[Radiochemotherapy of cervical carcinoma. (Necessity of dose reduction in chemotherapy)].
The concurrent radiochemotherapy used in the treatment of high risk and locally advanced cervical cancer therapy seems to be standard practice. Studies carried out in 1999 and 2000, reported the results of five large-scale prospective randomized investigations using radiotherapy which showed progression-free and overall survival rate increase compared to use of solely radiotherapy (Gynecology Oncology Group (GOG) 123, South West Oncology Group (SWOG) 8797, Radiotherapy Oncology Group (RTOG) 9001, Gynecology Oncology Group (GOG) 85, Gynecology Oncology Group (GOG) 120). The aim of the investigation was to report our early findings of cervical cancer radiotherapy detailing the arising radiogen toxicity. This is a report of a study carried out at the Oncoradiology Centre of Budapest, (between July 2002 and March 2005) on 66 cervical cancer patients. In concurrent radiotherapy the total dose of high photon energy percutaneous radiotherapy (megavolt therapy) for the pelvic region was 50.4 Gy, in 1.8 Gy fractions and with the weekly dosage of 40 mg/m2 cisplatin prior to the radiotherapy. The planned cytostatic treatment could be carried out on 27 patients (41%) on five treatments. At the same time, the number of treatments on the other patients had to be reduced due to haematological toxicity in the following way: 4 treatments on 16 patients (24%), 3 treatments on 7 patients (11%), 2 treatments on 10 patients (15%) and once on 6 patients (9%). Altogether it was necessary to reduce the dosage from the planned protocol, on 44 patients (67%). The optimal radiotherapy time of 56 days as reported in the literature, was exceeded in 17 cases (26%) on account of the radiogen toxicity. On the basis of our own results it is not advisable to raise the cisplatin weekly dosage to above 20 mg/m2.


A primary spinal extradural atypical teratoid/rhabdoid tumor of the cervical spine with bony involvement.
Primary spinal atypical teratoid/rhabdoid tumors are extremely rare and most commonly occur as intramedural or extramedural intradural. The location of extradural type is rarely reported. A 10-year-old girl presented with a 2-month history of nape pain. Computed tomography (CT) and magnetic resonance imaging (MRI) revealed an extradural tumor from C2-C5 with bony destruction of the C3 vertebral body. Subtotal removal of the tumor was performed and atypical teratoid/rhabdoid tumor was proven histologically. But 2 months after surgery, the neck pain became worse. There were metastasic lesions in bilateral lung fields and multiple enlarged lymph nodes around the carotid sheath. She died 8 months after the initial symptoms. The present case is the third detailed report of spinal extradural. We describe the CT and MRI findings of this case and review the literature describing this rare disease.


The question of virginity testing in Turkey.
Pre-marital sex for a woman is regarded as wrong in my country. As a result, it is socially forbidden for a woman to engage in this act. In order to present a woman as a virgin on her marriage day, she is subjected to pressure, and put under control both by her family and societal norms. However, a man is free and never made to suffer any of the above. A woman found to be a virgin on her first night of marriage is seen as a normal person while one suspected to have lost her virginity is made to undergo a series of medical examinations to bring clarity to her situation.


Investigation in chronic lung disease - Too much, too little, just right!
Lung problems are common in general practice. History and examination are invaluable; however considered selection of investigations can assist the clinician to reach a diagnosis. To outline the indications for common respiratory investigations to assist in selecting the most appropriate investigation for a clinical problem related to chronic lung disease. The vast majority of problems related to chronic lung disease can be assessed with a full history and examination, a plain chest X-ray, a spirometer and a pulse oximeter. Chest X-ray should always be the initial radiological test. It can distinguish pneumonia from bronchitis and diagnose breathlessness caused by pneumonia, heart failure, pneumothorax, pleural effusion and interstitial lung disease. Computerised tomography scanning is not a useful test in investigation of symptoms such as breathlessness or cough when a chest X-ray is normal. Spirometry can be useful in the evaluation of chronic cough, wheezing, breathlessness or chest pain. Baseline oximetry should be performed on all dyspnoeic patients and those with abnormal spirometry.


Radiation induced valvular disease: the internist's prospective.
Radiation-induced cardiac injury entails a wide spectrum of cardiovascular complications such as cardiomyopathy and valvular diseases among others. We present the internist's perspective and the challenges faced in managing these patients. There are guidelines addressing radiation-induced valvular disease (RIVD) including screening and treatment, but are often unrecognised by most internist's practice. A thorough cardiovascular examination and screening echocardiography may detect RIVD at an earlier stage. Early screening with transthoracic echocardiogram should be considered in asymptomatic or low-risk patients and more frequently in symptomatic and high-risk patients. The internists should educate their patients with prior chest irradiation, regarding the possible radiation related adverse cardiovascular effects and recommended screening. Lifestyle changes and aggressive cardiovascular risk modification should be emphasised, as concomitant hypertension, coronary artery disease and cardiomyopathy can have unfavourable effects in these patients.


Surgical treatment of macrocheilia.
The authors report 27 cases of macrocheilia, discussing each cause individually. They classify macrocheilia according to its etiology, emphasizing the importance of an accurate diagnosis in treating the disease. The operative technique indicated for each cause is discussed. The technique basically consists of a fusiform resection, which may include a larger or smaller amount of lip tissue depending on the disease process. The incision may be interrupted at the mid-lip and W-plasty or lateral Z-plasties may be used to avoid the formation of dog ears.


Interactions between etonogestrel-releasing contraceptive implant and 3 antiretroviral regimens.
Long-acting reversible contraceptives are effective contraceptives for women with HIV, but there are limited data on etonogestrel implant and antiretroviral therapy pharmacokinetic drug-drug interactions. We evaluated etonogestrel/antiretroviral therapy drug-drug interactions, and the effects of etonogestrel on ritonavir-boosted-atazanavir, ritonavir-boosted-lopinavir, and efavirenz pharmacokinetics. We enrolled postpartum women using etonogestrel implants and receiving ritonavir-boosted-atazanavir, ritonavir-boosted-lopinavir, or efavirenz-based regimens between 2012 and 2015. Etonogestrel implants were inserted 2 to 12 weeks postpartum. We performed pharmacokinetic sampling pre-etonogestrel insertion and 6 to 7 weeks postinsertion. We measured antiretroviral concentrations pre and postetonogestrel insertion, and compared etonogestrel concentrations between antiretroviral regimens. We considered a minimum serum etonogestrel concentration of 90 pg/mL adequate for ovulation suppression. We collected pharmacokinetic data for 74 postpartum women, 22 on ritonavir-boosted-atazanavir, 26 on ritonavir-boosted-lopinavir, and 26 on efavirenz. The median serum concentrations of etonogestrel when co-administered were highest with etonogestrel/ritonavir-boosted-atazanavir (604 pg/mL) and etonogestrel/ritonavir-boosted-lopinavir (428 pg/mL), and lowest with etonogestrel/efavirenz (125 pg/mL); p < 0.001. Minimum concentration (Cmin) of ritonavir-boosted-atazanavir and ritonavir-boosted-lopinavir were lower after etonogestrel implant insertion, but overall exposure, predose concentrations, clearance, and half-lives were unchanged. We found no significant change in efavirenz exposure after etonogestrel insertion. Unlike efavirenz, ritonavir-boosted-atazanavir and ritonavir-boosted-lopinavir were not associated with significant decreases in etonogestrel concentrations. Efavirenz was associated with a significant decrease in etonogestrel concentrations. The findings demonstrate no interactions between etonogestrel and ritonavir-boosted-lopinavir or ritonavir-boosted-atazanavir, but confirm the decreased efficacy of etonogestrel with efavirenz-based antiretrovirals. This information should be used to counsel women with HIV who desire long-acting reversible contraceptives.


Changes of hydraulic conductivity during dehydration and rehydration in Quercus serrata Thunb. and Betula platyphylla var. japonica Hara: the effect of xylem structures.
Xylem cavitation and its recovery were studied in 1-year-old stems of ring-porous Quercus serrata Thunb. and diffuse-porous Betula platyphylla var. japonica Hara. The Q. serrata had 5-100 microm vessel diameter in the functional current xylem and 5-75 microm in nonconducting 1-year-old xylem; B. platyphylla had a narrower range of vessel diameters of 5-55 microm and more than double the number of vessels in both functional growth rings. Although hydraulic conductivity of Q. serrata appeared to decrease after release of moderate water stress of a half loss of native hydraulic conductivity--about -2 MPa in xylem water potential--no significant recovery of hydraulic conductivity was observed, probably because of intraspecific variation in vessel diameter distribution, which induced variable vulnerability to cavitation. Furthermore, in terms of xylem anatomy, larger and more efficient vessels of the current xylem did not show obvious refilling. In B. platyphylla, after release of water stress, rapid (1 h) recoveries of both hydraulic conductivity and water potential were apparent after rewatering: so-called 'novel refilling'. During that time, a high degree of vessel refilling was observed in both xylems. At 12 h after rewatering, embolized vessels of the current xylem had refilled completely, although about 20% of vessels were still embolized in 1-year-old xylem. This different pattern of vessel refilling in relation to xylem age for B. platyphylla might be attributable to structural faults in the 1-year-old xylem, such as pit degradation or perhaps xylem aging itself. Results show that Q. serrata performs water conduction using highly efficient large vessels instead of unclear vessel refilling. In contrast, B. platyphylla transports water via less efficient but numerous vessels. If cavitation occurs, B. platyphylla improves water conduction by increasing the degree of vessel refilling.


Serving the Vulnerable: The World Health Organization's Scaled Support to Countries During the First Year of the COVID-19 Pandemic.
The Inter-Agency Standing Committee (IASC), created by the United Nations (UN) General Assembly in 1991, serves as the global humanitarian coordination forum of the UN s system. The IASC brings 18 agencies together, including the World Health Organization (WHO), for humanitarian preparedness and response policies and action. Early in the COVID-19 pandemic, the IASC recognized the importance of providing intensified support to countries with conflict, humanitarian, or complex emergencies due to their weak health systems and fragile contexts. A Global Humanitarian Response Plan (GHRP) was rapidly developed in March 2020, which reflected the international support needed for 63 target countries deemed to have humanitarian vulnerability. This paper assessed whether WHO provided intensified technical, financial, and commodity inputs to GHRP countries (n = 63) compared to non-GHRP countries (n = 131) in the first year of the COVID-19 pandemic. The analysis showed that WHO supported all 194 countries regardless of humanitarian vulnerability. Health commodities were supplied to most countries globally (86%), and WHO implemented most (67%) of the $1.268 billion spent in 2020 at country level. However, proportionally more GHRP countries received health commodities and nearly four times as much was spent in GHRP countries per capita compared to non-GHRP countries ($232 vs. $60 per 1,000 capita). In countries with WHO country offices (n = 149), proportionally more GHRP countries received WHO support for developing national response plans and monitoring frameworks, training of technical staff, facilitating logistics, publication of situation updates, and participation in research activities prior to the characterization of the pandemic or first in-country COVID-19 case. This affirms WHO's capacity to scale country support according to its humanitarian mandate. Further work is needed to assess the impact of WHO's inputs on health outcomes during the COVID-19 pandemic, which will strengthen WHO's scaled support to countries during future health emergencies.


