Temporal and spatial dynamic propagation of electroencephalogram by combining power spectral and synchronization in childhood absence epilepsy.
During the transition from normal to seizure and then to termination, electroencephalography (EEG) signals have complex changes in time-frequency-spatial characteristics. The quantitative analysis of EEG characteristics and the exploration of their dynamic propagation in this paper would help to provide new biomarkers for distinguishing between pre-ictal and inter-ictal states and to better understand the seizure mechanisms. Thirty-three children with absence epilepsy were investigated with EEG signals. Power spectral and synchronization were combined to provide the time-frequency-spatial characteristics of EEG and analyze the spatial distribution and propagation of EEG in the brain with topographic maps. To understand the mechanism of spatial-temporal evolution, we compared inter-ictal, pre-ictal, and ictal states in EEG power spectral and synchronization network and its rhythms in each frequency band. Power, frequency, and spatial synchronization are all enhanced during the absence seizures to jointly dominate the epilepsy process. We confirmed that a rapid diffusion at the onset accompanied by the frontal region predominance exists. The EEG power rapidly bursts in 2-4 Hz through the whole brain within a few seconds after the onset. This spatiotemporal evolution is associated with spatial diffusion and brain regions interaction, with a similar pattern, increasing first and then decreasing, in both the diffusion of the EEG power and the connectivity of the brain network during the childhood absence epilepsy (CAE) seizures. Compared with the inter-ictal group, we observed increases in power of delta and theta rhythms in the pre-ictal group (P < 0.05). Meanwhile, the synchronization of delta rhythm decreased while that of alpha rhythm enhanced. The initiation and propagation of CAE seizures are related to the abnormal discharge diffusion and the synchronization network. During the seizures, brain activity is completely changed with the main component delta rhythm. Furthermore, this article demonstrated for the first time that alpha inhibition, which is consistent with the brain's feedback regulation mechanism, is caused by the enhancement of the network connection. Temporal and spatial evolution of EEG is of great significance for the transmission mechanism, clinical diagnosis and automatic detection of absence epilepsy seizures.


On dynamic heterogeneity in supercooled liquids.
A simplified molecular theory for the dynamics of liquids near the glass transition temperature T(g) is developed and compared with experimental viscosity and diffusion behavior. Its basis is the spatial fluctuations of local density, a property that depends on isothermal compressibility and thus occurs naturally in all liquids at equilibrium. Instantaneous liquid structure is approximated by randomly distributed arrays of two domains having either higher or lower density than the average. The time dependence of fluctuations is represented by a sequence of such structures, each having a lifetime that varies with the macroscopic density. The dynamic environment of a molecule within a domain (slow or fast) depends on the density of its domain (high or low). Translational diffusion and orientational relaxation depend on different averages of the slow and fast domain contributions and lead, on approaching T(g), to a progressive departure from the Stoke-Einstein relationship. Predictions are made using macroscopic viscosity-density relationships within the individual domains. They depend only on the choice of domain size, which, according to this formulation, is insensitive to temperature. The data for three well-studied nonpolymeric liquids were found to be in reasonable accord with NMR assessments of domain size.


Level V Metastasis, a Novel Predicative Factor for Recurrence in N1b Papillary Thyroid Carcinoma.
Lymph nodal (LN) metastasis, classified as pN1b, is considered as an independent poor prognostic factor for Papillary thyroid carcinoma (PTC) patients. However, whether LN metastasis can serve as a predictive factor for recurrence or disease-free survival of N1b PTC is still plagued by controversy. The N1b PTC patients who underwent total thyroidectomy and unilateral modified radical neck dissection (MRND) by the same surgical team in Ningbo NO.2 Hospital from March, 1998 to March, 2015 were included in this study. The clinical and pathological characteristics of each patient were recorded in detail. Univariate and multivariate Cox proportional hazards regression models were performed to analyze the associations between clinicopathological characteristics with recurrence. Kaplan-Meier analysis and log-rank test were used for the analysis of overall RFS and level V metastasis. A total of 214 patients were eligible for the final analyses. Of the 214 finally included patients with N1b PTC, 39 patients were classified with recurrence and 175 without recurrence. The final univariate and multiple Cox proportional hazards analysis only suggested level V metastasis as the independent predictive factor of N1b PTC recurrence (HR: 4.11; 95% CI:1.22-11.05, P=0.028). The patients with level V metastasis showed a significantly lower 10-year RFS rate (P=0.031) as illustrated by Kaplan-Meier analysis and log-rank test. Level V metastasis is a novel indicator for tumor recurrence and 10-year RFS in patients with N1b PTC.


Alveolar cells: incorporation of carbohydrate into protein and evidence for intracellular protein transport.
Alveolar cells incubated with radioactive glucosamine, galactose, and mannose incorporate radioactivity into protein, that is, into material insoluble in cold and hot trichloroacetic acid and not extracted by lipid solvents. This incorporation is incompletely inhibited by puromycin hydrochloride. The kinetics of the subcellular distribution of radioactivity are consistent with a precursor-product relationship between microsomal protein and the protein of particles sedimenting at 15,000 g. It is thus suggested that alveolar cells incorporate these substrates intact into protein at the microsomal level with subsequent transfer of this newly formed material to particles sedimenting at 15,000 g.


Patterns of host use by brood parasitic Maculinea butterflies across Europe.
The range of hosts exploited by a parasite is determined by several factors, including host availability, infectivity and exploitability. Each of these can be the target of natural selection on both host and parasite, which will determine the local outcome of interactions, and potentially lead to coevolution. However, geographical variation in host use and specificity has rarely been investigated. Maculinea (= Phengaris) butterflies are brood parasites of Myrmica ants that are patchily distributed across the Palæarctic and have been studied extensively in Europe. Here, we review the published records of ant host use by the European Maculinea species, as well as providing new host ant records for more than 100 sites across Europe. This comprehensive survey demonstrates that while all but one of the Myrmica species found on Maculinea sites have been recorded as hosts, the most common is often disproportionately highly exploited. Host sharing and host switching are both relatively common, but there is evidence of specialization at many sites, which varies among Maculinea species. We show that most Maculinea display the features expected for coevolution to occur in a geographic mosaic, which has probably allowed these rare butterflies to persist in Europe. This article is part of the theme issue 'The coevolutionary biology of brood parasitism: from mechanism to pattern'.


Understanding the molecular mechanism of the 1,3-dipolar cycloaddition between fulminic acid and acetylene in terms of the electron localization function and catastrophe theory.
The potential-energy profile of the 1,3-dipolar cycloaddition of fulminic acid and ethyne has been investigated theoretically within the framework provided by the electron localization function (ELF) analysis. This has been achieved by carrying out density functional theory (B3 LYP approach) calculations using the bonding evolution theory. Eight different domains of structural stability have been identified along the reaction path, as well as the bifurcation catastrophes responsible for the changes in the topology of the system. The analysis provides a chemical description of the reaction mechanism in terms of heterolytic concerted nonsynchronous bond formation: the first four catastrophes enable the simultaneous formation of the C-C bond and a lone pair on the nitrogen atom, whereas the remaining ones lead to the ring closure. The valence basin populations calculated along the reaction path do not support any mechanism involving pentavalent nitrogen. The simulation of the solvent effect, by means of a continuum model, does not indicate any significant difference of the mechanism of reaction between the gas phase and solution.


Cellular mechanisms for trazodone-induced cardiotoxicity.
The second-generation selective 5-HT2 receptor antagonists and reuptake inhibitors (SARIs) class antidepressants are known to have fewer cardiovascular side effects than the older ones. However, several case reports showed that trazodone, one of the second-generation SARIs, induces QT prolongation, cardiac arrhythmia, and ventricular tachycardia. Although these clinical cases suggested trazodone-induced cardiotoxicity, the toxicological actions of trazodone on cardiac action potentials (APs) beyond the human ether-a-go-go related gene (hERG) remain unclear. To elucidate the cellular mechanism for the adverse cardiac effects of trazodone, we investigated its effects on cardiac APs and ion channels using whole-cell patch clamp techniques in human-induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) and transiently transfected human embryonic kidney cells (HEK293) with cardiac ion channel complementary DNA. Trazodone dose-dependently decreased the maximum upstroke velocity (Vmax) and prolonged the AP duration, inducing early after depolarizations at 3 and 10 μM that triggered ventricular arrhythmias in hiPSC-CMs. Trazodone also inhibited all of the major ion channels (IKr, IKs, INa, and ICa), with an especially high inhibitory potency on hERG. These data indicate that the prolonged AP duration and decreased Vmax due to trazodone are mainly the result of hERG and sodium ion inhibition, and its inhibitory effects on cardiac ion channels can be exhibited in hiPSC-CMs.


[Jiangsu Diabetic Eye Disease Study:epidemiological survey of blindness and moderate or severe visual impairment in people with type 2 diabetes over 50 years old in Funing County].
Objective: To investigate the prevalence, causes and risk factors of moderate or severe visual impairment and blindness in people with type 2 diabetes over 50 years old in Funing County, Yancheng. Methods: This is a cross-sectional study. Using cluster random sampling, 84 survey sites were selected, and eye examination was performed on people with type 2 diabetes over 50 years old who were registered with the chronic disease information center of Funing County Center for Disease Control and Prevention in Yancheng, Jiangsu. The prevalence of moderate or severe visual impairment and blindness were calculated by different ages and genders. The causes of blindness and visual impairment were determined, and their influencing factors were analyzed by univariate and multivarite logistic regression. Results: A total of 2 067 people were investigated in this study, and 1 909 people were included. The response rate was 92.4%. Based on PVA, the prevalence of blindness and moderate to severe visual impairment was 5.29% (95%CI: 4.29%-6.30%) and 18.54% (95%CI: 16.80%-20.29%). The prevalence of blindness was related to age, marital status, education, duration of diabetes, history of diabetic nephropathy, systolic blood pressure and nuclear opacity. The prevalence of moderate or severe visual impairment was related to age, gender, educational level, diabetes treatment, exercise, and glycated hemoglobin. The prevalence of blindness and moderate to severe visual impairment was 3.67% (95%CI: 2.82%-4.51%) and 9.80% (95%CI: 8.46%-11.13%) based on BCVA. The prevalence of blindness was related to age, marital status, education, duration of diabetes, history of diabetic nephropathy, exercise and systolic blood pressure, while the prevalence of moderate or severe visual impairment was related to age, educational level, diabetes treatment and nuclear opacity. The primary cause of blindness and visual impairment is cataract, followed by diabetic retinopathy. Conclusions: The prevalence of moderate or severe visual impairment and blindness in people with type 2 diabetes in Funing County is relatively high. Attention should be paid to the prevention of blindness in this population. (Chin J Ophthalmol, 2020, 56: 593-599).


