobacter heilmannii-like organism; however, no clear correlation was found between bacterial burden and the number of protozoa. The primarily mononuclear cellular infiltrate appeared to coincide with the presence of protozoa only in a few animals. Changes in mucous epithelial cells mainly occurred in animals that were part of a 39-week study. Mucous epithelial cells in affected glands contained an increased amount of mucus composed of predominantly acid mucosubstances compared to the normally present neutral mucosubstances. C. muris-like protozoa are newly recognized etiologies for opportunistic infections in the stomach of immunocompromized nonhuman primates. This is the first report of C. muris-like parasite in stomachs of monkeys.


Current-Induced Manipulation of the Exchange Bias in a Pt/Co/NiO Structure.
An experimental study of the phenomenon of electric current influence on the value and orientation of the exchange bias field (HEB) in the Pt/Co/NiO structure is carried out. Depending on the direction of the magnetization in a ferromagnet (FM) layer and the current pulse amplitude, the value of the HEB field can be changed repeatedly in the range of ±7.5 mT. A few experiments are performed to separate the contributions from two current-induced effects: (i) an injection of the spin current into an antiferromagnet layer (AFM) and (ii) Joule heating. As a result, we conclude that the modification in the HEB field during current pulse transmission in the Pt/Co/NiO structure is due to heating and the low value of Néel temperature (TN = 162 °C). This fact explains the absence of the exchange bias effect on the spin-orbit torque (SOT)-assisted magnetization switching. The most striking observation to emerge from the experimental data analysis is that depending on the initial spin configuration of the domain structure in the FM layer and the current pulse amplitude, the exchange bias can be changed locally. This opens up prospects for creating exchange-coupled FM/AFM structures with dynamically tuned parameters of the exchange bias, which can be used for the development of magnetic memory, neuromorphic, and logic devices based on magnetic nanosystems.


Quality control of traditional chinese medicine by monoclonal antibody method.
In a previous study, we reported the preparation, characterization, variation, specificity, and sensitivity of an anti-aristolochic acid-II (AA-II) monoclonal antibody. The preparation procedure was as follows. AA-II conjugated with bovine serum albumin was used as an antigen for immunizing BALB/c mice. Splenocytes isolated from the immunized mice were fused with an aminopterin-sensitive mouse myeloma cell line to produce hybridoma cells secreting a mono-clonal antibody (MAb) against AA-II. The selected MAb was subsequently cloned. Hapten number, isotype, and an esti-mated dissociation constant (KD) of the secreted MAb were determined. This MAb was used to establish an ELISA method. The linear range was 0.19-13 µg/ml. Anti-AA-II MAb showed extremely high specificity for AA-II, low cross-reactivity (CR) against other AAs or aristololactam-I, and negligible CR (<0.5%) toward other natural compounds with different chemical structures. This study describes the successful application of the ELISA method using anti-AA-II MAb to determine AA-II concentration in several crude drugs derived from Aristolochia species. The highest AA-II concentration (2.82 µg/mg) was observed in the stem of A. manshuriensis, followed by that in the fruit of A. contorta (0.81 µg/mg). In case of A. indica, AA-II concentration in the root was higher than that in the aerial parts. These data indicated that the established ELISA method can be used for the quality control of crude drugs derived from Aristolochia plants.


Tranexamic Acid for Intracerebral Hemorrhage in Patients on Non-Vitamin K Antagonist Oral Anticoagulants (TICH-NOAC): A Multicenter, Randomized, Placebo-Controlled, Phase 2 Trial.
Evidence-based hemostatic treatment for intracerebral hemorrhage (ICH) associated with non-vitamin K antagonist oral anticoagulants (NOACs) is lacking. Tranexamic acid (TXA) is an antifibrinolytic drug potentially limiting hematoma expansion. We aimed to assess the efficacy and safety of TXA in NOAC-ICH. We performed a double-blind, randomized, placebo-controlled trial at 6 Swiss stroke centers. Patients with NOAC-ICH within 12 hours of symptom onset and 48 hours of last NOAC intake were randomized (1:1) to receive either intravenous TXA (1 g over 10 minutes followed by 1 g over 8 hours) or matching placebo in addition to standard medical care via a centralized Web-based procedure with minimization on key prognostic factors. All participants and investigators were masked to treatment allocation. Primary outcome was hematoma expansion, defined as ≥33% relative or ≥6 mL absolute volume increase at 24 hours and analyzed using logistic regression adjusted for baseline hematoma volume on an intention-to-treat basis. Between December 12, 2016, and September 30, 2021, we randomized 63 patients (median age, 82 years [interquartile range, 76-86]; 40% women; median hematoma volume, 11.5 [4.8-27.4] mL) of the 109 intended sample size before premature trial discontinuation due to exhausted funding. The primary outcome did not differ between TXA (n=32) and placebo (n=31) arms (12 [38%] versus 14 [45%]; adjusted odds ratio, 0.63 [95% CI, 0.22-1.82]; P=0.40). There was a signal for interaction with onset-to-treatment time (Pinteraction=0.024), favoring TXA when administered within 6 hours of symptom onset. Between the TXA and placebo arms, the proportion of participants who died (15 [47%] versus 13 [42%]; adjusted odds ratio, 1.07 [0.37-3.04]; P=0.91) or had major thromboembolic complications within 90 days (4 [13%] versus 2 [6%]; odds ratio, 1.86 [0.37-9.50]; P=0.45) did not differ. All thromboembolic events occurred at least 2 weeks after study treatment, exclusively in participants not restarted on oral anticoagulation. In a smaller-than-intended NOAC-ICH patient sample, we found no evidence that TXA prevents hematoma expansion, but there were no major safety concerns. Larger trials on hemostatic treatments targeting an early treatment window are needed for NOAC-ICH. URL: https://clinicaltrials.gov; Unique identifier: NCT02866838.


Heavy-particle therapy in acromegaly and Cushing disease.
A total of 349 patients with pituitary tumors, including acromegaly, Cushing disease, Nelson syndrome, prolactin-secreting adenoma, and chromophobe adenoma, have been treated with heavy-particle radiation during the past 17 years. The incidence of side effects has been low. Only 30 patients, 8.6%, have died, most of preexisting cardiovascular complications. Heavy particle therapy provides a form of treatment with no mortality and extremely low morbidity, and its use in treating pituitary disorders has resulted in dramatic improvement in the signs and symptoms of patients with acromegaly and Cushing disease.


Nodular melanoma in an African American Japanese male.
Nodular melanoma (NM) is the third most common subtype of melanoma among African Americans trailing behind acral lentiginous melanoma and superficial spreading melanoma. This case of NM in an African American Japanese male was selected due to the rare occurrence of NM in people of color.


Apremilast (Otezla). No progress in plaque psoriasis or psoriatic arthritis.
When PUVA therapy and immunosuppressants such as methotrexate are ineffective, TNF alpha antagonists are an option for patients with severe plaque psoriasis, in the absence of a better alternative. This is also the case for patients with psoriatic arthritis after failure of a "disease-modifying" antirheumatic drug. Apremilast, an oral immunosuppressant that inhibits phosphodiesterase type 4, has been authorised in the European Union for use in these settings. In patients with plaque psoriasis, oral apremilast was compared with subcutaneous etanercept, aTNF alpha antagonist, in a randomised, doubleblind, placebo-controlled trial lasting 16 weeks and involving 250 patients in whom other treatments had failed or were inappropriate. This trial failed to show that apremilast was more effective than etanercept. And about one-quarter more patients experienced symptom relief compared with placebo. In patients with psoriatic arthritis, there are no clinical trials comparing apremilast with TNF alpha antagonists, and no interpretable trials of apremilast after failure of a TNF alpha antagonist. In three randomised, double-blind trials including a total of 1493 patients treated for 16 weeks, at least a modest improvement in joint status was reported in about 35% of patients treated with apremilast versus 19% with placebo. This would suggest that apremilast is less effective than a TNF alpha antagonist. In the trial versus etanercept, serious adverse events occurred in 3.6% of patients treated with apremilast versus 1.2% of those treated with the TNF alpha antagonist. The main adverse effects of apremilast are diarrhoea, nausea and vomiting, headache, sometimes marked weight loss, and infections. A risk of depression and cardiac arrhythmia must also be taken into account. A risk of cancer in the long-term is likely, given the immunosuppressive action of apremilast. Apremilast is a substrate of cytochrome P450 isoenzyme 3A4 and accumulates in patients with renal failure. This creates a risk of multiple pharmacokinetic interactions.


Effects of Cathode Direct-Current Electroacupuncture Stimulus of the Promixal Anterior Lower Limbs on Heart Rate and Lumbar Blood Flow.
Objective: There has been little research on direct-current acupuncture. This study was conducted to verify the effect of acupuncture current intensity and polarity on heart rate (HR) when applying direct-current electroacupuncture (DCEA) to the proximal anterior part of the lower limbs and to clarify the effect of cathodes (-) on lumbar blood flow. Materials and Methods: This study was conducted at Teikyo Heisei University, Chiba, Japan. The subjects were 144 healthy male volunteers (21.7 ± 0.6 years' old). These participants were divided into 1 control, 1 manual acupuncture (MA), and 3 DECEA groups (-25 μA, +75 μA, and -75 μA). Acupuncture was performed on the lower limbs (at ST 36), and HR and intertissue blood flow (ITBF) were observed as the main outcome measures. Results: For intensity, HR was significantly lower in the -75 μA group than in the control (P < 0.001), MA (P < 0.001), and -25 μA (P < 0.01) groups. For polarity, HR was significantly lower in the -75 μA group than in the +75 μA group (P = 0.0028). For blood flow, the volume of HbO2 in the L-4-L-5 region at 1 minute after stimulation was significantly higher in the -75 μA stimulus group than in the MA group (P < 0.05). There was no change in the T-7-T-8 region. Conclusions: A -75 μA stimulus to ST 36 reduced HR and increased ITBF.


