Rationale and design of the CV-PREVITAL study: an Italian multiple cohort randomised controlled trial investigating innovative digital strategies in primary cardiovascular prevention.
Prevention of cardiovascular disease (CVD) is of key importance in reducing morbidity, disability and mortality worldwide. Observational studies suggest that digital health interventions can be an effective strategy to reduce cardiovascular (CV) risk. However, evidence from large randomised clinical trials is lacking. The CV-PREVITAL study is a multicentre, prospective, randomised, controlled, open-label interventional trial designed to compare the effectiveness of an educational and motivational mobile health (mHealth) intervention versus usual care in reducing CV risk. The intervention aims at improving diet, physical activity, sleep quality, psycho-behavioural aspects, as well as promoting smoking cessation and adherence to pharmacological treatment for CV risk factors. The trial aims to enrol approximately 80 000 subjects without overt CVDs referring to general practitioners' offices, community pharmacies or clinics of Scientific Institute for Research, Hospitalization and Health Care (Italian acronym IRCCS) affiliated with the Italian Cardiology Network. All participants are evaluated at baseline and after 12 months to assess the effectiveness of the intervention on short-term endpoints, namely improvement in CV risk score and reduction of major CV risk factors. Beyond the funded life of the study, a long-term (7 years) follow-up is also planned to assess the effectiveness of the intervention on the incidence of major adverse CV events. A series of ancillary studies designed to evaluate the effect of the mHealth intervention on additional risk biomarkers are also performed. This study received ethics approval from the ethics committee of the coordinating centre (Monzino Cardiology Center; R1256/20-CCM 1319) and from all other relevant IRBs and ethics committees. Findings are disseminated through scientific meetings and peer-reviewed journals and via social media. Partners are informed about the study's course and findings through regular meetings. NCT05339841.


THE EFFECT OF HABITAT ON PARENTAL AND HYBRID FITNESS: TRANSPLANT EXPERIMENTS WITH LOUISIANA IRISES.
We performed transplant experiments with Louisiana irises to test the assumptions of three models of hybrid zone structure: the bounded hybrid superiority model, the mosaic model, and the tension zone model. Rhizomes of Iris fulva, I. hexagona, and F1 and F2 hybrids were planted at four sites in southeastern Louisiana in 1994. Wild irises grew at all four sites, but differed in genotypic composition among sites. The sites were characterized by (1) pure I. fulva plants; (2) I. fulva-like hybrids; (3) I. hexagona-like hybrids; and (4) pure I. hexagona plants. The sites differed significantly in light availability, soil moisture and chemical composition, and vegetation. Survival of transplants was high in all sites and did not differ significantly among plant classes. Iris hexagona produced significantly more leaf material than I. fulva at the I. hexagona and I. hexagona hybrid sites. The two species did not differ in leaf production at the I. fulva and I. fulva hybrid sites. Leaf production by both classes of hybrid was as great as, or significantly greater than, both parental classes in all sites. Iris hexagona rhizomes gained mass in the I. hexagona and I. hexagona hybrid sites, but lost mass in the I. fulva and I. fulva hybrid sites. Iris fulva rhizomes lost mass in all sites. There were no significant differences in rhizome growth among classes at the I. fulva site. At all other sites, F1 rhizomes grew significantly more than all other classes except for I. hexagona at the I. hexagona hybrid site. There were no significant differences among classes in the production of new ramets. Overall blooming frequencies were 30% for I. fulva, 10% for F1 s, 3% for F2 s, and 0.7% for I. hexagona. Blooming frequency did not differ among sites for I. fulva, but significantly more F1 s bloomed at the I. hexagona site than at the I. fulva site. These results are inconsistent with all three models of hybrid zone structure. They suggest that once rhizomes become established, hybrids can reproduce by clonal growth as successfully as parents in all habitats, and can outperform them in some habitats. Clonal reproduction may ensure the long-term survival of early generation hybrids and allow the establishment of introgressed populations, despite the fact that F1 hybrids are rarely produced in nature.


Acute effects of liver vein occlusion by stent-graft placed in transjugular intrahepatic portosystemic shunt channel: an experimental study.
The purpose of this study was to evaluate the effects of hepatic vein occlusion by stent-graft used in transjugular intrahepatic portosystemic shunt (TIPS). The experiments were performed in six healthy pigs under general anesthesia. Following percutaneous transhepatic implantation of a port-a-cath in the right hepatic vein, TIPS was created with a stent-graft (Viatorr; W L Gore, Flagstaff, AZ, USA). The outflow from the hepatic vein, blocked by the stent-graft was documented by injection of contrast medium and repeated injections of (99)Tc(m)-labeled human serum albumin through the port-a-cath. After 2 weeks, the outflow was re-evaluated, the pigs were sacrificed, and histopathologic examination of the liver was performed. Occlusion of the hepatic vein by a stent-graft had a short and temporary effect on the outflow. Histopathological examination from the affected liver segment showed no divergent pattern. Stent-grafts used in TIPS block the outflow from the liver vein, but do not have a prolonged circulatory effect and do not affect the liver parenchyma.


Evaluation of an insecticide dust band treatment method for controlling bed bugs.
Current bed bug, Cimex lectularius L., control usually involves insecticide applications that pose a high risk of insecticide exposure to residents and applicators. To minimize these risks and the amount of insecticides used, we designed and evaluated a dust band treatment technique. The laboratory assay showed that 1% cyfluthrin dust treated bands are highly effective in killing bed bugs. We further evaluated this technique in bed bug infested apartments. The "dust band" treatment consisted of installing a 3.8-cm-wide fabric band on furniture legs and brushing Tempo dust (1% cyfluthrin) (Bayer Environmental Science, Research Triangle Park, NC) onto the bands. In addition, interceptors were installed under furniture legs. Alpine (0.5% dinotefuran) aerosol spray was applied directly to live bed bugs found on furniture during biweekly inspections. This treatment was compared with two other treatments: "integrated pest management" (IPM) and "control." The IPM treatment included dust bands plus the following: applying hot steam to infested furniture and surrounding areas, installing mattress encasements, applying 1% cyfluthrin dust around room perimeters, and installing interceptors under furniture legs. Alpine aerosol was applied to live bed bugs found during biweekly inspections. In the control group, the apartments received cursory treatment with insecticide sprays by the existing pest control contractor hired by the property management office. Bed bug numbers before and after treatments were determined based on biweekly interceptor counts or a combination of interceptor counts and visual inspections. From 0 to 12 wk, mean bed bug counts of the dust band, IPM, and the control treatment decreased by 95, 92, and 85%, respectively. Both dust band and IPM resulted in higher bed bug reduction than the control. There was no significant difference in the final counts between dust band and IPM treatments. An additional field experiment showed installing 1% cyfluthrin dust band and interceptors in lightly infested apartments prevented bed bug population rebound. Results indicate applying insecticide dust bands to furniture legs is an effective bed bug control technique.


Heart rate prescriptions from performance and anthropometrical characteristics.
Heart rate (HR) is widely used to adjust exercise intensity in aerobic training. Training HR recommendations are calculated often from simple equations. Because at lactate steady state (LASS) may be an intensity of exercise eliciting similar objective measures of intensity and similar subjective measures of metabolism, it is an appropriate intensity upon which to base aerobic-training prescription. The purpose of this research was to develop regression equations using age and other easily accessible characteristics to estimate the HR associated with LASS (HRLASS). The data of 7397 healthy subjects (age >or= 10 yr; 5044 male, 2353 female) with different training habits were analyzed. All participants were tested in an incremental exercise test on the treadmill until subjective exhaustion. The LASS was determined by the concept of blood lactate at the "lactate threshold" plus a net increase of 1.5 mmol.L-1. The interdependence of further characteristics was tested by stepwise multiple regression. Age alone did not allow a precise prediction of lass=hText>HRLASS (r = 0.645 for all participants), regardless of adjustment by sex, training state, body mass, or performance characteristics using ANCOVA. Resting HR (HRrest) decreased steeply within the second life decade but not with further advancing age. The best discrete lactate-independent predictor for HRLASS was HRmax (r = 0.798). Inclusion of age and weight in the model resulted in only a small improvement of the prediction (r = 0.826). Other anthropometrical characteristics could not improve the model further. The use of age alone seems too imprecise for exactly driven aerobic training prescriptions. A minor improvement can be achieved in this objective by use of HRmax supplemented by age using a multiple regression model.


Cx26 knockout predisposes the mammary gland to primary mammary tumors in a DMBA-induced mouse model of breast cancer.
Down-regulation of the gap junction protein connexin26 (Cx26) is an early event following breast cancer onset and has led to Cx26 being classically described as a tumor suppressor. Interestingly, mutations in theCx26 gene (GJB2) reduce or ablate Cx26 gap junction channel function and are the most common cause of genetic deafness. It is unknown if patients with loss-of-function GJB2 mutations have a greater susceptibility to breast tumorigenesis or aggressive breast cancer progression. To investigate these possibilities, 7, 12-dimethylbenz[α]anthracene (DMBA)-induced tumor development was evaluated in BLG-Cre; Cx26fl/fl mice expressing Cre under the β-Lactoglobulin promoter (Cre+) compared to Cx26fl/fl controlmice (Cre-) following pituitary isograft driven Cx26 knockout. A significantly increased number of DMBA-treated Cre+ mice developed primary mammary tumors, as well as developed multiple tumors, compared to Cre- mice. Primary tumors of Cre+ mice were of multiple histological subtypes and had similar palpable tumour onset and growth rate compared to tumors from Cre- mice. Lungs were evaluated for evidence of metastases revealing a similar percentage of lung metastases in Cre+ and Cre- mice. Together, our results suggest that loss of Cx26 predisposes the mammary gland to chemically induced mammary tumour formation which may have important implications to patients with GJB2 mutations.


Hedyotis diffusa plus Scutellaria barbata Suppress the Growth of Non-Small-Cell Lung Cancer via NLRP3/NF-κB/MAPK Signaling Pathways.
Hedyotis diffusa (HD) plus Scutellaria barbata (SB) have been widely used in antitumor clinical prescribes as one of herb pairs in China. We investigated the effect of aqueous extract from Hedyotis diffusa plus Scutellaria barbata at the equal weight ratio (HDSB11) in inhibiting the growth of murine non-small-cell lung cancer cell (NSCLC) line LLC in vivo and in vitro in this study. Compared with other aqueous extracts, HDSB11 showed the lowest IC50 in inhibiting cell proliferation at 0.43 mg/ml. Besides, HDSB11 effectively suppressed colony formation and induced cell apoptosis. The further assessment of HDSB11 on the murine Lewis-lung-carcinoma-bearing mouse model showed it significantly inhibited tumors' bioluminescence at the dose of 30 g crude drug/kg. Mechanistically, HDSB11 attenuated the expressions of NLRP3, procaspase-1, caspase-1, PRAP, Bcl-2, and cyclin D1 and downregulated the phosphorylation levels of NF-κB, ERK, JNK, and p38 MAPK. In conclusion, HDSB11 could alleviate cell proliferation and colony formation and induce apoptosis in vitro and tumor growth in vivo, partly via NF-κB and MAPK signaling pathways to suppress NLRP3 expression.


