Water use strategies of Nitraria tangutorum in the lake-basin region of the Badain Jaran Desert.
Information regarding plant water-use strategies is essential for understanding the hydrological processes and plant survival adaptation mechanisms in desert lake basin regions. To examine the water use strategies of plants in desert lake basin areas, water uptake patterns, water use efficiency, and water potential of Nitraria tangutorum were investigated at different distances from the lake duringhe growing seasons in the lake basin regions of the Badain Jaran Desert. The results indicate that N. tangutorum primarily absorbed groundwater in May (63.8%) and August (53.5%), relied on deep soil water in June (75.1%), and uniformly absorbed soil water from different layers in July. These observations could be explained by periodic fluctuations in the groundwater level and the consequent decrease in soil water availability, as well as plant root adjustments. As soil water availability decreases, N. tangutorum adapts to water variation by increasing its water use efficiency (WUE) and reducing its leaf water potential (Ψ). With intensified water stress, N. tangutorum gradually shifted from adventurous anisohydric regulation to conservative isohydric regulation. Thus, N. tangutorum responds to diverse degrees of environmental changes by altering its water-use strategy. A better understanding of the adaptive water use strategies developed by desert plants under varying water availability conditions provides insight into the diversity of species' reactions to long-term drought and quantifies the hydrological cycle of desert ecosystems against the background of worldwide climate warming.


The effect of the protective face mask on cardiorespiratory response during aerobic exercise.
The protective face mask (PFM) has been widely used for safety purposes and, after the advent of the COVID-19 pandemic, its use is growing steadily, not only among healthcare personnel but also the general population. While the PFM is important to preserve the wearer from contaminating agents present in the airflow, they are well known to increase the subjective perception of breathing difficulty. Although some studies have demonstrated that PFM use worsens exercise tolerance, several studies state that there is no such limitation with the use of PFM. Moreover, no serious adverse effects during physical exercise have been found in the literature. Physical exercise represents a significant challenge to the human body through a series of integrated changes in function that involve most of its physiologic systems. In this respect, cardiovascular and respiratory systems provide the capacity to sustain physical tasks over extended periods. Within this scenario, both convective oxygen (O2 ) transport (product of arterial O2 content × blood flow) to the working locomotor muscles and O2 diffusive transport from muscle capillaries to mitochondria are of paramount importance to endurance performance. Interestingly, the effects of PFM on cardiorespiratory response during aerobic exercise depends on the type of mask and exercise (i.e., walking, running, or cycling), the ventilatory demands, arterial oxygen levels, maximal oxygen consumption and endurance performance. The purpose of this review is to elucidate the effect of protective face mask-wearing on (1) cardiorespiratory responses during aerobic exercise and (2) endurance performance.


Phase II trial of high-dose conformal radiation therapy with concurrent hepatic artery floxuridine for unresectable intrahepatic malignancies.
A phase II trial was conducted to determine if high-dose radiation with concurrent hepatic arterial floxuridine would improve survival in patients with unresectable intrahepatic malignancies. Three-dimensional conformal high-dose radiation therapy was delivered concurrently with hepatic arterial floxuridine in 128 patients. The radiation dose was based on a normal-tissue complication probability model and subjected the patient to an estimated maximum risk of radiation-induced liver disease of 10% to 15%. The study design provided more than 80% power to detect a two-fold increase in median survival compared with historical controls at a 5% significance level. The median radiation dose delivered was 60.75 Gy (1.5-Gy fractions bid). At a median follow-up time of 16 months (26 months in patients who were alive) the median survival was 15.8 months (95% CI, 12.6 to 18.3 months), significantly longer than in the historical control. The actuarial 3-year survival was 17%. The total dose was the only significant predictor of survival. Primary hepatobiliary tumors had a significantly greater tendency to remain confined to the liver than did colorectal cancer metastases. Overall toxicity was acceptable, with 27 patients (21%) and 11 patients (9%) developing grade 3 and 4 toxicity, respectively, and one treatment-related death. The results suggest that, compared with historical controls, high-dose focal liver irradiation with hepatic artery floxuridine prolongs survival in patients with unresectable chemotherapy-refractory metastatic colorectal cancer and primary hepatobiliary tumors. This provides a rationale for intensification of local therapy for unresectable hepatobiliary cancers and integration of this regimen with newer systemic therapy for patients with colorectal cancer.


A note on the primary structure and expression of an Erwinia carotovora polygalacturonase-encoding gene (peh1) in Escherichia coli and Saccharomyces cerevisiae.
A 1209-base pair (bp) DNA fragment containing the endopolygalacturonase-encoding gene (peh1) from Erwinia carotovora subsp. carotovora was amplified by the polymerase chain reaction (PCR) technique and expressed in Escherichia coli. The nucleotide sequence of the PCR product was determined and found to be highly homologous to the primary structures of other polygalacturonase-encoding genes. The peh1 DNA fragment encoding the mature polygalacturonase was inserted between two different yeast expression-secretion cassettes and a yeast gene terminator, generating recombinant yeast-integrating shuttle plasmids pAMS10 and pAMS11. These YIp5-derived plasmids were transformed and stably integrated into the genome of a laboratory strain of Saccharomyces cerevisiae. Transcription initiation signals present in these expression-secretion cassettes were derived from the yeast alcohol dehydrogenase (ADC1P) or mating pheromone alpha-factor (MF alpha 1P) gene promoters. The transcription termination signals were derived from the yeast tryptophan synthase gene terminator (TRP5T). Secretion of polygalacturonase was directed by the signal sequence of the yeast mating pheromone alpha-factor (MF alpha 1S). Northern blot analysis revealed the presence of peh1 mRNA in the yeast transformants and a polypectate agarose test was used to monitor polygalacturonase production.


Executive Order 12866: advantages and disadvantages of the administration's new regulatory plan on risk, benefit, and costs.
The 1993 Executive Order 12866 as implemented by the 1996 OMB document proposes a new paradigm for the evaluation of risks, benefits, and costs. The new regulatory plan would replace the current methodology in two ways. In place of the current methodology for risk assessment based on conservative generic default assumptions that provide an upper-bound risk value that is treated as the "benefit," the new regulatory plan establishes a state of the art guidance for the economic evaluation of risks, benefits, and costs. Second, the new plan requires changes in risk assessment to provide the necessary foundation for the new economic evaluation of risks, benefits, and costs. The advantages and disadvantages of the new regulatory plan are discussed.


Antigen-provoked increase in histamine reactivity. Observations on mechanisms.
To investigate the effect of antigen provocation on nonspecific reactivity to histamine, nine allergic individuals underwent multiple nasal challenges with histamine, or antigen. The response to challenge was assessed by counting the number of sneezes and measuring the levels of albumin and TAME-esterase (TAME; [3H]N-alpha-tosyl-L-arginine methyl ester) activity in recovered nasal lavages. In the case of antigen, levels of histamine were also measured. In response to histamine, the subjects sneezed and had increased levels of albumin and TAME. The responses to antigen or histamine were unchanged 24 h after histamine provocation. The responses to histamine provocations were increased with respect to symptom scores and to the levels of TAME activity and albumin in nasal lavages compared to baseline challenge, however, 24 h after antigen provocation. Increasing antigen exposure from 1 to 3 days did not further increase the responsiveness to histamine. Histamine reactivity returned to baseline 12 days after antigen exposure. The number of eosinophils, neutrophils, and alcian blue-positive cells in the lavages after antigen challenge and before the histamine challenges correlated with the changes in response to histamine. The increase in sneezing induced by antigen stimulation correlated with the increase in the same parameter after histamine provocation 24 hr after antigen challenge (r = 0.88; p less than 0.01). Surprisingly, the other parameters assessed did not show similar correlations.(ABSTRACT TRUNCATED AT 250 WORDS)


[Progress in the diagnosis of minimal hepatic encephalopathy].
Hepatic encephalopathy (HE) is a common serious complication of liver cirrhosis, with sudden onset, indicating a poor prognosis in patients with chronic liver disease. Minimal hepatic encephalopathy (MHE) is an early stage of HE with no apparent symptoms, but it shows abnormal results in neuropsychological and/or neurophysiological tests. MHE affects patients' quality of life, employability, driving ability, and has a high risk of developing overt hepatic encephalopathy (OHE). This article aims to explore various diagnostic methods, strengthen the routine work of clinicians in diagnosis and treatment, and develop an effective MHE screening protocol.


Defining the role of arginine 96 in green fluorescent protein fluorophore biosynthesis.
Aequoria victoria green fluorescent protein (GFP) is a revolutionary molecular biology tool because of its spontaneous peptide backbone cyclization and chromophore formation from residues Ser65, Tyr66, and Gly67. Here we use structure-based design, comprehensive targeted mutagenesis, and high-resolution crystallography to probe the significant functional role of conserved Arg96 (R96) in chromophore maturation. The R96M GFP variant, in which the R96M side chain is similar in volume but lacks the R96 positive charge, exhibits dramatically slower chromophore maturation kinetics (from hours to months). Comparison of the precyclized conformation of the chromophore-forming residues with the mature R96M chromophore reveals a similar Y66 conformer, contrary to the large Y66 conformational change previously defined in the slowly maturing R96A variant [Barondeau, D. P., Putnam, C. D., Kassmann, C. J., Tainer, J. A., and Getzoff, E. D. (2003) Proc. Natl. Acad. Sci. U.S.A. 100, 12111-12116]. Comprehensive R96 mutagenesis and fluorescent colony screening indicate that only the R96K substitution restores wild-type maturation kinetics. Further, we show that the slowly maturing R96A variant can be complemented with a Q183R second-site mutation designed to restore the missing R96 positive charge and rapid fluorophore biosynthesis. Moreover, comparative structural analysis of R96M, R96K, R96A/Q183R, and wild-type GFP reveals the importance of the presence of positive charge, rather than its exact position. Together, these structural, mutational, and biochemical results establish a pivotal role for the R96 positive charge in accelerating the GFP post-translational modification, with implications for peptide backbone cyclization in GFP, its homologues, and related biological systems.


Gold(I) and gold(III) corroles.
Corrole complexes with gold(I) and gold(III) were synthesized and their structural, photophysical, and electrochemical properties investigated. This work includes the X-ray crystallography characterization of gold(I) and gold(III) complexes, both chelated by a corrole with fully brominated β-pyrrole carbon atoms. The mononuclear and chiral gold(I) corrole appears to be the first of its kind within the porphyrinoid family, while the most unique property of the gold(III) corrole is that it displays phosphorescence at ambient temperatures.