[Acupuncture and traditional Chinese medicine].
Acupuncture and other therapeutic techniques of traditional Chinese medicine (moxibustion, herbal therapy, massage and physiokinesitherapy, Chinese medical exercises) were introduced in Italy and Europe after the Second World War. Especially acupuncture is utilized in private and public health services; in Italy only medical doctors can practice acupuncture because it is considered a "medical act" from 1982. Some private schools organize four years courses of acupuncture and Chinese medicine and have acquired an interesting experience in teaching, clinical practice and editing in this field. The National Institutes of Health (NIH) in USA stated, in a consensus conference held in November 1977, that "there is clear evidence that needle acupuncture is efficacious for adult post-operative and chemotherapy nausea and vomiting and probably for the nausea of pregnancy".


Reduced Graphene Oxide-Based Silver Nanoparticle-Containing Composite Hydrogel as Highly Efficient Dye Catalysts for Wastewater Treatment.
New reduced graphene oxide-based silver nanoparticle-containing composite hydrogels were successfully prepared in situ through the simultaneous reduction of GO and noble metal precursors within the GO gel matrix. The as-formed hydrogels are composed of a network structure of cross-linked nanosheets. The reported method is based on the in situ co-reduction of GO and silver acetate within the hydrogel matrix to form RGO-based composite gel. The stabilization of silver nanoparticles was also achieved simultaneously within the gel composite system. The as-formed silver nanoparticles were found to be homogeneously and uniformly dispersed on the surface of the RGO nanosheets within the composite gel. More importantly, this RGO-based silver nanoparticle-containing composite hydrogel matrix acts as a potential catalyst for removing organic dye pollutants from an aqueous environment. Interestingly, the as-prepared catalytic composite matrix structure can be conveniently separated from an aqueous environment after the reaction, suggesting the potentially large-scale applications of the reduced graphene oxide-based nanoparticle-containing composite hydrogels for organic dye removal and wastewater treatment.


[In vitro drug susceptibility test of Plasmodium falciparum using a portable thermostat and CO2 gas generator].
We have recently developed a method of in vitro cultivation of P. falciparum using a portable incubator and AnaeroPack.CO2 (Onda et al.), we applied semi-microtechnique drug susceptibility tests to the culture method to evaluate the system using several P. falciparum strains or isolates of different susceptibilities to chloroquine (SGE-1, FCR-3, K-1, Patient 1 and 2). The new method gave comparable results to those shown by the standard test employing a modular incubator chamber with standard gas composition of 5% O2, 5% CO2 and 90% N2. Many useful data on the epidemiology of drug resistant malaria such as the emergence of multi-drug resistant isolates could be collected by applying this new method to the field survey.


Differential Transport of Escherichia coli Isolates Compared to Abiotic Tracers in a Karst Aquifer.
Lack of filtration and rapid transport of groundwater and particulate matter make karst aquifers susceptible to bacterial contamination. This study utilized quantitative polymerase chain reaction (qPCR) to examine the transport and attenuation of two nonvirulent isolates of Escherichia coli (E. coli) in relation to traditional groundwater tracers (rhodamine WT dye and 1-µm diameter latex microspheres) in a karst-conduit aquifer in central Kentucky. Bacterial isolates were labeled with stable isotopes (15 N and 13 C). All tracers were detected more than 6 km downstream from the injection site and demonstrated overlapping breakthrough curves, with differential transport observed between the two bacterial strains. The E. coli isolate containing the kps gene (low attachment) arrived at sampling sites 1.25 to 36 h prior to the bacterial isolate containing the iha gene (high attachment) and was detected in samples collected following storm events in which the iha isolate was not detected. The storage potential of contaminants within karst systems was demonstrated by the remobilization of all tracers during storm events more than 1 month after injection. Bacteria-sized microspheres were more easily remobilized during periods of increased discharge compared to other tracers. The study demonstrated that molecular biology techniques such as qPCR can be utilized as a sensitive analysis of bacterial tracers in karst aquifers and may prove to be a more sensitive analytical technique than stable isotope analysis for field-scale traces.


[Respiratory control in obstructive sleep apnea hypopnea syndrome].
To evaluate the role of ventilatory control in obstructive sleep apnea hypopnea syndrome (OSAHS). Thirty-five patients with OSAHS were compared with 15 obese controls in pulmonary function, hypoxic ventilatory response (HVR), hypercapnic ventilatory response (HCVR) and polysomnography (PSG). (1) There were no differences in HVR and HCVR between patients with OSAHS and the control (t = 1.28, 0.57; P > 0.05). In OSAHS patients, HVR was correlated with nadir nocturnal oxygen saturation (MmS(P)O(2)) (r = -0.54, P < 0.01) and HCVR (r = 0.57, P < 0.01). (2) Patients with mild and moderate OSAHS had higher HVR than those with severe OSAHS (t = 2.74, P < 0.01). When 5 < or = apnea and hypopnea index (AHI) < 40, HVR was negatively correlated to forced expiratory volume in one second (FEV(1))/peak expiratory flow (PEF) (r = -0.42, P < 0.05) and AHI (r = -0.68, P < 0.01). For those whose AHI > or = 40, HVR was negatively correlated with MmSpO(2) (r = -0.58, P < 0.05) and positively correlated with HCVR (r = 0.59, P < 0.05). In OSAHS patients, HCVR did not show significant change, but HVR showed two phasic change-increase first and then decrease-following the elevation of AHI, which was also related to MmSpO(2) and HCVR.


Domestic Violence and Education: Examining the Impact of Domestic Violence on Young Children, Children, and Young People and the Potential Role of Schools.
This article examines how domestic violence impacts the lives and education of young children, children, and young people and how they can be supported within the education system. Schools are often the service in closest and longest contact with a child living with domestic violence; teachers can play a vital role in helping families access welfare services. In the wake of high profile cases of child abuse and neglect, concerns have been raised about the effectiveness of multi-agency responses to children living with abuse. In the United Kingdom, the case of 4-year-old Daniel Pelka who died in 2012 following abuse and starvation by his mother, who experienced domestic violence, and her partner, led to a serious case review. It found recording systems in Daniel's school were not used consistently, and details held by different agencies were not collated to enable the formation of a coherent assessment. The lack of integrated working cited in the report echoes findings from previous serious case reviews. A strong correlation exists between domestic abuse and child abuse, with approximately half of all domestic violence situations involving direct child abuse. Children can also be affected indirectly by violence occurring in their home by seeing or hearing it taking place. This article examines the impact of domestic violence on the mental health of children, and the impact on their education. Violence in children's lives often causes disruption to their schooling and harms the quality of their educational experiences and outcomes. The abuse children experience can result in emotional trauma, physical and psychological barriers to learning, and disruptive behavior in school, while the underlying causes of these problems remain hidden. Knowing when and how to seek advice from multi-agency professionals is an essential part of effective practice among school staff. Despite their vital role in identifying signs of abuse and signposting referral pathways, research indicates teachers often lack confidence and knowledge for such work. The article examines how the professional learning and professional confidence of teachers can be developed, and how recent policy and practice developments in the United Kingdom have the potential to influence work in this area.


Decision region partition aided MLSE for O-band 65-Gbaud PAM-4 system over 40-km transmission with a severe bandwidth constraint.
Maximum likelihood sequence estimation (MLSE) is an optimal solution to realize sequence detection in the digital signal processing (DSP) of short reach O-band intensity modulation/direct detection (IM/DD) systems with bandwidth limitation. However, traditional MLSE requires relatively high computational complexity for short reach optical interconnect. Although the computational complexity of single-symbol sequence detection is quite low, the capability of combating with the inter symbol interference (ISI) is inadequate. To combine the low computational complexity of single-symbol sequence detection with the high reliability of multi-symbol sequence detection in MLSE, decision region partition aided MLSE (DRP-MLSE) is proposed and verified with 60-Gbaud and 65-Gbaud PAM-4 IM/DD systems over 40-km single-mode fiber (SMF) transmission. The experimental results show that the DRP-MLSE can realize similar performance of conventional MLSE with negligible penalty and significantly lower computational complexity.


An aquatic perspective on the concepts of Ingestad relating plant nutrition to plant growth.
The Ingestad approach to the culture of higher terrestrial plants for physiological studies is discussed in relation to a number of resources, organisms and growth situations that were not part of the original design and rationale of Ingestad's methodology. The additional resource considered is photosynthetically active radiation, and difficulties of applying the Ingestad approach to this resource as well as to atmospheric CO2 are considered. The relationship of the Ingestad approach to reductionist studies based on enzyme kinetic studies is then briefly considered. The organisms considered next are aquatic plants, including both micro- and macrophytes. The consideration of photosynthetic microorganisms leads to a comparison of the Ingestad approach with growth in batch, and in continuous (chemostat and turbidostat) cultures, and with studies on growth in synchronous cultures in which cyclic changes in cell composition in the cell growth and division cycle can be identified. The natural environmental conditions for these organisms are a natural extension of the light/dark synchronization of laboratory cultures, and the bloom (batch culture equivalent to new production) and of grazing and parasitism removing biomass and recycling nutrients (chemostat or turbidostat culture equivalent to recycled production) situations for phytoplankton. The overall conclusion is that, while the Ingestad approach is a useful mirror in which to examine other concepts of plant resource acquisition and manipulation, the Ingestad methodology seems to make assumptions about the intrinsic growth rate and composition of plants that cannot be independently verified.