From evolution to revolution: miRNAs as pharmacological targets for modulating cholesterol efflux and reverse cholesterol transport.
There has been strong evolutionary pressure to ensure that an animal cell maintains levels of cholesterol within tight limits for normal function. Imbalances in cellular cholesterol levels are a major player in the development of different pathologies associated to dietary excess. Although epidemiological studies indicate that elevated levels of high-density lipoprotein (HDL)-cholesterol reduce the risk of cardiovascular disease, recent genetic evidence and pharmacological therapies to raise HDL levels do not support their beneficial effects. Cholesterol efflux as the first and probably the most important step in reverse cholesterol transport is an important biological process relevant to HDL function. Small non-coding RNAs (microRNAs), post-transcriptional control different aspects of cellular cholesterol homeostasis including cholesterol efflux. miRNA families miR-33, miR-758, miR-10b, miR-26 and miR-106b directly modulates cholesterol efflux by targeting the ATP-binding cassette transporter A1 (ABCA1). Pre-clinical studies with anti-miR therapies to inhibit some of these miRNAs have increased cellular cholesterol efflux, reverse cholesterol transport and reduce pathologies associated to dyslipidemia. Although miRNAs as therapy have benefits from existing antisense technology, different obstacles need to be solved before we incorporate such research into clinical care. Here we focus on the clinical potential of miRNAs as therapeutic target to increase cholesterol efflux and reverse cholesterol transport as a new alternative to ameliorate cholesterol-related pathologies.


Computing converged free energy differences between levels of theory via nonequilibrium work methods: Challenges and opportunities.
We demonstrate that Jarzynski's equation can be used to reliably compute free energy differences between low and high level representations of systems. The need for such a calculation arises when employing the so-called "indirect" approach to free energy simulations with mixed quantum mechanical/molecular mechanical (QM/MM) Hamiltonians; a popular technique for circumventing extensive simulations involving quantum chemical computations. We have applied this methodology to several small and medium sized organic molecules, both in the gas phase and explicit solvent. Test cases include several systems for which the standard approach; that is, free energy perturbation between low and high level description, fails to converge. Finally, we identify three major areas in which the difference between low and high level representations make the calculation of ΔAlow→high difficult: bond stretching and angle bending, different preferred conformations, and the response of the MM region to the charge distribution of the QM region. © 2016 Wiley Periodicals, Inc.


Circulating levels of prekallikrein and kallikrein in pregnancy and labor.
Plasma levels of prekallikrein and kallikrein were measured in 147 pregnant women by the chromogenic substrate S2302 method. At the same time, individual fibrinolytic inhibitors (alpha 2-plasmin inhibitor, alpha 1-antitrypsin, alpha 2-macroglobulin, antithrombin-III, and Cl-inactivator) were determined by the radial immunodiffusion method. The plasma levels of prekallikrein increased significantly during pregnancy and thereafter decreased during delivery. In patients with severe toxemia of pregnancy and hydatidiform mole, plasma prekallikrein levels were low, below the normal range. On the other hand, plasma kallikrein concentrations were within non-pregnant levels until the end of pregnancy, but the levels increased just before delivery. Although no significant correlation was found between prekallikrein levels and fibrinolytic inhibitory activity in pregnancy, Cl-inactivator concentrations tended to be low only when the prekallikrein level was high. These changes in the prekallikrein-kallikrein system in late pregnancy may be related to activation of the kinin, which results in labor pain.


Genome-wide survey and phylogenetic analysis on subunit sequences of eukaryotic DNA polymerase delta.
DNA polymerase d is not only the major replicative enzyme in eukaryotic chromosomal DNA synthesis but is also the primary polymerase for most DNA repair pathways. However, the subunit composition of polymerase d varies in different organisms. While polymerase d in many eukaryotic species has all 4 subunits (POLD1, 2, 3, and 4), many other organisms do not possess POLD4. Whether POLD4 is indispensable and why these differences exist are unknown. In the present study, we identified the POLD4 protein sequences of 218 eukaryotic species and determined the POLD1, 2, and 3 protein sequences of 55 species representing various taxonomic groups. No insect and nematode species examined possessed POLD4. Approximately 80% of protozoan species did not contain POLD4. Nearly 50% of fungal species did not contain POLD4. Other animal and plant species are expected to contain POLD4. Phylogenetic analyses of POLD1, 2, 3, and 4 sequences revealed that most animal and plant species inherited DNA polymerase d from protozoa, whereas some other animal and plant species may have inherited polymerase d directly from fungi. Because a large number of protozoan and fungal species do not possess POLD4, current insect and nematode species lacking POLD4 may have evolved from ancestor protozoan species lacking POLD4; thus, other protozoan and animal species lacking POLD4 may share a similar evolutionary history. Future studies should examine the origin and indispensability of POLD4 in various organisms.


Histone 4 lysine 20 tri-methylation: a key epigenetic regulator in chromatin structure and disease.
Chromatin is a vital and dynamic structure that is carefully regulated to maintain proper cell homeostasis. A great deal of this regulation is dependent on histone proteins which have the ability to be dynamically modified on their tails via various post-translational modifications (PTMs). While multiple histone PTMs are studied and often work in concert to facilitate gene expression, here we focus on the tri-methylation of histone H4 on lysine 20 (H4K20me3) and its function in chromatin structure, cell cycle, DNA repair, and development. The recent studies evaluated in this review have shed light on how H4K20me3 is established and regulated by various interacting partners and how H4K20me3 and the proteins that interact with this PTM are involved in various diseases. Through analyzing the current literature on H4K20me3 function and regulation, we aim to summarize this knowledge and highlights gaps that remain in the field.


Early grammatical marking development in Mandarin-speaking toddlers.
The current study examined early grammatical marking in a relatively understudied language, Mandarin, by using the Mandarin version of MacArthur-Bates Communicative Development Inventory. Two waves of data collection included 338 monolingual children (17-36 months; 143 female) at Time 1 and 308 children (32-55 months; 139 female) at Time 2 and their caregivers, whose education ranged from third grade (elementary school) or below to postgraduate with a median of high school. Our data showed a clear order of grammatical marking acquisition among these children and supported findings on the linguistic specificity of morphological development such that early- and late-acquired markers in Mandarin are not acquired in the same order as English or other languages. Negative "mei2," "bu4," possessive "-de," classifiers, and the aspect marker "le" were the earliest-acquired markers, followed by modals, negative "bie2," adverbs, sentence final particles, resultative verb compounds, and aspect markers "guo4" and "yao4." Complex clauses and the aspect marker "zheng4" were acquired the latest. Furthermore, consistent with previous cross-linguistic studies, the development patterns of a wide range of Mandarin grammatical markers indicate that markers that are more perceptually salient and obligatory, have clear form-meaning mappings, and often appear in isolation or utterance-final position were acquired earlier than others. (PsycInfo Database Record (c) 2022 APA, all rights reserved).


Foot and Ankle Conditions: Midfoot and Forefoot Conditions.
The midfoot and forefoot are the regions of the foot distal to the talus and calcaneus and are critical to weight bearing and movement. They help support the arch of the foot, provide shock absorption, and convert vertically oriented forces into horizontal forward and propulsive movement. A spectrum of acute, subacute, and chronic conditions in these regions can cause pain and decreased function. A thorough history and physical examination should include foot and leg biomechanics, alignment, and posture in addition to palpation of painful areas. All patients with traumatic or overuse midfoot and forefoot injuries should be evaluated with x-rays, with the need for advanced imaging determined based on initial findings. Appropriate diagnosis and management of Lisfranc joint injuries and navicular and base of the fifth metatarsal stress fractures can prevent adverse outcomes. Management of these injuries commonly includes a period of non-weight-bearing immobilization and referral to an orthopedic surgeon. Turf toe, hallux rigidus, metatarsalgia, and Morton neuroma are common causes of forefoot pain. Treatment should be individualized and may include shoe and orthotic adjustments, injections, and, occasionally, surgical intervention.


Characterization of Bacterionema matruchotii calcification nucleator.
The nucleator of Bacterionema matruchotii calcification was characterized. Parameters examined were: proteolipid purity and singularity, amino acid composition and relative polarity, phospholipid composition, apoprotein homogeneity, essentiality of the complex for nucleation, and ordered structure. The data fulfill a requirement for comparisons among apatite-nucleating proteolipids.


Remediation of heavy metals contaminated soils by ball milling.
In the present work, the use of ball milling reactors for the remediation of lead contaminated soils was investigated. Lead immobilization was achieved without the use of additional reactants but only through the exploitation of weak transformations induced on the treated soil by mechanical loads taking place during collisions among milling media. The degree of metal immobilization was evaluated by analyzing the leachable fraction of Pb(II) obtained through the "synthetic precipitation leaching procedure". The reduction of leachable Pb(II) from certain synthetic soils, i.e., bentonitic, sandy and kaolinitc ones, was obtained under specific milling regimes. For example, for the case of bentonitic soils characterized by a Pb(II) concentration in the solid phase equal to 954.4 mg kg(-1), leachable Pb(II) was reduced, after 7 h of mechanical treatment, from 1.3 mg l(-1) to a concentration lower than the USEPA regulatory threshold (i.e., 0.015 mg l(-1) for drinkable water). Similar results were obtained for sandy and kaolinitic soils. X-ray diffraction, scanning electron microscopy, electron dispersive spectroscopy and granulometric analyses revealed no significant alterations of the intrinsic character of sandy and bentonitic soils after milling except for a relatively small increase of particles size and a partial amorphization of the treated soil. On the other hand, the mechanical treatment caused the total amorphization of kaolinitic soil. The increase of immobilization efficiency can be probably ascribed to specific phenomena induced by mechanical treatment such as entrapment of Pb(II) into aggregates due to aggregation, solid diffusion of Pb(II) into crystalline reticulum of soil particles as well as the formation of new fresh surfaces (through particle breakage) onto which Pb(II) may be irreversibly adsorbed.