"Tuned into a different channel": Autistic transgender adults' experiences of intersectional stigma.
In this critical-constructivist grounded theory study, we interviewed 13 autistic-transgender, nonbinary, and/or gender diverse (TNG) individuals on the intersection of their autistic-TNG identities and how they resisted marginalization related to these experiences. Analysis revealed the experiences of living in a world that "doesn't seem quite set up the right way" and situated autistic-TNG experiences in complex set of intersectional processes that require navigating relationships, health care systems, and safety challenges living in a heterosexist, cissexist, and ableist society. Participants had to constantly assess the safety and disclosure of their identities in the face of oppressive systems while claiming space and creating community that affirmed them. We conclude by highlighting the importance of taking an intersectional lens to highlight the many positive aspects of being autistic and TNG, which have been largely absent in research and clinical dialogues. We provide some suggestions for providing culturally responsive mental health and ways neurotypical and cisgender people can begin to challenge ableist and cissexist narratives in their clinical practice and research, alongside autistic-TNG people. (PsycInfo Database Record (c) 2022 APA, all rights reserved).


Contemporary diagnosis and management of preterm premature rupture of membranes.
Spontaneous rupture of membranes (ROM) is a normal component of labor and delivery. Premature ROM (PROM) refers to rupture of the fetal membranes prior to the onset of labor irrespective of gestational age. Once the membranes rupture, delivery is recommended when the risk of ascending infection outweighs the risk of prematurity. When PROM occurs at term, labor typically ensues spontaneously or is induced within 12 to 24 hours. The management of pregnancies complicated by preterm PROM (defined as PROM occurring prior to 37 weeks of gestation) is more challenging. Preterm PROM complicates 2% to 20% of all deliveries and is associated with 18% to 20% of perinatal deaths. Management options include admission to hospital, amniocentesis to exclude intra-amniotic infection, and administration of antenatal corticosteroids and broad-spectrum antibiotics, if indicated. This article reviews in detail the contemporary diagnosis and management of preterm PROM.


The use of an extracorporeal membrane oxygenation anticoagulation laboratory protocol is associated with decreased blood product use, decreased hemorrhagic complications, and increased circuit life.
To determine if a comprehensive extracorporeal membrane oxygenation anticoagulation monitoring protocol results in fewer hemorrhagic complications, reduced blood product usage, and increased circuit life. In September 2011, we augmented our standard extracorporeal membrane oxygenation laboratory protocol to include anti-factor Xa assays, thromboelastography, and antithrombin measurements. We performed a retrospective chart review to determine outcomes for patients placed on extracorporeal membrane oxygenation prior to and after the initiation of our anticoagulation laboratory protocol. Tertiary care, academic children's hospital. All patients who were placed on extracorporeal membrane oxygenation at our institution from January 1, 2007, to September 30, 2013. None. There were 261 extracorporeal membrane oxygenation runs before the initiation of the protocol and 105 extracorporeal membrane oxygenation runs after the initiation of the protocol. There were no major changes to our extracorporeal membrane oxygenation circuit or changes to our transfusion threshold during the study period. The indication for extracorporeal membrane oxygenation, age, and severity of illness of the patients were similar before and after protocol initiation. Median blood product usage for packed RBCs, fresh frozen plasma, platelets, and cryoprecipitate decreased significantly after protocol initiation. The occurrence of cannula site bleeding decreased from 22% to 12% (p = 0.04), and surgical site bleeding decreased from 38% to 25% (p = 0.02). Median extracorporeal membrane oxygenation circuit life increased from 3.6 to 4.3 days (p = 0.02). A trend toward increased patient survival was noted, but it did not reach statistical significance. We demonstrate an association between an extracorporeal membrane oxygenation anticoagulation laboratory protocol using anti-factor Xa assays, thromboelastography, and antithrombin measurements and a decrease in blood product transfusion, a decrease in hemorrhagic complications, and an increase in circuit life. To our knowledge, this is the first study to demonstrate clinical benefit associated with the use of these laboratory values for patients on extracorporeal membrane oxygenation.


[Analysis of factors of increased phase differences between chest flow and mouth flow at rest breathing in patients with obstructive disorders].
The factors which increase phase differences between mouth flow and chest flow in patients with obstructive disorders were analyzed. From airway resistance, thoracic gas volume and measured chest flow, phase difference was predicted by the Runge-Kutta (R.K.) method assuming respiratory system to be a single compartment model. The ratio of the measured phase differences to the predicted value by the R.K. method in normal subjects was 0.99 +/- 0.25. These results suggest that a single compartment model can be applied to normal respiratory system. In contrast, predicted phase differences were remarkably higher than measured values in patients with obstructive disorders (CPE: 1.83 +/- 0.63, DPB: 1.50 +/- 0.48). This phenomenon could be explained by the existence of parallel inhomogeneity of alveolar pressure.


Nitric oxide enhancement of erythropoietin production in the isolated perfused rat kidney.
We have previously reported that nitric oxide (NO) and guanosine 3',5'-cyclic monophosphate (cGMP) may be involved in the regulation of erythropoietin (Epo) production in response to hypoxia both in vivo and in vitro (20). In the present studies, we have used the isolated perfused rat kidney to assess the role of NO in oxygen sensing and Epo production. When arterial PO2 was reduced from 100 mmHg (normoxemic) to 30 mmHg (hypoxemic) in the perfusate of this system, perfusate levels of Epo were significantly increased. This hypoxia-induced increase in Epo production was significantly decreased by the addition of NG-nitro-L-arginine methyl ester (L-NAME; 1 mM) to the perfusates. Hypoxemic perfusion also produced a significant increase, and L-NAME significantly inhibited this increase, in intracellular cGMP levels in the kidney when compared with normoxemic perfused kidneys. Quantitative reverse transcription-polymerase chain reaction also revealed that hypoxemic perfusion produced significant increases in Epo mRNA levels in the kidney, which was blocked by L-NAME. Our findings further support an important role for the NO/cGMP system in hypoxic regulation of Epo production.


Resistance-associated mutations to etravirine (TMC-125) in antiretroviral-naïve patients infected with non-B HIV-1 subtypes.
Susceptibility to etravirine (ETR), an expanded-spectrum nonnucleoside reverse transcriptase inhibitor (NNRTI), is dependent on the type and number of NNRTI resistance-associated mutations (RAMs). Studies have shown that some HIV-1 subtypes may have natural polymorphisms described as ETR RAMs. This study addresses the prevalence of ETR RAMs in treatment-naïve patients infected with HIV-1 non-B subtypes and its potential impact on ETR susceptibility. The prevalence of ETR RAMs in 726 antiretroviral-naïve patients infected with non-B HIV-1 subtypes was studied. ETR genotypic resistance was interpreted according to Agence Nationale de Recherches sur le SIDA and Stanford algorithms. NNRTI phenotypic susceptibilities of samples with at least one ETR RAM were measured. Overall, 75 (10.3%) of 726 sequences harbored at least one ETR RAM: sequences from 72 patients (10%) each had one ETR RAM, and sequences from 3 patients (0.4%) each had two ETR RAMs (V90I and Y181C in one case and V90I and A98G in two cases). None of the viruses had three or more ETR RAMs, and none were consequently classified as resistant to ETR. All sequences with two ETR RAMs belonged to subtype CRF02_AG. The presence of one ETR RAM was statistically more frequent in subtype CRF02_AG than in other non-B subtypes (P=0.004). Three new mutation profiles (E138A and V179I, Y181C and H221Y, and V90I and Y181C) showing decreased ETR phenotypic susceptibility were identified. In conclusion, although the prevalence of ETR RAMs in treatment-naïve patients infected with non-B HIV-1 subtypes was 10%, in most cases this had no significant impact on ETR susceptibility. However, the transmission of drug-resistant viruses with Y181C in a non-B genetic background has a potential for impact on ETR susceptibility.


SHOX in short stature syndromes.
Linear growth is a multifactorial trait that is influenced and regulated by a combination of environmental and internal factors. Among the intrinsic determinants of final body height, genetic factors have become more and more prominent, and the list of genes involved in growth-related processes has been extended accordingly. One of the most exciting additions to this list is represented by the discovery of the pseudoautosomal gene SHOX. Originally described as a gene responsible for idiopathic short stature, it has become clear that SHOX mutations can also cause mesomelic short stature and Madelung deformity in Léri-Weill syndrome. In addition, recent studies implicate SHOX haploinsufficiency in a variety of somatic Turner syndrome stigmata.


Mechanistic Study of the Effects of Agricultural Amendments on Photochemical Processes in Paddy Water during Rice Growth.
The photochemical properties of paddy water might be affected by the commonly used amendments in rice fields owing to the associated changes in water chemistry; however, this important aspect has rarely been explored. We examined the effects of agricultural amendments on the photochemistry of paddy water during rice growth. The amendments significantly influenced the photogenerated reactive intermediates (RIs) in paddy water, such as triplet dissolved organic matter (3DOM*), singlet oxygen, and hydroxyl radicals. Compared with control experiments without amendments, the application of straw and lime increased the RI concentrations by up to 16.8 and 11.1 times, respectively, while biochar addition had limited effects on RI generation from paddy water in in situ experiments under sunlight. Fluorescence emission-excitation matrix spectroscopy, Fourier transform ion cyclotron resonance mass spectrometry, and structural equation modeling revealed that upon the addition of straw and lime amendments, humified DOM substances contained lignins, proteins, and fulvic acids, which could produce more RIs under irradiation. Moreover, the amendments significantly accelerated the degradation rate of 2,4-dichlorophenol but led to the 3DOM*-mediated formation of more toxic and stable dimeric products. This study provides new insights into the effects of amendments on the photochemistry of paddy water and the pathways of abiotic degradation of organic contaminants in paddy fields.