Ultrasound Features of Mammographic Developing Asymmetries and Correlation With Histopathologic Findings.
The purpose of this study is to review the ultrasound (US) features of developing asymmetries and correlate them with histopathologic findings. We searched the mammography database of an academic medical center, affiliated cancer center, and two ambulatory imaging facilities from 2009 to 2012 and identified 201 patients with developing asymmetries, 187 of whom had US at the time of, or within 1 month of, diagnostic mammography evaluation. Seventy-five (40.1%) of these 187 patients had a US correlate, and three additional patients had a positive second-look US after MRI (US results were initially negative), and one patient had a US correlate for a newly palpable developing asymmetry 1 month after receiving a BI-RADS category 3 mammography-only assessment. These 78 developing asymmetries with US correlates comprised the study cases. US features were obtained by consensus image review; patient demographic characteristics and outcomes were obtained from the electronic medical record. Thirty-six of 78 US correlates (46.2%) were masses, the echotexture of which was as follows: 26 (72.2%) were hypoechoic, four (11.1%) were hyperechoic, three (8.3%) were mixed hyperechoic and hypoechoic, and three (8.3%) were anechoic. Forty-two of 78 US correlates (53.8%) were nonmass findings, the echotexture of which was as follows: 24 (57.1%) were mixed hyperechoic and hypoechoic, 13 (31.0%) were hypoechoic, and five (11.9%) were hyperechoic. Twenty-one of 78 lesions (26.9%) were malignant; of these, eight were invasive ductal carcinoma, seven were invasive lobular carcinoma, three were mixed invasive ductal and lobular carcinoma, and three were ductal carcinoma in situ. Malignant findings on US included 17 masses (81.0%) (13 hypoechoic and four mixed hyperechoic and hypoechoic), and four nonmass findings (19.0%) (three mixed hyperechoic and hypoechoic and one hypoechoic). When present, US correlates for developing asymmetries are often nonmass findings with mixed echotexture. Most malignant developing asymmetries with US correlates present as a hypoechoic mass, but 19% present as a nonmass finding with either mixed hyperechoic and hypoechoic echotexture or hypoechoic echotexture.


[A set of check-up means for an automatic microplate photometer for immunologic studies].
The title set consists of six pairs of neutral filters with different optical density ranging from 0.03 to 1.5 B, a pair of filters made of colour yellow glass, and a holder having the same dimensions as the microplate and serving for the installation of the filters in the photometer checked. Every pair consists of two filters with identical optical parameters. The dimensions of the pair of filters allow covering all eight channels of the photometer simultaneously. The filters are certified with the error not more than +/- 0.003 B in the spectral range 360-700 nm. The yellow glass filter allows checking the dual wavelength mode of investigation.


'Sentinel' mutations in standard population sequencing can predict the presence of HIV-1 reverse transcriptase major mutations detectable only by ultra-deep pyrosequencing.
This proof-of-concept study aimed to identify whether mutations considered not yet relevant for drug resistance (but located at key drug-resistance positions) can act as 'sentinels' of minority resistant variants in HIV-1 drug-naive patients. We focused our attention on three reverse transcriptase (RT) mutations (T69S, L210M and K103R) easily detected by standard population sequencing [i.e. the genotypic resistance test (GRT)]. Ultra-deep pyrosequencing (UDPS) of HIV-1 RT was performed using GS-FLX Roche, on plasma RNA from 40 drug-naive patients infected with HIV-1 subtype B without primary resistance detected by GRT. Only RT drug resistance mutations detected at >0.1% in both forward and reverse directions were considered. Associations between GRT sentinel mutations and UDPS drug resistance were assessed using Fisher's exact test. UDPS detected drug resistance mutations in 18/40 drug-naive patients. Patients carrying HIV-1 strains with T69S and L210M by GRT showed a trend to greater infection by minority drug-resistant variants than control patients infected by HIV-1 without these mutations (5/10 and 7/10 versus 3/10; P = not significant). No association was found for K103R by GRT. Notably, T69S and L210M (but not K103R or control viruses) were associated with GRT minority drug-resistant variants with a prevalence >1% (3/10 and 4/10 versus 0/20 in K103R and controls; P = 0.03 and P = 0.008, respectively). Moreover, the presence of L210M or T69S viruses by GRT significantly correlated with that of minority thymidine analogue mutations by UDPS (6/20 patients carrying HIV-1 strains with T69S/L210M versus 0/20 patients carrying HIV-1 having K103R or none of these mutations; P = 0.03). This proof-of-concept study suggests the existence of genetic markers, detectable by routine testing, potentially acting as sentinel mutations of minority drug resistance. Their identification may help in the selection of patients at high risk of resistance in reservoirs without the necessity of using UDPS.


Macrophage-mediated inflammation in metabolic disease.
Metabolism and immunity are two fundamental systems of metazoans. The presence of immune cells, such as macrophages, in metabolic tissues suggests dynamic, ongoing crosstalk between these two regulatory systems. Here, we discuss how changes in the recruitment and activation of macrophages contribute to metabolic homeostasis. In particular, we focus our discussion on the pathogenic and protective functions of classically and alternatively activated macrophages, respectively, in experimental models of obesity and metabolic disease.


A comparison of oral and intravenous diazepam sedation for periodontal surgery.
Intravenous and oral diazepam were evaluated as to their effectiveness in conscious sedation during two similar surgical episodes. Ten patients, six females and four males, from 30 to 60 years of age were included in the study. Patients received either 10 mg oral diazepam and saline intravenous injection or oral placebo and 10 mg intravenous (IV) diazepam at each trial. Half the patients received the oral diazepam first and the other half received the IV diazepam first. Patients were not informed as to the route of administration during each trial. Physiologic stress was measured by monitoring blood pressure, heart rate, skin temperature, galvanic skin response, and plasma catecholamine levels. Patients evaluated their comfort and nervousness levels on a questionnaire. Anterograde amnesia was tested by patient's ability to recall objects shown them during the procedure. As evidenced by the physiologic and biochemical parameters, intravenous diazepam was more effective in reducing anxiety and stress as compared with an equivalent oral dose. Patients' subjective ratings were consistent with these findings. Intravenous diazepam was effective in producing anterograde amnesia in the majority of patients, whereas no amnesic effect was noted with oral diazepam. Correlation statistics demonstrated a relative independence of the parameters measured in the present study indicating that all parameters must be considered in overall patient evaluation. Reduction of anxiety during the first surgery resulted in less anxiety on the subsequent visit.


The birth of therapy with cultured cells.
Long ago, I set out to solve a problem, but something happened along the way: I was diverted by an unexpected observation. Thereafter, the direction of my research was guided at each stage by increasing familiarity with the experimental material and what could be done with it. The result was the birth of therapy with cultured keratinocytes. Subsequent developments soon led to the formation of the company Biosurface Technology (later taken over by the Genzyme Corporation), which provided autologous cultures for burn victims in many parts of the world. Further progress by others led to new therapeutic applications of cultured keratinocytes, such as treatment of an ocular disease and gene therapy. Unfortunately, there have developed serious regulatory problems that are a danger to future progress. As described in this brief history, the initial stages of development of cell therapy for the treatment of human disease were possible only because there was no restraint by committees or governmental regulations.


Development of an XTT tetrazolium salt-based assay for detection of specific hyperthermia sensitizers in a high-flux screening programme.
It is now possible to search for new drugs using high-throughput screening of chemical libraries accumulated over the past few years. To detect potential new hyperthermia sensitizers, we are screening for chemical inhibitors of thermotolerance. For the screening of a large chemical library, a rapid and simple assay based on the XTT-tetrazolium salt with the addition of intermediate electron acceptor, phenazine methosulphate (PMS) as a promoter, was developed. It was found that the sensitivity of the XTT/PMS assay is sufficient for assessing thermal cell killing and thermotolerance, although it was highly dependent on cell number and type. When the formazan assay system was challenged with the bioflavonoid drug quercetin (up to 25mm) and validated against the clonogenic cell survival assay, significant decreases in thermotolerant cell viability were observed, directly reflecting inhibition of thermotolerance. Although short-term assays can, in some instances, underestimate overall cell killing, the dose dependency of inhibition of thermotolerance by quercetin recorded in this study by clonogenic and XTT/PMS assays was similar. Application of the XTT/PMS assay in chemical library screening was highly effective in differentiating potential thermotolerance inhibitors from both chemicals with lack of efficacy and from toxic compounds. Taken together, these results show that the XTT/PMS assay, when carried out under careful conditions, is well suited for primary high-flux screen of many thousands of compounds, thus opening up new areas for discovery of hyperthermia sensitizers.


Argininosuccinate synthase 1 and periportal gene expression in sonic hedgehog hepatocellular adenomas.
Genetic alterations define different molecular subclasses of hepatocellular adenoma (HCA) linked with risk factors, histology and clinical behavior. Recently, Argininosuccinate Synthase 1 (ASS1), a major periportal protein, was proposed as a marker of HCA with a high risk of hemorrhage. We aimed to assess the significance of ASS1 expression through the scope of the HCA molecular classification. ASS1 expression was evaluated using RNAseq, quantitative reverse transcriptase polymerase chain reaction (RT-PCR) and Immunohistochemistry. ASS1 and glioma-associated oncogene 1 (GLI1) expression were analyzed in vitro after modulation of GLI1 expression. Using RNAseq in 27 HCA and five nontumor liver samples, ASS1 expression was highly correlated with GLI1 expression (P<0.0001, R=0.75). In the overall series of 408 HCA, ASS1 overexpression was significantly associated with sonic hedgehog HCA (shHCA) compared to other molecular subgroups (P<0.0001), suggesting that sonic hedgehog signaling controls ASS1 expression. GLI1 expression silencing by siRNA induced a downregulation of ASS1 in PLC/PFR5 and SNU878 cell lines. In 390 HCA, we showed that ASS1 expression belonged to the periportal expression program that was maintained in shHCA but down-regulated in all the other HCA subtypes. In contrast, HCA with β-catenin activation showed an activation of a perivenous program. Despite the significant association between GLI1 and ASS1 expression, ASS1 mRNA expression was not associated with specific clinical features. At the protein level using immunohistochemistry, prostaglandin D synthase (PTGDS) was strongly and specifically overexpressed in shHCA. ASS1 is associated with sonic hedgehog activation as part of a periportal program expressed in shHCA, a molecular subgroup defined by INHBE-GLI1 gene fusion. (Hepatology 2018).


Deciphering the flexibility and dynamics of Geobacillus zalihae strain T1 lipase at high temperatures by molecular dynamics simulation.
The stability of biocatalysts is an important criterion for a sustainable industrial operation economically. T1 lipase is a thermoalkalophilic enzyme derived from Geobacillus zalihae strain T1 (T1 lipase) that was isolated from palm oil mill effluent (POME) in Malaysia. We report here the results of high temperatures molecular dynamics (MD) simulations of T1 lipase in explicit solvent. We found that the N-terminal moiety of this enzyme was accompanied by a large flexibility and dynamics during temperature-induced unfolding simulations which preceded and followed by clear structural changes in two specific regions; the small domain (consisting of helices alpha3 and alpha5, strands beta1 and beta2, and connecting loops) and the main catalytic domain or core domain (consisting of helices alpha6- alpha9 and connecting loops which located above the active site) of the enzyme. The results suggest that the small domain of model enzyme is a critical region to the thermostability of this organism.