Genetic alterations in prostate cancer as diagnostic and prognostic markers.
Prostate cancer is the second-most frequently diagnosed cancer in men worldwide. Serum prostatespecific antigen is currently used for the early detection of prostate cancer. However, new biomarkers are needed to decrease over diagnosis and over treatment of prostate cancer due to limitations of prostate-specific antigen. Recently, molecular biomarkers have shown promising results for diagnosis and prognosis of prostate cancer. Molecular biomarkers have improved the sensitivity and specificity of prostate-specific antigen and studies are ongoing to identify molecular biomarkers as a replacement for prostate-specific antigen. This review aims to give an overview of emerging molecular biomarkers for diagnosis and prognosis of prostate cancer.


The Borealis basin and the origin of the martian crustal dichotomy.
The most prominent feature on the surface of Mars is the near-hemispheric dichotomy between the southern highlands and northern lowlands. The root of this dichotomy is a change in crustal thickness along an apparently irregular boundary, which can be traced around the planet, except where it is presumably buried beneath the Tharsis volcanic rise. The isostatic compensation of these distinct provinces and the ancient population of impact craters buried beneath the young lowlands surface suggest that the dichotomy is one of the most ancient features on the planet. However, the origin of this dichotomy has remained uncertain, with little evidence to distinguish between the suggested causes: a giant impact or mantle convection/overturn. Here we use the gravity and topography of Mars to constrain the location of the dichotomy boundary beneath Tharsis, taking advantage of the different modes of compensation for Tharsis and the dichotomy to separate their effects. We find that the dichotomy boundary along its entire path around the planet is accurately fitted by an ellipse measuring approximately 10,600 by 8,500 km, centred at 67 degrees N, 208 degrees E. We suggest that the elliptical nature of the crustal dichotomy is most simply explained by a giant impact, representing the largest such structure thus far identified in the Solar System.


MEK inhibitors in cancer treatment: structural insights, regulation, recent advances and future perspectives.
MEK1/2 are critical components of the RAS-RAF-MEK-ERK or MAPK signalling pathway that regulates a variety of cellular functions including proliferation, survival, and differentiation. In 1997, a lung cancer cell line was first found to have a MEK mutation (encoding MEK2P298L). MEK is involved in various human cancers such as non-small cell lung cancer (NSCLC), spurious melanoma, and pancreatic, colorectal, basal, breast, and liver cancer. To date, 4 MEK inhibitors i.e., trametinib, cobimetinib, selumetinib, and binimetinib have been approved by the FDA and several are under clinical trials. In this review, we have highlighted structural insights into the MEK1/2 proteins, such as the αC-helix, catalytic loop, P-loop, F-helix, hydrophobic pocket, and DFG motif. We have also discussed current issues with all FDA-approved MEK inhibitors or drugs under clinical trials and combination therapies to improve the efficacy of clinical drugs. Finally, this study addressed recent developments on synthetic MEK inhibitors (from their discovery in 1997 to 2022), their unique properties, and their relevance to MEK mutant inhibition.


Comparing marginal microleakage of three Bulk Fill composites in Class II cavities using confocal microscope: An in vitro study.
This study aims to evaluate and compare microleakage at the occlusal wall and cervical wall in Class II cavities restored with one SonicFill Bulk Fill composite and two conventional Bulk Fill composites. Thirty freshly extracted teeth were divided into three groups of 10 teeth each. Standardized Class II cavities were made on the mesial and distal surfaces of each tooth and restored using SonicFill Bulk Fill composite and two conventional Bulk Fill composites, Tetric Evo Ceram, and X-tra fil. After storage, thermocycling and immersion in 0.6% rhodamine dye solution specimens were sectioned and evaluated for microleakage at the occlusal and cervical walls using confocal microscope. Kruskal-Wallis test, Wilcoxon Signed-Rank test and Mann-Whitney U-test. The results demonstrated that in the occlusal wall and cervical wall, SonicFill Bulk Fill composite, showed significantly less marginal microleakage than the other groups. Based on the results of this study, SonicFill Bulk Fill composite showed less microleakage than the other conventional Bulk Fill composites.


Multiple cell lines from patients with malignant melanoma: morphology, karyology, and biochemical analysis.
Of 23 cell lines representing 8 patients with malignant melanoma, one cell line from each patient has been extensively characterized by means of phase morphology, ultrastructural morphology, biochemical markers, steroid receptor protein analysis, and steroid hormone production. Extensive cytogenetic characterization was compiled from seven of the eight cell lines. The melanocytic derivation of the tumor cell lines was supported by the detection of the catecholamines epinephrine, norepinephrine, and dopamine. In addition, well-defined melanosomes were present in six of the seven lines whose ultrastructure were examined morphologically. None of the lines produced alpha-fetoprotein chorionic gonadotropin, or carcinoembryonic antigen in detectable amounts. The individuality of the cell lines was confirmed by phenotypic patterns of isozymes and by karyology.


Convergence of alarmone and cell cycle signaling from trans-encoded sensory domains.
Despite the myriad of different sensory domains encoded in bacterial genomes, only a few are known to control the cell cycle. Here, suppressor genetics was used to unveil the regulatory interplay between the PAS (Per-Arnt-Sim) domain protein MopJ and the uncharacterized GAF (cyclic GMP-phosphodiesterase-adenylyl cyclase-FhlA) domain protein PtsP, which resembles an alternative component of the phosphoenolpyruvate (PEP) transferase system. Both of these systems indirectly target the Caulobacter crescentus cell cycle master regulator CtrA, but in different ways. While MopJ acts on CtrA via the cell cycle kinases DivJ and DivL, which control the removal of CtrA at the G1-S transition, our data show that PtsP signals through the conserved alarmone (p)ppGpp, which prevents CtrA cycling under nutritional stress and in stationary phase. We found that PtsP interacts genetically and physically with the (p)ppGpp synthase/hydrolase SpoT and that it modulates several promoters that are directly activated by the cell cycle transcriptional regulator GcrA. Thus, parallel systems integrate nutritional and systemic signals within the cell cycle transcriptional network, converging on the essential alphaproteobacterial regulator CtrA while also affecting global cell cycle transcription in other ways. Many alphaproteobacteria divide asymmetrically, and their cell cycle progression is carefully regulated. How these bacteria control the cell cycle in response to nutrient limitation is not well understood. Here, we identify a multicomponent signaling pathway that acts on the cell cycle when nutrients become scarce in stationary phase. We show that efficient accumulation of the master cell cycle regulator CtrA in stationary-phase Caulobacter crescentus cells requires the previously identified stationary-phase/cell cycle regulator MopJ as well as the phosphoenolpyruvate protein phosphotransferase PtsP, which acts via the conserved (p)ppGpp synthase SpoT. We identify cell cycle-regulated promoters that are affected by this pathway, providing an explanation of how (p)ppGpp-signaling might couple starvation to control cell cycle progression in Caulobacter spp. and likely other Alphaproteobacteria. This pathway has the potential to integrate carbon fluctuation into cell cycle control, since in phosphotransferase systems it is the glycolytic product phosphenolpyruvate (PEP) rather than ATP that is used as the phosphor donor for phosphorylation.


Seroprevalence of eastern equine encephalomyelitis virus in birds and larval survey of Culiseta melanura Coquillett during an interepizootic period in central Ohio.
From June through August in 1999 and 2000, we conducted an avian serosurvey for eastern equine encephalomyelitis (EEE) virus at Killbuck Marsh Wildlife Area (KMWA), a focus of infection in central Ohio. We also monitored abundance of the suspected enzootic vector, Culiseta melanura Coquillett, in Brown's Lake Bog, an adjacent wetland. Of the 363 birds of 30 species sampled in 1999, three gray catbirds (Dumetella carolinensis) were positive for antibodies to EEE virus, representing 1.2% of the avian samples and 4.2% of the gray catbirds sampled. Given these results and the abundance of gray catbirds at this site, this species became the focus of our sampling efforts in 2000. However, none of the 109 samples collected from 98 catbirds in 2000 was positive for the virus. Culiseta melanura adults were monitored using resting boxes and CDC CO, light traps at both sites in 1999. Culiseta melanura larvae were monitored in 1999 and 2000 at Brown's Lake Bog, the closest known source of this species, approximately 5km from the avian serosurvey site. We suggest that dry conditions reduced the breeding and abundance of Cs. melanura in 2000 and possibly the transmission of EEE virus at KMWA.


Molecular dynamics simulations of steady-state crystal growth and homogeneous nucleation in polyethylene-like polymer.
Molecular mechanisms of crystal growth and homogeneous nucleation from the melt of polyethylene-like linear polymer are investigated by molecular dynamics simulations. The present paper is aimed at extending our previous work with respect to the system size and the boundary condition, thereby enabling detailed studies on the structures of sufficiently large lamellae and fully equilibrated melt. Lamellae of uniform thickness but with marked tapered edges are found to grow at constant velocity from the substrate. Three-dimensional shape of the growing lamellae exhibits peculiar undulation at the growth front, the origin of which is suggested to be the inhomogeneous thickness distribution within the lamellae. Trajectories of chains crystallizing onto the growth front reveal an unexpected pathway for chain folding, where a partially attached chain stem forms a new fold by plunging its head back into a neighboring stem position through slithering snake motions of the chain. Detailed statistics of folds and cilia show that the folds are rather neat and mostly make re-entries into the nearest or the second or third nearest neighboring stem positions, whereas the cilia are generally short but with a small number of longer cilia forming thick amorphous layers. Structure of supercooled melt investigated versus temperature reveals that, at moderate degree of supercooling, the overall chain conformation remains Gaussian random coil but the persistent length of chains increases monotonically with increasing supercooling. Exceptions are at the largest supercooling where homogeneous nucleation takes place; usual melt structure becomes rapidly unstable and emerges many crystallites of random orientations. During early 10-20 ns after the quench, density of melt, radius of gyration of chains, and fraction of kinked bonds show marked alterations. These structural changes are highly cooperative and are considered simply due to the emergence of many embryonic crystals in the melt. Conformations of the chains forming nuclei are also traced to reveal that the homogeneous nuclei are fringed micelle like aggregates of chains, but the chains as a whole have folded conformations, which are similar to those reported in previous simulations on a single polyethylene in a vacuum.


36-Month Evaluation of Intravitreous Aflibercept Injection for Wet Age-Related Macular Degeneration in Patients Previously Treated With Ranibizumab or Bevacizumab.
In the ASSESS study, patients with neovascular age-related macular degeneration transitioned from other anti-vascular endothelial growth factor therapies to intravitreous aflibercept (Eylea; Regeneron, Tarrytown, NY) injections (IAI). The purpose was to determine the 36-month outcomes following the change from a fixed 24-month IAI dosing regimen to a routine clinical practice regimen. Patients were treated with a fixed bimonthly regimen for the first 2 years. In the third year, patients were managed according to routine clinical practice. A total of 18 patients completed the 36 months and were considered for statistical analyses. At 36 months, a nonsignificant decrease of -37.8 μm in central subfield thickness and a nonsignificant gain of 5.8 letters from baseline were observed. Despite the significant visual and anatomical gains observed in the 2 years of fixed-dosing IAI, there was gradual decline in these improvements when patients were transitioned to a variable regimen. [Ophthalmic Surg Lasers Imaging Retina. 2018;49:179-185.].