Advances in pharmacogenomics technologies.
The past decade has seen major advances in our understanding of genomics, with the development of newer and refined technologies. Improvements in the sensitivity and precision of DNA microarrays coupled with the emergence of massively parallel sequencing techniques have redefined how we interrogate the human genome. These tools have facilitated rapid biomarker discovery, uncovered novel targets for therapeutic intervention and enabled mechanistic studies that have helped unravel the mode of drug action. The assessment of drug toxicity based on genomic signatures associated with disease and high-throughput screening for polymorphic interindividual variability in drug responses are procedures that have greatly aided the quality of patient care. The integration of pharmacogenetic approaches for therapeutic monitoring, and health management approaches for advance clinical treatments, will be based on unique patient phenotype profiles and aimed at minimizing adverse drug reactions. In this brief commentary, the evolution and development of key genomics technologies over the past decade is reviewed.


Cardiorespiratory fitness, but not physical activity, is associated with academic achievement in children and adolescents.
Cardiorespiratory fitness (CRF) and physical activity (PA) seem to have positive effects on academic achievement (AA), although in most studies, objective methods of assessment have not been used. To examine the associations of CRF and PA with AA. A sample of 640 youngsters (10-18 years) participated in this cross-sectional study. CRF was estimated with the 20-metre shuttle run test and PA was measured using accelerometers. School grades were used to describe AA using mathematics and native language final grades. The relationship between CRF and PA with AA was analysed using ANCOVA. Results show a significant effect of CRF levels on native language grades, after adjustment for confounders [F(3,414) = 3,99 p < 0.05], but not for mathematics [F(3,360) = 0.95 p > 0.05]. No significant effects of PA levels on AA were found. CRF is associated with moderate-to-vigorous PA (MVPA) and higher levels of CRF may influence AA. CRF is positively correlated with MVPA, suggesting that higher amounts of MVPA might improve CRF and indirectly influence AA. Since CRF is dependent on higher intensities of PA, we can suggest a focus on implementing improvement strategies to increase the intensity of physical education lessons.


Interactions between Fermi polarons in monolayer WS2.
Interactions between quasiparticles are of fundamental importance and ultimately determine the macroscopic properties of quantum matter. A famous example is the phenomenon of superconductivity, which arises from attractive electron-electron interactions that are mediated by phonons or even other more exotic fluctuations in the material. Here we introduce mobile exciton impurities into a two-dimensional electron gas and investigate the interactions between the resulting Fermi polaron quasiparticles. We employ multi-dimensional coherent spectroscopy on monolayer WS2, which provides an ideal platform for determining the nature of polaron-polaron interactions due to the underlying trion fine structure and the valley specific optical selection rules. At low electron doping densities, we find that the dominant interactions are between polaron states that are dressed by the same Fermi sea. In the absence of bound polaron pairs (bipolarons), we show using a minimal microscopic model that these interactions originate from a phase-space filling effect, where excitons compete for the same electrons. We furthermore reveal the existence of a bipolaron bound state with remarkably large binding energy, involving excitons in different valleys cooperatively bound to the same electron. Our work lays the foundation for probing and understanding strong electron correlation effects in two-dimensional layered structures such as moiré superlattices.


Changes in the number of CD31-CD45-Sca-1+ cells and Shh signaling pathway involvement in the lungs of mice with emphysema and relevant effects of acute adenovirus infection.
COPD is a leading cause of mortality worldwide, and cigarette smoke is a pivotal risk factor. Adenovirus is a common cause of acute exacerbations of COPD and expedites COPD progression. Lung stem/progenitor cells play an important role in the development of COPD, while the relevant mechanism remains elusive. Here, we investigated the number of lung CD31-CD45-Sca-1+ cells and sonic hedgehog (Shh) signaling pathway expression levels in cigarette smoke extract (CSE)-induced emphysema mice, as well as the relevant effects of acute adenovirus infection (AAI). BALB/c mice were treated with CSE by intraperitoneal injection and/or adenovirus endotracheal instillation at different time points for 28 days. Lung function, lung histomorphology, CD31-CD45-Sca-1+ cell count, and expression levels of major components in the Shh signaling pathway in the lungs were measured. CSE intraperitoneal injection and adenovirus endotracheal instillation successfully induced emphysema and AAI in mice, respectively. In the lungs of emphysema mice, both the number of CD31-CD45-Sca-1+ cells and expression levels of Shh signaling pathway molecules were reduced. However, AAI increased the number of inhibited CD31-CD45-Sca-1+ cells and activated the suppression of the Shh signaling pathway. Both CD31-CD45-Sca-1+ cell numbers and Shh signaling pathway expression levels were downregulated in the lungs of emphysema mice induced by CSE intraperitoneal injection, which likely contributes to the pathogenesis of emphysema. Additionally, these inhibited lung CD31-CD45-Sca-1+ cells and Shh signaling pathway molecules were upregulated during AAI, indicating that they play a protective role in the epithelial repair process after AAI injury.


Efficacy of hydralazine and valproate in cutaneous T-cell lymphoma, a phase II study.
To evaluate the activity and safety of hydralazine and valproate (Transkrip) in cutaneous T-cell lymphoma (CTCL). Previously untreated and progressive/refractory CTCL patients received hydralazine at 83 mg or 182 mg/day for slow and rapid acetylators respectively plus magnesium valproate at a total dose of 30 mg/Kg t.i.d daily in continuous 28-day cycles in this phase II study. The primary objective was overall response rate (ORR) measured by the modified severity weighted assessment tool (m-SWAT), secondary end-points were time to response (TTR), time to progression (TTP), duration of response (DOR), progression-free survival (PFS), overall survival (OS) and safety. Fourteen patients were enrolled (7 untreated and 7 pretreated). ORR was 71% with 50% complete and 21% partial. Two had stable disease and two progressed. At a median follow-up of 36 months (5-52), median TTR was 2 months (1-4); median DOR was 28 months (5-45); median PFS 36 and not reached for OS. There were no differences in median TTR, DOR, and PFS between treated and pretreated patients. Pruritus relieve was complete in 13 out of 14 patients. No grade 3 or 4 toxicities were observed. The combination of hydralazine and valproate is safe, very well tolerated and effective in CTCL.


[Pneumoconiosis research in Switzerland in the past and today].
The history of pneumoconiosis research in Switzerland from the 16th century to the present day is briefly summarized. The concerns and aims of a silicosis research group founded at the end of World War II by faculty members of Zurich University, Federal Institute of Technology (ETHZ) and by the SUVA (Swiss national accident insurance) are presented. The salient results of interdisciplinary research on the pathogenicity of particle size and fibrogenicity of various mineral and non-mineral dusts are discussed, and related questions of cancer epidemiology are considered.


Getting to the grass roots of the nursing shortage.
Providers are familiar with the nursing shortage epidemic in some manner, regardless of the setting in which they work. To date, it appears that strategies to reverse the shortage have been minimally effective. This article stresses the importance of changes in the work environment of care to address the problem. It explores observations of and solutions to the present nursing shortage, based on the author's own expertise and insights as a registered nurse and healthcare consultant. It also stresses the importance of nurses' involvement in any changes that take place.


Co-analysis of cucumber rhizosphere metabolites and microbial PLFAs under excessive fertilization in solar greenhouse.
Fertilizer application is the most common measure in agricultural production, which can promote the productivity of crops such as cucumbers, but the problem of excessive fertilization occurs frequently in solar greenhouses. However, the effects of fertilization levels on cucumber rhizosphere soil microbes and metabolites and their relationships are still unclear. In order to determine how fertilization levels affect the rhizosphere microenvironment, we set up four treatments in the solar greenhouse: no-fertilization (N0P0K0), normal fertilization (N1P1K1), slight excessive fertilization (N2P2K2), and extreme excessive fertilization (N3P3K3). The results showed that fertilization treatments significantly increased cucumber yield compared to no-fertilization, but, the yield of N3P3K3 was significantly lower than that of N1P1K1 and N2P2K2. Fertilization levels had significant effects on rhizosphere microorganisms, and pH, NH4 +-N and AP were the main environmental factors that affected the changes in microbial communities. The total PLFAs, the percentages of fungi and arbuscular mycorrhizal fungi (AMF) were significantly reduced and bacteria percentage was significantly increased in N3P3K3 compared to other fertilization treatments. Differential metabolites under different fertilization levels were mainly organic acids, esters and sugars. Soil phenols with autotoxic effect under fertilization treatments were higher than that of N0P0K0. In addition, compared with soil organic acids and alkanes of N0P0K0, N2P2K2 was significantly increased, and N3P3K3 was not significantly different. This suggested that cucumber could maintain microbial communities by secreting beneficial metabolites under slight excessive fertilization (N2P2K2). But under extremely excessive fertilization (N3P3K3), the self-regulating ability of cucumber plants and rhizosphere soil was insufficient to cope with high salt stress. Furthermore, co-occurrence network showed that 16:1ω5c (AMF) was positively correlated with 2-palmitoylglycerol, hentriacontane, 11-octadecenoic acid, decane,4-methyl- and d-trehalose, and negatively correlated with 9-octadecenoic acid at different fertilization levels. This indicated that the beneficial microorganisms in the cucumber rhizosphere soil promoted with beneficial metabolites and antagonized with harmful metabolites. But with the deepening of overfertilization, the content of beneficial microorganisms and metabolites decreased. The study provided new insights into the interaction of plant rhizosphere soil metabolites and soil microbiomes under the different fertilization levels.


Seasonal variation in black fly (Diptera: Simuliidae) taxocenoses from the Brazilian Savannah (Tocantins, Brazil).
We investigated the spatial and temporal distribution of blackfly larvae on a mesohabitat scale atfour different breeding sites in the Brazilian savannah "Cerrado." A total of 2,385 larvae of 12 different species were collected, and three of the sampling sites revealedspecies richness and diversity peaks in April. A principal components analysis was performed to reduce abiotic data into a smaller set of independent variables, such as precipitation and river size, and subsequent linear regressions showed that Simulium subpallidum was positively correlated with precipitation. This species, along with S. nigrimanum, was negatively correlated withriver size, whereasS. perflavum was negatively correlated with precipitation. Beta diversity was negatively correlated withprecipitation, and black fly taxocenoses were markedly different between wet and dry seasons, as shown through nonmetric multidimensional scaling, suggesting that precipitation playsa major role in structuring these communities, probably because of enhanced drift and the dendritic nature of lotic metacommunities.