Planning for alternative futures in the NHS.
'The NHS needs the ability to move much more quickly' (The Griffiths Report, 1983, p13) This paper grew out of preliminary research undertaken for the research project on which we both work, entitled the Management of Change in the NHS. The project is based in the Centre for Corporate Strategy and Change at the University of Warwick, and is directed by Professor Andrew Pettigrew, who has previously undertaken a longitudinal study of strategic change in ICI (Pettigrew, 1985), and also a pilot study within the NHS which identified the implementation of strategic intent as the jugular problem confronting NHS managers. But a central research problem is why it is that some Health Districts manage to achieve a faster rate of change than others. Hence there was a need to trace the evolution of local systems through time, with the result that the historical analysis of changing is a key aspect of this research. The project is financed jointly by the NHSTA and a consortium of eight of the English Regions and ten case study districts are included. The research design focusses on strategic service changes in both the acute and priority group sectors and incorporates developments and contractions. The choice of strategic changes was informed by a detailed review of the most recent regional strategic plans and the review itself prompted this paper. It led us to a number of observations about the content of the change agenda. First, there is a high rate of change projected in the current strategic round and earlier studies of incrementalist approaches to change may have to be revised (Hunter, 1980; Ham, 1981). Secondly, these regional change agendas to a great extent reflect national/central policy and the pattern is one of uniformity. These standard agendas include RAWP; the construction of a DGH network; the run-down of long-stay mental illness/handicap hospitals; cost improvements and an increase in health promotion activity. Thirdly, alongside the top-down mechanisms to secure implementation of national objectives, another mode of planning emerges which more closely approaches the concept of 'local learning' (Glennester et al, 1983) where organisations seek to explore possible forces for change and how they might respond. Planning here is seen as a means of 'problem-sensing' and awareness building (Quinn, 1980) and getting new issues onto the agenda (Pettigrew, 1985). The paper will explore the content of the change agenda in detail and the nature of the planning process.(ABSTRACT TRUNCATED AT 400 WORDS)


Indirect detection of labile solute proton spectra via the water signal using frequency-labeled exchange (FLEX) transfer.
We report an "exchange-rate-filtered" magnetic resonance approach that allows the detection of exchangeable protons of low-concentration solutes without interference from nonexchanging protons. This indirect detection of signals of multiple rapidly exchanging protons through the water signal can be achieved while retaining chemical shift specificity and increasing the sensitivity by several orders of magnitude with respect to standard spectroscopy. This frequency-labeled exchange (FLEX) transfer principle is applied to detect previously "invisible" protons of some nucleic acids and peptides as well as rapidly exchanging protons (k > 300 s(-1)) in so-called chemical exchange saturation transfer (CEST) magnetic resonance imaging (MRI) contrast agents. The FLEX methodology is expected to provide a practical approach for the study of highly dynamic regions of nucleic acids and proteins where amide, amino, and imino groups are rapidly moving between a closed solvent-inaccessible state and an exposed state where exchange occurs. This alternative method of labeling and detecting exchangeable protons is also expected to greatly benefit the development of new exchange-based MRI contrast agents, providing a method for multifrequency detection using frequency transfer instead of saturation transfer.


Electromyographic amplitude normalization methods: improving their sensitivity as diagnostic tools in gait analysis.
The effect of four amplitude normalization methods on intersubject variability of electromyographic (EMG) profiles in normal gait was examined. Bipolar silver/silver chloride surface electrodes were applied to the rectus femoris, vastus lateralis, biceps femoris, tibialis anterior, and soleus muscles of the right lower extremity, in 11 healthy subjects. The myoelectric signals were telemetered via an FM multichannel biotelemetry system, full-wave rectified and low-pass filtered, then A/D converted together with the footswitch signal. Within-subject ensemble-average patterns were generated from the linear envelope EMG of at least six strides for each subject. Each subject's ensemble average was then normalized to the following: (a) the average EMG over three 50% isometric maximum voluntary contractions (MVC), (b) the EMG per unit isometric moment of force, (c) the peak of the subject ensemble average, (d) the mean of the subject ensemble average. Intersubject variability was quantified for each of the normalization methods by the coefficient of variation (CV). The normalization to either the peak ensemble or the mean ensemble drastically reduced intersubject variability, by 12%-73%. In contrast, normalization to the average EMG during 50% MVC or to the EMG per unit moment increased intersubject variability. It was concluded that the reduction of intersubject variability by appropriate amplitude normalization is possible, thereby increasing the sensitivity of surface EMG as a diagnostic tool in gait analysis.


Immunological characterization of in vitro forms of homoserine dehydrogenase from carrot suspension cultures.
Multiple forms of homoserine dehydrogenase (HSDH) from carrot (Daucus carota L.) have been identified. One form of HSDH (T-form) has a relative molecular weight of 240,000 and is strongly inhibited by threonine. Another form (K-form) has a relative molecular weight of 180,000 and is insensitive to inhibition by threonine. The interconversion of these two forms is dependent upon the presence or absence of threonine and potassium. Polyacrylamide electrophoretic gels stained for HSDH activity and protein, paralleled with Western blot analysis, verified the interconversion of the T- and K-forms in 5 millimolar threonine and 100 millimolar potassium, respectively. Carrot HSDH also aggregates to form higher molecular weight complexes of 240,000 up to 720,000 M(r.) Polyclonal antibody from mouse was raised against the T-form (240,000 M(r)) of carrot HSDH. Specificity of the mouse antisera to carrot HSDH was verified by immunoprecipitation and Western blot analysis. The T-form, K-form, and all of the higher molecular aggregates of carrot HSDH cross-reacted with the anti-HSDH antiserum. The antiserum also cross-reacted with soybean HSDH, but did not cross-react with either of the two HSDH forms found in Escherichia coli. A model for the in vivo regulation of threonine biosynthesis in the chloroplast is presented. The model is based on the interconversion of the HSDH forms by potassium and threonine.


Sex differences in executive functioning and latent herpesvirus reactivation among bereaved and nonbereaved individuals.
The death of a spouse is a highly stressful event. Better executive functioning has been shown to benefit men to a greater degree than women during stress. We evaluated potential sex differences in stress and immune dysregulation among control and bereaved participants who completed a self-report measure of perceived stress, neuropsychological measures of inhibition and updating/monitoring of information in working memory, and a blood draw to measure Epstein-Barr virus (EBV) antibody titres. Moderation analyses were conducted to test the hypothesis that better inhibition would be associated with less stress and immune dysregulation among male bereaved participants compared with female bereaved participants. Bereaved females demonstrated greater EBV antibody titres than bereaved males. Male bereaved participants benefited from better inhibition, as evidenced by fewer EBV antibody titres, whereas bereaved female participants did not. In the control group, males with high inhibition reported lower stress than males with low inhibition. Present study results are an important step towards identifying those at greatest risk of stress and poor health.


Free amino acids and glycine betaine in leaf osmoregulation of spinach responding to increasing salt stress.
• The aim of the paper was to determine nitrogen compounds contributing to leaf cell osmoregulation of spinach (Spinacia oleracea) submitted to increasing salt stress. • Sodium, free amino acids and glycine betaine contents were determined in the last fully expanded leaf of plants stressed by daily irrigation with saline water (0.17 M NaCl). • After 20 d of treatment, when Na+ content was c. 55 umol g-1 f. wt above the control, and the reduction of stomatal conductance lowered photosynthesis to c. 60% of the control, the free amino acids of the leaves, especially glycine and serine, strongly increased. Proline and glycine betaine also increased significantly. After 27 d of treatment, when the Na+ content was c. 100 umol g-1 f. wt above the control and photosynthesis was 33% of the control, the free amino acid content, especially glycine and serine, declined. Gycine betaine, but not proline, increased further. • Glycine betaine comprised c. 15% of the overall nitrogen osmolytes at mild salt-stress, but represented 55% of the total, when the stress became more severe. The increase of glycine betaine balanced the decline in free amino acids, mainly replacing glycine and serine (the precursors of glycine betaine) in the osmotic adjustment of the cells. Photorespiration, which increased during salt stress, was also suggested to have a role in supplying metabolites to produce compatible osmolytes.


Effects of an oil spill and discharge of domestic sewage on the insect fauna of Cururu stream, Manaus, AM, Brazil.
Assemblages of aquatic and edaphic insects in three streams in Central Amazonia were used to evaluate the impact on one of the streams (Cururu) caused by an oil spill that occurred in August 1999. The Cururu stream had already been impacted by domestic sewage. These three streams were evaluated during four different periods of the regional hydrological cycle (falling-, low-, rising- and high-water), from September 2000 to May 2001. An Eckman dredge, an aquatic entomological net and a manual auger were used to collect insects, which were used to estimate the taxonomic richness (at the family level) and insect density in each stream. Anoxic and eutrophic conditions were determined in each stream based on the mean concentration of dissolved oxygen, total nitrogen and phosphorus. Richness and abundance of insect fauna were higher in the Cristalino stream (not impacted) than in the Bom Jardim stream (impacted by domestic sewage) and in the Cururu stream, with the exception of samples collected along the stream banks (littoral fauna). The mean dissolved oxygen was lower in the Cururu stream than in the other two, while the mean concentrations of total nitrogen and phosphorus were higher. These elements showed intermediate values in the Bom Jardim stream, while the opposite pattern was observed in the Cristalino stream, with higher concentrations of dissolved oxygen and lower concentrations of total nitrogen and phosphorus. The concentrations of these variables reflect the modifications resulting from anthropogenic eutrophication caused by the discharge of domestic sewage into Bom Jardim and Cururu and by the oil spill in Cururu, which negatively affected the richness and abundance of insects in these streams.


Energy Relaxation and Electron-Phonon Coupling in Laser-Excited Metals.
The rate of energy transfer between electrons and phonons is investigated by a first-principles framework for electron temperatures up to Te = 50,000 K while considering the lattice at ground state. Two typical but differently complex metals are investigated: aluminum and copper. In order to reasonably take the electronic excitation effect into account, we adopt finite temperature density functional theory and linear response to determine the electron temperature-dependent Eliashberg function and electron density of states. Of the three branch-dependent electron-phonon coupling strengths, the longitudinal acoustic mode plays a dominant role in the electron-phonon coupling for aluminum for all temperatures considered here, but for copper it only dominates above an electron temperature of Te = 40,000 K. The second moment of the Eliashberg function and the electron phonon coupling constant at room temperature Te=315 K show good agreement with other results. For increasing electron temperatures, we show the limits of the T=0 approximation for the Eliashberg function. Our present work provides a rich perspective on the phonon dynamics and this will help to improve insight into the underlying mechanism of energy flow in ultra-fast laser-metal interaction.