Penile metastasis in prostate cancer patients: Two case reports, surgical excision technique, and literature review.
Two cases of penile metastasis from primary prostate cancer in a single center are presented, along with a literature review and description of the excision technique. Despite its rich vascularization, penile metastasis is rare, with 72 new cases from September 2006 to March 2021. There is a wide variety of diagnoses, treatments, and prognoses for penile metastatic lesions. Ga-68 prostatespecific membrane antigen positron emission tomography/computed tomography is the most sensitive imaging tool for detecting metastasis from primary prostate cancer. Magnetic resonance imaging of the penis is the most reliable technique for differentiating penile lesions. Histological diagnosis is mostly performed using fine-needle biopsy aspiration. Metastasis-directed treatment is not considered to contribute to prolonged survival. Local treatment is feasible and can be offered to symptomatic patients. Owing to a heterogeneous group, defining overall survival is difficult. Survival until 46months after detecting penile metastases is described.


Telephone follow-up following office anorectal surgery.
Patients with minor anorectal conditions are frequently reviewed at an 8-week out-patient appointment (OPA). This study was designed to assess whether telephone follow-up could reduce OPA numbers whilst maintaining patient satisfaction. Over an 11-month period, 46 patients (23 male) underwent banding of haemorrhoids and 14 were prescribed medical treatment for fissure-in-ano (3 male). All were telephoned at 6 weeks and were offered an 8-week OPA if they had continuing problems. Patients were telephoned at a later date by a member of the hospital's patient panel to assess satisfaction. Overall, 88% were contacted at 6 weeks, 60% at the first attempt; 40% required two or more attempts. Of those who underwent banding, 68% were asymptomatic, 17% requested an OPA for re-banding and 15% requested an OPA for a different problem. Of fissure patients, 25% were cured; the remainder were prescribed either second-line medical treatment (8%), anorectal physiology (42%) or surgery (25%). All avoided an OPA. Of a potential 60 OPAs, 47 were saved by telephone follow-up. None of 7 non-contactable patients accepted a written offer of an OPA. Overall, 89% of patients were contacted by the patient panel; of these patients, 93% reported a high level of satisfaction. Telephone follow-up can reduce the number of OPAs following out-patient treatment of minor anorectal conditions whilst maintaining a high level of patient satisfaction. However, it requires considerable consultant time. This process could be developed into either a nurse-led service with booked telephone appointments or a patient-led service to a dedicated hotline.


The CD46 ectodomain participates in human cytomegalovirus infection of epithelial cells.
Human cytomegalovirus (HCMV) primary infections are typically asymptomatic in healthy individuals yet can cause increased morbidity and mortality in organ transplant recipients, AIDS patients, neonates, and the elderly. The successful, widespread dissemination of this virus among the population can be attributed in part to its wide cellular tropism and ability to establish life-long latency. HCMV infection is a multi-step process that requires numerous cellular and viral factors. The viral envelope consists of envelope protein complexes that interact with cellular factors; such interactions dictate virus recognition and attachment to different cell types, followed by fusion either at the cell membrane or within an endocytic vesicle. Several HCMV entry factors, including neuropilin-2 (Nrp2), THBD, CD147, OR14I1, and CD46, are characterized as participating in HCMV pentamer-specific entry of non-fibroblast cells such as epithelial, trophoblast, and endothelial cells, respectively. This study focuses on characterizing the structural elements of CD46 that impact HCMV infection. Infectivity studies of wild-type and CD46 knockout epithelial cells demonstrated that levels of CD46 expressed on the cell surface were directly related to HCMV infectivity. Overexpression of CD46 isomers BC1, BC2, and C2 enhanced infection. Further, CD46 knockout epithelial cells expressing CD46 deletion and chimeric molecules identified that the intact ectodomain was critical for rescue of HCMV infection in CD46 knockout cells. Collectively, these data support a model that the extracellular domain of CD46 participates in HCMV infection due to its surface expression.


[Value of dexamethasone in purulent meningitis in children. Apropos of a comparative study of 85 children].
The beneficial effect of dexamethasone plus antibiotic therapy in bacterial meningitis is still controversial. Eighty-five children, aged 1 month to 14 years, were admitted between 1987 and 1990 for bacterial meningitis. They received the same antibiotic therapy for 10 days (7 days in meningococcal meningitis). The 44 children admitted since March 1989 were also given dexamethasone (0.15 mg/kg/6 hours for 4 days); the first injection was given before antibiotic therapy. Clinical (fever, neurological findings, audition) and laboratory data [CSF proteins, glucose, lactate, cell and bacterial counts; blood C-reactive protein (CRP), hemoglobin, leukocytes and platelets] were analyzed statistically. The group treated with antibiotics plus dexamethasone showed decreases significantly greater in CSF protein and lactate levels after 48 hours than the children given antibiotics alone and an early (6 hours after the start of treatment) increase in CSF glucose. The blood CRP level of the dexamethasone plus antibiotics group decreased significantly within 48 hours. The numbers of neurological sequelae and deaths in this group were clearly lower than for the antibiotic group, but the risk of deafness did not appear to be altered. These results confirm the beneficial effect of dexamethasone reported earlier. The relatively frequent transient recurrences of fever and increased CRP when dexamethasone was interrupted suggest that the dose and/or duration of dexamethasone treatment should be modified.


Preparation and Characterization of Novel Pimecrolimus Nanoparticles for Therapy of Allergic Conjunctivitis.
Pimecrolimus is a novel anti-inflammatory drug for treating allergic conjunctivitis. However, its high hydrophobicity is the bottleneck for clinical application on anti-allergic conjunctivitis. Although ongoing efforts have been made to increase its hydrophilicity through hydration, the results are discouraging. Now, we developed the nanoparticle-encapsule of pimecrolimus in a new material synthesized from polymannuronic acid and oleyl amine. The drug loading and encapsulation efficiency of pimecrolimus nanoparticle were measured by high-performance liquid chromatography, which were 12.38±0.04% and 94.58±0.07%, respectively. The mean particle size of pimecrolimus nanoparticle was 193.1±2.62 nm and polydisperse index was 0.176±0.018. Its spherical and homogeneous appearance were observed by transmission electron microscope. Furthermore, a mouse model of allergic conjunctivitis has been established to evaluate the efficacy of pimecrolimus nanoparticle. Treatment progress with clinical scoring and morphology of the conjunctiva histology were assessed in detail. The results have demonstrated that pimecrolimus nanoparticle could significantly relieve the inflammation signs of allergic conjunctivitis model mice and repair ocular surface goblet cells after a week of treatment twice a day. The improvement rate and inflammatory cell inhibition rate of the free pimecrolimus group versus pimecrolimus nanoparticle group were (49.18% vs. 71.26%), (67.43% vs. 81.18%), respectively. Such data further demonstrated pimecrolimus nanoparticle could be a good candidate as a promising ophthalmic agent for treating allergic conjunctivitis, meanwhile, a novel biodegradable seaweed polysaccharide derivative should be a potential carrier for lipophilic drug.


[The regional vaccination program in Europe (1991-1993)].
The European region is passing through a period of rapid transition with the most dramatic changes in the countries of central and eastern Europe (CCEE) and the former USSR. These countries are now facing serious economic problems, a dramatic rise in unemployment and social unrest which has had an impact on the development of the regional immunization programme. The provision of an adequate vaccine supply has become a priority for many States in the region in their efforts to sustain immunization activities. New operational targets for the EPI in Europe in the 1990s were established by the European Advisory Group (Copenhagen, February 1993). These operational targets identify the steps to be followed by countries in order to achieve, by the year 2000, no indigenous cases of poliomyelitis, diphtheria, neonatal tetanus, measles, mumps and congenital rubella. They also include a sustained and continuing reduction in the incidence and adverse consequences of other communicable diseases, notably HIV infection (European target 5). Immunization coverage is generally high and stable in the Region. It was observed in 1990-1992 that pockets of non-immunized persons in any country can lead to outbreaks of disease. Most Member States, however, do not yet use immunization coverage for operational purposes despite being encouraged to monitor by geographical unit. Insufficient protection against pertussis has been observed in countries including Italy, the Russian Federation and Sweden (where pertussis immunization is not obligatory) and represents the build-up of a large susceptible population.(ABSTRACT TRUNCATED AT 250 WORDS)


Differential ultrasonic indices of separation distress in the presence and absence of maternal cues in infant rats bred for high and low positive social affect.
Preclinical models of human mood disorders commonly focus on the study of negative affectivity, without comparably stressing the role of positive affects and their ability to promote resilient coping styles. We evaluated the role of background constitutional affect of rats by studying the separation and reunion responses of infants from low and high positive affect genetic lines (i.e., differentially selected for High and Low 50 kHz ultrasonic vocalisations (USVs). Infants from Low and High 50 kHz USV breeding lines were isolated from mothers and exposed to either social (familiar or unfamiliar bedding) or neutral (clean bedding) odour cues between two short isolation periods, and tested in homeothermic and hypothermic ambient temperatures. Negative affect was estimated by monitoring separation distress calls (35-45 kHz USVs). Low Line pups called at higher rates than High Line, and their rates were stable regardless of odour cue. In contrast, High Line pups increased vocalisations during the second compared with the first isolation periods and during exposure to both familiar and unfamiliar odour cues, but not to neutral odour. Furthermore, the greatest increase in USV emission was seen in the second isolation period following exposure to the unfamiliar odour. However, both lines showed comparable elevated distress USVs to the thermal stressor. High Line animals, selected for a positive affective phenotype (50 kHz USVs), exhibited reduced separation anxiety responses in infancy, making this a promising animal model for the role of constitutional affective states in emotional responsivity and potential resilience against emotional disorders.