Yawning, acute stressors, and arousal reduction in Nazca booby adults and nestlings.
Yawning is a familiar and phylogenetically widespread phenomenon, but no consensus exists regarding its functional significance. We tested the hypothesis that yawning communicates to others a transition from a state of physiological and/or psychological arousal (for example, due to action of a stressor) to a more relaxed state. This arousal reduction hypothesis predicts little yawning during arousal and more yawning (above baseline) during and after down-regulation of arousal. Experimental capture-restraint tests with wild adult Nazca boobies (Sula granti), a seabird, increased yawning frequency after release from restraint, but yawning was almost absent during tests. Natural maltreatment by non-parental adults also increased yawning by nestlings, but only after the maltreatment ended and the adult left. CORT (corticosterone) was a logical a priori element of the stress response affecting the stressor-yawning relationship under the arousal reduction hypothesis, and cannot be excluded as such for adults in capture-restraint tests but is apparently unimportant for nestlings being maltreated by adults. The arousal reduction hypothesis unites formerly disparate results on yawning: its socially contagious nature in some taxa, its clear pharmacological connection to the stress response, and its temporal linkage to transitions in arousal between consciousness and sleep.


True density analysis of a freeze-dried amorphous sugar matrix.
True density of an amorphous matrix represents the state of molecular packing in the matrix, which is closely related to the physical/chemical properties of the material. Dry gas pycnometry is one possible technique for measuring the true density of an amorphous sugar matrix prepared by freeze-drying. We herein report on the influence of conditions used for pycnometry on the measured density value and propose a protocol for obtaining the true density. The technique is sufficiently accurate to permit values for matrices comprised of different types of sugar to be compared. Using the protocol, the true densities of several amorphous sugar samples containing different types of sugar, freeze-drying conditions (temperature and sugar concentration at the time of freezing of an aqueous sugar solution), pretreatment (compaction and grind) were determined and the results were compared. A model for simulating an amorphous matrix of sugar (trehalose) was constructed using molecular dynamics/mechanics calculations, and the true density of the simulated sugar matrix was found to agree with the value experimentally determined using the proposed protocol. The relationship among the true density, the states of intermolecular interactions, and strain of sugar molecules in the matrix are discussed using the simulated amorphous sugar matrix.


Clinical Score to Differentiate Scrub Typhus and Dengue: A Tool to Differentiate Scrub Typhus and Dengue.
Dengue and scrub typhus share similar clinical and epidemiological features, and are difficult to differentiate at initial presentation. Many places are endemic to both these infections where they comprise the majority of acute undifferentiated febrile illnesses. We aimed to develop a score that can differentiate scrub typhus from dengue. In this cross-sectional study, 188 cases of scrub typhus and 201 cases of dengue infection who presented to the emergency department or medicine outpatient clinic from September 2012 to April 2013 were included. Univariate followed by multivariate logistic regression analysis was performed to identify clinical features and laboratory results that were significantly different between the two groups. Each variable was assigned scores based on the strength of association and receiver operating characteristics area under the curve (ROC-AUC) was generated and compared. Six scoring models were explored to ascertain the model with the best fit. Model 2 was developed using the following six variables: oxygen saturation (>90%, ≤90%), total white blood cell count (<4000, 4001-7000 and >7000 cells/cumm), hemoglobin (≤14 and >14 g/dL), total bilirubin (<2 and ≥2 mg/dL), serum glutamic oxaloacetic transaminase (>200 and ≥200 IU/dL), and altered sensorium (present or absent). Each variable was assigned scores based on its strength of association. The AUC-ROC curve (95% confidence interval) for model 2 was 0.84 (0.79-0.89). At the cut off score of 13, the sensitivity and specificity were 85% and 77% respectively, with a higher score favoring dengue. In areas of high burden of ST and dengue, model 2 (the "clinical score to differentiate scrub typhus and dengue fever") is a simple and rapid clinical scoring system that may be used to differentiate scrub typhus and dengue at initial presentation.


A case of progressive orthopnoea and shoulder pain secondary to bilateral diaphragmatic paralysis.
A 45-year-old man with a raised body mass index presented with an acute history of right lower chest pain and increasing breathlessness. C reactive protein, D dimer and cardiac echocardiography were negative, with mild bibasal atelectasis the only positive reported finding from erect chest X-ray and CT pulmonary angiogram. He was discharged with antibiotics for a chest infection. He remained severely breathless and was referred to the sleep-related breathing disorders clinic. He described shoulder pain, daytime tiredness and sleeping upright due to a ââ'¬Ëœsuffocatingââ'¬â"¢ sensation. The video demonstrates the clinical findings. The CT topogram confirmed bilateral diaphragmatic paralysis. Spirometry demonstrated an 80% reduction in forced vital capacity in the supine position, when compared with erect. Consultation with a neurologist yielded the diagnosis of neuralgic amyotrophy, leading to bilateral diaphragmatic paralysis. The respiratory symptoms have been controlled with night-time non-invasive ventilation, allowing him to sleep supine.


Application of Gold Nanorods for Photothermal Therapy in Ex Vivo Human Oesophagogastric Adenocarcinoma.
Gold nanoparticles are chemically fabricated and tuned to strongly absorb near infrared (NIR) light, enabling deep optical penetration and therapy within human tissues, where sufficient heating induces tumour necrosis. In our studies we aim to establish the optimal gold nanorod (GNR) concentration and laser power for inducing hyperthermic effects in tissues and test this photothermal effect on ex vivo human oesophagogastric adenocarcinoma. The ideal GNR concentration and NIR laser power that would elicit sufficient hyperthermia for tumour necrosis was pre-determined on porcine oesophageal tissues. Human ex vivo oesophageal and gastric adenocarcinoma tissues were incubated with GNR solutions and a GNR-free control solution with corresponding healthy tissues for comparison, then irradiated with NIR light for 10 minutes. Temperature rise was found to vary linearly with both the concentration of GNRs and the laser power. Human ex vivo oesophageal and gastric tissues consistently demonstrated a significant temperature rise when incubated in an optimally concentrated GNR solution (3 x 10(10) GNRs/ml) prior to NIR irradiation delivered at an optimal power (2 W/cm2). A mean temperature rise of 27 degrees C was observed in tissues incubated with GNRs, whereas only a modest 2 degrees C rise in tissues not exposed to any GNRs. This study evaluates the photothermal effects of GNRs on oesophagogastric tissue examines their application in the minimally invasive therapeutics of oesophageal and gastric adenocarcinomas. This could potentially be an effective method of clinically inducing irreversible oesophagogastric tumour photodestruction, with minimal collateral damage expected in (healthy) tissues free from GNRs.


Discriminative effect of rifampin of RNA replication of various RNA bacteriophages.
Rifampin interferes exclusively with RNA replication in vivo of the group I phages MS2, f2, and R17, whereas QbetaRNA replication is unaffected by the drug. In addition, rifampin has a discriminative effect of group I phage RNA replication. In the experimental system employed by us the antibiotic differentially interferes with the synthesis of minus RNA strands in f2, whereas it has almost no effect on the synthesis of progeny plus strands. In MS2, the drug differentially arrests the synthesis of progeny plus strands and almost fails to affect the synthesis of minus RNA strands. In R17 both steps of its RNA replication are affected by rifampin, although each step is only partially (approximately 50%) inhibited. The relation of the present results to the possible role of bacterial proteins and tertiary structure of phage RNA in the process of template recognition is discussed.


Induction of neurite outgrowth in 3D hydrogel-based environments.
The ability of peripheral nervous system (PNS) axons to regenerate and re-innervate their targets after an injury has been widely recognized. However, despite the considerable advances made in microsurgical techniques, complete functional recovery is rarely achieved, especially for severe peripheral nerve injuries (PNIs). Therefore, alternative therapies that can successfully repair peripheral nerves are still essential. In recent years the use of biodegradable hydrogels enriched with growth-supporting and guidance cues, cell transplantation, and biomolecular therapies have been explored for the treatment of PNIs. Bearing this in mind, the aim of this study was to assess whether Gly-Arg-Gly-Asp-Ser synthetic peptide (GRGDS)-modified gellan gum (GG) based hydrogels could foster an amenable environment for neurite/axonal growth. Additionally, strategies to further improve the rate of neurite outgrowth were also tested, namely the use of adipose tissue derived stem cells (ASCs), as well as the glial derived neurotrophic factor (GDNF). In order to increase its stability and enhance its bioactivity, the GDNF was conjugated covalently to iron oxide nanoparticles (IONPs). The impact of hydrogel modification as well as the effect of the GDNF-IONPs on ASC behavior was also screened. The results revealed that the GRGDS-GG hydrogel was able to support dorsal root ganglia (DRG)-based neurite outgrowth, which was not observed for non-modified hydrogels. Moreover, the modified hydrogels were also able to support ASCs attachment. In contrast, the presence of the GDNF-IONPs had no positive or negative impact on ASC behavior. Further experiments revealed that the presence of ASCs in the hydrogel improved axonal growth. On the other hand, GDNF-IONPs alone or combined with ASCs significantly increased neurite outgrowth from DRGs, suggesting a beneficial role of the proposed strategy for future applications in PNI regenerative medicine.


Alkylamine salts and amides: in vitro inhibition of S mutans 6715.
Our studies with the salts and amides of alkylamines have shown that the undecylenate salts have significant in vitro activity against S mutans No 6715, suggesting that these agents are worthy of additional evaluation. The attempt to increase activity by combining undecylenic acid with the alkylamines was not successful; however, better attachment to tooth surfaces and/or retention during washing did occur. Our results suggest that the free amino group of alkylamines and the free acid group of undecylenic acid are required for these two classes of agents to demonstrate antibacterial activity.


Equity Promotion Policies in Health for vulnerable groups: the role of the Ministry of Health.
This article aims to analyze Equity Promotion Policies in Health implemented by the Ministry of Health for vulnerable groups, through the Department of Strategy and Participative Management based on race, ethnicity, gender and lifestyle markers. The three structural elements of these policies are identified as: participatory management, transversality and awareness / professional qualifications. In carrying out research for this article, different documental sources were used including: policies, videos, conferences and minutes from council meetings as well as information from health committees. The results showed positive aspects and shortcomings in the implementation process of these policies. Also, they revealed that there are permanent tensions between equality policies and equity policies which pose challenges to guaranteeing the right to health of these populations. Finally, it can be reaffirmed that only in democratic societies can these rights be recognized and guaranteed.