Quantitative proteomics to study carbapenem resistance in Acinetobacter baumannii.
Acinetobacter baumannii is an opportunistic pathogen causing pneumonia, respiratory infections and urinary tract infections. The prevalence of this lethal pathogen increases gradually in the clinical setup where it can grow on artificial surfaces, utilize ethanol as a carbon source. Moreover it resists desiccation. Carbapenems, a β-lactam, are the most commonly prescribed drugs against A. baumannii. Resistance against carbapenem has emerged in Acinetobacter baumannii which can create significant health problems and is responsible for high morbidity and mortality. With the development of quantitative proteomics, a considerable progress has been made in the study of carbapenem resistance of Acinetobacter baumannii. Recent updates showed that quantitative proteomics has now emerged as an important tool to understand the carbapenem resistance mechanism in Acinetobacter baumannii. Present review also highlights the complementary nature of different quantitative proteomic methods used to study carbapenem resistance and suggests to combine multiple proteomic methods for understanding the response to antibiotics by Acinetobacter baumannii.


Folding thermodynamics of pseudoknotted chain conformations.
We develop a statistical mechanical framework for the folding thermodynamics of pseudoknotted structures. As applications of the theory, we investigate the folding stability and the free energy landscapes for both the thermal and the mechanical unfolding of pseudoknotted chains. For the mechanical unfolding process, we predict the force-extension curves, from which we can obtain the information about structural transitions in the unfolding process. In general, a pseudoknotted structure unfolds through multiple structural transitions. The interplay between the helix stems and the loops plays an important role in the folding stability of pseudoknots. For instance, variations in loop sizes can lead to the destabilization of some intermediate states and change the (equilibrium) folding pathways (e.g., two helix stems unfold either cooperatively or sequentially). In both thermal and mechanical unfolding, depending on the nucleotide sequence, misfolded intermediate states can emerge in the folding process. In addition, thermal and mechanical unfoldings often have different (equilibrium) pathways. For example, for certain sequences, the misfolded intermediates, which generally have longer tails, can fold, unfold, and refold again in the pulling process, which means that these intermediates can switch between two different average end-end extensions.


Systemic bevacizumab (Avastin) therapy for exudative neovascular age-related macular degeneration. The BEAT-AMD-Study.
Double-blinded, randomised, prospective, pilot-study to determine the effect of systemic bevacizumab therapy. Subjects with fibrovascular pigment epithelial detachment, subfoveal choroidal neovascularisation extending under the geometric centre of the foveal avascular zone and/or macular thickness of at least 300 microm in both eyes were included. Sixteen eyes were included and randomised equally to receive either three infusions of 5 mg/kg Avastin or 100 ml of 0.9% sodium chloride every 2 weeks. The main outcome measure was the lesion size. The follow-up time was 24 weeks. Throughout the 24-week follow-up, the lesion size and macular thickness decreased in the Avastin group by 0.5 (SD 0.08) mm and 103.6 (14.9) microl respectively. In both groups, visual acuity remained stable in seven eyes and decreased in one eye. At the end of follow-up, 50% of the eyes in the Avastin group became fibrotic, 37.5% remained unchanged, and 12.5% developed a subretinal bleeding. There was a treatable rise in blood pressure after Avastin treatment. Systemic Avastin could be offered to patients with exudative age-related macular degeneration in both eyes and/or patients who refuse intravitreal injections if blood pressure is normal and there is no history of thrombosis.


Overproduction of petunia chloroplastic copper/zinc superoxide dismutase does not confer ozone tolerance in transgenic tobacco.
Transgenic tobacco (Nicotiana tabacum cultivar W38) plants that overproduce petunia chloroplastic Cu/Zn superoxide dismutase were exposed to ozone dosages that injure control tobacco plants. Based on foliar injury ratings, there was no consistent protection provided to the transgenic plants. These data indicate that an increase in the chloroplastic Cu/Zn superoxide dismutase alone is not sufficient to reduce ozone toxicity.


Partial fusion activity of influenza virus toward liposomes and erythrocyte ghosts is distinct from viral inactivation.
Final extents of fusion of influenza virus (A/PR/8/34 strain) with neutral and partially acidic liposomes were monitored with (i) a fluorescence resonance energy-transfer assay in which the liposomes were labeled and (ii) by the dequenching of octadecylrhodamine, initially incorporated in the viral membrane. The latter assay was also employed in the fusion of influenza virus and Sendai virus with erythrocyte ghosts. In all cases, a phenomenon of partial fusion activity of the virus was observed, which is distinct from low pH inactivation. The unfused influenza or Sendai virions, which were separated by sucrose gradient centrifugation from liposomes or erythrocyte ghosts exhibited again partial fusion activity toward freshly added liposomes or ghosts, respectively. The conclusion is that the fraction of initially bound and unfused virions does not consist of defective particles, but rather of particles bound to the target membranes via inactive sites on the virus (or on cellular membranes), or else, partial fusion activity is a manifestation of a certain probability of production of fusion inactive sites by irreversible association of viral glycoproteins or peptides in the target membrane.


Noncoding RNAs Interplay in Ovarian Cancer Therapy and Drug Resistance.
Noncoding RNAs (ncRNAs) are several types of RNA that do not encode proteins, but are essential for cell regulation. Ovarian cancer (OC) is a type of gynecological cancer with a high mortality rate and a 5-year prognosis. OC is becoming more common with each passing year, and the symptoms of early-stage OC are sometimes undetectable. Meanwhile, early-stage OC has no symptoms and is difficult to diagnose. Because ncRNA has been shown to affect the development of OC and is widely distributed, it could be employed as a new biomarker for early OC. Furthermore, ncRNA has the potential to promote or inhibit drug resistance in OC, potentially giving a solution to multiple drug resistance. Various prior studies have found that different ncRNAs perform differently in OC. This article examines how mainstream ncRNAs have been expressed in OC in recent years, as well as their function in tumor growth.


Phytochemical composition of "mountain tea" from Sideritis clandestina subsp. clandestina and evaluation of its behavioral and oxidant/antioxidant effects on adult mice.
The goals of this study were to monitor the effect of drinking of herbal tea from Sideritis clandestina subsp. clandestina for 6 weeks on behavioral and oxidant/antioxidant parameters of adult male mice and also to evaluate its phytochemical composition. The phytochemical profile of the Sideritis tea was determined by liquid chromatography-UV diode array coupled to ion-trap mass spectrometry with electrospray ionization interface. The effects of two doses of the herbal infusion (2 and 4% w/v, daily) intake on anxiety-like state in mice were studied by the assessment of their thigmotactic behavior. The oxidant/antioxidant status of brain (-Ce), liver and heart of adult male Balb-c mice following the consumption of Sideritis tea was also evaluated via the measurement of malondialdehyde (MDA) and reduced glutathione (GSH) levels using fluorometric assays. Our study was further extended to determine the antioxidant effects of the herbal tea on specific brain regions (cerebral cortex, cerebellum and midbrain). The identified compounds were classified into several natural product classes: quinic acid derivatives, iridoids, phenylethanol glycosides and flavonoids. Our results showed that only the 4% Sideritis tea exhibited anxiolytic-like properties as evidenced by statistically significant (p < 0.05) decrease in the thigmotaxis time and increase in the number of entries to the central zone in comparison with the control group. Consumption of both tea doses (2 and 4% w/v) elevated GSH (12 and 28%, respectively, p < 0.05) and decreased MDA (16 and 29%, p < 0.05) levels in brain (-Ce), while liver and heart remained unaffected. In regard to the effect of herbal tea drinking (2 and 4% w/v) on specific brain regions, it caused a significant increase in GSH of cerebellum (13 and 36%, respectively, p < 0.05) and midbrain (17 and 36%, p < 0.05). Similarly, MDA levels were decreased in cerebellum (45 and 79%, respectively, p < 0.05) and midbrain (50 and 63%, respectively, p < 0.05), whereas cerebral cortex remained unaffected. Mountain tea drinking prevents anxiety-related behaviors and confers antioxidant protection to rodent's tissues in a region-specific, dose-dependent manner, and its phytochemical constituents are shown for the first time.


Binding of calcium and carbonate to polyacrylates.
Polyacrylate molecules can be used to slow the growth of calcium carbonate. However, little is known about the mechanism by which the molecules impede the growth rate. A recent computational study (Bulo et al. Macromolecules 2007, 40, 3437) used metadynamics to investigate the binding of calcium to polyacrylate chains and has thrown some light on the coiling and precipitation of these polymers. We extend these simulations to examine the binding of calcium and carbonate to polyacrylate chains. We show that calcium complexed with both carbonate and polyacrylate is a very stable species. The free energies of calcium-carbonate-polyacrylate complexes, with different polymer configurations, are calculated, and differences in the free energy of the binding of carbonate are shown to be due to differences in the amount of steric hindrance about the calcium, which prevents the approach of the carbonate ion.


[Application of meticulous capsular dissection technique in thyroidectomy].
To explore the application of meticulous capsular dissection techique in thyroidectomy. Forty four cases of thyroid operation in 38 patients were analyzed retrospectively. Meticulous capsular dissection in thyroidectomy could protect recurrent laryngeal nerve and parathroid gland. Of all the 44 cases, no one experienced postoperatively hypocalcemia. The recurrent laryngeal nerves were found. No one suffered from laryngeal nerve injury except 1 case with postoperative horseness. The meticulous capsular dissection techique plays a key role in ensuring the safety of thyroidectomy.


The first Alzheimer disease case: a metachromatic leukodystrophy?
A reconsideration of the original report of Alzheimer and of the description of case 1 by Perusini in 1908, published in 1910, suggests that they were describing the same case. Both the temporal evidence and the clinical description make this conclusion inescapable. The histopathology of this first case shows some features that are not characteristic of the histological pattern of the modern Alzheimer, namely demyelination of the central white matter and metachromatic deposits in the spinal cord.


Urologic applications of botulinum toxin.
The neuromuscular blocker botulinum toxin has a wide variety of medical applications, including overactive bladder and neurogenic detrusor overactivity in patients in whom drug therapy fails or is not well tolerated. Botulinum toxin therapy for these conditions has been shown to be safe and effective in several large multicenter randomized controlled trials. Off-label uses in urology include detrusor external sphincter dyssynergia and pelvic pain syndromes.