Sensing Antibiotics in Wastewater Using Surface-Enhanced Raman Scattering.
Rapid and cost-effective detection of antibiotics in wastewater and through wastewater treatment processes is an important first step in developing effective strategies for their removal. Surface-enhanced Raman scattering (SERS) has the potential for label-free, real-time sensing of antibiotic contamination in the environment. This study reports the testing of two gold nanostructures as SERS substrates for the label-free detection of quinoline, a small-molecular-weight antibiotic that is commonly found in wastewater. The results showed that the self-assembled SERS substrate was able to quantify quinoline spiked in wastewater with a lower limit of detection (LoD) of 5.01 ppb. The SERStrate (commercially available SERS substrate with gold nanopillars) had a similar sensitivity for quinoline quantification in pure water (LoD of 1.15 ppb) but did not perform well for quinoline quantification in wastewater (LoD of 97.5 ppm) due to interferences from non-target molecules in the wastewater. Models constructed based on machine learning algorithms could improve the separation and identification of quinoline Raman spectra from those of interference molecules to some degree, but the selectivity of SERS intensification was more critical to achieve the identification and quantification of the target analyte. The results of this study are a proof-of-concept for SERS applications in label-free sensing of environmental contaminants. Further research is warranted to transform the concept into a practical technology for environmental monitoring.


The shape of the lateral edge of the first metatarsal head as a risk factor for recurrence of hallux valgus.
The relationship between the shape of the first metatarsal head and hallux valgus deformity remains controversial. The purpose of the present study was to retrospectively analyze differences in the radiographic appearance of the shape of the lateral edge of the first metatarsal head between women with normal feet and those with hallux valgus and to clarify the relationship between the shape of the lateral edge and the postoperative recurrence of hallux valgus deformity. Dorsoplantar weight-bearing radiographs of sixty normal feet in women (the control group) and sixty feet in women with hallux valgus (the hallux valgus group) were reviewed. The feet in the hallux valgus group were treated with a proximal metatarsal osteotomy, and the radiographs of those feet were assessed preoperatively, at the time of early follow-up (mean, 3.4 months), and at the time of the most recent follow-up (mean, forty-eight months). The shape of the lateral edge, which was defined as consisting of the articular and lateral surfaces of the first metatarsal head, was examined. The shape of the lateral edge was classified as one of three types: round (type R), angular (type A), and intermediate (type I). We defined the round sign as being positive when the shape of the lateral edge was classified as type R. Prior to surgery, the prevalence of the type-R shape was significantly greater in the hallux valgus group than it was in the control group (78.3% compared with 1.7%; p < 0.0001) and the prevalence of type-A shape was significantly lower in the hallux valgus group than in the control group (3.3% compared with 81.7%; p < 0.0001). In the hallux valgus group, the prevalence of the type-R shape at the time of the early follow-up after surgery was significantly lower than that before surgery (p < 0.0001). Feet with a positive round sign at the time of the early follow-up had a greater risk of having recurrence of the hallux valgus deformity at the time of the most recent follow-up than did those without a round sign at the time of the early follow-up (odds ratio, 12.71; 95% confidence interval, 3.21 to 50.36). There is a significant relationship between a round-shaped lateral edge of the first metatarsal head and hallux valgus, and a positive round sign after a proximal first metatarsal osteotomy can be a risk factor for the recurrence of hallux valgus.


Quantitative profiling of tissue drug distribution by MS imaging.
This article highlights recent advancements in the quantitative measurement of drug distribution by MS imaging (MSI). Quantitation by MSI was recently considering the primary disadvantage of MSI approaches particularly when compared with widely used autoradiography techniques. These approaches show significant progress in the area of quantitative MSI and have been used in numerous drug and metabolite distribution measurements. As quantitative limitations are overcome, the use of MSI in drug development should increase significantly providing key insights into both tissue-target validation as well as identifying off tissue-target issues with drug delivery.


Health disparities in receipt of screening mammography in Latinas: a critical review of recent literature.
Increased use of screening mammography is associated with lower death rates from breast cancer in the United States. Despite recommendations that women over 40 years of age should obtain regular screening mammography at least every 2 years, many women do not adhere to these guidelines. Historically, women from underserved and minority populations have been less likely to receive screening mammography. A critical review of recent research literature was conducted to evaluate whether Latinas are less likely to receive screening mammography, determine whether disparities in screening mammography persist when controlling for other variables, and examine what other variables are associated with screening mammography. The articles were obtained from a search of the PubMed database. Fifteen published articles met the inclusion criteria and were critically reviewed. The unadjusted odds ratios (ORs) of the association between Hispanic ethnicity and screening mammography ranged from 0.40 to 0.93. For the most part, the ORs adjusted for other variables in multiple logistic regression analyses increased (range: 0.3 to 1.67). Age, education, income, health insurance, having a usual source of care, and having a recent visit to a physician were consistently related to screening mammography in multiple logistic regression analysis. Hispanic ethnicity is a risk factor for lack of adherence to screening mammography. However, other demographic, socioeconomic, and health system variables account for some of the disparity related to Hispanic ethnicity.


Clinical and translational pharmacology of the cathepsin K inhibitor odanacatib studied for osteoporosis.
Cathepsin K (CatK) is a cysteine protease abundantly expressed by osteoclasts and localized in the lysosomes and resorption lacunae of these cells. CatK is the principal enzyme responsible for the degradation of bone collagen. Odanacatib is a selective, reversible inhibitor of CatK at subnanomolar potency. The pharmacokinetics of odanacatib have been extensively studied and are similar in young healthy men, postmenopausal women and elderly men, and were qualitatively similar throughout Phase 1 development and in-patient studies. Following 3 weeks of 50 mg once weekly dosing the geometric mean area under the curve from 0 to 168 hours was 41.1 μM h, the concentration at 168 hours was 126 nM and the harmonic mean apparent terminal half-life was 84.8 hr. Odanacatib exposure increased in a less than dose proportional manner due to solubility limited absorption. It is estimated that approximately 70% of the absorbed dose of odanacatib is eliminated via metabolism, 20% is excreted as unchanged drug in the bile or faeces, and 10% is excreted as unchanged drug in the urine. The systemic clearance was low (approximately 13 mL/min). Odanacatib decreases the degradation of bone matrix proteins and reduces the efficiency of bone resorption with target engagement confirmed by a robust decrease in serum C-telopeptides of type 1 collagen (approximately 60%), urinary aminoterminal crosslinked telopeptides of type 1 collagen to creatinine ratio (approximately 50%) and total urine deoxypyridinoline/Cr (approximately 30%), with an increase in serum cross-linked carboxy-terminal telopeptide of type 1 collagen (approximately 55%). The 50-mg weekly dosing regimen evaluated in Phase 3 achieved near maximal reduction in bone resorption throughout the treatment period. The extensive clinical programme for odanacatib, together with more limited clinical experience with other CatK inhibitors (balicatib and ONO-5334), provides important insights into the clinical pharmacology of CatK inhibition and the potential role of CatK in bone turnover and mineral homeostasis. Key findings include the ability of this mechanism to: (i) provide sustained reductions in resorption markers, increases in bone mineral density, and demonstrated fracture risk reduction; (ii) be associated with relative formation-sparing effects such that sustained resorption reduction is achieved without accompanying meaningful reductions in bone formation; and (iii) lead to increases in osteoclast number as well as other osteoclast activity (including build-up of CatK enzyme), which may yield transient increases in resorption following treatment discontinuation and the potential for nonmonotonic responses at subtherapeutic doses.


Multiple Factors Determine the Structure of Bacterial Communities Associated With Aedes albopictus Under Artificial Rearing Conditions.
Insect symbionts are major manipulators of host's behavior. Their effect on parameters such as fecundity, male mating competitiveness, and biological quality in general, can have a major influence on the effectiveness of the sterile insect technique (SIT). SIT is currently being developed and applied against human disease vectors, including Ae. albopictus, as an environment-friendly method of population suppression, therefore there is a renewed interest on both the characterization of gut microbiota and their exploitation in artificial rearing. In the present study, bacterial communities of eggs, larvae, and adults (both males and females) of artificially reared Ae. albopictus, were characterized using both culture-dependent and culture-independent approaches. Mosquito-associated bacteria corresponding to thirteen and five bacteria genera were isolated from the larval food and the sugar solution (adult food), respectively. The symbiont community of the females was affected by the provision of a blood meal. Pseudomonas and Enterobacter were either introduced or enhanced with the blood meal, whereas Serratia were relatively stable during the adult stage of females. Maintenance of these taxa in female guts is probably related with blood digestion. Gut-associated microbiota of males and females were different, starting early after emergence and continuing in older stages. Our results indicate that eggs contained bacteria from more than fifteen genera including Bacillus, Chryseobacterium, and Escherichia-Shigella, which were also main components of gut microbiota of female adults before and after blood feeding, indicating potential transmission among generations. Our results provided a thorough study of the egg- and gut-associated bacteria of artificially reared Ae. albopictus, which can be important for further studies using probiotic bacteria to improve the effectiveness of mosquito artificial rearing and SIT applications.


Neuromuscular Electrical Stimulation Training vs. Conventional Strength Training: A Systematic Review and Meta-Analysis of the Effect on Strength Development.
Happ, KA, and Behringer, M. Neuromuscular electrical stimulation Training vs. conventional strength training: a systematic review and meta-analysis of the effect on strength development. J Strength Cond Res 36(12): 3527-3540, 2022-A systematic review of the current state of literature and a meta-analysis were conducted to compare the strength development between neuromuscular electrical stimulation (NMES) and conventional strength training when training volume is matched. Searches of PubMed and several other databases were conducted for studies that met the following primary inclusion criteria: randomized studies of >20 days duration with a sample size of >4 subjects in each group ("voluntary contraction" [VC] and "electrically stimulated" [ES]) conducted with percutaneous stimulation only in healthy individuals at equal training volume. Finally, a total of 19 studies were included in the analysis. When comparing strength gains between groups (ES-VC), no favorable effect toward a training method could be observed (0.023 hg [95% CI: -0.198 to 0.246, p = 0.836]). Subgroup analyses were performed based on the application type (NMES evoked and NMES onto voluntary contractions) and stimulation frequency. Both analyses revealed no favorable effect and significant difference of groups (significance level set at 0.05). A meta-regression evaluated the relationship between stimulation frequency and effect size difference. The regression showed a tendency of higher stimulation frequencies being associated with higher study effect size differences (predicted effect size = -0.599 + 0.008 (Hz) ( p = 0.176)). The findings indicate that training with NMES results in virtually identical strength gains compared with conventional strength training when training volume is matched. If training with NMES is preferred, the stimulation frequency type (regular or Burst Mode Alternating Current) can be chosen according to preference without loss of effectiveness.