[Clinical effects of supplemental enteral nutrition solution in severe polytrauma].
Previous studies in critically ill patients have shown the beneficial effects of early enteral nutrition supplemented with arginine, omega-3 fatty acids and nucleotides (Impact) on immunological response, infection rate and length of stay in hospital. No specific data exist for patients with severe multiple injury, who represent a high risk group for systemic inflammatory response syndrome (SIRS), septic complications and multiple organ failure (MOF). In this prospective, randomized, double-blind controlled clinical study on patients after severe trauma (ISS ca. 40) the primary study endpoints were incidence of SIRS and MOF [definitions according to Am Soc Crit Care Med (5) and Goris (23), Sauaia (43)]. Thirty-two patients enrolled in the study, and 29 were eligible for analysis: test (Impact) (n = 16), control (n = 13). Both groups were comparable according to age, body mass index and severity of trauma (PTS-test: 38.8 +/- 12.5, PTS-control: 40.8 +/- 15.5, ISS-test: 39.6 +/- 11.4, ISS-control: 40.5 +/- 9.2). Patients were randomized to receive either Impact (test) or an isonitrogenous isocaloric diet (control). Feeding was started on the 2nd day after trauma via endoscopically placed nasoduodenal or jejunal feeding tubes. The experimental diet was safe and well tolerated. During the 1st week the enteral feeding amount was about 2000 ml without significant difference. Test-fed patients developed SIRS significantly less frequently between day 1 and day 28 (8 vs 13.3; P < 0.05) and especially between day 8 and day 14 (3 vs 6.2; P < 0.001). In the control group the Goris score was significantly worse (P < 0.05) on days 3, 4, 6, 7, 10, 11, 16 and 17 and the Sauaia score on days 8, 9, 10 and 11 (P < 0.05; P < 0.01). Mortality rate did not significantly differ (test 2/16, control 4/13), nor did length of ICU or hospital stay. With regard to the acute-phase response, C-reactive protein was significantly lower on day 4 in the test group (test: 131 +/- 67 mg/l, control: 221 +/- 110 mg/l) as was fibrinogen on day 12 (6.6 +/- 1.4 vs 7.5 +/- 1.4 g/l) and day 14 (7.1 +/- 1.3 vs 7.8 +/- 0.8 g/l). No significant difference could be observed for CD4/CD8 ratio, CD45 isotope on activated T-cells and lymphocytic interleukin (II)-2-receptor- and II-6 level. However, HLA-DR antigen presentation on peripheral monocytes was significantly elevated on day 7 in the test group (P < 0.05). According to the results, arginine, omega-3 fatty acids and nucleotides-enriched diet during early enteral feeding leads to reduction of SIRS after severe multiple injury. There is evidence for improvement of post-traumatic immunological response which helps to overcome the immunological depression after trauma.


Effect of changes in the pH and carbon dioxide evolution rate on the measured respiratory quotient of fermentations.
The total concentration of dissolved carbon dioxide in fermentation broths is one to two orders of magnitude greater than that of oxygen for pH > 6.5. The rate of change in this total concentration can be sufficiently large to produce a discrepancy between the carbon dioxide transfer rate (CTR) across the gas-liquid interface, available from gas analyses, and the carbon dioxide evolution rate (CER) of biomass in the fermentor. The CER is the variable of most interest to fermentation technologists but cannot be measured directly. The CTR is commonly used to yield the measured respiratory quotient (called here the TQ, or transfer quotient). Evaluation of the real underlying respiratory quotient (RQ), however, requiures the unmeasureable CER. Equations defining the problem are presented and are found to accurately predict the discrepancy between the TQ and the RQ in fed-batch fermentations of Escherichia coli. During the exponential growth phase, the TQ is less than the RQ. A changing pH can cause the TQ to be bigger or smaller than the RQ, while pH fluctuations associated with on-off pH controller action make the CTR and hence the TQ noisy. The RQ is estimated on-line during an E. coli fermentation and is shown to be constant during the fermentation, even though the TQ varies greatly.


A fluorescence-based assay for in vitro screening of Saprolegnia inhibitors.
The incidence of fish pathogenic oomycetes, Saprolegnia, has increased significantly in aquaculture since the ban of malachite green. For the efficient characterization of anti-Saprolegnia therapeutics, simple accurate methods are required. However, the current screening methods are limited by time, and none of them are confirming the viability of treated spores or hyphae. In this study, a modified fluorescence-based assay for the in vitro screening of Saprolegnia inhibitors has been developed. This method involves the use of FUN-1 viability dye combined with calcofluor white M2R, and is based on the formation of orange-red cylindrical intravacuolar structures (CIVS) in metabolically active spores, hyphae and biofilms. Heat-killed and bronopol-treated Saprolegnia spores, hyphae and biofilms exhibited diffuse bright green fluorescence which confirms complete loss of viability. For boric acid-treated spores, no germination was observed. However, tiny CIVS were observed in 50% of treated spores which indicated reduction in their viability. Our results proved that FUN-1 dye is an efficient tool to distinguish between live and dead Saprolegnia spores, hyphae and biofilms and to monitor the change in Saprolegnia viability during qualitative evaluation of potential anti-Saprolegnia compounds.


Identification of a novel integrin beta subunit expressed on cultured monocytes (macrophages). Evidence that one alpha subunit can associate with multiple beta subunits.
The vitronectin receptor (VnR) is one member of a subset of cell adhesion receptors within the integrin supergene family which shares the beta 3 subunit (IIIa). We show here that the VnR is absent from the surface of monocytes freshly isolated from blood but is expressed on these cells after a period of in vitro culture. Such cultured monocytes (macrophages) from a patient with type I Glanzmann's thrombasthenia, however, failed to express the VnR. Instead, immunoprecipitation with a monoclonal antibody directed to the VnR alpha chain (alpha v) revealed a novel integrin comprising alpha v associated noncovalently with a 100-kDa beta subunit (beta 3b), immunologically unrelated to the VnR beta subunit (beta 3a). This same novel integrin complex was also identified on 10-day-old macrophages from healthy donors, but on these cells, the beta 3b subunit was co-expressed with the classical VnR complex of alpha v beta 3a. The novel beta 3b subunit was not identified by monoclonal or polyclonal antibodies to IIIa (beta 3a) nor by a monoclonal antibody to the classical VnR complex. The beta 3b subunit could be distinguished from beta 3a by its relatively greater migration on sodium dodecyl sulfate-polyacrylamide gel electrophoresis after reduction, by its distinct isoelectric point upon two-dimensional gel electrophoresis, and by one-dimensional peptide mapping. Neither platelets nor B lymphoblasts from this patient with Glanzmann's thrombasthenia expressed any VnR on their surface, whereas control cells from a normal donor expressed the classical VnR but not the beta 3b subunit. The two beta chains, and hence also the combined receptor complexes, appeared to be differentially regulated. These findings provide the first example of an integrin alpha chain complexed with more than a single beta chain in the same cell. Furthermore, the differential regulation of expression of the different beta subunits that associate with the VnR alpha chain on cultured monocytes suggests a role for the novel receptor complex during monocyte/macrophage differentiation.


Dynamics of thin liquid films on surfaces with a time-periodic wettability.
The dynamics of thin liquid films on surfaces whose wettability changes in a time-periodic manner are examined in this work. A nonlinear evolution equation based on the lubrication approximation is used to describe the film height, and attractions due to van der Waals forces are incorporated. Film wettability is varied through an imposed sinusoidal modulation of the Hamaker constant. A linear stability analysis predicts that if the mean Hamaker constant is negative, disturbances at the film surface will eventually decay regardless of the amplitude and frequency of the oscillation. However, numerical solution of the evolution equation shows that the film can rupture at a given frequency if the amplitude is sufficiently large. The associated characteristic wavelength can be predicted from results for constant-wettability surfaces if an appropriate effective Hamaker constant is used. For positive mean Hamaker constants, film rupture can be accelerated, delayed, or prevented depending on how the Hamaker constant changes early in the oscillation cycle. The effects of spatial gradients in wettability are also considered, and it is found that oscillation can delay but not prevent rupture. Inclusion of short-range repulsive forces leads to the formation of droplet-like structures separated by ultra-thin films, but this can be prevented by sufficiently large and slow oscillations of the Hamaker constant. The results of this work may find use in applications that make use of surfaces whose wettability can be controlled by external stimuli.


Induction of robust type-I CD8+ T-cell responses in WHO grade 2 low-grade glioma patients receiving peptide-based vaccines in combination with poly-ICLC.
WHO grade 2 low-grade gliomas (LGG) with high risk factors for recurrence are mostly lethal despite current treatments. We conducted a phase I study to evaluate the safety and immunogenicity of subcutaneous vaccinations with synthetic peptides for glioma-associated antigen (GAA) epitopes in HLA-A2(+) adults with high-risk LGGs in the following three cohorts: (i) patients without prior progression, chemotherapy, or radiotherapy (RT); (ii) patients without prior progression or chemotherapy but with prior RT; and (iii) recurrent patients. GAAs were IL13Rα2, EphA2, WT1, and Survivin. Synthetic peptides were emulsified in Montanide-ISA-51 and given every 3 weeks for eight courses with intramuscular injections of poly-ICLC, followed by q12 week booster vaccines. Cohorts 1, 2, and 3 enrolled 12, 1, and 10 patients, respectively. No regimen-limiting toxicity was encountered except for one case with grade 3 fever, fatigue, and mood disturbance (cohort 1). ELISPOT assays demonstrated robust IFNγ responses against at least three of the four GAA epitopes in 10 and 4 cases of cohorts 1 and 3, respectively. Cohort 1 patients demonstrated significantly higher IFNγ responses than cohort 3 patients. Median progression-free survival (PFS) periods since the first vaccine are 17 months in cohort 1 (range, 10-47+) and 12 months in cohort 3 (range, 3-41+). The only patient with large astrocytoma in cohort 2 has been progression-free for more than 67 months since diagnosis. The current regimen is well tolerated and induces robust GAA-specific responses in WHO grade 2 glioma patients. These results warrant further evaluations of this approach. Clin Cancer Res; 21(2); 286-94. ©2014 AACR.


