Climate change adaptation in conflict-affected countries: A systematic assessment of evidence.
People affected by conflict are particularly vulnerable to climate shocks and climate change, yet little is known about climate change adaptation in fragile contexts. While climate events are one of the many contributing drivers of conflict, feedback from conflict increases vulnerability, thereby creating conditions for a vicious cycle of conflict. In this study, we carry out a systematic review of peer-reviewed literature, taking from the Global Adaptation Mapping Initiative (GAMI) dataset to documenting climate change adaptation occurring in 15 conflict-affected countries and compare the findings with records of climate adaptation finance flows and climate-related disasters in each country. Academic literature is sparse for most conflict-affected countries, and available studies tend to have a narrow focus, particularly on agriculture-related adaptation in rural contexts and adaptation by low-income actors. In contrast, multilateral and bilateral funding for climate change adaptation addresses a greater diversity of adaptation needs, including water systems, humanitarian programming, and urban areas. Even among the conflict-affected countries selected, we find disparity, with several countries being the focus of substantial research and funding, and others seeing little to none. Results indicate that people in conflict-affected contexts are adapting to climate change, but there is a pressing need for diverse scholarship across various sectors that documents a broader range of adaptation types and their results.


Phytochemistry and medicinal plants.
A truncated history of the contribution of plants to medicine is given with reference to some of the less well known ancestors of the Harborne family. Six of the top 20 prescriptions dispensed in 1996 were natural products and the clinical use of drugs such as artemisinin, etoposide and taxol has once more focussed attention on plants as sources of novel drug entities. High through-put robotic screens have been developed by industry and it is possible to carry out 50,000 tests per day in the search for compounds which have specificity of action against a key enzyme or a subset of receptors. Bioassay-guided fractionation of plant extracts linked to chromatographic separation techniques leads to the isolation of biologically active molecules whose chemical structures can readily be determined by modern spectroscopic methods. The role of academics in the search for new drugs is discussed by reference to some of our research into natural products with activity on the central nervous system, on pain receptors, the malaria parasite Plasmodium falciparum, the wound healing properties of the sap of species of Croton (Dragon's blood), and a traditional Chinese medicine used to treat eczema. Expertise in phytochemistry has been essential for this research and the strong lead shown by Professor Jeffrey Harborne is gratefully acknowledged.


Determinants of Rbp1p localization in specific cytoplasmic mRNA-processing foci, P-bodies.
Rbp1p, a yeast RNA-binding protein, decreases the level of mitochondrial porin mRNA by enhancing its degradation, but the intracellular location of the Rbp1p-mediated degradation complex remains unknown. We show here that Rbp1p in xrn1Delta mutant yeast localizes in specific cytoplasmic foci that are known as P-bodies. The N-terminal and RNA recognition motif (RRM) 1 domains of Rbp1p are necessary but not sufficient for its localization in P bodies. Rbp1p forms oligomers through its C-terminal domain in vivo; N-terminal-delete, or RRM1-mutated Rbp1p can be more efficiently recruited to P-bodies in an xrn1Delta strain, expressing a full-length Rbp1p. Although POR1 mRNA is localized to P bodies in an xrn1Delta strain, this localization does not depend on Rbp1p. Decapping activator Dhh1p directly interacts with Rbp1p. However, the recruitment of Rbp1p to P-bodies does not require Dhh1p or Ccr4p. In wild-type cells, Rbp1p can localize to P-bodies under glucose deprivation or treatment with KCl. In addition, Rbp1p-mediated porin mRNA decay is elicited by Xrn1p, a 5 ' to 3 ' exonuclease. These results provide new insight into the mechanism of Rbp1p function.


The effect of photomirex on the in vitro perfused ovary of the rat.
Photomirex, a photodegradation product of the insecticide mirex, is an environmental contaminant that has been identified in Great Lakes fish, soil, and human adipose tissue. Because of the potential for human exposure, the present study was designed to investigate the short-term effects of photomirex on the in vitro perfused ovary of the rat. Adult Sprague-Dawley rat ovaries were isolated and perfused for a total of 6 h with Medium 199. Following a 2-h baseline period, 10(-4) M of photomirex was administered to the medium. Control ovaries received medium or DMSO (vehicle control). Significant effects of perfusion and chemical intervention were identified using lactate dehydrogenase enzyme, glucose utilization, lactate, pyruvate, and flow:pressure ratio as markers of toxicity (P < 0.05). Lactate:pyruvate ratio, glutathione, and oxygen consumption did not demonstrate significant effects. Post hoc tests showed that there were significant differences between the DMSO + photomirex group and the control group (M199) using lactate dehydrogenase as a marker of toxicity. Pyruvate concentration was also reduced significantly after perfusion with DMSO + photomirex compared to M199 only and DMSO only (P < 0.05). Histopathologic changes were not discernible by light microscopy. These results suggest that metabolic and respiratory processes of the ovary are acutely sensitive to perturbation with photomirex in the in vitro perfused rat ovary model.