Morbidity of flank incision in 100 renal donors.
The purpose of this study is to determine the morbidity of lumbotomy incision used in the last 100 living related donor nephrectomies retrospectively. Since March 1991, 100 donor nephrectomies were made to living donors with lumbar incision. Incisions made in lateral decubitus position, subcostally or by an 11th or 12th rib resection. Left nephrectomy to 83, and right nephrectomy to 17 donors was performed. In 2 patients, there had been a peritoneal defect which was closed with primary sutures. In 19 patients 3 cm or shorter and in 5 patients longer than 3 cm of pleural entry had occurred. In all of the patients laceration was repaired without placement of a chest tube, however a chest tube had to be placed in 2 donors after obtaining a control chest x-ray postoperatively. All the patients mobilized and began to take orally in the first post-operative day. Wound infection, pneumonia and deep vein thrombosis had detected in none of the patients. The patients were discharged on the 4th and 5th postoperative day. During their control after 1 month from the operation it was found that all of them had returned to their daily life. In the postoperative period incisional hernia occurred in 7 patients which didn't need surgical repair and none of them complained of cosmetic problem. There was no any other late term complication was seen due to flank incision. Lumbotomy incision in donor nephrectomy, either a rib resection or supracostal approach, is reliable, provides excellent exposure for surgeon and has minimal morbidity.


Design of Fault Prediction System for Electromechanical Sensor Equipment Based on Deep Learning.
With the increasing complexity, scale, and intelligentization of modern equipment, the maintenance cost of equipment is increasing day by day. Moreover, once an unexpected major failure occurs, it will cause loss and damage to production, economy, and safety. Based on the considerations of system reliability and safety, fault prediction has gradually become a hot topic in the field of reliability. As a new branch of machine learning, deep learning realizes deep abstract feature extraction and expression of complex nonlinear relations by stacking deep neural networks and makes its methods solve bad problems in many traditional machine learning fields. The improvement and excellent results have been achieved. This article first introduces the model structure and working principle of the classic deep learning model noise reduction autoencoder and combines the feature extraction results of the experimental data of electromechanical sensor equipment and the model characteristics to analyze that this type of model can be trained using only normal samples. Under the restriction, the reason for abnormal features can also be correctly filtered. Then, in order to suppress the overfitting of training, the dropout layer is used in this article. The dropout layer will make the hidden layer nodes to be dropped with probability p according to the set probability. Because the lost nodes are random, each training is equivalent to training a new model. It achieves an effect similar to independently training the model and then superimposing it. Experiments prove that the dropout layer is very effective in solving overfitting. Finally, this paper conducts experimental verification on the improved algorithm. The results show that the improved model has a certain improvement in accuracy under the limited training algebra. Under the same training parameters, the accuracy is increased by approximately 2.44%, and the improved model has a better training effect and can be used for electromechanical effective prediction of sensor equipment failure.


First emergence of acrAB and oqxAB mediated tigecycline resistance in clinical isolates of Klebsiella pneumoniae pre-dating the use of tigecycline in a Chinese hospital.
Tigecycline is one of the few therapeutic options for treating infections caused by some multi-drug resistant pathogens, such as Klebsiella pneumoniae. However, tigecycline-resistant K. pneumoniae has been discovered recently in China. From 2009 to 2013, nine tigecycline-resistant K. pneumoniae isolates were identified in our hospital. Six of nine strains were identified before using tigecycline. To investigate the efflux-mediated resistance mechanisms of K. pneumoniae, the expression of efflux pump genes (acrA, acrB, tolC, oqxA and oqxB) and pump regulators (acrR, marA, soxS, rarA, rob and ramA) were examined by real-time RT-PCR. Molecular typing of the tigecycline resistant strains was performed. ST11 was the predominant clone of K. pneumoniae strains, while ST1414 and ST1415 were novel STs. Efflux pump inhibitor (EPI)-carbonyl cyanide chlorophenylhydrazone (CCCP) was able to reverse the resistance patterns of 5 resistant K. pneumoniae strains. In comparison with strain A111, a tigecycline-susceptible strain (negative control), we found that the expression levels of efflux pump genes and pump regulators were higher in a majority of resistant strains. Higher expression levels of regulators rarA (2.41-fold, 9.55-fold, 28.44-fold and 18.31-fold, respectively) and pump gene oqxB (3.87-fold, 31.96-fold, 50.61-fold and 29.45-fold, respectively) were observed in four tigecycline resistant strains (A363, A361, A368, A373, respectively). Increased expression of acrB was associated with ramA and marA expression. To our knowledge, studies on tigecycline resistance mechanism in K. pneumoniae are limited especially in China. In our study, we found that both efflux pump AcrAB-TolC and OqxAB contributed to tigecycline resistance in K. pneumoniae isolates.


Cervical Cancer Mortality Trends in China, 1991-2013, and Predictions for the Future.
To analyze cervical cancer mortality trends in China from 1991-2013 and forecast the mortality distribution in future five years (2014-2018), and provide clues for prevention and treatment. Mortality data for cervical cancer in China from 1991 to 2013 were used to describe the epidemiological characteristics and distribution, including the trend of the standardized mortality rate, urban-rural differences, and age variation. Trend-surface analysis was used to analyze the geographical distribution of mortality. Curve estimation, time series, gray modeling, and joinpoint regression were performed to predict and forecast mortality trends. In recent years, the mortality rate of cervical cancer has increased, and there is also a steady increase in the incidence from 2003 to 2013 in China. Mortality rates in rural areas are higher than in urban areas. The mortality dramatically increases in the 40+ yr age group, reaching a peak in the >85 yr age group. In addition, geographical analysis showed that the cervical cancer mortality increased from the southwest to west-central and from the southeast to northeast of the country. The incidence rate and the mortality rate are increasing from 1991 to 2013, and the predictions show this will continue in the future. Thus, implementation of prevention and management programs for cervical cancer are necessary in China, especially for rural areas, young women in urban areas, and high risk regions (the west-central).


Self-supported interconnected Pt nanoassemblies as highly stable electrocatalysts for low-temperature fuel cells.
In it for the long haul: Clusters of Pt nanowires (3D Pt nanoassemblies, Pt NA) serve as an electrocatalyst for low-temperature fuel cells. These Pt nanoassemblies exhibit remarkably high stability following thousands of voltage cycles and good catalytic activity, when compared with a commercial Pt catalyst and 20 % wt Pt catalyst supported on carbon black (20 % Pt/CB).


Implementation of a loss-of-function system to determine growth and stress-associated mutagenesis in Bacillus subtilis.
A forward mutagenesis system based on the acquisition of mutations that inactivate the thymidylate synthase gene (TMS) and confer a trimethoprim resistant (Tmpr) phenotype was developed and utilized to study transcription-mediated mutagenesis (TMM). In addition to thyA, Bacillus subtilis possesses thyB, whose expression occurs under conditions of cell stress; therefore, we generated a thyB- thyA+ mutant strain. Tmpr colonies of this strain were produced with a spontaneous mutation frequency of ~1.4 × 10-9. Genetic disruption of the canonical mismatch (MMR) and guanine oxidized (GO) repair pathways increased the Tmpr frequency of mutation by ~2-3 orders of magnitude. A wide spectrum of base substitutions as well as insertion and deletions in the ORF of thyA were found to confer a Tmpr phenotype. Stationary-phase-associated mutagenesis (SPM) assays revealed that colonies with a Tmpr phenotype, accumulated over a period of ten days with a frequency of ~ 60 ×10-7. The Tmpr system was further modified to study TMM by constructing a ΔthyA ΔthyB strain carrying an IPTG-inducible Pspac-thyA cassette. In conditions of transcriptional induction of thyA, the generation of Tmpr colonies increased ~3-fold compared to conditions of transcriptional repression. Further, the Mfd and GreA factors were necessary for the generation of Tmpr colonies in the presence of IPTG in B. subtilis. Because GreA and Mfd facilitate transcription-coupled repair, our results suggest that TMM is a mechanim to produce genetic diversity in highly transcribed regions in growth-limited B. subtilis cells.


[The anesthetic management of cesarean section for multiple pregnant patients].
Anesthetic management of cesarean section for twenty multiple pregnant patients, who were pregnant with triplet or quadruplet, was compared with that for 325 single pregnant patients and 21 twin pregnant patients. For anesthetic methods, spinal anesthesia was chosen most frequently in the multiple pregnant patients, as in single and twin (more than 75 percent). In multiple pregnant patients, the incidence of emergency operation was less. In multiple pregnant patients who received spinal anesthesia, gestational age was lower; birth weight was lighter; length of fundus uteri was longer; and blood loss including amniotic fluid was larger. In triplets, the third infants' UID-time was prolonged and their Apgar score was lower.


Lysosomal enzyme activity influenced by various types of respiration during extracorporeal circulation.
The hypoxic damage of the lung as seen after extracorporeal circulation (ECC) is in correlation to lysosomal hydrolase and protease activation. In the recent study the effect of various types of respiration during ECC on lysosomal enzyme release were studied. 53 patients undergoing open heart surgery were divided into 4 groups: Apnoea, low frequency, continuous positive airway pressure, combination of low frequency and continuous positive airway pressure. Paired blood samples were withdrawn from the superior vena cava (SVC) and the left atrium (LA) throughout the cardiopulmonary bypass. A continuous increase of N-azetyl-beta-D-Glucosaminidase (NAG) in venous plasma and significant differences (SVC-LA) with higher activities in the LA in the apnoea group were detectable (p less than or equal to 0.05-p less than or equal to 0.01). In the other groups a time dependent course could also be evaluated, but the changes of the activities were not significant. The different types of respiration during ECC influenced the clinical course and outcome of the patients in correlation to the release of lysosomal enzymes from the lung. It is concluded that concentration gradients of lysosomal enzymes are an index for pulmonary damage due to the extracorporeal perfusion in open heart surgery. The activation of lysosomal enzymes in the lung circulation are positively influenced by "ventilation" during ECC.