The Psychometric Properties of the Patient Health Questionnaire-4 for Pregnant Women.
Background: Perinatal anxiety and depression are common complications during pregnancy. The purpose of this study was to examine the item characteristics, reliability, validity, and factorial structure of the four-item Patient Health Questionnaire-4 (PHQ-4) and to determine the associations between scale scores and sociodemographic factors in a sample of pregnant women from Spain. Method: A total of 845 pregnant women were recruited from two public hospitals in Spain between 2014 and 2016. Participants completed a self-report questionnaire that included Patient Health Questionnaire-4, including the two-item Patient Health Questionnaire and the two-item Generalized Anxiety Disorder Screener. Results: Exploratory and confirmatory factor analysis and scale inter-correlations between the PHQ-4 and PHQ-9 revealed that the PHQ-4 has a bivariate structure and adequately assesses the dimensions of antenatal anxiety and depression. Conclusion: The PHQ-4 is a reliable and valid instrument to screen for depression and anxiety during pregnancy. The PHQ-4 is an ultra-brief measure that can be used to screen for antenatal depression and anxiety to prevent the negative consequences associated with these mental health conditions among mothers and infants.


Cerebellum size is related to fear memory and domestication of chickens.
Red Junglefowl (Gallus gallus) were selected for divergent levels of fear of humans during eight generations, causing the selection lines to differ in fear levels as well as in the proportional brain and cerebellum masses. Birds from the two lines were then crossed to obtain an F3 intercross in order to study the correlations between brain mass and fear learning. We exposed 105 F3-animals individually to a fear habituation and memory test at 8 days of age, where the reactions to repeated light flashes were assessed on 2 consecutive days. After culling, the absolute and relative sizes of each of four brain regions were measured. Stepwise regression was used to analyse the effects of the size of each brain region on habituation and memory. There were no effects of any brain region on the habituation on day one. However, birds with a larger absolute size of cerebellum had significantly reduced reactions to the fearful stimuli on day two, indicating a better memory of the stimuli. No other regions had significant effects. We conclude that increased cerebellum size may have been important in facilitating chicken domestication, allowing them to adapt to a life with humans.


The full spectrum of climate change adaptation: testing an analytical framework in Tyrolean mountain agriculture (Austria).
Our scientific view on climate change adaptation (CCA) is unsatisfying in many ways: It is often dominated by a modernistic perspective of planned pro-active adaptation, with a selective focus on measures directly responding to climate change impacts and thus it is far from real-life conditions of those who are actually affected by climate change. Farmers have to simultaneously adapt to multiple changes. Therefore, also empirical climate change adaptation research needs a more integrative perspective on real-life climate change adaptations. This also has to consider "hidden" adaptations, which are not explicitly and directly motivated by CCA but actually contribute to the sector's adaptability to climate change. The aim of the present study is to develop and test an analytic framework that contributes to a broader understanding of CCA and to bridge the gap between scientific expertise and practical action. The framework distinguishes three types of CCA according to their climate related motivations: explicit adaptations, multi-purpose adaptations, and hidden adaptations. Although agriculture is among the sectors that are most affected by climate change, results from the case study of Tyrolean mountain agriculture show that climate change is ranked behind other more pressing "real-life-challenges" such as changing agricultural policies or market conditions. We identified numerous hidden adaptations which make a valuable contribution when dealing with climate change impacts. We conclude that these hidden adaptations have not only to be considered to get an integrative und more realistic view on CCA; they also provide a great opportunity for linking adaptation strategies to farmers' realities.


How to help your staff strengthen customer service: a do-able approach.
In today's high-pressure, speed-oriented environment, health-care managers face the challenge of helping their staff achieve a higher level of customer service without overwhelming them. Although raising the bar on customer service is crucial to stay competitive, if managers expect staff to institute many customer service improvements at once, staff often respond with confusion, frustration, and resistance. Then results are disappointing, and managers flounder in their efforts to inspire staff to stretch toward higher standards. By prioritizing customer service goals and selecting one goal at a time as the focus, you and your team can institute and sustain improvements successfully. Whether the goal is improving "meeting and greeting," response time, handling complaints more effectively, providing better instructions, or other customer service goals, the one-goal-at-a-time focus makes it possible for staff to understand the desired change, embrace it, learn it, practice it, and savor positive results. By following a simple 6-step process and applying this same process to one goal after another, staff become familiar with the process and it becomes easier to apply in pursuit of future goals. The result: a higher return on the investment of your efforts and your staff's precious time and attention.


Doping and thrombosis in sports.
Historically, humans have long sought to enhance their "athletic" performance to increase body weight, aggressiveness, mental concentration and physical strength, contextually reducing fatigue, pain, and improving recovery. Although regular training is the mainstay for achieving these targets, the ancillary use of ergogenic aids has become commonplace in all sports. The demarcation between ergogenic aids and doping substances or practices is continuously challenging and mostly based on perceptions regarding the corruption of the fairness of competition and the potential side effects or adverse events arising from the use of otherwise unnecessary ergogenic substances. A kaleidoscope of side effects has been associated with the use of doping agents, including behavioral, skeletal, endocrinologic, metabolic, hemodynamic, and cardiovascular imbalances. Among the various doping substances, the most striking association with thrombotic complications has been reported for androgenic anabolic steroids (i.e., cardiomyopathy, fatal and nonfatal arrhythmias, myocardial infarction [MI], intracardiac thrombosis, stroke, venous thromboembolism [VTE], limb arterial thrombosis, branch retinal vein occlusion, cerebral venous sinus thrombosis) and blood boosting (i.e., VTE and MI, especially for epoetin and analogs). The potential thrombotic complication arising from misuse of other doping agents such as the administration of cortisol, growth hormone, prolactin, cocaine, and platelet-derived preparations is instead speculative or anecdotal at best. The present article provides an overview on the epidemiological association as well as the underlying biochemical and biological mechanisms linking the practice of doping in sports with the development of thrombosis.


Cloning and characterization of the beta subunit of human proximal sequence element-binding transcription factor and its involvement in transcription of small nuclear RNA genes by RNA polymerases II and III.
The proximal sequence element (PSE)-binding transcription factor (PTF), which binds the PSE of both RNA polymerase II- and RNA polymerase III-transcribed mammalian small nuclear RNA (snRNA) genes, is essential for their transcription. We previously reported the purification of human PTF, a complex of four subunits, and the molecular cloning and characterization of PTF gamma and delta subunits. Here we describe the isolation and expression of a cDNA encoding PTF beta, as well as functional studies using anti-PTF beta antibodies. Native PTF beta, in either protein fractions or a PTF-Oct-1-DNA complex, can be recognized by polyclonal antibodies raised against recombinant PTF beta. Immunodepletion studies show that PTF beta is required for transcription of both classes of snRNA genes in vitro. In addition, immunoprecipitation analyses demonstrate that substantial and similar molar amounts of TATA-binding protein (TBP) and TFIIIB90 can weakly associate with PTF at low salt conditions, but this association is dramatically reduced at high salt concentrations. Along with our previous demonstration of both physical interactions between PTF gamma/PTF delta and TBP and the involvement of TFIIIB90 in the transcription of class III snRNA genes, these results are consistent with the notion that a TBP-containing complex related to TFIIIB is required for the transcription of class III snRNA genes, and acts through weak interaction with the four-subunit PTF.


[Ultrastructure of human normal and pathological reassembled collagen fibers].
It is possible, in vitro, to break down human skin then reassemble the collagen fibres of the dermis, essentially type I collagen. The authors have developed a biophysical process for the manufacture of type I autocollagen. They present the electron microscopic study of this collagen. These healthy collagen fibres are compared with the fibres obtained from radiation dermatitis skin and keloid scars. Major ultrastructural differences are demonstrated.


Mechanisms of gastric mucosal injury and protection.
This article emphasizes and reviews the premise that because the pathogenesis of acute gastric mucosal injury is multifactorial, several protective mechanisms should also be considered in analyzing gastric mucosal defense. The first part of the article reviews the pathogenesis of acute gastric mucosal injury by major etiologic factors such as hypoxia and chemical and biological agents, and emphasizes the common endogenous mediators of damage (e.g, endothelins, leukotrienes, thromboxane, platelet-activating factor, monoamines, free radicals, proteases, ammonia, hydrochloric acid, and bile acids--in decreasing potency). The second part of the review is devoted to the gastroprotective mechanisms that are analyzed by anatomical (histologic) location and biochemical processes. The endogenous mediators of acute gastroprotection include prostaglandins, sulfhydryl (SH) compounds, non-SH antioxidants, polyamines, and epidermal growth factor, whereas the protective and mediatory role of glucocorticoids, somatostatin, pentagastrin, histamine, gangliosides, and calcitonin gene-related peptide need further studies. A list of endogenous and exogenous chemicals that exert biphasic, damaging, and protective effects on the gastric mucosa in also included. The final common pathway of acute gastroprotection at the structural and functional level seems to be the preservation of subepithelial microvascular integrity leading to maintenance of mucosal blood flow that allows the energy-dependent rapid restitution (cell migration) from surviving gastric neck cells to repair the superficial epithelial defect. Very new data on the contribution of a histodilutional barrier and release of proteases to gastroprotective processes are also discussed.


The eyes and ears of status: how status colors perceptual judgment.
To those with high status, abundance is granted. Moving beyond the multitude of objective benefits, the authors explore how status, once conferred, colors the perceptual world people inhabit. In four experiments, participants' status state influenced their judgments of status-relevant features in their environment. Participants in a state of high status reported hearing applause (Experiment 1) and seeing facial expressions (Experiment 2), in reaction to their performance, as louder and more favorable. In addition, expectations of how others will respond--expectations stemming from one's current status state--accounted for this effect (Experiment 3). Finally, differences in judgments between participants experiencing high versus low status were observed only when the target of the evaluation was the self (Experiment 4). These results advance scholars' understanding of the psychological experience of status and contribute to the growing literature on the dominant influence psychological states have on people's judgments of their social world.


A porcine model of selective retinal capillary closure induced by embolization with fluorescent microspheres.
To investigate the feasibility of creating an animal model of selective retinal capillary closure to mimic the capillary closure that occurs in diabetic retinopathy. Fluorescent microspheres of 10- or 15-μm diameter were delivered to one eye of anesthetized pigs via a customized cannula advanced through the carotid arterial system to the origin of the external ophthalmic artery that supplies blood to the eye in this species. After preliminary trials in 10 pigs, embolization was performed in one eye of 34 animals that were allowed to survive for 7, 14, or 28 days. Embolized eyes were assessed by fluorescein angiography, electroretinography (ERG), and, after enucleation, light (LM) and electron (EM) microscopy. The microspheres were detectable in the retina immediately after embolization, were restricted to the nerve fiber layer of the retina, and remained thereafter within the retina for periods up to 28 days. They effectively occluded embolized capillaries and some precapillary arterioles. No systemic or cerebral adverse effects were noted, thus allowing survival and subsequent follow-up. Embolization caused a reduction in the b-wave amplitude and the oscillatory potentials of the rod-cone bright-flash ERG but did not affect the amplitude of the a-wave. Embolization induced extracellular and intracellular edema confined to the inner and mid retina, and as a result the retinas of embolized eyes were thicker than those of fellow, nonembolized eyes. The outer retina and RPE were unaffected. This survival model of retinal embolization with microspheres should be useful in the study of the retinal effects of the capillary closure that may occur in diabetic eyes.