An accurate method for determination of receptor-ligand and enzyme-inhibitor dissociation constants from displacement curves.
Receptor-ligand dissociation constants are usually calculated from the displacement curve of a radioactively labeled ligand bound to the receptor. The formula used is restricted to cases in which the concentration of receptor is negligible compared to the concentration of both the displacing ligand and the radioactive ligand used. In this study, we rigorously derive a simple equation that can be used for calculating receptor-ligand dissociation constants for any set of experimental conditions. A linearized form of this equation provides a convenient plot from which the dissociation constant of the displacing ligand can be directly obtained. The plot is also a test for the competitive mode of binding. This exact equation now allows us to estimate the error incurred by the conventionally used equations. Similarly, we show that for competitive inhibition in enzymology, one can derive the analogous formula. Our new formula is free of the usual restrictions--namely, that the enzyme concentration is very small compared to the concentration of both the substrate and the inhibitor. It may therefore be applied to any set of experimental conditions.


The effect of colchicine on physical growth in children with familial mediterranean fever.
Familial Mediterranean fever (FMF) is an autosomal recessive disease, characterized by recurrent, self-limited attacks of fever with serositis involving the peritoneum, pleura, and joints. There is very scarce information on physical growth of affected children. The aim of this study was to determine whether there is significant improvement in growth parameters in FMF patients after colchicine treatment. Patient files were retrospectively evaluated and patients that used colchicine for more than 1 year were included in the study. Demographic features, clinical findings before and after colchicine therapy, duration and dosage of therapy, weight, height, parentally adjusted height, and body mass index before and after colchicine therapy were noted and transformed into standard deviation scores (SDS). The study group consisted of 50 FMF (25 male and 25 female) patients. Median age at the time of diagnosis was 6.5 years. Median follow-up period was 3.6 (1-12.5) years. Mean height SDS increased from -0.19 +/- 1.01 to 0.13 +/- 0.99 (p = 0.026), and mean parentally adjusted height increased from -0.18 +/- 1.23 to 0.13 +/- 1.24 (p = 0.027), and both of them were found to be statistically significant. Mean body mass index SDS increased from -0.61 +/- 1.32 to -0.32 +/- 1.33, but this improvement was statistically insignificant (p = 0.18). In this study, we found that colchicine significantly improved height development in FMF patients.


Cervicofacial Cellulitis due to Staphylococcus aureus with Jugular Vein Thrombosis and Multiple Septic Pulmonary Embolism: A Lemierre-Like Syndrome.
This is the case of a 28-year-old male patient with no particular pathological history who presented with an inflammatory swelling of the right cheek with pus in an infectious context. Cervicofacial CT with contrast injection allowed the diagnosis of a right cervicofacial cellulitis, associated with a jugular venous thrombosis extending to the superior vena cava. It also revealed septic pulmonary metastases in the form of multiple excavated pulmonary nodules. The analysis of the pus sample allowed the isolation of Staphylococcus aureus as the causative germ. This led to the diagnosis of a Lemierre-like syndrome, which is a variant of the Lemierre syndrome. Despite appropriate antibiotic treatment and anticoagulation, the patient died after 16 days of hospitalization.


Derivation of the correct waveform of the human electrocardiogram by Willem Einthoven, 1890-1895.
In the period 1890 to 1895, Willem Einthoven greatly improved the quality of tracings that could be directly obtained with the capillary electrometer. He then introduced an ingenious correction for the poor frequency response of these instruments, using differential equations. This method allowed him to predict the correct form of the human electrocardiogram, as subsequently revealed by the new string galvanometer that he introduced in 1902. For Einthoven, who won the Nobel Prize for the development of the electrocardiogram in 1924, one of the most rewarding aspects of the high fidelity recording of the human electrocardiogram was its validation of his earlier theoretical predictions regarding the electrical activity of the heart.


Characterizing Thalamo-Cortical Structural Connectivity in Essential Tremor with Diffusional Kurtosis Imaging Tractography.
Neuromodulation of the cerebello-thalamo-cortical (CTC) circuit via thalamic stimulation is an effective therapy for essential tremor (ET). In order to develop non-invasive neuromodulation approaches, clinically relevant thalamo-cortical connections must be elucidated. Twenty-eight subjects (18 ET patients and 10 controls) underwent MRI diffusional kurtosis imaging (DKI). A deterministic fiber-tracking algorithm based on DKI was used, with a seeding region placed at the ventral intermediate nucleus (Vim-located based on intraoperative physiology) to the ending regions at the supplementary motor area (SMA), pre-SMA, or primary motor cortex. One-tailed t-tests were performed to compare groups, and associations with tremor severity were determined by Pearson correlations. All p-values were adjusted for multiple comparisons using Bonferroni correction. There was a decrease in the mean diffusivity (MD) in patients compared to controls in all three tracts: Vim-M1 (ET 0.87, control 0.96, p < 0.01), Vim-SMA (ET 0.86, control 0.96, p < 0.05), and Vim-pre-SMA (ET 0.87, control 0.95, p < 0.05). There was a significant positive correlation between Tremor Rating Scale score and MK (r = 0.471, p = 0.033) and mean FA (r = 0.438, p = 0.045) for the Vim-SMA tract, and no significant correlation for the Vim-pre-SMA or Vim-M1 tracts was found. Patients with ET demonstrated a reinforcement of Vim-cortical connectivity, with higher Vim-SMA connectivity being associated with greater tremor severity. This finding suggests that the Vim-SMA connection is relevant to the underlying pathophysiology of ET, and inhibition of the SMA may be an effective therapeutic approach.


Genetic circuit performance under conditions relevant for industrial bioreactors.
Synthetic genetic programs promise to enable novel applications in industrial processes. For such applications, the genetic circuits that compose programs will require fidelity in varying and complex environments. In this work, we report the performance of two synthetic circuits in Escherichia coli under industrially relevant conditions, including the selection of media, strain, and growth rate. We test and compare two transcriptional circuits: an AND and a NOR gate. In E. coli DH10B, the AND gate is inactive in minimal media; activity can be rescued by supplementing the media and transferring the gate into the industrial strain E. coli DS68637 where normal function is observed in minimal media. In contrast, the NOR gate is robust to media composition and functions similarly in both strains. The AND gate is evaluated at three stages of early scale-up: 100 mL shake flask experiments, a 1 mL MTP microreactor, and a 10 L bioreactor. A reference plasmid that constitutively produces a GFP reporter is used to make comparisons of circuit performance across conditions. The AND gate function is quantitatively different at each scale. The output deteriorates late in fermentation after the shift from exponential to constant feed rates, which induces rapid resource depletion and changes in growth rate. In addition, one of the output states of the AND gate failed in the bioreactor, effectively making it only responsive to a single input. Finally, cells carrying the AND gate show considerably less accumulation of biomass. Overall, these results highlight challenges and suggest modified strategies for developing and characterizing genetic circuits that function reliably during fermentation.


Development and validation of the parents' cognitive perception inventory of disaster effects on children's well-being (PCP-DCWB).
Parents' cognition about the type and nature of consequences a disaster may pose on the children's psychosocial health, could be a major protective factor against the long-term overwhelming complications. Given the lack of a reliable instrument to measure parents' cognition about disasters' effects on children's well-being, this study was conducted to develop and validate the parents' cognitive perception inventory of disaster effects on children's well-being (PCP-DCWB). In this cross-sectional study 300 parents of the survived primary school aged children from the Iran's northwest earthquake on August 2012 were recruited in the city of Varzegan. Exploratory factor analysis (EFA) was applied to identify the subcomponents and Cronbach's alpha and Guttmann Split-half coefficients were calculated to assess the internal consistency reliability of the scale. Structural indicators of the Kaiser-Meyer-Olkin measure (0.69) and Bartlett's test of Sphericity (P < 0.001, df = 153, X2 = 618.35) verified interpretability of the EFA output. Applying principal component analysis and direct oblimin rotation in the EFA four latent factors were identified (i.e., perception about child overall mental health, coping with trauma's long-term effects, children or parents' continuing memory of past disaster and perception about behavioral and educational problems) which explained 49.32% of the total variance. The estimated Cronbach's alpha and split-half reliability coefficients (0.71 and 0.52 respectively) supported good internal consistency of the instrument. The study findings revealed sound psychometric attributes of the PCP-DCWB to be applied in assessment of parents' cognition about psychological impacts of a traumatic event on the survived children. The instrument application can shed light on level of pre-disaster preparations in local, national and international scales and help effectiveness assessment of interventions that target maintenance of psycho-social well-being among disaster-affected survivors over time.


Impact of Small Intestine Bacterial Overgrowth on Response to a Nutritional Intervention in Bangladeshi Children from an Urban Community.
Small intestine bacterial overgrowth (SIBO) is prevalent among children living in low-income settings, leading to impaired growth and development. The aim of this study was to assess linear and ponderal growth parameters between malnourished SIBO-positive and SIBO-negative children aged 12-18 months who prospectively underwent a nutritional intervention. A glucose hydrogen breath test to detect SIBO was performed in 194 stunted (length-for-age Z score [LAZ] < -2 standard deviations) or at-risk of stunting (LAZ score between < -1 and -2 standard deviations) children. Participants received nutritional supplementation (egg and milk) in addition to their regular family meals 6 days per week for 90 days. Small intestine bacterial overgrowth was defined as a ≥ 12-ppm rise in breath hydrogen over the patient's baseline during the 3-hour test. Small intestine bacterial overgrowth status before intervention was forced into a multivariable linear regression model to examine its effects on anthropometric changes in response to the intervention. Sociodemographic data at enrollment was analyzed through multivariable logistic regression in an attempt to predict SIBO positivity. Overall, 14.9% (29/194) children were diagnosed with SIBO before the nutritional intervention. No statistically significant difference was observed among SIBO-positive and SIBO-negative groups in terms of their response to the nutritional intervention (SIBO-positive coefficient [95% confidence interval (CI)], P-value for ∆length-for-age Z score -0.003 [-0.14, 0.13], 0.96; ∆weight-for-age Z score -0.05 [-0.20, 0.09], 0.46; and ∆weight-for-length Z score -0.10 [-0.31, 0.10], 0.33). This study demonstrated that a noteworthy proportion of malnourished children living in a disadvantaged urban community were SIBO positive; however, it failed to reveal an association between SIBO status and response to nutritional intervention.