The role of phenylalanine hydroxylase in lipogenesis in the oleaginous fungus Mortierella alpina.
Phenylalanine hydroxylase (PAH) catalyses the irreversible hydroxylation of phenylalanine to tyrosine, which is the rate-limiting reaction in phenylalanine metabolism in animals. A variety of polyunsaturated fatty acids can be synthesized by the lipid-producing fungus Mortierella alpina, which has a wide range of industrial applications in the production of arachidonic acid. In this study, RNA interference (RNAi) with the gene PAH was used to explore the role of phenylalanine hydroxylation in lipid biosynthesis in M. alpina. Our results indicated that PAH knockdown decreased the PAH transcript level by approximately 55% and attenuated cellular fatty acid biosynthesis. Furthermore, the level of NADPH, which is a critical reducing agent and the limiting factor in lipogenesis, was decreased in response to PAH RNAi, in addition to the downregulated transcription of other genes involved in NADPH production. Our study indicates that PAH is part of an overall enzymatic and regulatory mechanism supplying NADPH required for lipogenesis in M. alpina.


Micronutrient status of Indian population.
Micronutrients play an important role in the proper growth and development of the human body and its deficiency affects the health contributing to low productivity and vicious cycle of malnutrition, underdevelopment as well as poverty. Micronutrient deficiency is a public health problem affecting more than one-fourth of the global population. Several programmes have been launched over the years in India to improve nutrition and health status of the population; however, a large portion of the population is still affected by micronutrient deficiency. Anaemia, the most common form of micronutrient deficiency affects almost 50 to 60 per cent preschool children and women, while vitamin A deficiency and iodine-deficiency disorders (IDD) have improved over the years. This review focuses on the current scenario of micronutrient (anaemia, vitamin A, iodine, vitamin B12, folate, ferritin, zinc, copper and vitamin C) status in the country covering national surveys as well as recent studies carried out.


Evolutionary conservation of DNA methylation in CpG sites within ultraconserved noncoding elements.
Ultraconserved noncoding elements (UCNEs) constitute less than 1 Mb of vertebrate genomes and are impervious to accumulating mutations. About 4000 UCNEs exist in vertebrate genomes, each at least 200 nucleotides in length, sharing greater than 95% sequence identity between human and chicken. Despite extreme sequence conservation over 400 million years of vertebrate evolution, we show both ordered interspecies and within-species interindividual variation in DNA methylation in these regions. Here, we surveyed UCNEs with high CpG density in 56 species finding half to be intermediately methylated and the remaining near 0% or 100%. Intermediately methylated UCNEs displayed a greater range of methylation between mouse tissues. In a human population, most UCNEs showed greater variation than the LINE1 transposon, a frequently used epigenetic biomarker. Global methylation was found to be inversely correlated to hydroxymethylation across 60 vertebrates. Within UCNEs, DNA methylation is flexible, conserved between related species, and relaxed from the underlying sequence selection pressure, while remaining heritable through speciation.


[Effects of ophiopogonin D on fatty acid metabolic enzymes in cardiomyocytes].
To explore the effect of ophiopogonin D on main fatty acid metabolic enzymes in human cardiomyocyte AC-16,so as to provide reference for cardiovascular protection mechanism and safe clinical application of Ophiopogon japonicus.CCK-8 (cell counting kit-8) was used to detect the effect of different concentrations of ophiopogonin D on the viability of cardiomyocytes.Meanwhile,the effect of different concentrations of ophiopogonin D on the morphology and quantity of cardiomyocytes was observed under microscope.The effect of ophiopogonin D on the mRNA expression of CYP2J2,CYP4F3,CYP4A11,CYP4A22 and CYP4F2 in cardiomyocytes was detected by RT-PCR.Western blot was used to detect the protein expression of CYP4F3 in different concentrations of ophiopogonin D.Compared with the control group,low-concentration ophiopogonin D had no effect on the viability of cardiomyocytes.However,ophiopogonin D with a concentration of higher than 20μmol·L~(-1)could promote the viability.Under the microscope,ophiopogonin D with a concentration of below 100μmol·L~(-1)had no significant effect on the morphology and number of cardiomyocytes.RT-PCR results showed that compared with the control group,5μmol·L~(-1)ophiopogonin D could slightly up-regulate mRNA expressions of CYP2J2 and CYP4F3,while high-concentration ophiopogonin D (10 and 20μmol·L~(-1)) could significantly induce mRNA expressions of CYP2J2and CYP4F3 in a dose-dependent manner (P<0.05).The same concentration of ophiopogonin D had a little effect on the mRNA expressions of CYP4A11,CYP4A22 and CYP4F2.Western blot results showed that 20μmol·L~(-1)ophiopogonin D could significantly induce the protein expression of CYP4F3 in a dose-dependent manner (P<0.05).Based on the above results,ophiopogonin D (less than100μmol·L~(-1)) has no effect on the viability of AC-16 cardiomyocytes.Ophiopogonin D (less than 100μmol·L~(-1)) can selectively induce the expressions of CYP2J2 and CYP4F3,regulate the metabolic pathway of fatty acid signaling molecules,and thus protecting the cardiovascular system.


A criterion for the selection of artificial posterior teeth.
Mandibular movement and masticatory performance were evaluated in the edentulous patients with an experimental denture using posterior artificial teeth of different occlusal schemes in order to determine the criterion for the selection of posterior artificial teeth. Lower masticatory performance was observed with non-anatomic posterior teeth than with semi-anatomic or anatomic ones regardless of the condition of residual ridge and inclination of the horizontal condylar guidance. The value of the lateral component of the masticatory cycle was closely related to the inclination of the cusp and the value of masticatory performance. This suggested strongly that the component could be a criteria for the selection of the type of the artificial posterior teeth.


Longitudinal patterns of mental health service utilisation by those with mental-physical comorbidity in the community.
Successful healthcare integration demands an understanding of current service utilisation by people with comorbidity. Physical illness may impact on mental health service use (MHSU), but longitudinal studies of comorbidity and MHSU are rare. This study 1) estimated associations between mental-physical comorbidity and longitudinal MHSU patterns; 2) tested whether associations between comorbidity and continuous MHSU are driven by "need". Survey data from a South East London community cohort were used (N = 1052). Common mental disorder symptoms (CMDS) were measured using the Clinical Interview Schedule Revised and self-report of long-standing disorders. A checklist of common conditions measured chronic physical conditions. MHSU captured self-reported use of mental health services in the past year at two time points. "Need" indicators included CMDS at follow-up, suicidal ideation, somatic symptom severity, self-rated health, daily functioning problems and perceived functioning limitations due to emotional health. Analyses used logistic and multinomial regression. Continuous MHSU (at both time-points) was twice as commonly reported by those with comorbidity than those without physical comorbidity (30.9% vs 12.3%). CMDS at follow-up, suicidal ideation, and perceived functioning limitations due to emotional health only partially explained the association between CMDS-physical comorbidity and continuous MHSU. In the adjusted model, comorbidity remained associated with continuous MHSU (RRR = 3.23, 95% CI: 1.39-7.51; p = .002), while the association for non-comorbid CMDS was fully attenuated (RRR = 1.08, 95% CI: 0.40-2.93; p = .85). CMDS-physical comorbidity was strongly associated with continuous MHSU, and "need" did not account for this association, suggesting that comorbidity itself represents a "need" indicator.


Actinomycosis in fine needle aspiration cytology.
Four cases of actinomycosis were diagnosed by fine needle aspiration (FNA) cytology and eight more cases were detected during a review of FNA smears reported as inflammatory. The age of these 12 cases ranged from 20 to 61 years with a median of 35 years. The male to female ratio was 3:1. The common regions of involvement were cervicofacial in seven cases (58.3%), thoracic in three (25.0%) and abdominal in two (16.7%). Four of the seven cervicofacial cases presented with intra-oral masses; the thoracic lesions were pulmonary in location, and the abdominal lesions presented as bowel masses. The possibility of actinomycosis was not considered clinically in any case. The main reason for missed cytodiagnosis in two thirds of the cases appeared to be observer error. It is suggested that when the aspiration smear from a mass is found to be an inflammatory exudate rich in neutrophils, special efforts must be made to look for this microorganism.


USP2 is an SKP2 deubiquitylase that stabilizes both SKP2 and its substrates.
The stability of a protein is regulated by a balance between its ubiquitylation and deubiquitylation. S-phase kinase-associated protein 2 (SKP2) is an oncogenic F-box protein that recognizes tumor suppressor substrates for targeted ubiquitylation by the E3 ligase SKP1-Cullin1-F-box and degradation by proteasome. SKP2 is itself ubiquitylated by the E3 ligases APC/CCDH1 and SCFFBXW2, and deubiquitylated by deubiquitylases (DUBs) USP10 and USP13. Given the biological significance of SKP2, it is likely that the other E3s or DUBs may also regulate its stability. Here, we report the identification and characterization of USP2 as a new DUB. We first screened a panel of DUBs and found that both USP2 and USP21 bound to endogenous SKP2, but only USP2 deubiquitylated and stabilized SKP2 protein. USP2 inactivation via siRNA knockdown or small-molecule inhibitor treatment remarkably shortened SKP2 protein half-life by enhancing its ubiquitylation and subsequent degradation. Unexpectedly, USP2-stabilized SKP2 did not destabilize its substrates p21 and p27. Mechanistically, USP2 bound to SKP2 via the leucine-rich repeat substrate-binding domain on SKP2 to disrupt the SKP2-substrate binding, leading to stabilization of both SKP2 and these substrates. Biologically, growth suppression induced by USP2 knockdown or USP2 inhibitor is partially mediated via modulation of SKP2 and its substrates. Our study revealed a new mechanism of the cross-talk among the E3-DUB substrates and its potential implication in targeting the USP2-SKP2 axis for cancer therapy.


Recurrent copy number alterations in young women with breast cancer.
Breast cancer diagnosis in young women has emerged as an independent prognostic factor with higher recurrence risk and death than their older counterparts. We aim to find recurrent somatic copy number alteration (CNA) regions identified from breast cancer microarray data and associate the CNA status of the genes harbored in the regions to the survival of young women with breast cancer. By using the interval graph-based algorithm we developed, and the CNA data consisting of a Discovery set with 130 young women and a Validation set with 125 young women, we identified 38 validated recurrent CNAs containing 39 protein encoding genes. CNA gain regions encompassing genes CAPN2, CDC73 and ASB13 are the top 3 with the highest occurring frequencies in both the Discovery and Validation dataset, while gene SGCZ ranked top for the recurrent CNA loss regions. The mutation status of 9 of the 39 genes shows significant associations with breast cancer specific survival. Interestingly, the expression level of 2 of the 9 genes, ASB13 and SGCZ, shows significant association with survival outcome. Patients with CNA mutations in both of these genes had a worse survival outcome when compared to patients without the gene mutations. The mutated CNA status in gene ASB13 was associated with a higher gene expression, which predicted patient survival outcome. Together, identification of the CNA events with prognostic significance in young women with breast cancer may be used in genomic-guided treatment.