Pharmacological chaperone design for reducing risk factor of Parkinson's disease from traditional chinese medicine.
Dysfunction of β -glucocerebrosidase (GCase) has no hydrolytic activity in patients of Gaucher's disease and increasing the risk factor for Parkinson's disease occurrence. Pharmacological chaperone design has been used to treat with misfolded protein in related disease, which utilized a small compound to cause protein folding correctly. This study employed the world largest traditional Chinese medicine (TCM) database for searching for potential lead compound as pharmacological chaperone, and we also performed molecular dynamics (MD) simulations to observe the stability of binding conformation between ligands and active site of GCase structure. The docking results from database screening show that N-methylmescaline and shihunine have high binding ability to GCase than tetrahydroxyazepanes. From MD simulation analysis, tetrahydroxyazepanes displayed high opportunity of ligand migration instead of our TCM candidates, and H-bonds number was decreased in the end of MD snapshot. Our result indicated that binding conformation of N-methylmescaline and shihunine remains stable during MD simulation, demonstrating that the two candidates are suitable for GCase binding and might be potential as pharmacological chaperone for GCase folding correctly.


Analysis of non-covalent protein complexes up to 290 kDa using electrospray ionization and ion trap mass spectrometry.
Non-covalently-bound subunit complexes of proteins have been measured by an ion trap mass spectrometer equipped with an orthogonal electrospray ionization source. For the analysis of the generated molecular ions with high mass/charge ratios, the mass/charge range of the ion trap was extended by increasing its radio frequency (rf) voltage to 15 kV (V(0-p)) and by resonant ion ejection. Ions of the non-covalent dimer of bovine serum albumin (BSA), as well as of subunit complexes of alcohol dehydrogenase (ADH) from bakers' yeast and from horse liver, have been detected at mass/charge values between 3000-9000 Th. The maximum observed molecular weight was that of a non-covalently-bound subunit-octamer of bakers' yeast ADH (two non-covalently-bound subunit-tetramers) at ca. 290 kDa.


Cluster Fusion: Face-Fused Nine-Atom Deltahedral Clusters in [Sn14 Ni(CO)](4.).
The title anion was synthesized by heating dimethylformamide (DMF) solution of the known Ni-centered and Ni(CO)-capped tin clusters [Ni@Sn9 Ni(CO)](3-) . The new anion represents the first example of face-fused nine-atom molecular clusters. The two clusters are identical elongated tricapped trigonal prisms of nido-[Sn8 Ni(CO)](6-) with nickel at one of the capping positions. They are fused along a triangular face adjacent to a trigonal prismatic base and made of two Sn and one Ni atoms. The new anion is structurally characterized by single-crystal X-ray diffraction in the compound (K[222-crypt])4 [Sn14 Ni(CO)]⋅DMF. Its presence in solution is corroborated by electrospray mass spectrometry.


Healthcare utilisation among patients discharged from hospital after intensive care.
Surviving critical illness can be life-changing and presents new healthcare challenges for patients after hospital discharge. This feasibility study aimed to examine healthcare service utilisation for patients discharged from hospital after intensive care unit stay. Following Ethics Committee approval, patients aged 18 years and older were recruited over three months. Those admitted after cardiac surgery, discharged to another facility or against medical advice were excluded. Patients were informed of the study by post and followed-up by telephone at two and six months after discharge. General practitioners were also contacted (44% responded). Among 187 patients discharged from hospital, 11 died, 25 declined to participate and 39 could not be contacted. For 112 patients (60%) who completed a survey, the majority (82%) went home from hospital and were cared for by their partner (53%). More than half of the patients (58%) reported taking the same number of medications after intensive care unit stay but 30% took more (P = 0.023). While there was no change in the number of visits to the general practitioner for 64% of patients, 29% reported an increase after intensive care unit stay. At six months, 40% of responders who were not retired were unemployed. Discharge summary surveys revealed 39 general practitioners (71%) were satisfied with details of ongoing healthcare needs. Twenty-one general practitioners wrote comments: 10 reported insufficient information about ongoing needs/rehabilitation and two reported no mention of intensive care unit stay. Survivors of critical illness had increased healthcare needs and despite most returning home, had a low workforce participation rate. This requires further investigation to maximise the benefits of survival from critical illness.


Human-Body-Temperature Triggerable Phase Transition of W-VO2@PEG Nanoprobes with Strong and Switchable NIR-II Absorption for Deep and Contrast-Enhanced Photoacoustic Imaging.
The immense potential of temperature-responsive nanomaterials for use as contrast agents has propelled much recent research and development in the field of photoacoustic (PA) imaging, while the exorbitant transition temperature exceeding the human-tolerable range and the low reversibility of the reported temperature-sensitive nanosystems are still two severe issues that hinder effective imaging and long-term monitoring in practical applications. Herein, we propose a high-performing thermoresponsive polyethylene glycol-coated tungsten-doped vanadium dioxide (W-VO2@PEG) nanoprobe (NP) with strong and switchable optical absorption in the near-infrared-II (NIR-II) biowindow (1000-1700 nm) near human-body temperature, to achieve deep and contrast-enhanced PA imaging. Our study shows that the PA signal amplitude of W-VO2@PEG NPs at 1064 nm increases up to 260% when the temperature increases from 35 °C to 45 °C, with a signal fluctuation of less than 10% after 10 temperature cycles, therefore enabling great potential of "off-to-on" dynamic contrast-enhanced imaging capability in deep-seated tissues. Experiments on tissue-mimicking phantoms and in vitro chicken breast showed that, by levering the prepared W-VO2@PEG NPs and dynamically modulating the temperature field with an external NIR optical stimulus, contrast-enhanced PA images of the target can be obtained with an imaging depth up to 1.5 cm. Furthermore, in vivo potential of the prepared thermoresponsive NPs for the detection and identification of deep-seated tumors by directly comparing to conventional "always on" NPs has been demonstrated. Our work will offer feasible guidance for the development of smart temperature-activatable PA NPs with improved imaging depth and imaging contrast.


Food safety knowledge, attitude, and practice toward compliance with abattoir laws among the abattoir workers in Malaysia.
Foodborne diseases are common in the developing countries due to the predominant poor food handling and sanitation practices, particularly as a result of inadequate food safety laws, weak regulatory structures, and inadequate funding as well as a lack of appropriate education for food-handlers. The most frequently involved foods in disease outbreaks are of animal origin. However, in spite of the adequate legislation and laws governing the abattoir operation in Malaysia, compliance with food safety requirements during meat processing and waste disposal is inadequate. Therefore, the present study was designed to assess the food safety knowledge, attitude, and practice toward compliance with abattoir laws among the workers in Terengganu, Malaysia. A cross-sectional survey was conducted using simple random sampling technique in the six districts of Terengganu: two districts were used for the pilot study and the remaining four were used for the main study. One hundred sixty-five abattoir workers from the selected districts were interviewed using a structured questionnaire. The mean and standard deviation of knowledge, attitude, and practice scores of the workers were 6.02 and 1.954, 45.16 and 4.496, and 18.03 and 3.186, respectively. The majority of the workers (38.8%) had a low level of knowledge and 91.7% had a positive attitude, while 77.7% had a good practice of compliance. Sex had a significant association with the level of knowledge (P<0.001) and practice (P=0.044) among the workers. The females had a higher level of knowledge than the males, while the males had a better practice of compliance than females. Similarly, knowledge also had a significant (P=0.009) association with the level of practice toward compliance with abattoir laws among the workers. The abattoir workers had a positive attitude and good practice, but a low level of knowledge toward compliance with the abattoir laws. Therefore, public awareness, workshops, and seminars relevant to the abattoir operations should be encouraged.


Effect of differential rearing on synapses and soma size in rat medial amygdaloid nucleus.
The effects of differential rearing on synaptic morphology and neuronal size were examined in the medial amygdaloid nucleus (MAN) of adult rats. Forty-day-old male rats were housed in one of three ways: individually (isolated condition, IC); with four males per cage (unisexual condition, UC); or with two males and two females per cage (social condition, SC). After 2 months, the animals were prepared for electron and light microscopy. Although there was no statistically significant difference in number of synapses per unit volume in MAN, the number of perforated (P) synapses, which are characterized by discontinuities in the postsynaptic density, were significantly greater in the UC and the SC than in the IC. The length of synaptic contact zone of P synapses was also longer in both the UC and the SC compared with the IC, whereas the length of nonperforated synapses was longer only in the SC. Soma area was also larger in the SC compared with the IC. These results demonstrate that exposure to different rearing conditions, in which the pheromonal environment can be substantially different, can induce striking morphological changes in both synapses and neurons in the MAN of adult rats.


Management of Gram-Negative Bloodstream Infections in the Era of Rapid Diagnostic Testing: Impact With and Without Antibiotic Stewardship.
Verigene Blood-Culture Gram-Negative is a rapid diagnostic test (RDT) that detects gram-negatives (GNs) and resistance within hours from gram stain. The majority of the data support the use of RDTs with antimicrobial stewardship (AMS) intervention in gram-positive bloodstream infection (BSI). Less is known about GN BSI. This was a retrospective quasi-experimental (nonrandomized) study of adult patients with RDT-target GN BSI comparing patients pre-RDT/AMS vs post-RDT/pre-AMS vs post-RDT/AMS. Optimal therapy was defined as appropriate coverage with the narrowest spectrum, accounting for source and co-infecting organisms. Time to optimal therapy was analyzed using Kaplan-Meier and multivariable Cox proportional hazards regression. Eight-hundred thirty-two patients were included; 237 pre-RDT/AMS vs 308 post-RDT/pre-AMS vs 237 post-RDT/AMS, respectively. The proportion of patients on optimal antibiotic therapy increased with each intervention (66.5% vs 78.9% vs 83.2%; P < .0001). Time to optimal therapy (interquartile range) decreased with introduction of RDT: 47 (7.9-67.7) hours vs 24.9 (12.4-55.2) hours vs 26.5 (10.3-66.5) hours (P = .09). Using multivariable modeling, infectious diseases (ID) consult was an effect modifier. Within the ID consult stratum, controlling for source and ICU stay, compared with the pre-RDT/AMS group, both post-RDT/pre-AMS (adjusted hazard ratio [aHR], 1.34; 95% CI, 1.04-1.72) and post-RDT/AMS (aHR, 1.28; 95% CI, 1.01-1.64), improved time to optimal therapy. This effect was not seen in the stratum without ID consult. With the introduction of RDT and AMS, both proportion and time to optimal antibiotic therapy improved, especially among those with an existing ID consult. This study highlights the beneficial role of RDTs in GN BSI.