Moonmilk deposits originate from specific bacterial communities in Altamira Cave (Spain).
The influence of bacterial communities on the formation of carbonate deposits such as moonmilk was investigated in Altamira Cave (Spain). The study focuses on the relationship between the bacterial communities at moonmilk deposits and those forming white colonizations, which develop sporadically throughout the cave. Using molecular fingerprinting of the metabolically active bacterial communities detected through RNA analyses, the development of white colonizations and moonmilk deposits showed similar bacterial profiles. White colonizations were able to raise the pH as a result of their metabolism (reaching in situ pH values above 8.5), which was proportional to the nutrient supply. Bacterial activity was analyzed by nanorespirometry showing higher metabolic activity from bacterial colonizations than uncolonized areas. Once carbonate deposits were formed, bacterial activity decreased drastically (down to 5.7% of the white colonization activity). This study reports on a specific type of bacterial community leading to moonmilk deposit formation in a cave environment as a result of bacterial metabolism. The consequence of this process is a macroscopic phenomenon of visible carbonate depositions and accumulation in cave environments.


Control of neural crest cell behavior and migration: Insights from live imaging.
Neural crest cells (NCCs) are a remarkable, dynamic group of cells that travel long distances in the embryo to reach their target sites. They are responsible for the formation of craniofacial bones and cartilage, neurons and glia in the peripheral nervous system, and pigment cells. Live imaging of NCCs as they traverse the embryo has been critical to increasing our knowledge of their biology. NCCs exhibit multiple behaviors and communicate with each other and their environment along each step of their journey. Imaging combined with molecular manipulations has led to insights into the mechanisms controlling these behaviors. In this review, we highlight studies that have used live imaging to provide novel insight into NCC migration and discuss how continued use of such techniques can advance our understanding of NCC biology.


Cocaine induces ubiquitination of Egr-1 in the rat dorsal striatum.
Early growth response (Egr) is a member of the zinc finger family of transcription factors that reflects neuronal activity induced by various stimuli. Acute cocaine administration elicits rapid and transient induction of several immediate early genes in brain neurons. However, the mechanism regulating the degradation of the Egr-1 protein is not clearly understood. In this study, rats were injected with cocaine and the relationships among locomotor activity, Egr-1 protein level, phosphorylation of upstream kinase extracellular regulated kinase (ERK)1/2, Egr-1 mRNA expression, and ubiquitination of the Egr-1 protein were measured in the dorsal striatum and the frontal cortex. Locomotor activity reached a peak at about 15 min, and phosphorylation of ERK1/2 and Egr-1 mRNA level also increased at that time. However, the Egr-1 protein level decreased initially in the dorsal striatum, probably due to ubiquitination-mediated degradation. When locomotor activity decreased substantially at 30 min, the phosphorylation of ERKs and expression levels of Egr-1 mRNA and protein reached their peak levels and the protein level subsequently increased. These findings indicate that immediate early gene protein levels would not be a reliable indicator of increased regional activity in the brain. Thus, observations spanning multiple time periods or the examination of mRNA rather than protein would be recommended in these situations.


COST OF PRIMARY HEALTH CARE IN PAKISTAN.
Detailed cost analysis is an important tool for review of health policy and reforms. We provide an estimate of cost of service and its detailed breakup on out-door patient visits (OPV) to basic health units (BHU) in Pakistan. Six BHUs were randomly selected from each of the five districts in Khyber Pukhtonkhawa (KPK) and two agencies in Federally Administered Tribal Areas (FATA) of Pakistan for this study. Actual expenditure data and utilization data in the year 2005-06 of 42 BHUs was collected from selected district health offices in KPK and FATA. Costs were estimated for outpatient visits to BHUs. Perspective on cost estimates was district-based health planning and management of BHUs. Average recurring cost was PKR.245 (USD 4.1) per OPV to BHU. Staff salaries constituted 90% of recurrent cost. On the average there were 16 OPV per day to the BHUs. CONCLUDION: Recurrent cost per OPV has doubled from the previous estimates of cost of OPV in Baluchistan. The estimated recurrent cost was six times higher than average consultation charges with the private general practitioner (GP) in the country (i.e., PKR 50/ GP consultation). Performance of majority of the BHUs was much lower than the performance target (50 patients per day) set in the sixth five-year plan of the government of Pakistan. The Government of Pakistan may use these analyses to revisit the performance target, staffinL and location of BHUs.


Acute and chronic toxicity studies of the water extract from dried fruits of Terminalia bellerica (Gaertn.) Roxb. In Spargue-Dawley rats.
Acute and chronic toxicities of the water extract from the dried fruits of Terminalia bellerica (Gaertn.) Roxb. were assessed in both female and male rats. For the study of acute toxicity, a single oral administration of the water extract at a dose of 5,000 mg/kg body weight (10 female, 10 male) was performed and the results showed no signs of toxicity such as general behavior changes, morbidity, mortality, changes on gross appearance or histopathological changes of the internal organs of rats. The study of chronic toxicity was determined by oral feeding both female and male rats (10 female, 10 male) daily with the test substance at the dose of 300, 600 and 1,200 mg/kg body weight continuously for 270 days. The examinations of signs of toxicity showed no abnormalities in the test groups compared to the controls. In addition, these rats were analyzed for final body and organ weights, necropsy, as well as hematological, blood chemical and histopathological parameters. Taken together, the water extract from the dried fruits of T. bellerica did not cause acute or chronic toxicities in either female or male rats.


Morbid Obesity's Silver Lining: An Armor for Hollow Viscus in Blunt Abdominal Trauma.
Morbid obesity is usually accompanied by both subcutaneous and visceral fat accumulation. Fat can mimic an air bag, absorbing the force of a collision. We hypothesized that morbid obesity is mechanically protective for hollow viscus organs in blunt abdominal trauma (BAT). The National Trauma Data Bank (NTDB) was queried for BAT patients from 2013 to 2015. We looked at the rate of gastrointestinal (GI) tract injuries in all BAT patients with different BMIs. A subset analysis of BAT patients with operative GI tract injuries was performed to evaluate the need for abdominal operation. Multivariate analyses were carried out to identify factors independently associated with increased GI tract injuries and associated abdominal operations. A total of 100,459 BAT patients were evaluated in the NTDB. Patients with GI tract injury had a lower proportion of morbidly obese patients [body weight index (BMI) ≥ 40 kg/m2)] (3.7% vs. 4.2%, p = 0.015) and instead had more underweight patients (BMI < 18.5) (5.9% vs. 5.0%, p < 0.001). The risk of GI tract injury decreased 11.6% independently in morbidly obese patients and increased 15.7% in underweight patients. Of the patients with GI tract injuries (N = 11,467), patients who needed a GI operation had a significantly lower proportion of morbidly obese patients (3.2% vs. 5.3%, p < 0.001). The risk of abdominal operation for GI tract injury decreased 57.3% independently in morbidly obese patients. Compared with underweight patients, morbidly obese patients had significantly less GI tract injury (6.0% vs. 13.3%, p < 0.001) and associated abdominal operation rates (65.2% vs. 73.3%, p < 0.001). Obesity is protective in BAT. This translates into lower rates of GI tract injury and operation in morbidly obese patients. In contrast, underweight patients appear to suffer a higher rate of GI tract injury and associated GI operations.


Repeat neuroimaging of mild traumatic brain-injured patients with acute traumatic intracranial hemorrhage: clinical outcomes and radiographic features.
Emergency department (ED) management of mild traumatic brain injury (TBI) patients with any form of traumatic intracranial hemorrhage (ICH) is variable. Since 2000, our center's standard practice has been to obtain a repeat head computed tomography (CT) at least 6 hours after initial imaging. Patients are eligible for discharge if clinical and CT findings are stable. Whether this practice is safe is unknown. This study characterized clinical outcomes in mild TBI patients with acute traumatic ICH seen on initial ED neuroimaging. This retrospective cohort study included patients presenting to the ED with blunt mild TBI with Glasgow Coma Scale (GCS) scores of 14 or 15 and stable vital signs, during the period from January 2001 to January 2010. Patients with any ICH on initial head CT and repeat head CT within 24 hours were eligible. Cases were excluded for initial GCS < 14, injury > 24 hours old, pregnancy, concomitant nonminor injuries, and coagulopathy. A single investigator abstracted data from records using a standardized case report form and data dictionary. Primary endpoints included death, neurosurgical procedures, and for discharged patients, return to the ED within 7 days. Differences in proportions were computed with 95% confidence intervals (CIs). Of 1,011 patients who presented to the ED and had two head CTs within 24 hours, 323 (32%) met inclusion criteria. The median time between CT scans was 6 hours (interquartile range = 5 to 7 hours). A total of 153 (47%) patients had subarachnoid hemorrhage, 132 (41%) patients had subdural hemorrhage, 11 (3%) patients had epidural hemorrhage, 78 (24%) patients had cerebral contusions, and 59 (18%) patients had intraparenchymal hemorrhage. Four of 323 (1.2%, 95% CI = 0.3% to 3.2%) patients died within 2 weeks of injury. Three of the patients who died had been admitted from the ED on their initial visits, and one had been discharged home. There were 206 patients (64%) discharged from the ED, 28 (13.6%) of whom returned to the ED within 1 week. Of the 92 who were hospitalized, three (0.9%, 95% CI = 0.2% to 2.7%) required neurosurgical intervention. Discharge after a repeat head CT and brief period of observation in the ED allowed early discharge of a cohort of mild TBI patients with traumatic ICH without delayed adverse outcomes. Whether this justifies the cost and radiation exposure involved with this pattern of practice requires further study.