Killing of primary CD4+ T cells by non-syncytium-inducing macrophage-tropic human immunodeficiency virus type 1.
Understanding the mechanism by which human immunodeficiency virus type 1 (HIV-1) kills CD4+ T lymphocytes is important to the development of therapeutic and prophylactic strategies. Recent studies have indicated that, in some cases, progression to AIDS is associated with the appearance of syncytium-inducing, T cell line-tropic HIV-1 variants. Nevertheless, approximately 50% of subjects with AIDS harbor only non-syncytium-inducing, macrophage-tropic (NSI-M) variants of HIV-1. In most asymptomatic patients, NSI-M HIV-1 isolates are the predominant virus type found. We report here that cytopathicity of NSI-M HIV-1 for primary CD4+ T lymphocytes can be directly detected in vitro. The extent of CD4+ T-cell killing was not completely correlated with the rate of viral replication, suggesting that other characteristics of HIV-1 contribute to its cytopathicity. Our findings suggest that: (i) direct killing by NSI-M HIV-1 may contribute to CD4+ T-lymphocyte depletion in vivo, and (ii) the determinants of HIV-1 cytopathicity for CD4+ T lymphocytes and cell tropism or syncytia-forming ability are not necessarily tightly linked.


Identification of two isoforms of aminopeptidase N in Aedes aegypti larval midgut.
The bacterium Bacillus thuringiensis produces toxin inclusions that are deleterious to target insect larvae. These toxins are believed to interact with a specific receptor protein(s) that is present on the gut epithelial cells of the larvae. In various insect species (in particular those belonging to the lepidopteran class), aminopeptidase N (APN) is one of the two receptor proteins that are considered to be involved in toxin-receptor interactions. However, in mosquitoes, the nature and identity of the receptor protein is unknown. Here, using RT-PCR, we identified two isoforms of the APN transcripts in the Aedes aegypti mosquito larval midgut. These results are congruent with a previous report of multiple isoforms of the APN gene expression in lepidopteran larvae. Which of the two isoforms (or other yet unidentified receptor proteins) is involved in the killing of mosquito larvae remains to be elucidated.


Prospective Fall-Risk Prediction Models for Older Adults Based on Wearable Sensors.
Wearable sensors can provide quantitative, gait-based assessments that can translate to point-of-care environments. This investigation generated elderly fall-risk predictive models based on wearable-sensor-derived gait data and prospective fall occurrence, and identified the optimal sensor type, location, and combination for single and dual-task walking. 75 individuals who reported six month prospective fall occurrence (75.2 ± 6.6 years; 47 non-fallers and 28 fallers) walked 7.62 m under single-task and dual-task conditions while wearing pressure-sensinginsoles and tri-axial accelerometers at the head, pelvis, and left and right shanks. Fall-risk classificationmodels were assessed for all sensor combinations and three model types: neural network, naïve Bayesian, and support vector machine. The best performing model used a neural network, dual-task gait data, and input parameters from head, pelvis, and left shank accelerometers (accuracy = 57%, sensitivity = 43%, and specificity = 65%). The best single-sensor model used a neural network, dual-task gait data, and pelvis accelerometer parameters (accuracy = 54%, sensitivity = 35%, and specificity = 67%). Single-task and dual-task gait assessments provided similar fall-risk model performance. Fall-risk predictive models developed for point-of-care environments should use multi-sensor dual-task gait assessment with the pelvis location considered if assessment is limited to a single sensor.


Targeting hepatic stellate cells for cell-specific treatment of liver fibrosis.
Since hepatic stellate cells (HSC) play a crucial role in the development of liver fibrosis, this cell is the major target for anti-fibrotic drugs. Most of the experimental drugs that influenced the HSC activity showed however low efficacy in vivo. Either a low uptake of the compounds in the cells that cause disease might account for this lack of effect, or side-effects in other cells may limit the dosage of the drugs. These side-effects may even counteract the beneficial effects. Therefore a selective delivery of drugs to the HSC may comprise a promising new way to improve liver fibrosis. The targeting to HSC has become a feasible option, because albumin-based carriers have been developed that preferentially distribute to HSC in fibrotic rat livers. In addition to the targeting of drugs, also the selective delivery of genes to HSC in fibrotic livers is of interest for therapeutic purposes and a start is made in this respect. The present review discusses the drugs to be targeted to HSC and summarizes some of the problems encountered during this novel strategy in the treatment of liver fibrosis.


Evidence for heterogeneous subsarcolemmal Na+ levels in rat ventricular myocytes.
The intracellular Na+ concentration ([Na+]) regulates cardiac contractility. Previous studies have suggested that subsarcolemmal [Na+] is higher than cytosolic [Na+] in cardiac myocytes, but this concept remains controversial. Here, we used electrophysiological experiments and mathematical modeling to test whether there are subsarcolemmal pools with different [Na+] and dynamics compared with the bulk cytosol in rat ventricular myocytes. A Na+ dependency curve for Na+-K+-ATPase (NKA) current was recorded with symmetrical Na+ solutions, i.e., the same [Na+] in the superfusate and internal solution. This curve was used to estimate [Na+] sensed by NKA in other experiments. Three experimental observations suggested that [Na+] is higher near NKA than in the bulk cytosol: 1) when extracellular [Na+] was high, [Na+] sensed by NKA was ~6 mM higher than the internal solution in quiescent cells; 2) long trains of Na+ channel activation almost doubled this gradient; compared with an even intracellular distribution of Na+, the increase of [Na+] sensed by NKA was 10 times higher than expected, suggesting a local Na+ domain; and 3) accumulation of Na+ near NKA after trains of Na+ channel activation dissipated very slowly. Finally, mathematical models assuming heterogeneity of [Na+] between NKA and the Na+ channel better reproduced experimental data than the homogeneous model. In conclusion, our data suggest that NKA-sensed [Na+] is higher than [Na+] in the bulk cytosol and that there are differential Na+ pools in the subsarcolemmal space, which could be important for cardiac contractility and arrhythmogenesis. NEW & NOTEWORTHY Our data suggest that the Na+-K+-ATPase-sensed Na+ concentration is higher than the Na+ concentration in the bulk cytosol and that there are differential Na+ pools in the subsarcolemmal space, which could be important for cardiac contractility and arrhythmogenesis. Listen to this article's corresponding podcast at https://ajpheart.podbean.com/e/heterogeneous-sodium-in-ventricular-myocytes/ .


Hypersensitivity to acetate dialysate: report of a case.
Acetate dialysate is currently the most widely used in hemodialysis. The adverse effect of acetate during hemodialysis is well known upon the cardiovascular system. However, hypersensitivity reactions related to acetate during dialysis therapy are rare. We report a patient who developed hypersensitivity reactions such as generalized skin itching, flushing, hypotension and shortness of breath within a few minutes of beginning hemodialysis with acetate dialysate. Changing dialyzer membranes failed to alleviate these symptoms. Using the same dialyzer and tubing, these reactions disappeared immediately when bicarbonate dialysate was substituted for acetate dialysate. The patient's serum IgE and total eosinophile counts were normal. We conclude that acetate may initiate hypersensitivity reactions during hemodialysis. The exact mechanism is still unclear.


The changing scene of adult acute lymphoblastic leukemia.
The review focuses on the most recent advances in the diagnostic and prognostic work-up of adult acute lymphoblastic leukemia (ALL) and its implications in the clinical management of the disease. ALL can be identified on the basis of morphologic, cytochemical and immunophenotypic criteria; modern management of ALL is also based on cytogenetic and genetic evaluations. New technologies, such as gene expression profile analysis, may allow us to further unravel the intrinsic biology of the disease, to improve diagnostic and prognostic stratification, and to design innovative therapeutic strategies. In potentially all cases, specific markers of the disease can be found and utilized together with the rearrangement of immunoglobulin and T-cell receptor genes to monitor minimal residual disease during clinical follow-up. These biologically-defined subgroups of patients may have a different clinical course, response to treatment and variable prognosis. Recent biologic advancements are progressively realising the possibility of designing targeted and individualized therapeutic strategies according to the more refined, molecularly defined features of leukemic cells and the presence or absence of residual disease in adult ALL.


What Drives Food Insecurity in Western Australia? How the Perceptions of People at Risk Differ to Those of Stakeholders.
Food insecurity is considered a "wicked" problem due to the highly complex and at times undefined casual factors. Although many stakeholders are working to address the problem, a possible divergence exists between their views on food insecurity and those of the people who are actually experiencing the problem. The purpose of this study was to investigate whether there was a difference between the opinions of those "at risk" and stakeholders. A total of seven focus groups (two stakeholder groups n = 10, five "at-risk" groups n = 34) and three interviews (stakeholders n = 3) were conducted to ascertain perceptions. Thematic analysis generated 329 (209 "at-risk" and 120 stakeholder) coded statements related to food insecurity drivers. Respondents were in agreement for the majority of factors, and limited income was considered the primary driver of food insecurity. However, there were notable deviations in the perceived importance of certain drivers, particularly around the price of food and the lack of food literacy. Differences in the perception of causes of food insecurity may in part be attributed to the varied role each group plays in working towards the resolution of the problem, either at the household or system level.


Predictors of successful neoadjuvant treatment in HER2‑positive breast cancer.
The prognosis of local or locally advanced human epidermal growth factor receptor 2 (HER2)-positive breast cancer after a complete response from neoadjuvant systemic treatment (NAT) is excellent. However, some of the patients succumb to their disease, so novel predictive factors to identify these patients at risk are needed. Retrospective data from 119 patients treated at the Helsinki University Hospital Comprehensive Cancer Centre (Helsinki, Finland) were collected. All patients had in situ hybridization-confirmed HER2-positive breast cancer and underwent NAT with a curative intention. The primary tumours were relatively large, most patients had cytologically confirmed lymph node metastases and the treatments used were current regimens. A total of 63 (52.1%) patients had a pathological complete response (pCR) to neoadjuvant therapy. Achieving pCR predicted longer disease-free survival (DFS; P=0.0083) but not overall survival (P=0.061). The patients with a pCR had an estimated DFS rate of 96.8% at 5 years, compared with only 59.7% of the patients with non-pCR. Radiological complete response (CR) was associated with pCR (P=0.00033), although imaging yielded 30.4% false-negative and 36.9% false-positive results. The association between the radiological CR and pCR was more obvious in oestrogen receptor-negative tumours. Moderate (compared with strong) immunohistochemical HER2 expression predicted a lower chance of pCR (P=0.0078) and worse breast cancer-specific survival (P=0.0015). In conclusion, pCR after NAT served as an important prognostic factor in women with high-risk HER2-positive breast cancer. The patients with only moderate immunohistochemical HER2 expression had a lower chance of reaching a pCR, as well as a shorter breast cancer-specific survival.