Criminal Code, 5 December 1986.
Under this Code, performing an illegal abortion or causing a woman to have an abortion are serious offenses reflecting the Mongolian State's interest in population growth. Abortions are allowed only in circumstances specified by medical authorities. The Code also provides for punishment for the use of coercion to force a woman to marry or to prevent her from marrying and for the obstruction of women's equal rights.


Impact of 60 days of head-down bed rest on large arteries.
The long-term cardiovascular consequences of microgravity on large arteries are a threat for long-term space missions. We hypothesized that changes in arterial properties differ according to the arterial territory (upper or lower body), and arterial structure (elastic vs. muscular arteries), in response to 60-day head-down bed rest (HDBR). Twenty healthy male volunteers were included and received a daily multivitamin supplementation in a double-blind fashion. At baseline, 29 and 52 days during strict HDBR, then 12 and 30 days after HDBR, aortic stiffness was measured using carotid-to-femoral pulse wave velocity (cf-PWV) and aortic MRI. Carotid, femoral, brachial and popliteal arteries were studied by ultrasound echo tracking, central blood pressure (BP) by tonometry and endothelial function by flow-mediated dilatation. Cf-PWV increased during HDBR (+0.8 and +1.1m/s, at D29 and D52, respectively, P = 0.004), corresponding to an increase in vascular age up to +11 years (P = 0.003). Changes were similar to those observed on MRI (+0.8 m/s at D52, P < 0.01) and were independent of BP and heart rate changes. After HDBR, cf-PWV showed a substantial recovery at R12 but still remained higher than baseline at R30 (+0.8 m/s, P = 0.018), corresponding to +6.5 years of vascular aging (P = 0.018). Thoracic aorta diameter increased significantly (+6%, P = 0.0008). During HDBR, femoral and popliteal arteries showed dimensional changes, leading to femoral inward hypotrophic remodeling (femoral diameter: -12%, P < 0.05; wall cross-sectional area: -25%, P = 0.014) and popliteal inward eutrophic remodeling (popliteal diameter: -25%, P < 0.05; wall cross-sectional area: -3%, P = 0.51). After HDBR, both arterial territories of the leg recovered. We did not observe any significant changes for carotid arteries nor for endothelial function during and after HDBR. Multivitamin supplementation did not affect vascular changes. HDBR was associated with an important increase in aortic stiffness, which did not completely recover 1 month after the end of HDBR. The thoracic aorta and the lower body muscular arteries underwent significant changes in dimensions whereas the common carotid arteries were preserved. These results should raise caution for those exposed to microgravity, real or simulated.


The biomechanics of the fastest sprinter with a unilateral transtibial amputation.
People have debated whether athletes with transtibial amputations should compete with nonamputees in track events despite insufficient information regarding how the use of running-specific prostheses (RSPs) affect athletic performance. Thus, we sought to quantify the spatiotemporal variables, ground reaction forces, and spring-mass mechanics of the fastest athlete with a unilateral transtibial amputation using an RSP to reveal how he adapts his biomechanics to achieve elite running speeds. Accordingly, we measured ground reaction forces during treadmill running trials spanning 2.87 to 11.55 m/s of the current male International Paralympic Committee T44 100- and 200-m world record holder. To achieve faster running speeds, the present study's athlete increased his affected leg (AL) step lengths ( P < 0.001) through longer contact lengths ( P < 0.001) and his unaffected leg (UL) step lengths ( P < 0.001) through longer contact lengths ( P < 0.001) and greater stance average vertical ground reaction forces ( P < 0.001). At faster running speeds, step time decreased for both legs ( P < 0.001) through shorter ground contact and aerial times ( P < 0.001). Unlike athletes with unilateral transtibial amputations, this athlete maintained constant AL and UL stiffness across running speeds ( P ≥ 0.569). Across speeds, AL step lengths were 8% longer ( P < 0.001) despite 16% lower AL stance average vertical ground reaction forces compared with the UL ( P < 0.001). The present study's athlete exhibited biomechanics that differed from those of athletes with bilateral and without transtibial amputations. Overall, we present the biomechanics of the fastest athlete with a unilateral transtibial amputation, providing insight into the functional abilities of athletes with transtibial amputations using running-specific prostheses. NEW & NOTEWORTHY The present study's athlete achieved the fastest treadmill running trial ever attained by an individual with a leg amputation (11.55 m/s). From 2.87 to 11.55 m/s, the present study's athlete maintained constant affected and unaffected leg stiffness, which is atypical for athletes with unilateral transtibial amputations. Furthermore, the asymmetric vertical ground reaction forces of athletes with unilateral transtibial amputations during running may be the result of leg length discrepancies.


Sensitive through-space dipolar correlations between nuclei of small organic molecules by partial alignment in a deuterated liquid solvent.
Through-space residual dipolar correlations in NMR spectra can be measured between nuclei of small organic molecules by partially aligning them with respect to the magnetic field in a pure deuterated liquid solvent, 4-pentyl-4'-cyanobiphenyl. A simple temperature change of this liquid phase enables spectra to be compared between samples under isotropic tumbling conditions and weakly oriented anisotropic states. This should provide access of a number of small nonpolar molecules to more sensitive through-space nuclear correlations than possible through NOE experiments, depending on the net orientation of specific nuclear pairs with respect to the magnetic field and the specific coherence transfers employed.


Horse liver alcohol dehydrogenase-catalyzed oxidation of aldehydes: dismutation precedes net production of reduced nicotinamide adenine dinucleotide.
The oxidation of aldehydes by horse liver alcohol dehydrogenase (HL-ADH) is more complex than previously recognized. At low enzyme concentrations and/or high aldehyde concentrations, a pronounced lag in the assay progress curve is observed when the reaction is monitored for NADH production at 340 nm. When the progress of the reaction is followed by 1H NMR spectroscopy, rapid dismutation of the aldehyde substrate into the corresponding acid and alcohol is observed during the lag phase. Steady-state production of NADH commences only after aldehyde concentrations drop below 5% of their initial value; thereafter, NADH production occurs with continuous adjustment of the equilibrium between aldehyde, alcohol, NADH, and NAD+. The steady-state NADH production exhibits normal Michaelis-Menten kinetics and is in accord with earlier studies using much higher enzyme concentrations where no lag phase was reported. These results establish that the ability of HL-ADH to oxidize aldehydes is much greater than previously thought. The relationship between aldehyde dismutase and aldehyde dehydrogenase activities of HL-ADH is discussed.


Recruiting underrepresented individuals in a double pandemic: Lessons learned in a randomized control trial.
The Building Up Trial is a cluster-randomized trial that aims to address the issue of the leaky career pathway for underrepresented (UR) faculty in biomedical fields. Regulatory approval and recruitment for the Building Up Trial took place during the COVID-19 pandemic and the anti-racism movement. The pandemic and anti-racism movement personally and professionally impacted the target population and made recruitment challenging at both the institution and participant level. The target sample size for this study was 208 postdoctoral fellows or early-career faculty across 26 predominately white institutions. Challenges and adaptations are described. The Building Up Trial was delayed by 3 months. In total, 225 participants from 26 institutions were enrolled. Participants are predominately female (80%), Hispanic/Latinx (34%) or non-Hispanic/Latinx Black (33%), and early-career faculty (53%). At the institution level, obtaining Institutional Review Board (IRB) approval through a single Institutional Review Board (sIRB) posed the biggest challenge. We adapted to COVID-19-related challenges through simplifying sIRB forms, modifying study practices, and increasing communication with institutions. Recruiting UR postdoctoral fellows and faculty during the COVID-19 pandemic and anti-racism movement was challenging but not impossible. Studies should be prepared to modify study and recruitment policies to overcome additional barriers posed by the pandemics.


Mechanisms for the regulation of memory B-cell recall responses in mice.
Upon infection by pathogens or vaccination, the adaptive immune system rapidly but transiently produces antibodies. Some weeks later, however, long-lasting immunity is established that protects the host against the same pathogens almost for life through continuous production of antibodies on one hand and the maintenance of cytotoxic T cells on the other, collectively called immunological memory. The antibody-mediated arm, also called serological memory, is mainly exerted by long-lived plasma cells and memory B cells (MBCs). MBCs express receptors for the specific pathogens and circulate to survey the body for almost a life-long period. Upon recognizing the pathogen, MBCs clonally expand and produce a large amount of the specific antibodies to stop the infection, the process called a (memory) recall response. Although such a function of MBCs has long been known, the mechanism of how their performance is regulated has been obscure. This is due to their paucity in the body, lack of definitive surface markers and obscure ontogeny. However, recent studies have revealed the multifold mechanisms by which the recall response of MBCs is regulated: rapid and enhanced antibody production is due to a mechanism intrinsic to MBCs, namely, up-regulated expression levels of surface molecules interacting with T cells and the property of IgG-class antigen receptors; to a property of the responsible subset of MBCs; and to co-stimulation through innate receptors and cytokines. It has also been unveiled that the recall response is negatively regulated by an inhibitory receptor on MBCs and by antigens with repetitive epitopes.


Heart rate and workload variations in actual and simulated flight.
The monitoring of heart rate in aviation research provides a global index of pilot workload. Heart rate variability is a promising measure but more complex to assess and therefore less often used, especially in dynamic task environments. The application of spectral analysis techniques of heart rate for workload assessment in aviation is illustrated and discussed. Ideally, workload assessment includes real-time or continuous measures to reveal variations in workload as pilots accomplish their tasks. Four studies are discussed that used heart rate measures for the assessment of: (1) training effectiveness; (2) stress of flight instruction; (3) simulator realism; and (4) flight task difficulty. Results indicate that cardiovascular measures are well suited to index different mental states of pilots as well as their dynamic responses to variations in workload.