Sensitivity of Echinochloa muricata and Echinochloa crus-galli to HPPD- and ALS-inhibiting herbicides in corn.
Until recently Echinochloa muricata var. microstachya Wiegand (rough barnyardgrass), an alien species native to North America, was completely overlooked in Belgium due to its close morphological resemblance to Echinochloa crus-galli (L.) P. Beauv. (barnyardgrass). E. muricata var. microstachya has gradually spread and is now locally naturalized and abundant in and along maize fields. One of the possible reasons for its expansion in maize fields, besides e.g. the lack of crop rotation, might be a lower sensitivity to postemergence herbicides acting against panicoid grasses, in particular 4-hydroxyphenyl pyruvate dioxygenase (HPPD)-inhibiting herbicides and acetolactate synthase (ALS) inhibiting herbicides. Dose-response pot experiments were conducted in the greenhouse to evaluate the effectiveness of four HPPD-inhibitor herbicides [topramezone (ARIETTA), mesotrione (CALLISTO), tembotrione (LAUDIS), sulcotrione (MIKADO) and the ALS-inhibitor herbicide nicosulfuron (KELVIN) for controlling local populations of E. crus-galli and E. muricata. Pots were planted with 25 seeds, thinned afterwards to 5 plants (one week after sowing) and irrigated by overhead sprinklers. Herbicides were applied at the 3-4 leaf stage (BBCH stage 13-14). Fresh biomass was harvested 28 d after treatment. In another dose-response pot experiment, the influence of leaf stage at time of herbicide application on efficacy of topramezone for (rough) barnyardgrass control was evaluated. Sensitivity to HPPD-inhibitor herbicides topramezone and sulcotrione was significantly lower for E. muricata populations than for E. crus-galli populations. However, nicosulfuron sensitivity of both species was similar. Compared to E. crus-galli, sensitivity of E. muricata to topramezone was more dependent on leaf stage. Due to the intragenus variability in sensitivity to HPPD-inhibitor herbicides, higher awareness is required for presence of E. muricata plants in maize fields in order to avoid insufficient "barnyardgrass" control.


Modulation of activin expression by type beta transforming growth factors.
Activins are potentially important regulators of early developmental processes in vertebrates. Although the different forms of activin appear to be differentially expressed during early amphibian, avian, and murine development, little is known about the factors that regulate their expression. In this study we report the qualitative effects of several growth and differentiation factors on the expression of inhibin subunits in three differentiated cell lines derived from P19 embryonal carcinoma cells. These cell lines include mesodermal (MES-1), neuroepithelial (EPI-7), and visceral endoderm-like (END-2) cell types, expressing both inhibin beta A and beta B subunit mRNAs. We have shown for the first time that this expression is modulated by transforming growth factor (TGF)beta 1 and TGF beta 2 but not significantly by other growth factors such as leukemia inhibitory factor or members of the fibroblast growth factor family (aFGF, bFGF, or kFGF). beta A mRNA expression is increased while beta B expression is simultaneously decreased by TGF beta. Furthermore, TGF beta increased the amount of bioactive activin secreted by MES-1 and END-2 cells. Inhibin alpha subunit mRNA expression is not affected by TGF beta. These results point to a possible role of type beta transforming growth factors as regulators of activin expression in embryonal cells.


Undiagnosed paraganglioma; A challenge during laparoscopic retroperitoneal resection.
Report our experience of the management of a patient with undiagnosed retroperitoneal paraganglioma and the intraoperative complications that the theatre team faced. We present a case of a 36-year-old patient who during oncological follow-up for a previous diagnosis of parotid acinar cell carcinoma was incidentally identified as having an interaortocaval tumour. Following routine preoperative assessment the patient was arranged to undergo a laparoscopic retroperitoneal tumour resection. After minimal tumour manipulation the patient developed cardiac rhythm abnormalities and became hypertensive. The tumour was successfully removed laparoscopically after a cautious inter- aortocaval dissection. Abruptly, prior to extraction of the tumour containing endobag, the patient developed cardiac arrest. Following 35 minutes of life support measures there was a return of spontaneous circulation. The endobag was laparoscopically removed from the abdominal cavity 24 hours later using the initial operative port sites. The patient´s progression was satisfactory and he could be discharged six days postoperatively. Asymptomatic undiagnosed paragangliomas represent a real challenge during laparoscopic operations. Haemodynamic changes and life-threatening events can arise acutely intraoperatively, where an immediate and coordinated response of the whole theatre team may be required to avoid fatal outcome.


Eyelid skin trichilemmoma and underlying local malignancy: is an aggressive treatment necessary?
Trichilemmoma is a benign tumour derived from the outer root sheath of hair follicles. Trichilemmoma can be associated with basal cell carcinoma (BCC), either as a collision lesion or from malignant transformation. This study evaluates malignancy associated with eyelid trichilemmoma and principles of treatment. Retrospective study involving biopsy-proven eyelid trichilemmoma cases over 14 years encountered at a tertiary referral centre. Presenting features, differential diagnosis, type and number of operations required and histopathological features including coexisting BCC were analysed. We identified 36 cases with an average age of 66 years. The clinical differential diagnoses were mainly BCC (44%), papilloma (36%) and squamous cell carcinoma (SCC) (3%). Three patients (8%) had trichilemmoma with associated BCC. Of the 19 cases (53%) of trichilemmomas without BCC with equivocal surgical margins, seven patients (19%) opted for further excision while 12 patients (33%) opted for observation and were discharged. A patient re-presented two years later with invasive BCC. Overall, 11% of our biopsy-proven eyelid trichilemmoma cases were associated with BCC. Patients should be informed that a proportion of incompletely excised eyelid trichilemmomas may conceal underlying BCC. Therefore, further surgery to achieve clear surgical margins should be offered. Patients who opt for observation should be offered 6-monthly follow-up for three to five years. Alternatively, they can be discharged with advice to report any recurrence of lumps, skin changes or loss of lashes at the site of previous lesion.


How bodily expressions of emotion after norm violation influence perceivers' moral judgments and prevent social exclusion: A socio-functional approach to nonverbal shame display.
According to a socio-functional perspective on emotions, displaying shame with averted gaze and a slumped posture following a norm violation signals that the person is ready to conform to the group's moral standards, which in turn protects the person from social isolation and punishment. Although the assumption is intuitive, direct empirical evidence for it remains surprisingly limited and the mediating social-psychological mechanisms are poorly understood. Therefore, three experimental studies were conducted to investigate the social function of nonverbal displays of shame in the context of everyday norm violations. In Study 1, participants evaluated ten different expressions of emotion in regard to their affective valence, arousal, dominance, as well as social meaning in the context of norm violations. Displays of shame and sadness were seen as the most similar expressions with respect to the three affective dimensions and were perceived to communicate the perpetrator's understanding of the group's moral standards most effectively. In Study 2, participants read vignettes concerning norm violations and afterward saw a photograph of the perpetrator displaying nonverbal shame, sadness or a neutral expression. Perpetrators' displays of shame and sadness increased perceived moral sense and amplified the observers' willingness to cooperate with the perpetrators. However, neither display weakened the observer's willingness to punish the perpetrator. In Study 3, the perpetrator was shown to display shame, sadness, anger or a neutral expression after getting caught at mild or severe norm violation. The results replicated previous findings but revealed also that the social effects of shame and sadness displays on punitive and cooperative intentions were mediated by different social appraisals. For example, display of shame uniquely reduced punitive intentions by increasing the perpetrator's perceived moral sense, whereas expressions of both shame and sadness evoked empathy in the observers, which in turn reduced the punitive intentions. These results give support to the assumption that nonverbal shame displays serve a unique social function in preventing moral punishment and social exclusion. However, this support is only partial as the social functions of displaying shame are largely parallel to those of expressing sadness in the situation.


Immunomodulation of Telmisartan-Loaded PCL/PVP Scaffolds on Macrophages Promotes Endogenous Bone Regeneration.
Biomaterial-immune system interactions play an important role in postimplantation osseointegration to retain the functionality of healthy and intact bones. Therefore, appropriate osteoimmunomodulation of implants has been considered and validated as an efficient strategy to alleviate inflammation and enhance new bone formation. Here, we fabricated a nanostructured PCL/PVP (polycaprolactone/polyvinylpyrrolidone) electrospinning scaffold for cell adhesion, tissue ingrowth, and bone defect padding. In addition, telmisartan, an angiotensin 2 receptor blocker with distinct immune bioactivity, was doped into PCL-/PVP-electrospun scaffolds at different proportions [1% (TPP-1), 5% (TPP-5), and 10% (TPP-10)] to investigate its immunomodulatory effects and osteoinductivity/conductivity. Telmisartan-loaded scaffolds displayed in vitro anti-inflammatory bioactivity on lipopolysaccharide-induced M1 macrophages by polarizing them to an M2-like phenotype and exhibited pro-osteogenic properties on bone marrow-derived mesenchymal stem cells (BMSCs). Histological analysis and micro-CT results of a rat skull defect model also showed that the telmisartan-loaded scaffolds induced a higher M2/M1 ratio, less inflammatory infiltration, and better bone regenerative patterns. Furthermore, activation of the BMP2 (bone morphogenetic protein-2)-Smad signaling pathway was found to be dominant in telmisartan-loaded scaffold-mediated macrophage-BMSC interactions. These findings indicate that telmisartan incorporation with PCL/PVP nanofibrous scaffolds is a potential therapeutic strategy for promoting bone healing by modulating M1 macrophages to a more M2 phenotype at early stages of postimplantation.