Isotopically enriched polymorphs of dysprosium single molecule magnets.
A triclinic polymorph Dy(t) and a monoclinic polymorph Dy(m) of [Dy(tta)3(L)] with L = 4-[6-(1,3-benzothiazol-2-yl)pyridin-3-yl]-4',5'-bis(methylthio)tetrathiafulvene behave as Single-Molecule Magnets with hysteresis loops opened at zero field. Magnetic properties were enhanced through magnetic dilution and 164Dy isotopic enrichment which definitively support the importance of isotopes for the control of quantum magnets.


Impact of Optically Pumped Nonequilibrium Steady States on Luminescence Emission of Atomically Thin Semiconductor Excitons.
The interplay of the nonequivalent corners in the Brillouin zone of transition metal dichalcogenides (TMDCs) has been investigated extensively. While experimental and theoretical works contributed to a detailed understanding of the relaxation of selective optical excitations and the related relaxation rates, only limited microscopic descriptions of stationary experiments are available so far. Here we present microscopic calculations for the nonequilibrium steady state properties of excitons during continuous wave pumping exemplary for monolayer MoSe_{2}. We find sharp features in photoluminescence excitation spectra and degree of polarization which result from phonon assisted excitonic transitions dominating over exciton recombination and intervalley exchange coupling.


[Study of pharmacological properties of betulin bishemiphthalate].
The results of pharmacological tests showed that betulin bishemiphthalate possesses hepatoprotector, antioxidant, and immunotropic properties. Administered in combination with hydroxymethyluracil, that betulin bishemiphthalate prevented the loss of experimental animals upon irradiation.


A simple method for estimating the absolute solvation free energy of monovalent ions in different solvents.
The solvation Gibbs free energies (SGFE) of 39 ions were estimated in protic and aprotic solvents including methanol, ethanol, N,N-dimethylformamide (DMF) and acetonitrile (ACN) using a proposed approach. In this method, the error of the applied computational method, used for estimating the SGFE of a specific ion in water and dimethyl sulfoxide (DMSO) solvents, was used as a reference value to correct the calculated SGFE of the ion in other protic and aprotic solvents, respectively. The estimated values of SGFE of ions, obtained in this work, show good agreement with those obtained using the other methods reported in literature. New correlation equations were also proposed for correlating the estimated values of SGFE of ions in a specific solvent to the corresponding values in water and DMSO for protic and aprotic solvent. By using the proposed method in this work, it is possible to estimate the values of SGFE of ions in the solvents that there are no experimental and theoretical reports on them in literature provided that the appropriate and correct reference solvent is selected. Typically, this method was applied on two most popular solvents in organic chemistry including acetone and 1-propanol to estimate the SGFE of the considered ions in them for the first time.


Serial QuantiFERON-TB Gold In-Tube assay and tuberculin skin test to diagnose latent tuberculosis in household Mexican contacts: conversion and reversion rates and associated factors using conventional and borderline zone definitions.
A cohort of 123 adult contacts was followed for 18-24 months (86 completed the follow-up) to compare conversion and reversion rates based on two serial measures of QuantiFERON (QFT) and tuberculin skin test (TST) (PPD from TUBERSOL, Aventis Pasteur, Canada) for diagnosing latent tuberculosis (TB) in household contacts of TB patients using conventional (C) and borderline zone (BZ) definitions. Questionnaires were used to obtain information regarding TB exposure, TB risk factors and socio-demographic data. QFT (IU/mL) conversion was defined as <0.35 to ≥0.35 (C) or <0.35 to >0.70 (BZ) and reversion was defined as ≥0.35 to <0.35 (C) or ≥0.35 to <0.20 (BZ); TST (mm) conversion was defined as <5 to ≥5 (C) or <5 to >10 (BZ) and reversion was defined as ≥5 to <5 (C). The QFT conversion and reversion rates were 10.5% and 7% with C and 8.1% and 4.7% with the BZ definitions, respectively. The TST rates were higher compared with QFT, especially with the C definitions (conversion 23.3%, reversion 9.3%). The QFT conversion and reversion rates were higher for TST ≥5; for TST, both rates were lower for QFT <0.35. No risk factors were associated with the probability of converting or reverting. The inconsistency and apparent randomness of serial testing is confusing and adds to the limitations of these tests and definitions to follow-up close TB contacts.


Examination for sexual abuse in prepubertal children: an update.
The complete physical examination of prepubertal children should always include a genital examination. Most children, even those who have been sexually abused, will have a normal genital examination. A child's acceptance and tolerance for this aspect of the examination will be enhanced by use of the techniques described. Sexually abused children may be identified through routine review of systems and history, including behavioral and psychosocial, and open-ended questions regarding sexual abuse. Regular genital examinations will also help to identify sexually abused children. Although the diagnosis of sexual abuse can never rely solely on physical findings, abnormal findings suspicious for sexual abuse are significantly more useful if there have been prior documented normal examinations. When sexually abused children initially present to their medical practitioner, the practitioner should obtain a complete medical and psychosocial history and perform a thorough examination. The practitioner need not be an expert in the interpretation of the possible legal significance of specific genital findings but should recognize normal, abnormal, and suspicious findings. Reassurance from a trusted practitioner relating to a normal body can be the most valuable treatment for a child's emotional healing. Practitioners need to be aware of the resources in their community for medical evaluations for sexual abuse, legal investigations, and mental health referrals. If there is a local center for child abuse evaluations, such as a Child Advocacy Center or Center of Excellence for child protection, practitioners should consider referrals to and consultations with these resources.


[Intervention measures in geriatrics from the viewpoint of a geriatric clinic with special reference to pharmacotherapy].
The objective of intervention is to produce an improved state of physical, psychological, and sociological well-being. To reach this state a complex therapeutic program is required that offers the best of pharmacotherapy, nutrition, occupational and activity therapies, and the advice of specialists during the course of therapy. Consultations with the patients' family-doctors are also important. The practice of geriatrics will be improved when we include its special considerations in our school curriculum .


Translational genetics for diagnosis of human disorders of sex development.
Disorders of sex development (DSDs) are congenital conditions with discrepancies between the chromosomal, gonadal, and phenotypic sex of the individual. Such disorders have historically been difficult to diagnose and cause great stress to patients and their families. Genetic analysis of human samples has been instrumental in elucidating the molecules and pathways involved in the development of the bipotential gonad into a functioning testis or ovary. However, many DSD patients still do not receive a genetic diagnosis. New genetic and genomic technologies are expanding our knowledge of the underlying mechanism of DSDs and opening new avenues for clinical diagnosis. We review the genetic technologies that have elucidated the genes that are well established in sex determination in humans, discuss findings from more recent genomic technologies, and propose a new paradigm for clinical diagnosis of DSDs.


Sex Differences and Menstrual Cycle Dependent Changes in Cognitive Strategies during Spatial Navigation and Verbal Fluency.
Men typically outperform women in spatial navigation tasks, while the advantage of women in verbal fluency is more controversial. Sex differences in cognitive abilities have been related to sex-specific cognitive strategies on the one hand and sex hormone influences on the other hand. However, sex hormone and menstrual cycle influences on cognitive strategies have not been previously investigated. In the present study we assessed cognitive strategy use during spatial navigation and verbal fluency in 51 men and 49 women. In order to evaluate sex hormone influences, all participants completed two test sessions, which were time-locked to the early follicular (low estradiol and progesterone) and mid-luteal cycle phase (high estradiol and progesterone) in women. As hypothesized, men outperformed women in navigation, whereas women outperformed men in phonemic verbal fluency. Furthermore, women switched more often between categories in the phonemic fluency condition, compared to men, indicating sex-specific strategy use. Sex differences in strategy use during navigation did, however, not follow the expected pattern. Menstrual cycle phase, however, did modulate strategy use during navigation as expected, with improved performance with the landmark strategy in the luteal, compared to the follicular phase. No menstrual cycle effects were observed on clustering or switching during verbal fluency. This suggests a modulation of cognitive strategy use during spatial navigation, but not during verbal fluency, by relative hormone increases during the luteal phase of the menstrual cycle.


The value of computerised axial tomography in the assessment of workers exposed to asbestos.
Nineteen men who had been exposed to asbestos for long periods were subjected to an examination of the lungs by means of computerised axial tomography (CT). Some features of asbestos-related disease are shown better on CT than on conventional roentgenograms, and occasionally features not shown at all on conventional films may be demonstrated on CT. It was concluded that CT may be useful in cases with borderline and doubtful signs on conventional films, and very occasionally in persons with long exposure who have normal conventional films.


Inhibition of mesangial iNOS by reduced extracellular pH is associated with uncoupling of NADPH oxidation.
Since chronic renal failure is associated with metabolic acidosis and down-regulation of intrarenal nitric oxide (NO) synthesis, I tested the hypothesis that acidosis may impair the intrarenal NO synthesis. The effects of alterations in extracellular pH were examined on inducible NO synthesis in murine mesangial cells (MMC) in culture. NO synthesis was induced in MMC by bacterial lipopolysaccharide and tumor necrosis factor-alpha and assayed by an NO analyzer that measured nitrites and nitrates (NOx). The activity of inducible NO synthase (iNOS) enzyme was assayed by conversion of [3H]-arginine to [3H]-citrulline. Experimental groups included cells cultured with a pH of 7.3 (normal), or 7.0 (low) or 7.6 (high), and the assigned pH values were maintained by HEPES and Tris. NOx was decreased in MMC exposed to the reduced pH compared to other groups. [3H]-citrulline assay showed an 80% reduction in iNOS activity in stimulated MMC exposed to a reduced pH versus control pH (P < 0.01). iNOS mRNA and protein expression were similar in control and low pH cells. The iNOS inhibition was not reversed by supplementation of MMC with either l-arginine or tetrahydrobiopterin, a major co-factor for NOS enzyme. MMC re-incubated in control pH after being exposed to the low pH demonstrated re-inducibility of NOS activity. Furthermore, MMC exposed to low pH were associated with a higher NADP+/+[H]-citrulline ratio (3.2) compared to standard pH (1.7), indicating an increase in NADP+/+[H]-citrulline stoichiometries and uncoupling of nicotinamide adenine dinucleotide phosphate (NADPH) oxidation. In contrast, macrophages exposed to the reduced pH did not demonstrate uncoupling of NADPH oxidation. Acidosis impairs iNOS activity in MMC by a post-translational mechanism that involves uncoupling of NADPH oxidation.