Clinical Utility of Pharmacogenetic Testing and a Clinical Decision Support Tool to Enhance the Identification of Drug Therapy Problems Through Medication Therapy Management in Polypharmacy Patients.
In polypharmacy patients, medication therapy management (MTM) services provide a comprehensive review of current medications and future treatment goals. Pharmacogenetics (PGx) may further optimize the identification of potential drug therapy problems (DTPs); however, the clinical utility of PGx information with a clinical decision support tool (CDST) in an MTM setting in identifying DTPs has not been systematically assessed. To assess the clinical utility of an MTM service enhanced by pharmacogenetic test results and a clinical decision support tool. This study was a post hoc analysis of the data obtained from an open-label, randomized, observational trial. Polypharmacy patients eligible for MTM service were randomly assigned to 3 intervention arms: standard MTM (SMTM), MTM incorporating CDST (CMTM), and CMTM further enhanced by PGx test results of CYP450 and VKORC1 enzymes (PGxMTM). Allocation for this post hoc analysis was based on patient adherence to the research protocol and completion of a PGx test. The number of DTPs per patient was compared across the 3 arms using analysis of variance. In addition, the frequency of serious DTPs as a categorical variable (grade 3 or above vs. lower grade) was compared across the 3 arms between PGx driven and non-PGx driven DTP recommendations. Statistical significance was tested using the chi-square test. The level of agreement between the DTP seriousness and the acceptance made by prescribers was presented as Cohen's kappa coefficient. Numbers of patients after cohort reallocation based on completion of PGx testing were 104, 180, and 58 for the SMTM, CMTM, and PGxMTM arms, respectively. On average, 3.08 DTPs were identified for each patient, which was nearly identical across all 3 arms. Blinded clinical pharmacists considered seriousness (grade 3 or 4) in 31% of the PGx-related DTPs in comparison with 4.9% of the non-PGx DTPs (P < 0.001). The more serious (i.e., grade 3 or above) DTP recommendations were more likely to be accepted by prescribers with the odds ratios of 1.95 (P = 0.05) and 2.39 (P = 0.15), when the analysis was performed for all DTPs and DTPs from the PGxMTM arm only, respectively. MTM enhanced by PGx testing and the clinical decision support tool did not increase the number of DTPs identified. However, PGx testing and the decision support software helps pharmacists determine more serious DTPs, and resulting subsequent recommendations were more readily accepted by a prescriber. Future study of the patient safety outcomes and overall health care costs associated with the utility of the decision support is warranted. No funding was received for conducting the post hoc analysis presented in this study. Magness is employed by Magellan Health, which received funding from Genelex for costs to administrate the medication management program. The open-label randomized trial was sponsored by Genelex (Clinicaltrials.gov ID number NCT02428660). PGx tests were provided and laboratory analysis was performed by Genelex. Valerie Baron is an employee of YouScript, which created the clinical decision support tool used in this study and formerly was part of Genelex. The other authors have nothing to disclose.


Histone proteins determined in a human colon cancer by high-performance liquid chromatography and mass spectrometry.
The application of reversed-phase high-pressure liquid chromatography under gradient conditions and electrospray ion trap mass spectrometry (LC-ESI-MS) to the analysis of global modification levels of core histones is described. The optimised LC-ESI-MS method was applied for the first time to the characterisation of histones extracted from HT29, a human colon cancer cell line. Eight histones (H1-1, H1-2, H2A-1, H2A-2, H2B, H3-1, H3-2, H4) were separated on a C4 stationary phase with complete resolution, never reached in previous HPLC-MS methods, by using a gradient elution with the combined presence of heptafluorobutyric acid and formic acid as acidic modifiers in the mobile phase. Heptafluorobutyric acid was found to improve selectivity, whereas the presence of formic acid decreased ion suppression. Histones eluted from the column were detected with an ion trap mass spectrometer with an electrospray source. The peak averaged mass spectra were reconstructed by Mag Tran 1.0 software and the mass of the various isoforms of histones were derived. Method validation was conducted by performing the same sample analysis by coupling LC-ESI to a quadrupole-time-of-flight mass spectrometer (Q-TOF). The number of histone forms and their mass were found to differ not significantly from those obtained by ion trap mass spectrometer. Also the relative modifications abundance within the same histone type was found following the same trend as the two mass analysers. This method was then applied to the characterisation of changes in histone modification in HT29, never analysed by LC-MS before, treated with histone deacetylase inhibitors such as valproate and sodium butyrate, also used in preclinical trials as anticancer drugs. In particular, both the inhibitors produced a significant increase in H4 histone acetylated forms: 89% increase of the diacetyl dimethyl H4 form was observed with 1mM valproate supplementation, whereas 5 mM butyrate led to a 68% increase of the same form. Triacetyl monomethyl H4 (11,377 Da) and triacetyl dimethyl H4 (11,390 Da) were found only in cells treated with butyrate. Selective changes of H3 histone were detected with butyrate, in agreement with recently reported western blotting studies. Modifications in the H2A histone degree of acetylation were revealed by treatment of the cells with butyrate (H2A-1, H2A-2) and valproate (H2A-2). The results of the proposed methodology confirmed that inhibition of histone deacetylases caused histone hyperacetylation, responsible for decondensation and reorganization of interphase dynamic chromatin. This method resulted in selective and sensitive method to monitor variations in the acetylation and methylation state of histones after treatment of HT29 with inhibitors, and is therefore suitable for further application in new drug discovery for tumour therapy.


Determinants and detection of anaerobic threshold and consequences of exercise above it.
During exercise, the level of oxygen consumption (VO2) above which aerobic energy production is supplemented by anaerobic mechanisms causing a sustained increase in lactate and metabolic acidosis is termed the anaerobic threshold. The VO2 at which the anaerobic threshold occurs is influenced by the factors that affect oxygen delivery to the tissues, being increased when oxygen flow is enhanced and decreased when oxygen flow is diminished. The anaerobic threshold is an important functional demarcation since the physiologic responses to exercise are different above the anaerobic threshold as compared with below the anaerobic threshold. Above the anaerobic threshold, in addition to the development of metabolic acidosis, exercise endurance is reduced, VO2 kinetics are slowed so that a steady state is delayed, and minute ventilation increases disproportionately to the metabolic requirement and a progressive tachypnea develops. The anaerobic threshold can be measured directly from lactate concentration with good threshold detection from a log-log transformation of lactate and VO2. This threshold defines the VO2 at which the lactate/pyruvate ratio increases. As bicarbonate changes reciprocally with lactate, its measurement can also be used to estimate the lactate threshold. But most conveniently, changes in gas exchange caused by the physical-chemical event of buffering of lactic acid by bicarbonate can be used to detect the anaerobic threshold during exercise.


Sometimes nothing is simply nothing: Automatic processing of empty sets.
Previous work using the numerical comparison task has shown that an empty set, the nonsymbolic manifestation of zero, can be represented as the smallest quantity of the numerical magnitude system. In this study, we examined whether an empty set can be represented as such under conditions of automatic processing in which deliberate processing of stimuli magnitudes is not required by the task. In Experiment 1, participants performed physical and numerical comparisons of empty sets (i.e., empty frames) and of other numerosities presented as framed arrays of 1 to 9 dots. The physical sizes of the frames varied within pairs. Both tasks revealed a size congruity effect (SCE) for comparisons of non-empty sets. In contrast, comparisons to empty sets produced an inverted SCE in the physical comparison task, whereas no SCE was found for comparisons to empty sets in the numerical comparison task. In Experiment 2, participants performed an area comparison task using the same stimuli as Experiment 1 to examine the effect of visual cues on the automatic processing of empty sets. The results replicated the findings of the physical comparison task in Experiment 1. Taken together, our findings indicate that empty sets are not perceived as "zero," but rather as "nothing," when processed automatically. Hence, the perceptual dominance of empty sets seems to play a more important role under conditions of automatic processing, making it harder to abstract the numerical meaning of zero from empty sets.


Effect of patient position on the sagittal-plane profile of the thoracolumbar spine.
Although the normal sagittal profile of the thoracolumbar spine has been described, this has been obtained primarily by using young individuals standing. We sought to describe the sagittal profile of the thoracolumbar spine in an older population in the supine cross-table lateral position compared with that standing. We enrolled 50 volunteers with no history of back pain or spine deformity and 50 matched subjects with mechanical back pain (LBP) only. Lateral radiographs of the thoracolumbar spine (T10-S1) in both standing and cross-table supine positions were obtained. Lordosis from L1 to S1, kyphosis from T10 to L1, and the changes seen moving from the supine position to standing were calculated. There were few differences comparing the two groups in either the standing or cross-table supine position, or when changing positions. Within each group, however, there were small, but significant, differences in the midlumbar and thoracolumbar spine when comparing supine versus standing. Both asymptomatic individuals and those with a history of LBP demonstrated similar small but statistically significant increases in lumbar lordosis and thoracolumbar kyphosis when standing versus supine. The clinical significance of these findings remains to be determined.


Engineering polysialic acid on Schwann cells using polysialyltransferase gene transfer or purified enzyme exposure for spinal cord injury transplantation.
Polysialic acid (PolySia) is a critical post-translational modification on the neural cell adhesion molecule (NCAM, a.k.a., CD56), important for cell migration and axon growth during nervous system development, plasticity and repair. PolySia induction on Schwann cells (SCs) enhances their migration, axon growth support and ability to improve functional recovery after spinal cord injury (SCI) transplantation. In the current investigation two methods of PolySia induction on SCs, lentiviral vector transduction of the mouse polysialytransferase gene ST8SIA4 (LV-PST) or enzymatic engineering with a recombinant bacterial PST (PSTNm), were examined comparatively for their effects on PolySia induction, SC migration, the innate immune response and axon growth after acute SCI. PSTNm produced significant PolySia induction and a greater diversity of surface molecule polysialylation on SCs as evidenced by immunoblot. In the scratch wound assay, PSTNm was superior to LV-PST in the promotion of SC migration and gap closure. At 24 h after SCI transplantation, PolySia induction on SCs was most pronounced with LV-PST. Co-delivery of PSTNm with SCs, but not transient cell exposure, led to broader induction of PolySia within the injured spinal cord due to polysialylation upon both host cells and transplanted SCs. The innate immune response after SCI, measured by CD68 immunoreactivity, was similar among PolySia induction methods. LV-PST or PSTNm co-delivery with SCs provided a similar enhancement of SC migration and axon growth support above that of unmodified SCs. These studies demonstrate that LV-PST and PSTNm provide comparable acute effects on SC polysialation, the immune response and neurorepair after SCI.