Primary screening with liquid-based cytology in an unscreened population in rural China, with an emphasis on reprocessing unsatisfactory samples.
To determine the sensitivity and specificity of liquid-based cytology in a high-risk, unscreened population. A cross-sectional comparative trial of multiple screening techniques. This report focuses on the performance of liquid-based cytology using biopsy as the standard. In total, 1,997 women were screened. All subjects had a minimum of five cervical biopsies. Of the subjects, 4.3% had CIN 2 on biopsy. The ThinPrep Pap with ASCUS as positive had a sensitivity for CIN 2 of 94% and specificity of 78%; the sensitivity for CIN 3 was 98% and for cancer, 100%. The unsatisfactory rate due to bloody specimens was 7.9% (158/1,997). After reprocessing, the unsatisfactory rate was 0.15% (3/1,997). Reprocessing effectively recovers ThinPrep samples otherwise unsatisfactory due to blood and mucus. The ThinPrep Pap test is a highly sensitive screening test when used in a high-risk, unscreened population.


Satellite-to-ground optical downlink model using mode mismatching multi-mode photonic lanterns.
Photonics lanterns (PLs) provide an effective mode diversity solution to mitigate atmospheric turbulence interference in free-space optical communications (FSOC). This paper presents mode-mismatching multimode photonic lanterns (MM-PLs) for diversity receiver in satellite-to-ground downlink scenarios. Our study evaluates the coupling characteristics of the mode-selective PLs (MSPLs) and non-mode-selective PLs (NSPLs) for the influence of strong-to-weak turbulence and confirms that MSPLs outperform NSPLs under weak turbulence conditions. The research further explores the impact of fiber position error (FPE) on the spatial light-to-fiber coupling, including the optimal focal length deviation and lateral offset of receiving fiber devices. We have calculated and compared the coupling power and signal-to-noise ratio (SNR) of few-mode PLs (FM-PLs) and MM-PLs for various turbulence intensities. The results indicate that the optimal focal length tolerance, which corresponds to a decrease of approximately 1 dB in the average coupling power, is 2-3 m and 5-6 m for FM-PLs and MM-PLs, respectively. Furthermore, regardless of whether it is strong or weak turbulence, MM-PL exhibits a lateral offset tolerance exceeding 12 µm for a 0.5 dB drop in the mean coupled power, whereas the lateral offset tolerance of FM-PL is only 3 µm under weak turbulence. Additionally, the decrease in the average SNR of MM-PLs is gentle, only 0.67-1.16 dB at a 12 µm offset under weak turbulence, whereas there is a significant reduction of 6.50-8.49 dB in the average SNR of FM-PLs. These findings demonstrate the superiority of MM-PLs over FM-PLs in turbulence resistance and fiber position tolerance in the satellite-ground downlink.


The predictive value of the clinical features of malignancy in cases of preoperative follicular thyroid neoplasia.
It is generally impossible to make a distinction between benign and malign with a cytopathological examination using a fine needle aspiration biopsy (FNAB) in follicular lesions of the thyroid gland. This is the reason why lesions are frequently reported as follicular neoplasia (FN). Our study aims to examine the predictive value of carcinoma detection of different clinical features in cases with determined FN with FNAB. Clinical and histopathological data of a total of 116 patients (26 male, 90 female) subjected to surgery because of thyroid gland pathology with FN between March 1997 and December 2011 were retrospectively examined in two different centers. Results of the histopathological examinations were reported as: carcinoma in 33 (28.4%) cases (18 [54.5%] cases with papillary thyroid cancer, 11 [33.3%] cases with follicular thyroid cancer and 4 [12.1%] cases with papillary thyroid cancer follicular variant), as follicular adenoma (FA) in 32 (27.6%) patients and as a benign colloidal nodule in 51 (43.9%) patients. No statistical significance was determined between advanced age, male sex, solid single nodule, increased nodule diameter, hypoactive nodule existence and malignancy (P>0.05). Malignancy was found in 28.4% cases with FN detected as a result of FNAB in our study series, a ratio which is significantly higher than that reported in the literature. We think that the characteristics of the patient and the tumor are not effective in diagnosing cancer. In the case of the existence of bilateral thyroid pathology, the surgical therapy option should be bilateral total thyroidectomy due to such a high ratio of cancer occurrence.


Reduced photobleaching of chromophores close to a metal surface.
The photobleaching of chromophores in front of a metal film is measured by recording the emitted fluorescence intensity from an ensemble of chromophores as a function of time. A strong dependence of the photostability on the distance from the metal surface is found. The experimental data are well described in a classical electromagnetic model with the additional assumption that photobleaching occurs at a constant rate from the excited state. The metal interface influences the photostability of the chromophores in two ways, first by altering the excitation rate by local enhancement of the electromagnetic field and second by altering the electromagnetic decay rate.


A case of coagulation factor V deficiency complicated with intracranial hemorrhage.
Factor V deficiency is a relatively uncommon disorder, inherited as an autosomal recessive trait that manifests clinically only in individuals who inherit the defective gene from both parents. The hemorrhage of nasal and oral cavity and ecchymosis are common but intracranial hemorrhage is very rare. We experienced a 53 year old male patient with intracranial hemorrhage due to factor V deficiency. The laboratory tests showed prolongation of APTT and PT, normal bleeding time and normal thrombin time. The levels of the coagulation profiles on the patient revealed a significant decrease factor V, below 1% of normal range (60-140%). Other coagulation factors were normal. He was treated with fresh frozen plasma and completely recovered 3 weeks after treatment.


Modified Faden operation -A new surgical technique.
Faden operation was first described in 1912. It weakens the muscle in its field of action without much slackening and alteration in the primary position. When combined with recession the weakening effect is more. It is a useful surgery in esotropia with high accommodative convergence, nystagmus blockage syndrome, dissociated vertical deviation, Duane's retraction syndrome with up or downshoots, and in sixth nerve paresis, where it is performed on the contralateral normal yoke muscle to increase the field of binocular vision. The conventional procedure is cumbersome due to small working space, entanglement of sutures, and posterior location of Faden site which is not easily accessible. We have modified the Faden operation by using a single 5-0 double-armed polyester suture, which is much easier and simpler to perform, and have done it in a series of small angle esotropias combined with recession. This paper demonstrates the surgical technique so that this surgery can be performed with ease by more surgeons.


Young women's narratives of same-sex sexual desire in adolescence.
The aim of this study was to investigate young women's retrospective narratives of their experiences of same-sex sexual desire in adolescence. Seven women aged 19-25 were interviewed. An across-narrative analysis was conducted, producing five major themes. It is anticipated that this research will help to redress the missing discourse of desire in social constructions of younger women's sexuality and contribute to the development of knowledge and research related to queer female adolescent sexuality and sexual health.


Comparing the cost-effectiveness of FOLFIRINOX, nab-paclitaxel plus gemcitabine, gemcitabine and S-1 for the treatment of metastatic pancreatic cancer.
The recommended chemotherapy regimens for pancreatic cancer include the combination of 5-fluorouracil/leucovorin, oxaliplatin and irinotecan (FOLFIRINOX), nab-paclitaxel (nab-PTX) plus gemcitabine (GEM), GEM alone and tegafur/gimeracil/oteracil potassium (S-1) alone. Although the cost-effectiveness of metastatic pancreatic cancer chemotherapies has been extensively investigated, to the best of our knowledge, no study has specifically compared the cost-effectiveness among FOLFIRINOX, nab-PTX + GEM, GEM and S-1 regimens to date. The aim of the present study was to examine the cost-effectiveness of these four regimens. The expected costs were calculated based on data from patients with metastatic pancreatic cancer who were treated with the FOLFIRINOX, nab-PTX + GEM, GEM alone or S-1 alone. The median survival time (MST) from randomized controlled trials in the literature was used to evaluate the therapeutic effect of these regimens. The cost-effectiveness ratio was calculated using expected costs and MST for these four regimens. The expected costs per patient for the FOLFIRINOX, nab-PTX + GEM, GEM or S-1 regimens were ¥6,361,191.4, ¥4,802,063.6, ¥540,091.4 and ¥528,514.6, respectively, and the cost-effectiveness ratios per month were ¥642,544.6/MST, ¥470,790.5/MST, ¥81,832.0/MST and ¥55,633.1/MST, respectively. In conclusion, the nab-PTX + GEM and FOLFIRINOX regimens were associated with a high therapeutic efficacy and high cost. The GEM regimen exhibited a lower therapeutic efficacy compared with the nab-PTX + GEM and FOLFIRINOX regimens, but the findings of this study indicated that the GEM and S-1 regimens were the most cost-effective regimens.


A dual role of the extracellular domain of Drosophila Crumbs for morphogenesis of the embryonic neuroectoderm.
Epithelia are highly polarised tissues and several highly conserved polarity protein complexes serve to establish and maintain polarity. The transmembrane protein Crumbs (Crb), the central component of the Crb protein complex, is required, among others, for the maintenance of polarity in most epithelia in the Drosophila embryo. However, different epithelia exhibit different phenotypic severity upon loss of crb Using a transgenomic approach allowed us to more accurately define the role of crb in different epithelia. In particular, we provide evidence that the loss of epithelial tissue integrity in the ventral epidermis of crb mutant embryos is due to impaired actomyosin activity and an excess number of neuroblasts. We demonstrate that the intracellular domain of Crb could only partially rescue this phenotype, while it is able to completely restore tissue integrity in other epithelia. Based on these results we suggest a dual role of the extracellular domain of Crb in the ventral neuroectoderm. First, it is required for apical enrichment of the Crb protein, which in turn regulates actomyosin activity and thereby ensures tissue integrity; and second, the extracellular domain of Crb stabilises the Notch receptor and thereby ensures proper Notch signalling and specification of the correct number of neuroblasts.