Evaluation of Endocrine Disrupting Compounds Migration in Household Food Containers under Domestic Use Conditions.
Plasticizers and plastic monomers are commonly used in packaging. Most of them act as endocrine disrupters and are susceptible to migrate from the packaging to the food. We evaluated the migration of endocrine disrupting compounds from three different household food containers to four food simulants under different domestic treatments and for different periods of time, with the aim of reproducing real domestic conditions. The results showed that the migration to the simulants increased with the storage time, up to more than 50 times in certain cases. The heating power seemed to increase the migration processes (up to more than 30 times), and reusing containers produced an increase or decrease of the concentrations depending on the container type and the simulant. The concentrations found were lower than other concentrations reported (always less than 4000 pg/mL, down to less than 20 pg/mL), which might be a consequence of the domestic conditions used.


Parametrial involvement and decreased survival of women with FIGO stage IIIC1 cervical cancer.
To evaluate the effect of parametrial status on FIGO stage IIIC1 cervical cancer. A retrospective study was conducted from June 1, 2009, to December 31, 2018.Patients with stage IIIC1 cervical cancer were included and stratified into two groups based on the status of parametrial involvement. Patients with IIIA or IIIB were selected as control. The primary outcomes are overall survival (OS) and progression-free survival (PFS). Of 586 patients included, 377 patients were stage IIIC1 (group A) and 209 patients were stage IIIA/IIIB (group B). Compared control, stage IIIC1 was not associated with worse 5-year OS or PFS. Of the stage IIIC1 patients, 58.1% without parametrial involvement (group A1) and 41.9% with parametrial involvement (group A2). Patients of group A1 showed a better prognosis than group A2 both in 5-year rates of OS (79.09% vs. 59.43%, p<0.001) and PFS (73.27% vs. 56.95%, p=0.0002). However, patients of group A1 showed a better prognosis than group B both in OS and PFS. Also, patients of group A2 showed a comparable prognosis to group B both in OS and PFS. Reclassification of stage IIIC1 cervical cancer without parametrial into a new stage is more appropriate and improves discriminatory ability.


Pacemaker potentials for the periodic burst discharge in the heart ganglion of a stomatopod, Squilla oratoria.
From somata of the pacemaker neurons in the Squilla heart ganglion, pacemaker potentials for the spontaneous periodic burst discharge are recorded with intracellular electrodes. The electrical activity is composed of slow potentials and superimposed spikes, and is divided into four types, which are: (a) "mammalian heart" type, (b) "slow generator" type, (c) "slow grower" type, and (d) "slow deficient" type. Since axons which are far from the somata do not produce slow potentials, the soma and dendrites must be where the slow potentials are generated. Hyperpolarization impedes generation of the slow potential, showing that it is an electrically excitable response. Membrane impedance increases on depolarization. Brief hyperpolarizing current can abolish the plateau but brief tetanic inhibitory fiber stimulation is more effective for the abolition. A single stimulus to the axon evokes the slow potential when the stimulus is applied some time after a previous burst. Repetitive stimuli to the axon are more effective in eliciting the slow potential, but the depolarization is not maintained on continuous stimulation. Synchronization of the slow potential among neurons is achieved by: (a) the electrotonic connections, with periodic change in resistance of the soma membrane, (b) active spread of the slow potential, and (c) synchronization through spikes.


Analyzing the concept of fluid overload in Chronic Kidney Disease patients in dialysis therapy: an integrative review.
Objective To analyze the concept of fluid overload in Chronic Kidney Disease patients undergoing dialysis therapy and comparing it to the Nursing Diagnosis of Excess fluid volume present in the NANDA International. Method An integrative literature review carried out in the LILACS, CINAHL and SCOPUS databases. Results The sample was comprised of 22 articles. The defining attributes of the concept were: fluid retention, fluid buildup in the body, and weight gain over a short period; while the attributes composing the definition were: fluid retention in the body (intracellular/extracellular space) expressed by weight gain over short period of time. Twenty-one (21) antecedents and 22 consequents of fluid overload in patients with renal disease in dialysis therapy were identified. Conclusion The definition evidenced by the NANDA International taxonomy for the Excess fluid volume Nursing Diagnosis and the components of this diagnosis need to be complemented in order to better target the care of patients with kidney disease undergoing dialysis therapy.


Describing and Measuring the Pathway to Suicide Attempts: A Preliminary Study.
To die by suicide, one must think about suicide, make a plan, and then carry it out. Prior research has examined the presence and predictors of these outcomes; however, virtually no studies have characterized how these steps unfold along the pathway to suicide. A novel instrument was administered to 30 recent suicide attempters. Results revealed that although the median onset for suicidal ideation occurs 1 to 5 years prior to attempting, the median for 6 of the 10 steps measured was within 6 hours of attempting. Overall, 86.5% of proximal planning steps took place within 1 week of attempting and 66.6% occurred within 12 hours.


Acyclic Schiff base salts derived from 1,3-diaminopropane and 1,3-diamino-2-hydroxypropane.
Two salts of acyclic Schiff base cationic ligands, namely N,N'-bis(2-nitrobenzyl)propane-1,3-diammonium dichloride monohydrate, C(17)H(22)N(4)O(4)(2+).2Cl(-).H(2)O, (I), and 2-hydroxy-N,N'-bis(2-nitrobenzyl)propane-1,3-diammonium dichloride, C(17)H(22)N(4)O(5)(2+).2Cl(-), (II), were synthesized as precursors in order to obtain new acyclic and macrocyclic multidentate ligands and complexes. The cation conformations in compounds (I) and (II) are different in the solid state, although the cations are closely related chemically. Similarly, the hydrogen-bonding networks involving ammonium cations, hydroxyl groups and chloride anions are also different. In the cation of compound (II), the hydroxyl group is disordered over two sets of sites, with occupancies of 0.785 (8) and 0.215 (8).


Machine learning in haematological malignancies.
Machine learning is a branch of computer science and statistics that generates predictive or descriptive models by learning from training data rather than by being rigidly programmed. It has attracted substantial attention for its many applications in medicine, both as a catalyst for research and as a means of improving clinical care across the cycle of diagnosis, prognosis, and treatment of disease. These applications include the management of haematological malignancy, in which machine learning has created inroads in pathology, radiology, genomics, and the analysis of electronic health record data. As computational power becomes cheaper and the tools for implementing machine learning become increasingly democratised, it is likely to become increasingly integrated into the research and practice landscape of haematology. As such, machine learning merits understanding and attention from researchers and clinicians alike. This narrative Review describes important concepts in machine learning for unfamiliar readers, details machine learning's current applications in haematological malignancy, and summarises important concepts for clinicians to be aware of when appraising research that uses machine learning.


MEN1 Degradation Induced by Neddylation and the CUL4B-DCAF7 Axis Promotes Pancreatic Neuroendocrine Tumor Progression.
Pancreatic neuroendocrine tumors (PanNET) are a group of rare sporadic malignant tumors in the pancreas. MEN1 is the most frequently mutated gene in PanNETs. The MEN1-encoded protein is a typical tumor suppressor that forms a complex with epigenetic and transcription factors and is an attractive target for therapeutic interventions for patients with PanNET. A better understanding of the regulation of MEN1 protein expression in PanNETs could identify strategies for targeting MEN1. Here, we found that the neddylation pathway and DCAF7-mediated ubiquitination regulated MEN1 protein expression. Increased expression of members of the neddylation pathway and DCAF7 was found in PanNET tissues compared with paired-adjacent tissues and was associated with poor prognosis in patients with PanNET. Suppression of neddylation using the neddylation inhibitor MLN4924 or RNA interference significantly induced MEN1 accumulation and repressed cancer-related malignant phenotypes. CUL4B and DCAF7 promoted MEN1 degradation by binding and catalyzing its ubiquitination. In PanNET cells resistant to everolimus, a pharmacologic mTOR inhibitor widely used for advanced PanNET patient treatment, the downregulation of DCAF7 expression overcame resistance and synergized with everolimus to suppress mTOR activation and to inhibit cancer cell growth. The effects of DCAF7 loss could be counteracted by the simultaneous knockdown of MEN1 both in vitro and in vivo. The inverse correlation between DCAF7 and MEN1 was further validated in clinical specimens. This study revealed that the posttranslational control of MEN1 expression in PanNET is mediated by neddylation and the CUL4B-DCAF7 axis and identifies potential therapeutic targets in patients with MEN1-associated PanNET. Identification of neddylation and ubiquitination pathways that regulate MEN1 protein stability provides an opportunity for therapeutic interventions for treating patients with pancreatic neuroendocrine tumors.


The effect of two grading systems on the performance of medical students during oral examinations.
Either a pass/fail approach or a seven-point grading scale are used to evaluate students at the Danish universities. The aim of this study was to explore any effect of the assessment methods on student performances during oral exams. In a prospective study including 1,037 examinations in three medical subjects, we investigated the difference in the test scores between the spring- and autumn semester. In the spring semester, the students could either pass or fail the subject (pass/fail) while in the following autumn semester, the students were assessed by tiered grading (seven-point grading scale). Unknown to the students, the examiners assessed the students by the seven-point grading scale also in the spring semester. Students at the international classes who were officially assessed by the seven-point grading scale during both semesters served as control group. The grading scores were significantly higher among students who were aware of being evaluated with the seven-point grading scores compared with the pass/fail group (p < 0.0001). In comparison, no significant difference between the exam results was observed from the spring- to the autumn semester for the control group (p = 0.45). Moreover, the average mark was higher among the international students (mean = 10.3, on the seven-point grading scale) than in the Danish speaking classes (mean = 9.1). The seven-point grading scale seems to motivate students to yield a better performance; hence tiered-grading should probably be preferred to a simple pass/fail approach. none. not relevant.


Differences in Pediatric Residents' Social Needs Screening Practices Across Health Care Settings.
The American Academy of Pediatrics recommends that all pediatricians screen for social determinants of health to identify families in need and connect them to available resources. We examined pediatric residents' screening practices for social needs in different clinical settings and explored the influence of electronic health record (EHR) prompts on screening. In this cross-sectional study, pediatric residents participated in a brief electronic survey assessing (1) screening practices for unmet social needs and (2) perceived barriers to and facilitators of routine screening in the inpatient and outpatient settings. The differences in screening by care setting were assessed by using Fisher's exact test. Mixed-effects logistic regression was used to examine the association between EHR prompts and resident screening practices. Ninety-two pediatric residents (64% of the residency program) responded to the survey. Respondents reported significantly higher rates of social needs screening in the outpatient as compared with the inpatient setting (98% vs 37%; P < .001). Residents cited time constraints, lack of knowledge about available resources, and discomfort with screening questions as barriers to screening in both settings. Residents were more likely to screen for social needs when screening questions were embedded in the EHR (odds ratio = 9.6; 95% confidence interval: 6.7-13.9). Pediatric residents were more likely to screen for unmet social needs in the outpatient than in the inpatient setting despite reporting similar barriers to screening in both settings. EHR-based social needs screening templates could be used to increase rates of screening and reach additional families in need.