Tumor encasement of the right coronary artery: role of anatomic and functional imaging in diagnosis and therapeutic management.
We presented two rare cases of mediastinal tumor encasing the right coronary artery (RCA), one with recurrent metastatic thymoma and another with primary poorly differentiated neoplasm. Different degrees and locations of RCA involvement were noted. The treatment approach varied from conservative to surgical. Coronary artery involvement by mediastinal tumors is important to be investigated with imaging as it may guide the surgical planning.


Long-Term Follow-Up of the Fellow Eye in Patients Undergoing Surgery on One Eye for Treating Myopic Traction Maculopathy.
Objective. To observe the fellow eye in patients undergoing surgery on one eye for treating myopic traction maculopathy. Methods. 99 fellow eyes of consecutive patients who underwent unilateral surgery to treat MTM were retrospectively evaluated. All patients underwent thorough ophthalmologic examinations, including age, gender, duration of follow-up, refraction, axial length, intraocular pressure, lens status, presence/absence of a staphyloma, and best-corrected visual acuity (BCVA). Fundus photographs and SD-OCT images were obtained. When feasible, MP-1 microperimetry was performed to evaluate macular sensitivity and fixation stability. Results. At an average follow-up time of 24.7 months, 7% fellow eyes exhibited partial or complete MTM resolution, 68% stabilized, and 25% exhibited progression of MTM. Of the 38 eyes with "normal" macular structure on initial examination, 11% exhibited disease progression. The difference in progression rates in Groups 2, 3, and 4 was statistically significant. Refraction, axial length, the frequency of a posterior staphyloma, chorioretinal atrophy, initial BCVA, final BCVA, and retinal sensitivity all differed significantly among Groups 1-4. Conclusions. Long axial length, chorioretinal atrophy, a posterior staphyloma, and anterior traction contribute to MTM development. Patients with high myopia and unilateral MTM require regular OCT monitoring of the fellow eye to assess progression to myopic pre-MTM. For cases exhibiting one or more potential risk factors, early surgical intervention may maximize the visual outcomes.


Increase in interleukin-6 following arterial injury is related to insulin resistance, the -174G-->C polymorphism and complex plaque morphology.
Interleukin-6 (IL-6) is associated with many disease states in humans. We prospectively sought to determine whether IL-6 levels increased following percutaneous coronary intervention (PCI) in the absence of myonecrosis. Additionally, we systematically assessed other clinical and anatomic factors associated with IL-6 levels in a population of patients with coronary atherosclerosis undergoing PCI. Blood samples were collected from 117 patients at baseline, 8 and 16 h following PCI. Samples were assayed for IL-6, creatine kinase-myocardial band (CK-MB), troponin-I (Tn-I), high sensitivity C-reactive protein, glucose, haemoglobin A1c, and a lipid profile. Genotyping of the -174G-->C polymorphism of the IL-6 gene was performed. IL-6 levels increased following PCI among the study group (slope = 0.4 pg/mL/h, P = 0.001). IL-6 levels increased to a similar degree in the absence of myonecrosis. Patients with the XC genotype (either having the GC or the CC allele) had higher IL-6-values at baseline compared to GG genotype patients (4.9 +/- 6.4 vs. 2.6 +/- 1.8 pg/mL, P = 0.02). Multivariable predictors of detectable baseline IL-6 levels included XC genotype (odds ratio [OR]: 4.14, 95% CI 1.58-10.82, P = 0.004), ACC/AHA type C lesion classification (OR: 4.08, 95% CI 1.54-10.84, P = 0.005), elevated baseline Tn-I (OR: 3.31, 95% CI 1.16-9.43, P = 0.025), diabetes (OR: 3.00, 95% CI 1.11-8.09, P = 0.030), and waist circumference (OR: 1.49, 95% CI 1.08-2.06, P = 0.015). Predictors of peak IL-6 following PCI included the XC genotype (estimate 1.4, 95% CI 1.06-1.87, P = 0.019), homeostasis model assessment (estimate 0.99, 95% 0.982-0.999, P = 0.042) and baseline Tn-I > upper limit of normal (estimate 0.7, 95% CI 0.50-0.96, P = 0.039). Lastly, IL-6 increased following PCI even in the absence of myonecrosis as measured by Tn-I elevation. IL-6 levels are also related to the -174G-->C polymorphism, arterial injury, lesion complexity, and insulin resistance.


Photodynamic therapy with hematoporphyrin derivative for recurrent plantar cutaneous squamous cell carcinoma: A case report.
Cutaneous squamous cell carcinoma (cSCC) is a prevalent malignant tumor typically treated through surgical removal. However, when the lesion is situated in specific areas like the hands, feet, or lips, particularly if it's sizable, surgical interventions can adversely impact appearance and function. In such cases, non-surgical treatments are preferable to preserve both aesthetics and functionality. We present a case of recurrent cSCC on the plantar region post-surgery. Given the extensive lesion area, deep infiltration, and the patient's reliance on foot function, hematoporphyrin derivative-photodynamic therapy (HpD-PDT) was chosen over traditional surgery. The lesion was successfully treated, and while a minor recurrence was observed after 20 months, it was localized and amenable to non-surgical intervention. We posit that HpD-PDT is a viable treatment for cSCC, especially in unique locations, with extensive lesions, and postoperative recurrence.


Substrate specificity of citrate lyase deacetylase of Rhodopseudomonas gelatinosa and Rhodopseudomonas palustris.
Citrate lyase (EC 184.108.40.206) isolated from Rhodopseudomonas palustris was investigated with regard to its kinetic properties and its subunit composition. This enzyme was inactivated by citrate lyase deacetylase (EC 3.1.2.-) of Rhodopseudomonas gelatinosa. A corresponding cross-reaction was measured with partially purified deacetylase of R. palustris and citrate lyase of R. gelatinosa. The three different subunit types (alpha, beta, and gamma) of citrate lyase from R. gelatinosa wee purified to homogeneity, and antibodies were prepared against each of the three subunits and against the native enzyme complex. In corresondence with the enzymatic interactions, immunological cross-reactions were found between anti-enzyme and anti-large subunit antibodies and citrate lyase from R. palustris. On the other hand, no immunological cross-reactions were detectable among each of the antibodies and citrate lyases from Enterobacter aerogenes, Streptococcus diacetilactis, and Clostridium sphenoides. Antibodies against the large subunit of citrate lyase inhibited the deacetylase, but antibodies against the middle and small subunits did not, indicating that the large subunits of citrate lyase are involved in binding the deacetylase.


Inheritance of Ag-stainability of the nucleolus organizer regions in domestic sheep, Ovis aries.
One of the nucleolus organizer regions of sheep is located on chromosome 25, which forms one arm of a Robertsonian translocation chromosome (t3). By mating sheep heterozygous and homozygous for the t3 chromosome, and with various Ag-staining frequencies and deposit sizes, the heritability of the Ag-stainability could be determined. The inheritance of Ag-stainability was studied in 54 sheep in five pedigree groups. It was shown that the Ag-staining of a NOR is a heritable property. Matings of animals heterozygous for Ag-stainability provided an estimate of recombination frequency of the short arm of t3.


Notes on the hosts of Trissolcus Ashmead (Hymenoptera: Scelionidae) from China.
Trissolcus Ashmead (Hymenoptera: Scelionidae) is a cosmopolitan genus of egg-parasitoid wasps associated with stink bugs (Pentatomidae, Scutelleridae, Urostylididae), many of which are important insect pests. Documentation of host associations for these wasps, which we here provide via museum specimens, can support their use as biological control agents of invasive stink bugs. The hosts of seven Trissolcus species are reported from China: Trissolcus cultratus (Mayr) (hosts: Hippotiscus dorsalis Stål, Pentatomidae; Urochela luteovaria Distant, Urostylididae), Trissolcus elasmuchae (Watanabe) (host: Niphe elongata (Dallas), Pentatomidae), Trissolcus japonicus (Ashmead) (hosts: Erthesina fullo (Thunberg), Pentatomidae; Rhaphigaster nebulosa (Poda), Pentatomidae), Trissolcus latisulcus (Crawford) (host: Poecilocoris latus Dallas, Scutelleridae), Trissolcus mitsukurii (Ashmead) (host: Pentatomidae), Trissolcus semistriatus (Nees von Esenbeck) (host: Eurydema sp., Scutelleridae), Trissolcus yamagishii Ryu (host: Niphe elongata (Dallas), Pentatomidae).


Another first for nursing.
Traditionally, doctors have ordered blood transfusions, but nurses are learning to take on this role. Since his training last year, nurse practitioner and prescriber Steve Wright has been authorising blood transfusions on a surgical ward in a London hospital and seeing the benefits for patients.


Cutaneous intravascular CD30+ T-cell pseudolymphoma occurring in a regressing keratoacanthoma.
Cutaneous intravascular CD30+ pseudolymphoma is an uncommon incidental finding that may mimic intravascular or angiotropic lymphoma. We describe a 78-year-old female with a traumatized regressing keratoacanthoma on her left cheek. A shave biopsy revealed intravascular staining of atypical lymphocytes positive for CD45, CD3 and CD30. Clinical exam revealed no other evidence of lymphoma, the patient denied constitutional symptoms, and routine blood work was normal. The patient is healthy and doing well 28 months after her first visit. CD30+ pseudolymphoma should be distinguished from malignant intravascular lymphoproliferative disorders.


Comparison of corneal endothelial cell images from a noncontact specular microscope and a scanning confocal microscope.
We compared endothelial cell density (ECD) from images recorded by the ConfoScan 3 confocal microscope and a noncontact specular microscope. Endothelial micrographs of 50 normal corneas of 25 subjects were acquired by a Konan Noncon Robo noncontact specular microscope (Konan Medical, Inc., Hyogo, Japan) and a ConfoScan 3 confocal microscope (Nidek Technologies, Inc, Greensboro, NC). ECD was determined in images from both instruments by using the HAI CAS System Corners Method (HAI Labs, Inc., Lexington, MA). Distances in the images from both machines were calibrated from images of an external scale. Images from the ConfoScan 3 were also assessed using the automated endothelial analysis software provided by the manufacturer, with and without manual correction. The ECD was 2634 +/- 186 cells/mm(2) (mean +/- SD) and 2664 +/- 173 cells/mm(2) by the Robo and ConfoScan 3 Corners methods, respectively. Differences between these 2 methods were not significant. When the automated analysis software was used, however, significant differences were found (P = 0.001). The uncorrected analysis program provided with the ConfoScan 3 indicated a higher ECD (2742 +/- 284 cells/mm(3)) than the Corners method did with images from the Robo and ConfoScan 3. The ECD from the manually corrected ConfoScan 3 method was 2716 +/- 229 cells/mm(3), not significantly different from the ConfoScan 3 Corners method but significantly different from the Robo Corners method. The ConfoScan 3 can be used interchangeably with the Robo when the Corners method is used to assess ECD and the magnification of both microscopes is calibrated with an external scale. If the proprietary software provided with the ConfoScan 3 is used, it should be manually corrected.