Dynamics of flexible fibers in shear flow.
Dynamics of flexible non-Brownian fibers in shear flow at low-Reynolds-number are analyzed numerically for a wide range of the ratios A of the fiber bending force to the viscous drag force. Initially, the fibers are aligned with the flow, and later they move in the plane perpendicular to the flow vorticity. A surprisingly rich spectrum of different modes is observed when the value of A is systematically changed, with sharp transitions between coiled and straightening out modes, period-doubling bifurcations from periodic to migrating solutions, irregular dynamics, and chaos.


Prophylactic infusion of phenylephrine increases the median effective dose of intrathecal hyperbaric bupivacaine in cesarean section: A prospective randomized study.
Phenylephrine infusion to prevent spinal-induced hypotension can attenuate cephalic spread of intrathecal bupivacaine. Therefore, we suspected the intrathecal dose requirement for bupivacaine may differ when using phenylephrine infusion to prevent spinal-induced hypotension in cesarean section. We designed a prospective, randomized study to determine the ED50 of hyperbaric bupivacaine for cesarean section under combined spinal-epidural anesthesia in healthy parturients with and without prophylactic phenylephrine infusion to prevent spinal-induced hypotension. Sixty healthy parturients rated American Society for Anesthesiology status I/II undergoing elective cesarean section were enrolled in this study, which was conducted July 2016 to February 2017 in the labor and delivery department of Jiaxing University Affiliated Women and Children Hospital. After enrollment, patients were randomized into 2 groups of 30 by blinded opaque envelopes sorted by computer-generated random allocation. Solutions were prepared by an anesthesiologist not involved in outcome measurement. Patients and anesthesiologists collecting data were blinded to group allocation. Group P (phenylephrine group) parturients received prophylactic infusion of phenylephrine at the time of intrathecal injection. Group S (saline group) parturients receive the same volume of saline. Doses of intrathecal bupivacaine for each patient were determined using an up-down allocation method; initial dose was 7 mg. Effective dose was defined as bilateral T6 or above sensory block level achieved within 10 minutes of intrathecal drug administration and no additional epidural lidocaine required for intraoperative pain. The Dixon and Massey formula was used to calculate ED50 values. The ED50 values for hyperbaric bupivacaine were 7.0 mg (95% confidence interval [CI]: 6.6-7.4 mg) and 4.9 mg (95% CI: 4.4-5.4 mg) for groups P and S, respectively (P < .001). There were significant differences in incidence of hypotension and pH of umbilical arterial blood between groups S and P (60% vs 10%, P = .04 and 7.31 ± 0.04 vs 7.28 ± 0.06, P = .003, respectively). The ED50 of intrathecal hyperbaric bupivacaine is higher when phenylephrine infusion is used to prevent spinal-induced hypotension than when it is not used.


Time-Restricted Feeding in Commercial Layer Chickens Improves Egg Quality in Old Age and Points to Lack of Adipostat Activity in Chickens.
In mammals, time-restricted feeding (TRF) with no caloric restriction provides health benefits and extends longevity, usually with a minor (∼3%) or no reduction in total food consumption. In the current study, a TRF regimen of 6 h free access to food (08:00-14:00 h) was applied to Leghorn chickens from 25 to 86 weeks of age; control birds ate freely during the light hours (06:00-20:00 h). Unexpectedly, the TRF-treated birds consumed, on average, 11.7% less food than the controls. This was manifested by an average reduction of 9.6% in body weight, 2.6-fold in visceral fat accumulation, and 6.5% in egg weight. Hen-housed egg production was reduced by 3.6% in the TRF group compared with the control, along the first 40 weeks of the follow-up (P < 0.05), and changed into a tendency of 0.7% higher egg production thereafter. Several parameters of egg quality showed significant improvement (P < 0.05) in the TRF group compared with the controls. A comparison of diurnal patterns of feed consumption revealed a higher rate of hourly consumption in the TRF group and increased consumption before dark in the control group. In conclusion, the reduced feed intake in response to the TRF treatment and loss in visceral fat accumulation supports the lack of a strong adipostat activity in chickens and different appetite regulation mechanisms compared with mammals. Therefore, future TRF studies in chickens should be adjusted by extending the ad libitum time window. The lower feed intake by the TRF-treated chickens compared with the ad libitum-fed controls seems to reduce the efficiency of egg production. Nevertheless, the improved egg quality and persistence of egg lay at the older age suggest that similarly to mammals, the TRF treatment delayed at least some of the negative impacts associated with advanced age.


Colocalization in pericentral hepatocytes in adult mice and similarity in developmental expression pattern of ornithine aminotransferase and glutamine synthetase mRNA.
In situ hybridization showed that the mRNA for ornithine aminotransferase (OAT; ornithine-oxo-acid aminotransferase; L-ornithine: 2-oxo-acid aminotransferase, EC 188.8.131.52) colocalized with glutamine synthetase [GS; glutamate-ammonia ligase; L-glutamate: ammonia ligase (ADP-forming), EC 184.108.40.206] in pericentral hepatocytes of the adult mouse liver. In addition to an identical distribution in adult hepatocytes, OAT and GS have very similar expression patterns in fetal and neonatal liver. As was earlier described for GS, there is a low level of OAT mRNA in fetal cells and increasing pericentral levels in neonates that reach adult patterns within 2 weeks. These results suggest that the transcriptional regulation of the two genes is similar in the liver. However, there was a lack of colocalization of the mRNAs for the two enzymes in cells of the kidney, intestine, and brain, suggesting different regulatory decisions for the OAT and GS genes in the cells of these different tissues. The metabolic consequences of these localized expression patterns favor ammonia clearance from the blood by the liver and urea synthesis by the kidney.


Therapeutic activity of two xanthones in a xenograft murine model of human chronic lymphocytic leukemia.
We previously reported that allanxanthone C and macluraxanthone, two xanthones purified from Guttiferae trees, display in vitro antiproliferative and proapoptotic activities in leukemic cells from chronic lymphocytic leukemia (CLL) and leukemia B cell lines. Here, we investigated the in vivo therapeutic effects of the two xanthones in a xenograft murine model of human CLL, developed by engrafting CD5-transfected chronic leukemia B cells into SCID mice. Treatment of the animals with five daily injections of either allanxanthone C or macluraxanthone resulted in a significant prolongation of their survival as compared to control animals injected with the solvent alone (p = 0.0006 and p = 0.0141, respectively). The same treatment of mice which were not xenografted induced no mortality. These data show for the first time the in vivo antileukemic activities of two plant-derived xanthones, and confirm their potential interest for CLL therapy.


Crystal structure of guanidinium hexafluoridovanadate(III), (CN3H6)3[VF6]: an unusual hybrid compound related to perovskite.
Vanadium fluorides with novel crystal-chemical features and interesting physical properties can be prepared by solvothermal synthetic routes. The title compound, guanidinium hexafluoridovanadate(III), has a cubic structure (space group Pa-3), exhibiting isolated regular VF6 octahedral units, which are hydrogen bonded to protonated guanidinium moieties. Although the VF6 octahedral units are not linked directly together, there are structural similarities between this crystal structure and those of the wider family of perovskite materials, in particular, hybrid perovskites based on extended ligands such as cyanide. In this context, the octahedral tilt system of the present compound is of interest and demonstrates that unusual tilt systems can be mediated via `molecular' linkers which allow only supramolecular rather than covalent interactions.


Short-days induce weight loss in Siberian hamsters despite overexpression of the agouti-related peptide gene.
Many vertebrates express profound annual cycles of body fattening, although it is not clear whether these represent differential activity of the central pathways known to mediate homeostatic control of food intake and energy expenditure, or whether the recent discovery of a major role for pars tuberalis-ependymal signalling points towards novel mechanisms. We examined this in the Siberian hamster (Phodopus sungorus) by using gene transfection to up-regulate a major orexigenic peptide, agouti-related peptide (AgRP), and then determined whether this increased anabolic drive could prevent the short-day induced winter catabolic state. Infusions of a recombinant adeno-associated virus encoding an AgRP construct into the hypothalamus of hamsters in the long-day obese phase of their seasonal cycle produced a 20% gain in body weight over 6 weeks compared to hamsters receiving a control reporter construct, reflecting a significant increase in food intake and a significant decrease in energy expenditure. However, all hamsters showed a significant, prolonged decrease in body weight when exposed to short photoperiods, despite the hamsters expressing the AgRP construct maintaining a higher food intake and lower energy expenditure relative to the control hamsters. Visualisation of the green fluorescent protein reporter and analysis of AgRP-immunoreactivity confirmed widespread expression of the construct in the hypothalamus, which was maintained for the 21-week duration of the study. In conclusion, the over-expression of AgRP in the hypothalamus produced a profoundly obese state but did not block the seasonal catabolic response, suggesting a separation of rheostatic mechanisms in seasonality from those maintaining homeostasis of energy metabolism.


Biogenic amines regulate avian immunity.
Alzet mini-osmotic pumps were implanted subcutaneously to administer norepinephrine (NE) and epinephrine (E) to 6-wk-old line UNH 105 chickens. Dose-time studies showed the most effective NE and E dose and exposure time on two chicken cellular immune responses: the phytohemagglutinin (PHA) wattle response and leukocyte migration. Administration of 1 microgram/h NE for 72 h suppressed significantly the wattle stimulation index [2.48 +/- .3 (SE)] compared to that of saline controls (4.1 +/- .3) but enhanced mean leukocyte migration (7.7 +/- .3 versus 4.9 +/- .3). Epinephrine at 1 microgram/h for 72 h significantly suppressed the wattle index (1.8 +/- .2) compared to that of controls (2.8 +/- .3) but E at 1 microgram/h for 48 h enhanced leukocyte migration (9.5 +/- .2 versus 6.4 +/- .2). Continuous administration of NE and E at physiological levels alters cell-mediated immunity and appears to have an immune regulatory role in the chicken.