Sarcoidosis: epidemiology, characteristics, and outcomes over 10 years - a single-center study in Pakistan.
Sarcoidosis is a multisystem granulomatous inflammatory disease which remains under-diagnosed in a tuberculosis endemic region such as Pakistan. To determine the distribution, clinical characteristics, diagnostic and treatment modalities and the disease course in the Pakistani population. A cross-sectional review of sarcoidosis patients from Jan-1,2010 to Dec-31,2019 was done. Multivariable logistic and cox-regression models were used to identify the independent risk-factors associated with disease relapse. Kaplan-Meier curves were used to assess the DFS. 222 patients, with mean age 44 ± 12 years, predominantly females (57.7%) and mean BMI 29 ± 6 were diagnosed sarcoidosis. Significant co-morbidities affected 36.5%, 90% were nonsmokers, and 50.3% belonged to moderate SES. Total 178 (80.2%) were symptomatic with 115 (51.8%) having multi-organ involvement. Stage-I radiological disease was predominant (52.5%). Histopathological diagnosis was obtained in 161 (72.5%) patients. Out of 113 mediastinal lymph-nodes, NNGI was present in 99, with highest yield in Station-07 (68.6%). Treatment was instituted in 108/178 (60.7%) symptomatic patients with steroids alone and in 26 (14.6%) with S+IS, with better clinical and radiological response duration in patients receiving steroid monotherapy (p-values=0.01 and 0.001,respectively, along with overall higher survival time (p-value = 0.04). Risk factors identified for relapse included high SES (AOR5.52;95%CI(1.10-28.40),0.04), steroid monotherapy (AOR0.22; 95%CI(0.10-0.87),0.03), symptomatic response after one year (AOR3.40; 95%CI(1.02-11.10),0.04), and radiological response duration (AOR1.10; 95%CI(1.05-1.20),0.04). Sarcoidosis is a dynamic disease with a variable clinical and geographical spectrum but good overall prognosis.


Information seeking about COVID-19 and associated factors among chronic patients in Bahir Dar city public hospitals, Northwest Ethiopia: a cross-sectional study.
The health impacts of COVID-19 are not evenly distributed in societies. Chronic patients are highly affected and develop dangerous symptoms of COVID-19. Understanding their information seeking about COVID-19 may help to improve the effectiveness of public health strategies in the future, the adoption of safety measures, and minimize the spread of the pandemic. However, there is little evidence on information seeking specifically on COVID-19 in this study setting. Therefore, this study aimed to assess information seeking about COVID-19 and associated factors among chronic patients. An institutional-based cross-sectional study supplemented with qualitative data was conducted at Bahir Dar city public hospitals in Northwest Ethiopia from April 8 to June 15, 2021. A total of 423 chronic patients were selected using systematic random sampling techniques with an interval of 5. Bi-variable and multivariable logistic regression analysis was fitted to identify factors associated with information seeking about COVID-19. A p-value < 0.05 was used to declare statistical significance. Qualitative data were analyzed using a thematic approach. Finally, it was triangulated with quantitative findings. The proportion of information seeking about COVID-19 among chronic patients was 44.0% (95% CI = 39.0, 49.0). Being living in urban [AOR = 4.4, 95% CI (2.01, 9.58)], having high perceived susceptibility to COVID-19 [AOR = 3.4, 95%CI (1.98, 5.70)], having high perceived severity to COVID-19 [AOR = 1.7, 95%CI (1.04, 2.91)], having high self-efficacy to COVID-19 [AOR = 4.3, 95%CI (2.52, 7.34)], and having adequate health literacy [AOR = 1.8, 95%CI (1.10, 3.03)] were significant factors associated with information-seeking about COVID-19. The overall proportion of information seeking about COVID-19 among chronic patients was low. Thus, health promotion programs should emphasize the chronic patients living in a rural area; enhance perceived risk and severity of COVID-19, enhancing self-efficacy and health literacy interventions to improve information seeking.


Protein kinases in vascular smooth muscle tone--role in the pulmonary vasculature and hypoxic pulmonary vasoconstriction.
Hypoxic pulmonary vasoconstriction (HPV) is an adaptive mechanism that in the normal animal diverts blood away from poorly ventilated areas of the lung, thereby maintaining optimal ventilation-perfusion matching. In global hypoxia however, such as in respiratory disease or at altitude, it causes detrimental increases in pulmonary vascular resistance and pulmonary artery (PA) pressure. The precise intracellular pathways and mechanisms underlying HPV remain unclear, although it is now recognised that both an elevation in smooth muscle intracellular [Ca2+] and a concomitant increase in Ca2+ sensitivity are involved. Several key intracellular protein kinases have been proposed as components of the signal transduction pathways leading to development of HPV, specifically Rho kinase, non-receptor tyrosine kinases (NRTK), p38 mitogen activated protein (MAP) kinase, and protein kinase C (PKC). All of these have been implicated to a greater or lesser extent in pathways leading to Ca2+ sensitisation, and in some cases regulation of intracellular [Ca2+] as well. In this article, we review the role of these key protein kinases in the regulation of vascular smooth muscle (VSM) constriction, applying what is known in the systemic circulation to the pulmonary circulation and HPV. We conclude that the strongest evidence for direct involvement of protein kinases in the mechanisms of HPV concerns a central role for Rho kinase in Ca2+ sensitisation, and a potential role for Src-family kinases in both modulation of Ca2+ entry via capacitative Ca2+ entry (CCE) and activation of Rho kinase, though others are likely to have indirect or modulatory influences. In addition, we speculate that Src family kinases may provide a central interface between the proposed hypoxia-induced generation of reactive oxygen species by mitochondria and both the elevation in intracellular [Ca2+] and Rho kinase mediated Ca2+ sensitisation.


Characterization of the Expression Profile and Genetic Polymorphism of the Cellular Retinol-Binding Protein (CRBP IV) Gene in Erlang Mountainous Chickens.
In this study, we cloned the coding sequence of chicken CRBP IV, quantified the mRNA expression in Erlang Mountainous Chickens, and investigated a polymorphism in this gene and its association with egg production traits among 349 individuals. The cloned fragment contained a 384 bp open reading frame, which encoded a predicted protein of 127 amino acids and was highly conserved among species. Expression of CRBP IV mRNA was detected in all eight tissues (small intestine, heart, liver, kidney, oviduct, ovary, pituitary, and hypothalamus) at different ages (12, 24, 32 and 45 w). High expression was found in small intestine, pituitary, kidney and liver, whereas it was low in the heart (p < 0.05). The CRBP IV mRNA levels changed with age in the various tissues, and were highly expressed in all tissues at 32 w, except for the heart. We identified one nucleotide substitution (c. 826T>C) in the second exon, which caused an amino acid change (p. S49L). Genotypes (TT, TC and CC) had significant effects on the age at first egg (AFE), total eggs for 300 days (TE300) and highest continuous laying days (HCLD). The CC genotype would be genetically advantageous to improve egg production traits due to earlier AFE, more TE300, and longer HCLD.


A rapid method for harvesting and immobilization of oleaginous microalgae using pellet-forming filamentous fungi and the application in phytoremediation of secondary effluent.
A rapid method for harvesting and immobilization of oleaginous microalgae using pellet-forming filamentous fungi was developed. The suitable conditions for pellet formation by filamentous fungi were determined. Among the strains tested, Trichoderma reesei QM 9414 showed superior pellet forming ability. Its pellets were used to harvest oleaginous microalga Scenedesmus sp. With increasing volume ratio of fungal pellets to microalgae culture up to 1:2, >94% of microalgal cells were rapidly harvested within 10 min. The ratio of fungal pellets could manipulate both harvesting time and initial concentration of microalgal cells in the pellets. The microalgae-fungal pellets were successfully used as immobilized cells for effective phytoremediation of secondary effluent from seafood processing plants under nonsterile condition. The chemical oxygen demand, total nitrogen, and total phosphorus removal were >74%, >44%, and >93%, respectively. The scanning electron microscopy showed that the microalgal cells were not only entrapped in the pellets but also got attached to the fungal hyphae with sticky exopolysaccharides, possibly secreted by the fungi. The extracted lipids from the pellets were mainly composed of C16-C18 (>83%) with their suitability as biodiesel feedstocks. This study has shown the promising strategy to rapidly harvest and immobilize microalgal cells and the possible application in phytoremediation of industrial effluent.


Estimating the costs of tsetse control options: an example for Uganda.
Decision-making and financial planning for tsetse control is complex, with a particularly wide range of choices to be made on location, timing, strategy and methods. This paper presents full cost estimates for eliminating or continuously controlling tsetse in a hypothetical area of 10,000km(2) located in south-eastern Uganda. Four tsetse control techniques were analysed: (i) artificial baits (insecticide-treated traps/targets), (ii) insecticide-treated cattle (ITC), (iii) aerial spraying using the sequential aerosol technique (SAT) and (iv) the addition of the sterile insect technique (SIT) to the insecticide-based methods (i-iii). For the creation of fly-free zones and using a 10% discount rate, the field costs per km(2) came to US$283 for traps (4 traps per km(2)), US$30 for ITC (5 treated cattle per km(2) using restricted application), US$380 for SAT and US$758 for adding SIT. The inclusion of entomological and other preliminary studies plus administrative overheads adds substantially to the overall cost, so that the total costs become US$482 for traps, US$220 for ITC, US$552 for SAT and US$993 - 1365 if SIT is added following suppression using another method. These basic costs would apply to trouble-free operations dealing with isolated tsetse populations. Estimates were also made for non-isolated populations, allowing for a barrier covering 10% of the intervention area, maintained for 3 years. Where traps were used as a barrier, the total cost of elimination increased by between 29% and 57% and for ITC barriers the increase was between 12% and 30%. In the case of continuous tsetse control operations, costs were estimated over a 20-year period and discounted at 10%. Total costs per km(2) came to US$368 for ITC, US$2114 for traps, all deployed continuously, and US$2442 for SAT applied at 3-year intervals. The lower costs compared favourably with the regular treatment of cattle with prophylactic trypanocides (US$3862 per km(2) assuming four doses per annum at 45 cattle per km(2)). Throughout the study, sensitivity analyses were conducted to explore the impact on cost estimates of different densities of ITC and traps, costs of baseline studies and discount rates. The present analysis highlights the cost differentials between the different intervention techniques, whilst attesting to the significant progress made over the years in reducing field costs. Results indicate that continuous control activities can be cost-effective in reducing tsetse populations, especially where the creation of fly-free zones is challenging and reinvasion pressure high.