Classification and relationships of rice strains with AA genome by identification of transposable elements at nine loci.
We analyzed the presence of p-SINE1 members at five loci in the rice strains belonging to seven species with AA genome in the Oryza genus by the methods including polymerase chain reaction (PCR). Four p-SINE1 members (p-SINE1-r3, r4, r5 and r7) were present at the corresponding loci in all the strains examined. One member (p-SINE1-r6) was, however, not present at the corresponding locus in most of the African strains of O. glaberrima and O. barthii, but was in the other strains. The PCR-amplified fragments containing p-SINE1-r4 in many strains were found to be larger due to insertion of either one of two transposable elements, named Tnr2 and Ret1, within or near p-SINE1-r4, respectively: Tnr2 is 157 bp in length with terminal inverted repeat sequences of about 56 bp; Ret1 is only 13 bp in length with a T stretch at its end. Tnr2 was not present in the corresponding locus in all the strains belonging to O. sativa Japonica and in some strains of O. rufipogon and O. longistaminata, while Ret1 was present only in the two strains of O. longistaminata. These results and previous ones obtained from the analysis of the other two p-SINE1 members (p-SINE1-r1 and r2) in the Wx gene indicate that the elements, such as p-SINE1-r6, Tnr2, Ret1 and p-SINE1-r2, have been inserted into the respective loci during divergence of the rice species with AA genome. The patterns for the presence and absence of the transposable elements at the respective loci enabled us to classify the rice strains with AA genome into ten groups and to infer their relationships.


Management of multicentric myopericytoma in the maxillofacial region: a case report.
Myopericytoma (MPC) is a rare kind of benign neoplasm, showing derivation from perivascular myoid cells. About 115 cases have been reported in the English literature; however, most of the literature focuses on the description and classification of pathology. The case presented here is that of a 42-year-old woman with a surgical management experience of multicentric MPC in the maxillofacial region. Although small MPC can be completely and easily excised, large MPC, especially in certain anatomic sites, necessitates careful preoperative preparation.


Ovarian reserve may influence the outcome of bone mineral density in patients with long-term use of dienogest.
Long-term administration of dienogest, which is known to have effect on bone mineral density, is frequently done in patients with endometriosis and adenomyosis, but a few studies focused on the bone mineral density changes after finishing the long-term therapy. This study aimed to reveal the factors that adversely affect lumbar bone mineral density. Fifty-seven premenopausal women who visited our hospital were diagnosed as either endometriosis or adenomyosis, and they were treated by dienogest for more than 115 weeks (26.5 months). Based on a previous report, bone mineral density changes less than 2% was categorized as the osteopenic group (n = 30), and the others were assigned to the unchanged group (n = 27). Bone mineral density was measured at the lumbar spine using dual-energy X-ray absorptiometry. A representative ovarian reserve marker, endogenous estradiol levels, and follicle-stimulating hormone levels were measured over time and were compared between the osteopenic and unchanged groups. Duration of dienogest intake was 59.5 months (osteopenic group) versus 57.5 months (unchanged group). These patients experienced ovarian surgeries in a similar frequency, but the ovarian reserve in osteopenic group was impaired as suggested by the decline of endogenous estradiol level during intake of dienogest compared to that of unchanged group (p = 0.0146). Endogenous follicle-stimulating hormone level between osteopenic group and unchanged group did not reach statistically significant difference, although the osteopenic group showed relatively higher level. This study might suggest that decreased ovarian reserve as judged by endogenous estradiol level is a factor that negatively affect bone mineral density, and measurement of endogenous estradiol level during intake of dienogest could have a predictive meaning of future decreased bone mineral density level.


Nutrition and health at contact in late prehistoric central Gulf Coast Florida.
This paper presents an analysis of human remains from Tatham Mound, a dual-component mortuary site from central Gulf Coast Florida. The human remains from Tatham are significant because they come from a limited time period during the initial contact with Europeans at AD 1525-1550. Dietary reconstruction demonstrates that at the time of European contact, maize was not a predominant dietary item. Low frequencies for several dental and skeletal pathological indicators are consistent with relatively good health as compared to other Southeastern late prehistoric and protohistoric populations. Despite the limited time period represented by the mound population, critical interactions occurred between Native Americans and Spaniards, as indicated by skeletal elements severed by metal weapons. The Tatham population is significant because it is one of the earliest studied populations contacted by Europeans in North America, and the only one with well-documented sharp-force trauma that represents intergroup hostility.


Renal anemia treatment with ESA in hemodialysis patients in relation to early versus late referral in everyday clinical practice in Central and Eastern European countries: baseline data.
The aim of the study was to collect retrospective data on renal anemia management, comorbidities and prospective data on 12-month standard care erythropoiesis-stimulating agent (ESA) therapy used in 398 hemodialyzed patients in selected Central and Eastern European countries (50 centers in 3 countries). Patients were divided into three groups according to ESA therapy start: group A-ESA (after start of hemodialysis, HD), B-ESA (within 3 months from start of HD), C-ESA (more than 3 months before HD). At the chronic kidney disease diagnosis, hemoglobin in all patients was 10.3 ± 2.3 g/dl; however, ferritin, iron, TSAT were within reference limits. Early ESA therapy (C) was administered to 10% of patients only. 47% of patients received ESA after start of dialysis. Before study, the mean weekly ESA dose in group C was statistically lower than in groups B and A (p < 0.001). At baseline visit, hemoglobin in group A patients was slightly lower than in group B and C patients (p = 0.025). In conclusion, in Central and Eastern European countries renal anemia therapy with ESA starts shortly before or after start of HD. This highlights important differences in standard care in Eastern Europe. However, paradoxically, due to the tight reimbursement policy we foresee the clinical implications of the TREAT trial for the chronic kidney disease population.


A practical strategy for responding to a case of lymphatic filariasis post-elimination in Pacific Islands.
Lymphatic filariasis (LF) due to Wuchereria bancrofti is being eliminated from Oceania under the Pacific Elimination of Lymphatic Filariasis Programme. LF was endemic in Solomon Islands but in the 2010-2020 Strategic Plan of the Global Programme to Eliminate LF, Solomon Islands was listed as non-endemic for LF. In countries now declared free of LF an important question is what monitoring strategy should be used to detect any residual foci of LF? The index case, a 44 year old male, presented to Atoifi Adventist Hospital, Malaita, Solomon Islands in April 2011 with elephantiasis of the lower leg. Persistent swelling had commenced 16 months previously. He was negative for antigen by TropBio Og4C3 ELISA and for microfilaria. A week later a survey of 197 people aged from 1 year to 68 years was conducted at Alasi, the index case's village, by a research team from Atoifi Adventist Hospital and Atoifi College of Nursing. This represented 66.3% of the village population. Blood was collected between 22:00 and 03:00 by finger-prick and made into thick smears to detect microfilaria and collected onto filter paper for W. bancrofti antigen tests. A second group of 110 specimens was similarly collected from residents of the Hospital campus and inpatients. W. bancrofti antigen was tested for using the Trop-Bio Og4C3 test. One sample (1/307) from an 18 year old male from Alsai was positive for W. bancrofti antigen. No samples were positive for microfilaria. Although antigen-positivity indicated a live worm, the case was regarded as having been acquired some years previously. We propose that when LF has been eliminated from a country, a case of elephantiasis should be a trigger to conduct a survey of the case's community using a decision pathway. W. bancrofti antigen should be tested for with screening for microfilariae in antigen positive cases. The field survey was designed and conducted by local researchers, highlighting the value of local research capacity in remote areas.


COVID-19 associated Paediatric Inflammatory Multisystem Syndrome (PIMS) in children.
The clinical course of the SARS-CoV-2 virus infection (COVID-19 disease) in paediatric patients is predominantly mild. However, in a small percentage of paediatric patients, the COVID-19 could lead to the development of with the Paediatric Inflammatory Multisystem Syndrome (PIMS) presenting as high fever, gastrointestinal symptoms, neurological symptomatology and even as multiorgan dysfunction. These three cases represent the first published report of critically ill paediatric patients with PIMS in the Czech Republic.


Identifying Potential New Gene Expression-Based Biomarkers in the Peripheral Blood Mononuclear Cells of Hepatitis B-Related Hepatocellular Carcinoma.
The analysis of the gene expression of peripheral blood mononuclear cells (PBMCs) is important to clarify the pathogenesis of hepatocellular carcinoma (HCC) and the detection of suitable biomarkers. The purpose of this investigation was to use RNA-sequencing to screen the appropriate differentially expressed genes (DEGs) in the PBMCs for the HCC. The comprehensive transcriptome of extracted RNA of PBMC (n = 20) from patients with chronic hepatitis B (CHB), liver cirrhosis, and early stage of HCC (5 samples per group) was carried out using RNA-sequencing. All raw RNA-sequencing data analyses were performed using conventional RNA-sequencing analysis tools. Next, gene ontology (GO) analyses were carried out to elucidate the biological processes of DEGs. Finally, relative transcript abundance of selected DEGs was verified using qRT-PCR on additional validation groups. Specifically, 13, 1262, and 1450 DEGs were identified for CHB, liver cirrhosis, and HCC, when compared with the healthy controls. GO enrichment analysis indicated that HCC is closely related to the immune response. Seven DEGs (TYMP, TYROBP, CD14, TGFBI, LILRA2, GNLY, and GZMB) were common to HCC, cirrhosis, and CHB when compared to healthy controls. The data revealed that the expressions of these 7 DEGs were consistent with those from the RNA-sequencing results. Also, the expressions of 7 representative genes that had higher sensitivity were obtained by receiver operating characteristic analysis, which indicated their important diagnostic accuracy for HBV-HCC. This study provides us with new horizons into the biological process and potential prospective clinical diagnosis and prognosis of HCC in the near future.