The Countess of Aberdeen's health promotion caravans.
Lady Aberdeen took up the leadership of the Women's National Health Association of Ireland on its foundation in 1907. The Association's main objective was to combat tuberculosis, which was a considerable health problem in Ireland at the beginning of the century. Exhibitions on tuberculosis prevention were organised and a horse-drawn caravan equipped with health education material was dispatched to the more remote parts of the island in 1908. It carried the Crusade to the north-west of Ireland until the caravan was unfortunately burnt in Co. Donegal in March 1909. Although there are ample reasons for suspecting that the fire might have been malicious, all the evidence points to an accidental cause. A local photographer took photographs of the caravan on fire. Its replacement, Phoenix, went on the road shortly afterwards, followed two years later by Blue Bird.


Admissibility Investigation and Validation of Infertility Distress Scale (IDS) in Iranian Infertile Women.
Psychological stress has a profound effect on infertility and its treatment. The aim of this study was to develop a specific scale to determine distress levels among Iranian infertile women. In this cross-sectional study the samples included 300 women (145 fertile and 155 infertile) who completed the Infertility Distress Scale (IDS) form. Data was analysed using correlation method and main component analysis. These results show that all 21 items had a high correlation with the overall scale. Cronbach's alpha value was 0.91 for the entire list. Factor analysis results with 5 element extraction could identify 88% of overall variance with a special value higher than 1. According to results, the IDS questionnaire has enough admissibility and va- lidity in the measurement of the infertility distress scale in Iranian infertile women.


The Protective Effect of Lavender Essential Oil and Its Main Component Linalool against the Cognitive Deficits Induced by D-Galactose and Aluminum Trichloride in Mice.
Lavender essential oil (LO) is a traditional medicine used for the treatment of Alzheimer's disease (AD). It was extracted from Lavandula angustifolia Mill. This study was designed to investigate the effects of lavender essential oil (LO) and its active component, linalool (LI), against cognitive impairment induced by D-galactose (D-gal) and AlCl3 in mice and to explore the related mechanisms. Our results revealed that LO (100 mg/kg) or LI (100 mg/kg) significantly protected the cognitive impairments as assessed by the Morris water maze test and step-though test. The mechanisms study demonstrated that LO and LI significantly protected the decreased activity of superoxide dismutase (SOD), glutathione peroxidase (GPX), and protected the increased activity of acetylcholinesterase (AChE) and content of malondialdehyde (MDA). Besides, they protected the suppressed nuclear factor-erythroid 2-related factor 2 (Nrf2) and heme oxygenase-1 (HO-1) expression significantly. Moreover, the decreased expression of synapse plasticity-related proteins, calcium-calmodulin-dependent protein kinase II (CaMKII), p-CaMKII, brain-derived neurotrophic factor (BDNF), and TrkB in the hippocampus were increased with drug treatment. In conclusion, LO and its active component LI have protected the oxidative stress, activity of cholinergic function and expression of proteins of Nrf2/HO-1 pathway, and synaptic plasticity. It suggest that LO, especially LI, could be a potential agent for improving cognitive impairment in AD.


Paragenesis of Palladium-Cobalt Nanoparticle in Nitrogen-Rich Carbon Nanotubes as a Bifunctional Electrocatalyst for Hydrogen-Evolution Reaction and Oxygen-Reduction Reaction.
The hydrogen evolution reaction (HER) and the oxygen reduction reaction (ORR) play important roles in many energy conversion and storage systems. To accelerate the reaction processes, there is a constant need for efficient new catalysts. In the present work, we have developed a facile pyrolysis-based process for the co-synthesis of palladium-cobalt nanoparticles supported on carbon nanotubes (Pd-CoCNTs), which exhibit superior catalytic activity for the HER and enhanced ORR performance. Non-agglomerated Pd nanoparticles of diameters 2-4 nm are uniformly distributed on the surface of CoCNTs, while the inner Co particles are an essential element in forming the framework of the CoCNTs. Compared to the Pd-free N-rich CoCNTs, Pd-CoCNTs have a more defective surface with a larger electrochemically active surface area (ECSA), and show enhanced ORR activity, outstanding methanol tolerance, and long-term stability in alkaline solution. At a low Pd loading of 0.0292 mg cm-2 , the Pd-CoCNTs require overpotentials of 0.024 V and 0.215 V to catalyze the HER and to drive a current density of 50 mA cm-2 in acidic solution, respectively. The palladium nanoparticles on the surface of the CoCNTs are considered to be highly active sites for HER, based on the results of control experiments, and it is easy to adjust the catalytic activity of the Pd-CoCNTs by changing the concentration of Pd therein. The proposed method provides a means of fabricating efficient bifunctional catalysts with controllable low contents of precious metals.


MCP-1 induces inflammatory activation of human tubular epithelial cells: involvement of the transcription factors, nuclear factor-kappaB and activating protein-1.
Monocyte chemoattractant protein-1 (MCP-1) is a potent chemokine synthesized by several cell types, e.g., inflammatory cells, such as monocytes, and resident renal cells, such as human tubular epithelial cells (TECs). Besides induction of monocyte recruitment, MCP-1 has been suggested to induce non-leukocytes to produce cytokines and adhesion molecules. Inflammation of the tubulointerstitium is a hallmark of many renal diseases and contributes to progression of renal failure; the purpose therefore of this study was to investigate the influence of MCP-1 on markers of inflammatory activation in human TECs. MCP-1 stimulated interleukin-6 (IL-6) secretion and intercellular adhesion molecule-1 (ICAM-1) synthesis in a time- and dose-dependent manner. In parallel, MCP-1 increased IL-6 and ICAM-1 mRNA expression in human TECs. Pretreatment with pertussis toxin, GF109203X, BAPTA-AM, and pyrrolidine dithiocarbamate inhibited MCP-1-dependent IL-6 and ICAM-1 synthesis, suggesting the involvement of Gi-proteins, protein kinase C, intracellular Ca(2+), and nuclear factor-kappaB (NF-kappaB) in MCP-1 signaling. Using electrophoretic gel mobility shift assay, we observed that MCP-1 stimulated binding activity of NF-kappaB. Binding activity of the activator protein-1 (AP-1), which has been implicated to regulate induction of the IL-6 gene together with NF-kappaB, was also stimulated by MCP-1. In the present experiments, NF-kappaB and AP-1 were involved in the MCP-1-mediated induction of IL-6, as demonstrated by cis element double-stranded (decoy) oligonucleotides (ODN). In contrast to IL-6 release, MCP-1-induced ICAM-1 expression was predominantly dependent on NF-kappaB activation. These results document for the first time that MCP-1 induces an inflammatory response in human TECs. This may be an important new mechanism in the pathogenesis of tubulointerstitial inflammation.


Functional Parcellation of the Cerebral Cortex Across the Human Adult Lifespan.
Adult aging is associated with differences in structure, function, and connectivity of brain areas. Age-based brain comparisons have typically rested on the assumption that brain areas exhibit a similar spatial organization across age; we evaluate this hypothesis directly. Area parcellation methods that identify locations where resting-state functional correlations (RSFC) exhibit abrupt transitions (boundary-mapping) are used to define cortical areas in cohorts of individuals sampled across a large range of the human adult lifespan (20-93 years). Most of the strongest areal boundaries are spatially consistent across age. Differences in parcellation boundaries are largely explained by differences in cortical thickness and anatomical alignment in older relative to younger adults. Despite the parcellation similarities, age-specific parcellations exhibit better internal validity relative to a young-adult parcellation applied to older adults' data, and age-specific parcels are better able to capture variability in task-evoked functional activity. Incorporating age-specific parcels as nodes in RSFC network analysis reveals that the spatial topography of the brain's large-scale system organization is comparable throughout aging, but confirms that the segregation of systems declines with increasing age. These observations demonstrate that many features of areal organization are consistent across adulthood, and reveal sources of age-related brain variation that contribute to the differences.


Childhood leukemia: perspectives 1978.
With intensive chemotherapy and a minimum of hospitalization, great progress has been made in extending the lives of children with acute lymphoblastic leukemia. Of equal importance is attentive support for those whose lives are lengthened and their families.


Justification For Re-Look Cystoscopy After Posterior Urethral Valve Fulguration.
Posterior urethral valve (PUV) is life-threatening congenital anomaly of the urinary tract that results in vesicoureteric reflux, recurrent UTI, voiding dysfunction and renal insufficiency if not treat timely. Endoscopic ablation of posterior urethral valves using cold knife or laser is the current gold standard therapy. Many urologists go for repeat cystoscopy to see residual valve or stricture while others repeat VCUG to measure the posterior to anterior urethral ratio for residual obstruction. In this study, we have standardized by regularly doing re-look cystoscopy at 3 months whether the child is symptomatic or not to see justification for re-look cystoscopy after PUV ablation. In this prospective study, first 50 cases that underwent posterior urethral valve fulguration were included. Diagnosis of posterior urethral valve was made by voiding symptoms, ultrasonography and confirmed by voiding cysto-urethrogram (VCUG). All children were treated by endoscopic fulguration of posterior urethral valves (PUV) using cold knife as urethral valvotome and were followed clinically for voiding symptoms and with ultrasonography and laboratory test at 3 and 6 months. All patients underwent re-look cystoscopy at three months to see residual valves irrespective of their clinical improvement. Mean age at presentation was 4.9±3.2 years. The most common symptoms were poor stream (76%), straining at voiding (72%), dribbling of urine (54%), fever (42%) and urinary retention (14%). Residual valves on re-look cystoscopy were seen in 78%. Four (8%) patients had urethral stricture on re-look cystoscopy. We suggest routine re-look cystoscopy after primary fulguration of PUV to pick more residual obstructive valves.