Community-Driven Hypothesis Testing: A Solution for the Tragedy of the Anticommons.
Shared ownership of property and resources is a longstanding challenge throughout history that has been amplifying with the increasing development of industrial and postindustrial societies. Where governments, project planners, and commercial developers seek to develop new infrastructure, industrial projects, and various other land-and resource-intensive tasks, veto power shared by various local stakeholders can complicate or halt progress. Risk communication has been used as an attempt to address stakeholder concerns in these contexts, but has demonstrated shortcomings. These coordination failures between project planners and stakeholders can be described as a specific kind of social dilemma that we describe as the "tragedy of the anticommons." To overcome such dilemmas, we demonstrate how a two-step process can directly address public mistrust of project planners and public perceptions of limited decision-making authority. This approach is examined via two separate empirical field experiments in Portugal and Tunisia, where public resistance and anticommons problems threatened to derail emerging industrial projects. In both applications, an intervention is undertaken to address initial public resistance to such projects, where specific public stakeholders and project sponsors collectively engaged in a hypothesis-testing process to identify and assess human and environmental health risks associated with proposed industrial facilities. These field experiments indicate that a rigorous attempt to address public mistrust and perceptions of power imbalances and change the pay-off structure of the given dilemma may help overcome such anticommons problems in specific cases, and may potentially generate enthusiasm and support for such projects by local publics moving forward.


Prevalence of abdominal obesity and associated risk factors among women civil servants in Addis Ababa, Ethiopia, 2021: an institution-based study.
Abdominal obesity increases the risk of cardio-metabolic diseases, disability, and poor quality of life, as well as health-care costs. It is a component of the metabolic syndrome, along with hypertension, diabetes, and dyslipidemia. The goal of this study was to determine the prevalence of abdominal obesity and associated risk factors among female civil servants in Addis Ababa, Ethiopia in 2021. An institution-based cross-sectional study was undertaken from March31st to April 15th, 2021.A multi-stage sampling technique was employed to select 478 study participants. Data was entered into EpiData version 3.1 and then exported to SPSS version 21 for analysis. A descriptive data analysis was used to present the distribution of study variables. Bivariable and multivariable analyses were used to assess the relationship between independent variables and abdominal obesity at 95% CI. The level of statistical significance was declared at a p-value less than 0.05. The prevalence of abdominal obesity defined by waist circumference was found to be29.5% (95% CI: 25.39-33.6%) and 32.8% (95% CI: 28.57%-37.03%) by waist hip ratio, respectively. Age group 29-37 years [AOR= 2.451, 95% CI: (1.199-5.013)], age group 38-46 years [AOR=3.807, 95% CI: (1.328-10.914)], age group 47-55 years [AOR=6.489, 95% CI: (1.367-30.805)], being married [AOR= 4.762, 95% CI: (2.321-9.721)],consumption of meat >=5 per week[ AOR= 4.764, 95% CI: (1.939-11.711)], having lunch daily[AOR= 0.388, 95% CI:(0.166-0.910)] and snack consumption [AOR=4.163, 95% CI:(1.503-11.534)] were significantly associated with abdominal obesity. The prevalence of abdominal obesity as measured by waist circumference and waist hip ratio was found to be moderate and high, respectively. Age, being married, high consumption of meat, and having lunch daily were identified as associated with abdominal obesity. Healthy diet health education and nutrition intervention should be considered, with a focus on married, meat-consuming, and older age-group female civil servants.


Electrochemical and Electrophysiological Performance of Platinum Electrodes Within the Ninety-Nine-Electrode Stimulating Nerve Cuff.
The trend in neural prostheses using selective nerve stimulation for electrical stimulation therapies is headed toward single-part systems having a large number of working electrodes (WEs), each of which selectively stimulate neural tissue or record neural response (NR). The present article reviews the electrochemical and electrophysiological performance of platinum WE within a ninety-nine-electrode spiral cuff for selective nerve stimulation and recording of peripheral nerves, with a focus on the vagus nerve (VN). The electrochemical properties of the WE were studied in vitro using the electrochemical impedance spectroscopy (EIS) technique. The equivalent circuit model (ECM) of the interface between the WE and neural tissue was extracted from the EIS data and simulated in the time domain using a preset current stimulus. Electrophysiological performance of in-space and fiber-type highly selective vagus nerve stimulation (VNS) was tested using an isolated segment of a porcine VN and carotid artery as a reference. A quasitrapezoidal current-controlled pulse (stimulus) was applied to the VN or arterial segment using an appointed group of three electrodes (triplet). The triplet and stimulus were configured to predominantly stimulate B-fibers and minimize the stimulation of A-fibers. The EIS results revealed capacitive charge transfer predominance, which is a highly desirable property. Electrophysiological performance testing indicated the potential existence of certain parameters and waveforms of the stimulus for which the contribution of the A-fibers to the NR decreased slightly and that of the B-fibers increased slightly. Findings show that the design of the stimulating electrodes, based on the EIS and ECM results, could act as a useful tool for nerve cuff development.


The Impostor Phenomenon Among Nursing Students and Nurses: A Scoping Review.
The impostor phenomenon (IP) refers to a false internal experience of low intelligence or ability that is associated with anxiety, depression, psychological distress, and burnout. The emotions associated with the IP affect not only personal mental health but also patient care. To address this issue, we need to completely understand the prevalence of and factors related to the IP and ways to resolve/overcome IP feelings. The aim of this scoping review was to identify the existing evidence regarding the IP among nursing students and nurses and determine gaps that can be addressed in future research. We conducted our study based on the scoping review methodological framework proposed by Arksey and O'Malley (2005) and advanced by Levac et al. (2010). After searching the Embase, PubMed, Cumulative Index to Nursing and Allied Health Literature (CINAHL), Cochrane Library, Web of Science and ProQuest databases, we identified 11 studies for inclusion in this review. We found that while the IP exists in nursing students and nurses, clinical nurse specialist students and final-year nursing students are at significant risk of impostor behavior. We also found that research in the nursing field has focused on the prevalence of and factors related to the IP, but few studies have addressed ways to resolve/overcome IP feelings. Thus, research in this area should be increased. This scoping review presents research gaps that may serve as a starting point for future work on the IP in the nursing field.


Scikit-ribo Enables Accurate Estimation and Robust Modeling of Translation Dynamics at Codon Resolution.
Ribosome profiling (Ribo-seq) is a powerful technique for measuring protein translation; however, sampling errors and biological biases are prevalent and poorly understood. Addressing these issues, we present Scikit-ribo (https://github.com/schatzlab/scikit-ribo), an open-source analysis package for accurate genome-wide A-site prediction and translation efficiency (TE) estimation from Ribo-seq and RNA sequencing data. Scikit-ribo accurately identifies A-site locations and reproduces codon elongation rates using several digestion protocols (r = 0.99). Next, we show that the commonly used reads per kilobase of transcript per million mapped reads-derived TE estimation is prone to biases, especially for low-abundance genes. Scikit-ribo introduces a codon-level generalized linear model with ridge penalty that correctly estimates TE, while accommodating variable codon elongation rates and mRNA secondary structure. This corrects the TE errors for over 2,000 genes in S. cerevisiae, which we validate using mass spectrometry of protein abundances (r = 0.81), and allows us to determine the Kozak-like sequence directly from Ribo-seq. We conclude with an analysis of coverage requirements needed for robust codon-level analysis and quantify the artifacts that can occur from cycloheximide treatment.


Quantitation of the sulfur mustard metabolites 1,1'-sulfonylbis[2-(methylthio)ethane] and thiodiglycol in urine using isotope-dilution Gas chromatography-tandem mass spectrometry.
Sulfur mustard (HD), or bis(2-chloroethyl)sulfide, has several urinary metabolites that can be measured to assess human exposure. These metabolites include the simple hydrolysis product thiodiglycol (TDG) and its oxidative analogue, TDG-sulfoxide, as well as metabolites of the glutathione/b-lyase pathway 1,1'-sulfonylbis[2-(methyl-sulfinyl)ethane] (SBMSE) and 1-methyl-sulfinyl-2-[(methylthio)ethyl-sulfonyl]ethane (MSMTESE). Current methods focus on either the TDG or the b-lyase metabolites. We have developed a single method that measures products of both metabolic branches, with the reduced compound of SBMSE and MSMTESE, 1,1'-sulfonylbis [2(methylthio)ethane] (SBMTE), as the definitive analyte and TDG as a confirmation analyte. Sample preparation included b-glucuronidase hydrolysis for TDG-glucuronide conjugates, titanium trichloride reduction of sulfoxides to SBMTE and TDG, solid-phase extraction, and a chemical derivatization. We analyzed samples using gas chromatography-tandem mass spectrometry with quantitation using isotope-dilution calibration. The method limits of detection for TDG and SBMTE were 0.5 ng/mL and 0.25 ng/mL, respectively, with relative standard deviations of less than 10%. Urine samples from individuals with no known exposure to mustard agent HD had measurable concentrations of TDG, but no SBMTE was detected. The geometric mean concentration of TDG was 3.43 ng/mL, with concentrations ranging from < 0.5 ng/mL to 20 ng/mL.


New intrauterine growth percentiles: a hospital-based study in Istanbul, Turkey.
To develop gender and gestation-specific growth percentiles for singleton live-born neonates and to compare new weight for age unisex percentiles with Lubchenco unisex percentiles. Cross-sectional birth data were collected from the neonatal registry from January 2000 to April 2006 (n = 15.509). After exclusion, the sample included 15.112 neonates. Newly developed weight for age, charts were compared with Lubchenco unisex percentiles, 91.8% of the subjects were classified in the same way (Kappa = 0.74, P < 0.001). Small for gestational age (SGA) and large for gestational age (LGA) according to the Lubchenco percentiles differed from the new percentiles (Mc Nemar test, P < 0.001). The percentage of SGA neonates was underestimated by Lubcheno percentile (5.8% vs. 10.6%, respectively), whereas the percentage of LGA neonates was overestimated by Lubcheno percentile (10.3% vs. 9.3%, respectively). New growth chart for newborn delivered at different gestational ages have been established, which can be used to define SGA and LGA in Turkish neonates. Studies comparing the Lubchenco percentiles with new percentiles are needed.