Safety and tolerability of linagliptin: a pooled analysis of data from randomized controlled trials in 3572 patients with type 2 diabetes mellitus.
To assess the safety and tolerability of the dipeptidyl peptidase-4 inhibitor linagliptin in patients with type 2 diabetes. Data were pooled from eight randomized, double-blind, placebo-controlled Phase III clinical trials lasting ≤24 weeks. Incidences were calculated with descriptive statistics for the overall population and for subgroups of elderly and renally impaired patients. A total of 2523 patients received linagliptin 5 mg once daily and 1049 patients received placebo. The overall incidence of adverse events (AEs) or serious AEs with linagliptin was similar to placebo (AEs 55.8% vs. 55.0%; serious AEs 2.8% vs. 2.7%). Overall aggregated infection incidence was 19.5% for linagliptin and 21.4% for placebo. Similar or reduced incidence of AEs versus placebo were seen with linagliptin for upper respiratory tract infection (3.3% vs. 4.9%), headache (2.9% vs. 3.1%), urinary tract infection (2.2% vs. 2.7%), blood and lymphatic disorders (1.0% vs. 1.2%), hypersensitivity (0.1% vs. 0.1%), hepatic enzyme increase (0.1% and 0.1%) and serum creatinine increase (0.0% and 0.1%). There was a slight increased frequency of nasopharyngitis (5.9% vs. 5.1%) and cough (1.7% vs. 1.0%) with linagliptin. Hypoglycaemia incidence was 8.2% for linagliptin and 5.1% for placebo; incidence was higher in patients with a background of sulphonylurea therapy (20.7% and 13.3%, respectively). In patients not receiving concomitant sulphonylurea, the hypoglycaemic incidence with linagliptin was very low in both the total population (<1%), and elderly and renally impaired patients (both <1%). This pooled analysis shows that linagliptin is well tolerated, with a low risk of hypoglycaemia.


Demonstration of system y+L activity on the basal plasma membrane surface of rat placenta and developmentally regulated expression of 4F2HC mRNA.
Na(+)-independent cationic amino acid transport in the rat placenta occurs by leucine-sensitive and leucine-insensitive pathways. The ontogeny of these transport mechanisms within the rat placenta has been described recently. To assign the leucine-inhibitable portion of uptake definitively the uptake of [3H]arginine was studied in the presence of both BCH (to inhibit system Bo,+) and varied concentrations of leucine. Uptake of arginine into basal-enriched membrane vesicles derived from rat placenta was, in the presence of sodium, inhibited by micromolar concentrations of leucine, consistent with assignment of this activity to system y+L. In contrast, the majority of arginine uptake into apical-enriched membrane vesicles was leucine insensitive. Messenger RNA derived from rat placenta at days 14, 16, 18 and 20 of gestation was hybridized with full-length rat cDNA probes against NBAT and 4F2HC (thought to encode proteins associated with system bo,+ and y+L activities, respectively). No NBAT mRNA was detected, whereas 4F2HC mRNA was present at all gestational stages, increasing 12-fold over the last third of gestation. It is concluded that system y+L is present in the basal plasma membrane of the rat placenta syncytium and is subject to developmental regulation by a mechanism that alters the steady content of 4F2HC mRNA.


Longitudinal study of Finnish nursing students' preferences for knowledge in nursing practice.
The curriculum of Finnish nursing education is based on nursing science. The aim is to educate nursing students to internalize the logic, concepts and major subject areas of nursing science. The purpose of this longitudinal study was to examine Finnish nursing students' knowledge base of nursing after 6, 18 and 30 months of education and at the end of the degree programme. The study group consisted of 158 students selected by means of stratified sampling from the six specialities of Finnish nursing education programs. Data were collected by means of a questionnaire from 26 institutes. A factor analysis of 21 items was done, where three factors emerged. The summarized variables based on the factors were subjected to one-way analysis of variance to elucidate the differences between the six groups of students. The students prioritized biomedical knowledge. Knowledge of diseases and anatomy was preferred to the other knowledge areas. The students also valued psychological knowledge. Nursing knowledge was the least preferred knowledge area at every phase of education. The students of the different specialities preferred knowledge areas congruent with the nursing practice of their speciality.


The Role of the Rho/ROCK Pathway in Ang II and TGF-β1-Induced Atrial Remodeling.
To study the role of the Rho/ROCK pathway in Ang II and TGF-β1-induced atrial remodeling. A canine atrial fibrillation (AF) model was established by rapid atrial pacing (RAP) of the left atrium. The roles of TGF-β1, the RhoA/ROCK signaling pathway and connective tissue growth factor (CTGF) in atrial remodeling were studied via both in vitro and in vivo experiments. Each of the dogs that received RAP developed persistent AF within 4 weeks. The mRNA expression levels of TGF-β1 (1.32±0.38), Collagen-I(1.33±0.91), CTGF(5.83±3.71), RhoA(1.23±0.57) and ROCK-1 (1.02±0.27) in the left atrium were significantly increased following 4 weeks of RAP. Angiotensin II (Ang II) induced the proliferation of atrial fibroblasts and up-regulated the expression of both CTGF and ROCK-1 in a dose-dependent manner. Simvastatin and Y27632 reversed Ang II-induced CFs proliferation, as well as ROCK-1(0.89±0.05 and 1.27±0.03, respectively) and CTGF (0.87±0.04 and 0.91±0.02, respectively) expression. The expression mRNA of ROCK-1(1.74±0.13) and CTGF (2.28±0.11) can upregulated by TGF-β1, and down-regulated by Simvastatin (1.22±0.03 vs 2.27±0.11), Y27632 (1.01±0.04 vs 1.64±0.03), Los (1.04±0.11 vs 1.26±0.05), respectively. Losartan and Simvastatin attenuated the effects of TGF-β1, inhibited RhoA activity as opposed to RhoA protein expression. Y27632 had no effect on either the expression or the activity of RhoA. The increased expression of profibrotic factors (CTGF, ROCK1 and Smad2/3) played an important role in our RAP-induced AF model. Increased atrial profibrotic factors involve the activation of either the TGF-β1/RhoA/ROCK-1 or the TGF-β1/Smad2/3 signaling pathway.


Cloning and functional analysis of the ndk1 gene encoding nucleoside-diphosphate kinase in Schizosaccharomyces pombe.
We cloned the ndk1 gene encoding a subunit of nucleoside-diphosphate kinase (NDK) from Schizosaccharomyces pombe, by using polymerase chain reaction. The deduced ndk1 gene product has 151 amino acid residues and is approximately 60% identical with both Saccharomyces cerevisiae and mammalian NDKs. The gene product exhibited NDK activity and cross-reacted with antibodies raised against rat NDK. Disruption of ndk1 greatly reduced the cellular NDK activity but caused no obvious phenotype in cell growth and sexual development of the organism. However, a mutated allele of ndk1 could inhibit sexual development in a dominant-negative manner. This allele carried a point mutation in cysteine 116, which locates next to the putative active center histidine 117, and the mutant gene product showed no NDK activity. Gene expression inducible in response to mating pheromone signaling was decreased in cells carrying the dominant-negative allele. Cases have been reported in higher eukaryotes in which NDK appears to play a more sophisticated role than a simple catalyst in cell physiology, and the results of this study suggest that S. pombe NDK may also perform such a role in regulation of sexual development in the fission yeast.


Influence of day length and temperature on the content of health-related compounds in broccoli (Brassica oleracea L. var. italica).
Vegetables grown at different latitudes are exposed to various temperatures and day lengths, which can affect the content of health- and sensory-related compounds in broccoli florets. A 2 × 2 factorial experiment was conducted under controlled growth conditions, with contrasting temperatures (15/9 and 21/15 °C) and day lengths (12 and 24 h), to investigate the effect on glucosinolates, vitamin C, flavonols, and soluble sugars. Aliphatic glucosinolates, quercetin, and kaempferol were at their highest levels at high temperatures combined with a 12 h day. Levels of total glucosinolates, d-glucose, and d-fructose were elevated by high temperatures. Conversely, the content of vitamin C was highest with a 12 h day length combined with 15/9 °C. Our results indicate that temperature and day length influence the contents of health-related compounds in broccoli florets in a complex way, suggesting no general superiority of any of the contrasting growth conditions.


Angiogenesis induced by tumor-host interaction in the rat.
There is a clear-cut cause-effect relationship between vascularization of a given tumor and its capacity to disseminate and metastasize. Hence, it is very important to study the contribution of the two main factors determining the generation of new blood vessels namely the tumor and the host where it grows. The influence of the tumor-host interaction on the induction of angiogenesis was studied in a tumor model-system composed by two lines of rats selected for resistance or susceptibility to a sarcoma (S-E100) and two transplantable tumors: Sarcoma E 100 and Lymphoma TACB. One line is resistant to the sarcoma but susceptible to the lymphoma while the other line behaves in the opposite way. Studying the angiogenesis generated by the s.c. implantation of each tumor in two different hosts we found that the same tumor induced different angiogenic responses according to the host in which it is growing and that the same host shows a different response according to the tumor with which it is challenged, suggesting that tumor-host interactions determine the intensity of the neovascularization process.


Radiosynthesis and characterization of 11C-GSK215083 as a PET radioligand for the 5-HT6 receptor.
The development of a PET radioligand for imaging 5-hydroxytryptamine (5-HT) 6 receptors in the brain would, for the first time, enable in vivo imaging of this target along with assessment of its involvement in disease pathophysiology. In addition, such a tool would assist in the development of novel drugs targeting the 5-HT6 receptor. On the basis of in vitro data, GSK215083 was identified as a promising 5-HT6 radioligand candidate and was radiolabeled with (11)C via methylation. The in vivo properties of (11)C-GSK215083 were evaluated first in pigs (to investigate brain penetration and specific binding), second in nonhuman primates (to confirm brain penetration, specific binding, selectivity, and kinetics), and third in human subjects (to confirm brain penetration and biodistribution). (11)C-GSK215083 readily entered the brain in all 3 species, leading to a heterogeneous distribution (striatum > cortex > cerebellum) consistent with reported 5-HT6 receptor densities and distribution determined by tissue-section autoradiography in preclinical species and humans. In vivo saturation studies using escalating doses of GSK215083 in primates demonstrated saturable, dose-dependent binding to the 5-HT6 receptor in the striatum. Importantly, (11)C-GSK215083 also exhibited affinity for the 5-HT2A receptor; however, given the differential localization of these 2 receptors in the central nervous system, the discrete 5-HT6 binding properties of this radioligand were able to be determined. These data demonstrate the utility of (11)C-GSK215083 as a promising PET radioligand for probing the 5-HT6 receptor in vivo in both preclinical and clinical species.