Effect of catalase on the proliferation of human lymphocytes to phorbol myristate acetate.
Phorbol esters have been documented to stimulate the proliferation of human blood mononuclear cell cultures. In addition, these agents are also known to stimulate the production and release of reactive oxygen species by monocytes. We demonstrated previously that H2O2, one of these oxygen metabolites, impairs the proliferative capacity of human blood lymphocytes. Therefore, in these experiments, we determined whether or not the H2O2 released by monocytes after activation by PMA modifies the proliferation of lymphocytes to this agent. Human blood mononuclear cells (80% lymphocytes and 20% monocytes) were incubated with PMA, and lymphoblastic transformation (LBT) was quantitated at 3 and 5 days by pulsing the cultures with thymidine. Initial experiments established that the concentration of PMA required for optimal LBT was 50 ng/ml. We then demonstrated that this concentration of PMA also induces a burst in hexose monophosphate shunt activity and H2O2 production of mononuclear cells as indicated by the enhanced oxidation of 14C-glucose and 14C-formate, respectively. The amount of H2O2 released into the medium was substantial. Our measurements indicate that the concentration of H2O2 could reach values as high as 0.008 mM during the first 2 hr of the cultures. The addition of catalase to PMA-treated cultures in concentrations sufficient to scavenge the H2O2 released by the monocytes was associated with an enhanced thymidine uptake (mean 79%). These results indicate that the hydrogen peroxide released by the monocytes modifies the response of lymphocytes to the PMA. Paradoxically, mononuclear cell cultures depleted of monocytes also had a lower proliferation to PMA than mononuclear cell cultures. This observation indicates that monocytes also produce factors required for lymphocyte proliferation to PMA such as an interleukin. In contrast, to PMA cultures, catalase did not alter the proliferation of mononuclear cell cultures stimulated by PHA. We previously documented that PHA does not stimulate an immediate burst in the oxidative metabolism of mononuclear cultures. Therefore, the effect of catalase in these two culture systems appears to correlate with the capacity of the mitogen to stimulate the oxidative metabolism of mononuclear cells. These observations suggest that the release of reactive oxygen species by monocytes may modify the response of lymphocytes to antigens both in vitro and in vivo.


Reconstructive procedures on lower extremities using Mitkovic external fixation system.
The results of limb lengthening, correction of limb deformities and solving of bone loss, by the use of Mitkovic external fixation system and minimally invasive technique on the series of 96 operations in 89 patients are shown. Only lower extremities were included in this series. The advantages of this external fixation system in comparison to other systems are pointed out. The main advantages are the optimal biomechanical conditions including unilateral but 3-dimensional frame, which provides conditions very similar to natural biomechanical features of the human long bones, simplicity of application and low cost. The received result was excellent or very good in 98.4%. Maximal limb lengthening was 18 cm (at the same time in the femur and the tibia). Angular deformity correction is extremely simplified with minimized possibility of complications. The frame for bone transport is very simple. It can be concluded that presented methods are suitable for routine use.


CNS axonal regeneration with peripheral nerve grafts cryopreserved by vitrification: cytological and functional aspects.
To test cool-warm protocols for storing peripheral nerves, 4-cm-long-nerve segments were removed from the hindleg of adult rats and cryopreserved using a vitrification solution (or cryoprotective mixture) containing a mixture of polyalcohols (2,3-butanediol, 1,2-propanediol, polyethylene glycol, and Belzer U.W. medium). Schwann cell viability and morphology were studied with regard to the effect of (i) cryoprotective mixture concentration (100, 50, and 30% diluted in human serum albumin at 4%), (ii) duration of exposure (10, 15, or 30 min in a single step) of nerves to the cryoprotective mixture, (iii) cooling rate (F1/F2, F3, and F4: 3, 12, and 231 degrees C/min, respectively), and (iv) type of replacement of cryoprotectant (T1, one step; or T2, perfusion) after warming. Nerves exposed 10 min to cryoprotective mixture 50% (2,3-butanediol, 1.926 mol.liter-1; 1,2-propanediol, 3.063 mol.liter-1; polyethylene glycol, 0.084 mol.liter-1; and Belzer U.W., 22.4 mosm-1) and cooled-warmed with the F2/F3/F4-T2 protocols contained live and correctly cryopreserved Schwann cells. The capacity of these cryopreserved nerve segments (n = 6) to be subsequently repopulated by regenerating axons from central neurons was compared to that of fresh nerves when used as peripheral nerve autografts implanted within the spinal cord at the level of the descending respiratory pathways. All cryopreserved nerve grafts were successfully reinnervated by regenerated central axons. Unitary spontaneous action potentials propagated along these axons were assessed by recording the discharge of tested nervous filaments (T) from the grafts in artificially ventilated and paralyzed animals. Out of 535 T, 32 (6 +/- 1.2%) presented spontaneous unitary activity with respiratory (R, n = 2) and nonrespiratory (NR, n = 30) pattern of discharge. The T mean number, the occurrence rate referenced to the total number of T (R/T, NR/T, and R + NR/T) and the mean number of spontaneous units (R, NR, R + NR) were compared to those of fresh spinal peripheral nerve grafts. Except for T, cryopreserved peripheral nerve grafts contained statistically significantly (P < 0.05) less spontaneous R and NR unitary activity, which represented, respectively, 6.2 +/- 6.2 and 26.8 +/- 5.7% of that found in the control group. These data indicate that nerves cryopreserved with the protocols described above contain viable Schwann cells which constitute a suitable support to induce regeneration of central fibers. The effectiveness of nerve cryopreservation by vitrification is discussed with regard to Schwann cell viability following cool-warm protocols and to subsequent reinnervation of the cryopreserved peripheral nerve grafts.


Selective in situ protein expression profiles correlate with distinct phenotypes of basal cell carcinoma and squamous cell carcinoma of the skin.
Non-melanoma skin cancer is the most common malignancy that shows increasing incidence due to our cumulative exposure to ultraviolet irradiation. Its major subtypes, basal cell carcinoma (BCC) and squamous cell carcinoma (SCC) differ in pathobiology, phenotype and clinical behavior, which must be reflected at the molecular level. In this study, protein expression profiles of BCC and SCC were tested in tissue microarrays and correlated with that of actinic keratosis, Bowen's disease, seborrheic keratosis and normal epidermis by detecting 22 proteins involved in cell interactions, growth, cell cycle regulation or apoptosis. The significantly more reduced collagen XVII, CD44v6, pan-Desmoglein levels and more evident E-Cadherin delocalization in BCC compared to SCC correlated with the de novo dermal invasion of BCC against the progressive invasion from in situ lesions in SCC development. EGFR was also expressed at a significantly higher level in SCC than in BCC. The upregulated cell communication protein connexin43 in BCC could contribute to the protection of BCC from metastatic invasion. Elevated cell replication in BCC was underlined by the increased topoisomerase IIα and reduced p21(waf1) and p27(kip1) positive cells fractions compared to SCC. Compared to differentiated keratinocytes, caspase-8 and -9 were equally upregulated in skin carcinoma subtypes for either mediating apoptosis induction or immune escape of tumor cells. Hierarchical cluster analysis grouped SCC and actinic keratosis cases exclusively together in support of their common origin and malignant phenotype. BCC cases were also clustered fully together. Differentially expressed proteins reflect the distinct pathobiology of skin carcinoma subtypes and can serve as surrogate markers in doubtful cases.


[Genetic engineering as a method for the improvement of photosynthesis].
The significant increase in crop productivity occurred in the second half o the 20th century. However, it is thought that nowadays yield of main crop species reached its maximum. As we expect that the demand for plant products is going to increase during next century, it is necessary to develop new methods for yield improvement, other than traditional breeding. The redesign of photosynthesis using genetic engineering is one of the approaches postulated. The present article covers the main directions of research aimed to increase photosynthetic efficiency. The research covered by this review are: improvement of light capture, improvement of Rubisco and the regeneration phase of Calvin cycle, introducing carbon concentrating mechanisms to main crop species and reducing loss caused by photorespiration.


Awareness Regarding Cervical Cancer among Reproductive Age Women Residing in Nuwakot District.
Background Cervical cancer is the most common malignancy among Nepalese women and it is main cause of death among reproductive age women in Nepal. Objective The objective of this study was to find out awareness regarding cervical cancer among reproductive age women residing in Nuwakot district. Method A descriptive cross-sectional study was conducted to assess the awareness about cervical cancer among reproductive age women of Nuwakot district from April to May 2021. A total of 190 respondents were interviewed using structured questionnaire. Descriptive and inferential analysis were conducted using SPSS version 23 not licenced but trail version. Result Among 190 reproductive age women, the mean age was 33.37±8.39 (Mean±SD). Nearly 10% of respondents answered the meaning of cervical cancer correctly. Among them 30% of respondents did not know about the cause. Similarly, only 7.4% of respondents answered that HPV Infection was risk factor, 2.6% of respondents knew about appropriate age for HPV vaccine. However, nearly 19% of respondents answered that cervical cancer screening was needed for sexually exposed women. There was a significant difference in mean of awareness among different ethnicity (p=0.014), educational level (p=0.001) and there was no significant difference in mean of awareness among different age group, marital status, occupation, family history of cervical cancer and smoking habit. Conclusion Most of the reproductive age women were unaware about meaning, causes, risk factors and preventive measures of cervical cancer. So, there is a need for the implementation of awareness programs on cervical cancer and its preventive measures in this community.