The Operative Burden of General Surgical Disease and Non-Battle Injury in a Deployed Military Treatment Facility in Afghanistan.
Contemporary medical operations support a mobile, nonconventional force involved in nation building, counterinsurgency, and humanitarian operations. Prior reports have described surgical care for disease and nonbattle injuries (DNBI). The purpose of this report is to describe the prevalence and scope of DNBI managed by general surgeons in a contemporary, deployed medical facility. A 2-year retrospective review of the operative logbook from the U.K. Role 3 Multinational Hospital, Camp Bastion, Afghanistan, was performed to determine the prevalence and makeup of procedures performed for DNBI by general surgeons. Nontrauma general surgical procedures accounted for 7.7% (n = 279 of 3,607 cases) of cases; appendectomy (n = 146) was the most common, followed by drainage of soft tissue (n = 55) and oral abscesses (n = 5), scrotal exploration (n = 12), and hernia repair (n = 7). A total of 7.2% (n = 20 of 279) of cases fell outside the standard scope of practice of an urban, civilian general surgeon. Although the prevalence of operative procedures for DNBI was low, the spectrum of cases included those not typically managed in the civilian setting of the United Kingdom. With an evolving decline in case volume performed in multiple anatomic locations due to subspecialization during surgical training, this gap in expertise is likely to increase.


Simultaneous posterior pharyngeal flap and tonsillectomy.
Posterior pharyngeal flap (PPF) construction in patients with hypertrophied tonsils raises a significant concern for adequate airway maintenance. Most often, tonsillectomy, as a separate procedure, is done first. The authors have preferred to do both the PPF and the tonsillectomy simultaneously. Twenty consecutive cases are reviewed retrospectively to determine whether this has increased morbidity. All patients underwent posterior pharyngeal flaps for correction of velopharyngeal incompetence (VPI). Postoperative fevers that resolved without specific treatment occurred in four patients. Three patients experienced postoperative bleeding problems, but only two were of tonsillar origin. No patient developed immediate airway obstruction, although a single patient was observed overnight in the intensive care unit. Another developed sleep apnea several months after the operation, which required that the posterior pharyngeal flap be taken down. This patient had an unusual amount of hypertrophic scar in the nasopharyngeal area, but not in the oropharynx. No other operative or postoperative complications were experienced. The average hospitalization was 4.2 days. It is concluded that simultaneous tonsillectomy and PPF construction may be performed safely in patients who need both procedures.


Different consequences of incorporating chloroplast ribosomal proteins L12 and S18 into the bacterial ribosomes of Escherichia coli.
We have incorporated chloroplast ribosomal proteins (R-proteins) L12 and S18 into Escherichia coli ribosomes and examined the hybrid ribosomes for their ability to form polysomes in vivo and perform poly(U)-dependent poly(Phe) synthesis in vitro. The rye chloroplast S18 used for the experiment is a highly divergent protein (170 amino acid residues; E. coil S18, 74 residues), containing a repeating, chloroplast-specific, heptapeptide motif, and has amino acid sequence identity of only 35% to E. coli S18. When expressed in E. coli, chloroplast S18 was assembled in E. coli ribosomes. The latter formed polysomes in vivo at about the same rate as the host ribosomes, indicating that the replacement of E. coli S18 with its chloroplast homologue has only a minor, if any, effect on function. The L12 protein is much more conserved in sequence and chain length, and is known to have a very important function. The Arabidopsis chloroplast L12 used in the experiment was incorporated into E. coli 50S subunits that associated with the 30S subunits to form ribosomes, but the latter were unable to form polysomes. This result indicates functional inactivation of E. coil ribosomes by a chloroplast R-protein. To further confirm this result, we overproduced chloroplast L12 through the use of a secretion vector and purified the protein to homogeneity. Chloroplast L12 could be efficiently incorporated in vitro into L7/12-lacking E. coli ribosomes, but the hybrid ribosomes were totally inactive in poly(U)-dependent poly(Phe) synthesis. Computer modeling of the spatial structure of all known chloroplast L12 proteins (using E. coli L12 coordinates) indicated a 'chloroplast loop' present only in chloroplast L12. The presence of this loop might have a role in the observed inactivation. Taken together with previously reported results (summarized in this paper), it would appear that the features of chloroplast R-proteins concerned with specific functions are more divergent than their assembly properties. We have previously described methods suitable for overproduction and purification of chloroplast R-proteins that are encoded in organellar DNA (approximately 20), but that gave poor yield for those encoded in the nuclear DNA (approximately 45). Here we describe a method that overcomes this problem and allows the purification of nucleus-encoded chloroplast R-proteins in milligram quantities.


Assessment of Clinicians' Satisfaction With Laboratories at a Public Sector Hospital in Karachi, Pakistan.
Objective The goal of this study was to assess the level of satisfaction of clinicians regarding the provision of information, accessibility, and services by clinical laboratories at a public sector hospital in Karachi, Pakistan. Methods We conducted a cross-sectional survey of 151 participants from a public sector hospital in Karachi to assess their satisfaction regarding the associated laboratories. A five-point Likert scale questionnaire, consisting of 18 study items total, was used. Apart from the sociodemographics, the questionnaire was divided into three main sections: Services, Accessibility, and Provision of Information. The study lasted six months from October 2018 to March 2019. Results Most study participants were women. Less than one-third of the participants were consultants (21.9%). The overall satisfaction score was 62/90, indicating that the respondents were satisfied with most of the items on the scale. Factors such as notification about abnormal test results and courier services provided by the laboratories had the lowest satisfaction score. Conclusion Laboratory services are lacking in certain areas, specifically notifications and courier services, that need development and improvement, both of which can be achieved through seminars and clear communication between the laboratory staff and the associated clinicians.


Key design and analysis principles for quality of life and patient-reported outcomes in clinical trials.
Advances in early detection and therapy have increased the number of prostate cancer survivors, leading to a greater emphasis on examining patient-reported outcomes (PROs). PROs augment clinical outcomes, providing a more comprehensive assessment of the patient experience, including symptoms and quality of life, that may impact the overall evaluation of new therapies. The successful incorporation of PROs into clinical trials requires adherence to key design and analysis principles. We present these principles and argue that adherence to these principles is vital to ensure valid interpretation of clinical trial findings, identify meaningful differences among investigational strategies, and better translate clinical trial results to diverse stakeholders.


Oxidative stress in dry age-related macular degeneration and exfoliation syndrome.
Oxidative stress refers to cellular or molecular damage caused by reactive oxygen species, which especially occurs in age-related conditions as a result of an imbalance between the production of reactive oxygen species and the antioxidant defense response. Dry age-related macular degeneration (AMD) and exfoliation syndrome (XFS) are two common and complex age-related conditions that can cause irreversible vision loss. Two subtypes of AMD, which is the leading cause of blindness in the Western world, exist: the most prevalent dry type and the most severe wet type. Early dry AMD is characterized by formation of drusen, which are sub-retinal deposits, in the macular area and may progress to geographic atrophy with more dramatic manifestation. XFS is a systemic disorder of the extracellular matrix characterized by the accumulation of elastic fibrils that leads, in most cases, to glaucoma development with progressive and irreversible vision loss. Due to the aging population, the prevalence of these already-widespread conditions is increasing and is resulting in significant economic and psychological costs for individuals and for society. The exact composition of the abnormal drusen and XFS material as well as the mechanisms responsible for their production and accumulation still remain elusive, and consequently treatment for both diseases is lacking. However, recent epidemiologic, genetic and molecular studies support a major role for oxidative stress in both dry AMD and XFS development. Understanding the early molecular events in their pathogenesis and the exact role of oxidative stress may provide novel opportunities for therapeutic intervention for the prevention of progression to advanced disease.


Effects of adenotonsillar hypertrophy on snoring in children.
A prospective study was performed to evaluate the effects of adenotonsillar hypertrophy on snoring in children. Thirty male patients were grouped with respect to the severity of snoring and were evaluated in terms of the noise level of the snoring sound, the lowest arterial oxygen saturation, degree of palatine tonsillar hypertrophy, body mass index and cephalometric findings that included the adenoidal-nasopharyngeal ratio, the angle between the lines sella turcica/nasion and most posterior point of anterior maxilla/nasion, the angle between the lines sella turcica/nasion and most posterior point of anterior mandible/nasion, the posterior airway space, the distance from the sella to the nasion, lower face height and the distance from the basion to the posterior nasal spine. The noise level of the snoring sound, the lowest arterial oxygen saturation and the adenoidal-nasopharyngeal ratio showed a significant correlation with the severity of snoring, but the degree of palatine tonsillar hypertrophy and the body mass index failed to disclose any significant relationship.


Plasma and Polymers: Recent Progress and Trends.
Plasma-enhanced synthesis and modification of polymers is a field that continues to expand and become increasingly more sophisticated. The highly reactive processing environments afforded by the inherently dynamic nature of plasma media are often superior to ambient or thermal environments, offering substantial advantages over other processing methods. The fluxes of energy and matter toward the surface enable rapid and efficient processing, whereas the charged nature of plasma-generated particles provides a means for their control. The range of materials that can be treated by plasmas is incredibly broad, spanning pure polymers, polymer-metal, polymer-wood, polymer-nanocarbon composites, and others. In this review, we briefly outline some of the recent examples of the state-of-the-art in the plasma-based polymer treatment and functionalization techniques.


[Preliminary study on treatment of lingual tonsil hypertrophy by endoscopic assisted coblation].
To investigate the feasibility and safety of lingual tonsil excision by endoscopic assisted coblation. Twenty seven cases with lingual tonsil hypertrophy were recruited in this study. Preoperative fibrolaryngoscope and CT and (or) MRI examination of the base of the tongue, lingual tonsil was removed by 70 degrees nasal endoscopy-assisted plasma radiofrequency after nasotracheal intubation. The tongue wound healing and post-operative bleeding were observed after operation, the advantages of the endoscopic-assisted plasma radiofrequency on lingual tonsil removal were analyzed, and its feasibility and safety were summarized. During the surgery the base of the tongue and epiglottis had satisfaction exposure in the same operative field. No complications happened in the surgery and endotracheal tube was plucked safely after operation. There was no primary bleeding, and the number of secondary bleeding were 4 cases, accounting for 14.81% (4/27), respectively occurred on the sixth, seventh, tenth and twelfth day with the amount of bleeding of 30-70 ml. The bleeding were cured after conservative treatment or re-application applicating of radiofrequency; 27 patients had no taste disturbance, and they were followed up for 6-30 months without recurrence. Lingual tonsil excision by nasal endoscopic-assisted coblation has enough exposure, complete resection and low recurrence rate. Stopping bleeding should be attentioned to prevent postoperative bleeding.