Conserved CTL epitopes on the adenovirus hexon protein expand subgroup cross-reactive and subgroup-specific CD8+ T cells.
Adenoviruses often cause lethal infections in immunocompromised individuals. Adoptive transfer of immune T cells offers a therapeutic option, but this strategy has been hindered by the paucity of information on molecular targets of cellular immunity and by the immunologic heterogeneity of the 51 human adenoviruses, which are grouped from A to F on the basis of genome size, composition, homology, and organization. Clonal analysis of the adenovirus-specific cytotoxic T lymphocyte (CTL) responses of seropositive individuals identified 5 novel CD8(+) T-cell epitopes, all located in conserved regions of the capsid protein hexon. Reactive T cells were cross-reactive between 2 to 4 groups, while no T cells specific for a single subgroup were detected. Thus, by exploiting these peptide targets, it is possible to prepare a T-cell population capable of reacting with most adenoviruses that cause disease in immunocompromised patients.


The management of Hodgkin's disease.
This paper presents a destillation of the authors' current views concerning the optimal management of Hodgkin's disease in relation to site(s) and stage of disease, constitutional symptoms, histopathology, and prior treatment, based on experience with a series of controlled clinical trials under way at Stanford University Medical Center since 1962.


Associations between Red Meat Intakes and the Micronutrient Intake and Status of UK Females: A Secondary Analysis of the UK National Diet and Nutrition Survey.
Blanket health messages to lower red meat intakes are being communicated at present. These could have adverse implications on the micronutrient quality of women's diets. The current paper evaluates the nutritional impact of lower red meat intakes on British women's micronutrient intakes and status. A secondary analysis of the UK National Diet and Nutrition Survey was undertaken using data from years 2008/2009 to 2011/2012. This was comprised of dietary and blood analyte data from 1384 and 641 females aged 11 to 64 years. Females consuming less than 40 g total red meat daily were more likely to have micronutrient intakes below the Lower Reference Nutrient Intake (LRNI) for zinc, iron, vitamin B12 and potassium and have lower habitual vitamin D intakes than females consuming between 40 and 69 g daily. After adjusting data for energy intake, zinc (% below the LRNI) and vitamin D (μg/day) remained statistically significant (p < 0.001). No significant differences were observed for blood biomarkers. Females consuming diets lower in red meat, i.e., <40 g daily, appear to have reduced micronutrient intakes, especially in the case of zinc and vitamin D. This should be considered when giving blanket advice for whole populations to reduce red meat intakes.


High Mobility Group Box 1 Protein: A Plausible Therapeutic Molecular Target in Parkinson's disease.
Parkinson's disease (PD) is a widespread neurodegenerative disorder that exerts a broad variety of detrimental effects on people's health. Accumulating evidence suggests that mitochondrial dysfunction, neuroinflammation, α-synuclein aggregation and autophagy dysfunction may all play a role in the development of PD. However, the molecular mechanisms behind these pathophysiological processes remain unknown. Currently, research in PD has focussed on high mobility group box 1 (HMGB1), and different laboratory approaches have shown promising outcomes to some level for blocking HMGB1. Given that HMGB1 regulates mitochondrial dysfunction, participates in neuroinflammation, and modulates autophagy and apoptosis, it is hypothesised that HMGB1 has significance in the onset of PD. In the current review, research targeting multiple roles of HMGB1 in PD pathology was integrated, and the issues that need future attention for targeted therapeutic approaches are mentioned.


Antioxidant and antibacterial activities of polysaccharides isolated and purified from Diaphragma juglandis fructus.
A water-soluble polysaccharide fraction (DJP-2) isolated from Diaphragma juglandis was successfully purified by ion-exchange chromatography (DEAE-cellulose) and gel-permeation chromatography (Sephadex G-100). The weight-average molecular weight (Mw) and number-average molecular weight (Mn) of DJP-2 were 4.95 and 3.99kDa, respectively. Monosaccharide component analysis indicated that DJP-2 comprised arabinose, galactose, glucose, xylose, and mannose in a molar ratio of 0.27:0.55:1:0.14:0.08. The evaluation of the antioxidant and antibacterial activities of polysaccharides from Diaphragma juglandis fructus indicated that they could be explored as promising natural antioxidant and bacteriostatic agents in the food and pharmaceutical industries.


Mutually tangled colloidal knots and induced defect loops in nematic fields.
Colloidal dispersions in liquid crystals can serve as a soft-matter toolkit for the self-assembly of composite materials with pre-engineered properties and structures that are highly dependent on particle-induced topological defects. Here, we demonstrate that bulk and surface defects in nematic fluids can be patterned by tuning the topology of colloidal particles dispersed in them. In particular, by taking advantage of two-photon photopolymerization techniques to make knot-shaped microparticles, we show that the interplay of the topologies of the knotted particles, the nematic field and the induced defects leads to knotted, linked and other topologically non-trivial field configurations. These structures match theoretical predictions made on the basis of the minimization of the elastic free energy and satisfy topological constraints. Our approach may find uses in self-assembled topological superstructures of knotted particles linked by nematic fields, in topological scaffolds supporting the decoration of defect networks with nanoparticles, and in modelling other physical systems exhibiting topologically analogous phenomena.


Pattern and nature of Neyshabur train explosion blast injuries.
Explosions are classified as both man-made and complex accidents. Explosive events can cause serious damage to people, property, and the environment. This study aimed to investigate the pattern and nature of damage incurred to the victims of the Neyshabur Train Explosion. The current study is a descriptive cross-sectional study that was retrospectively performed on 99 individuals using census method and documents victims hospitalized due to the Neyshabur train disaster (February 2004) in 2016. In this study, different variables such as age, sex, type of injury, treatment, etc. were examined using a questionnaire and were analyzed using SPSS16. The results showed that 50.5% of victims were males with mean age of 30.33 ± 4.27 years and most of them were in 20- to 40-year age group. A total of 98 victims were discharged after treatment, and 1 victim died due to the severity of injuries after 3 days of hospitalization. Second type of injuries caused by the explosion accounted for most of the injuries (55.6%), and most treatments (54.5%) were related to the specific field of orthopedics. Handling and transportation of fuels and chemicals via rail transport system is one of the potential hazards that threatens human life. The results showed that the highest numbers of victims were in 20- to 40-year age group, which is the age of economic efficiency. The prevention and reduction of human and financial losses resulting from accidents require proper national planning.


Acalculous cholecystitis.
During a two year period, 1981 to 1982, 21 of 262 patients undergoing cholecystectomy had acalculous cholecystitis. The majority of these patients had chronic disease, and more than 50 per cent of them were in the older age group and had other chronic medical problems. The signs and symptoms are similar to that of calculous cholecystitis, although the cause is unclear. However, the patient with these complaints deserves thorough evaluation in order to rule out other disorders of the upper part of the gastrointestinal tract, because cholecystectomy for chronic acalculous cholecystitis will relieve the symptoms in more than 80 per cent of the patients. Acalculous cholecystitis is a true organic problem which, if diagnosed accurately, can be effectively treated with cholecystectomy.


Dual Use of Nicotine and Cannabis Through Vaping Among Adolescents.
This study seeks to identify adolescent nicotine and cannabis vaping patterns and the characteristics of those adolescents who comprised each pattern. This prospective longitudinal survey study measured the relationship between nicotine and cannabis vaping among 1,835 adolescents from 4 public high schools outside of Philadelphia, Pennsylvania. Adolescents completed in-classroom surveys, including questions of lifetime and past 30-day nicotine and cannabis vaping, at Wave 1 (fall 2016, ninth grade) and 6-month intervals for the following 36 months (fall 2019, 12th grade). Data were analyzed in 2021. A sequential processes growth mixture model revealed 4 latent conjoint classes of nicotine and cannabis vaping: early, declining dual use (Class 1: n=259); rapidly increasing dual use (Class 2: n=128); later, slower dual use (Class 3: n=313); and no use (Class 4: n=1,136). Increased odds of belonging to Class 1 and Class 2 versus belonging to Class 4 were significantly associated with cigarette smoking (OR=3.71, OR=2.21), alcohol use (OR=2.55, OR=4.39), peer vaping (OR=1.24, OR=1.20), sensation seeking (OR=1.03, OR=1.11), positive E-cigarette expectations (OR=1.21, OR=1.17), and cigar smoking (OR=2.39 Class 2 only). Increased odds of belonging to Class 3 versus Class 4 were significantly associated with alcohol use (OR=1.66), perceived benefits of E-cigarette use (OR=1.03), positive E-cigarette expectations (OR=1.08), depressive symptoms (OR=1.02), and sensation seeking (OR=1.03). From middle to late adolescence, vaping of nicotine and cannabis develop in close parallel. Regulatory policy and prevention interventions should consider the interplay between these 2 substances during this period of adolescence.


Association between cheilitis granulomatosa and odontogenic infections: A case-control study.
The association between cheilitis granulomatosa and dental infections (dental caries and apical periodontitis) is still not well understood. Herein, we aimed to investigate the association in large hospital cases with cohort controls. Cheilitis granulomatosa cases (n = 181) were retrieved from Peking University Hospital of Stomatology and age- and sex-matched to controls (n = 181). The χ2 -test, Student's t-test, and Mann-Whitney U-test were used to compare the differences between groups. The χ2 -test and odds ratio were used to verify if there was an association and risk relationship. The results showed that both dental caries and apical periodontitis were associated with cheilitis granulomatosa (p < 0.001). Individuals with cheilitis granulomatosa had approximately a twofold increased frequency of dental caries than those without cheilitis granulomatosa (104/181, 57.5% vs. 53/181, 29.3%) (p < 0.001). The odds ratio of dental caries occurring in the case group compared to the control group was 3.211. The frequency of apical periodontitis in patients with cheilitis granulomatosa was significantly greater than in those without cheilitis granulomatosa (109/181, 60.2% vs. 28/181, 15.5%) (p < 0.001). The odds ratio was 8.272. Moreover, apical periodontitis was also locationally related to cheilitis granulomatosa (p < 0.001). Collectively, our study showed that the foci of dental infections are associated with cheilitis granulomatosa, suggesting that proper treatment of focal teeth may be important in the management of cheilitis granulomatosa.