CD4+ T cell-derived IL-22 enhances liver metastasis by promoting angiogenesis.
Metastasis is a cancer-related systemic disease and is responsible for the greatest mortality rate among cancer patients. Interestingly, the interaction between the immune system and cancer cells seems to play a key role in metastasis formation in the target organ. However, this complex network is only partially understood. We previously found that IL-22 produced by tissue resident iNKT17 cells promotes cancer cell extravasation, the early step of metastasis. Based on these data, we aimed here to decipher the role of IL-22 in the last step of metastasis formation. We found that IL-22 levels were increased in established metastatic sites in both human and mouse. We also found that Th22 cells were the key source of IL-22 in established metastasis sites, and that deletion of IL-22 in CD4+ T cells was protective in liver metastasis formation. Accordingly, the administration of a murine IL-22 neutralizing antibody in the establishment of metastasis formation significantly reduced the metastatic burden in a mouse model. Mechanistically, IL-22-producing Th22 cells promoted angiogenesis in established metastasis sites. In conclusion, our findings highlight that IL-22 is equally as important in contributing to metastasis formation at late metastatic stages, and thus, identify it as a novel therapeutic target in established metastasis.


Multiple imaging using various types of simple phase gratings.
Diffraction gratings can be used to form multiple images in optical systems utilizing incoherent, monochromatic light. The properties of two-dimensional phase gratings having periodic rectangular, sinusoidal, or triangular surface corrugation have been investigated. It is shown that these gratings can be used to form an array of equally intense images by an optical cascading process, each step in the cascade increasing the number of images by a factor of 9. These simple gratings would be particularly useful for forming relatively small numbers of large images. The efficiency per step would be between 70% and 80% and the distortion less than 2%. If spatially incoherent laser light is used, the resolution and general image quality would be limited mainly by the lenses used. These conclusions are corroborated by experimental results obtained with rectangular-type phase gratings.


Identification of a novel human kinesin-related gene (HK2) by the cDNA differential display technique.
We have used the cDNA differential display technique to isolate genes regulated by the synthetic retinoid N-(4-hydroxyphenyl)-all-trans-retinamide (HPR), a cancer chemopreventive agent in vivo and a powerful inducer of apoptotic cell death in vitro. Here we report the identification of a novel gene, the expression of which is markedly up-regulated in tumor cells after treatment for 30-60 min with HPR. The full-length cDNA of this gene, determined by screening of a human placenta cDNA, is 3.5 kb long and contains an open reading frame of 2037 nt. The gene is > 90% homologous to the mouse KIF2, a gene belonging to the family of kinesin-related motor proteins, and we therefore named it HK2 (human kinesin 2). A shorter form of the HK2 mRNA (HK2s), containing a 57-nt deletion in the open reading frame, has also been detected. Northern analysis revealed that HK2 is widely expressed among hemopoietic and nonhemopoietic cell lines and tissues. By the use of radiation hybrids, HK2 has been localized to chromosome 5q12-q13. Kinesins constitute a superfamily of motor proteins that use energy liberated from ATP hydrolysis to move cargo along microtubules and are implicated in mechanisms of mitosis or meiosis. The role of HK2 in the growth-inhibitory and apoptotic responses elicited by HPR remains to be established.


Delirium, Frailty, and Fast-Track Surgery in Oncogeriatrics: Is There a Link?
Postoperative delirium (POD) is more frequent in elderly patients undergoing major cancer surgery. The interplay between individual clinical vulnerability and a series of perioperative factors seems to play a relevant role. Surgery is the first-line treatment option for cancer, and fast-track surgery (FTS) has been documented to decrease postoperative complications. The study sought to assess, after comprehensive geriatric assessment (CGA) and frailty stratification (Rockwood 40 items index), which perioperative parameters were predictive of POD development in elderly patients undergoing FTS for colorectal cancer. A total of 107 consecutive subjects admitted for elective colorectal FTS were enrolled. All patients underwent CGA, frailly stratification, Timed up & go (TUG) test, 4AT test for delirium screening, anesthesiologists physical status classification, and Dindo-Clavien classification. The incidence of POD was 12.3%. Patients' prevalent clinical phenotype was pre-frail. The multivariate analysis indicated physical performance (TUG in seconds) as the most significant predictor of POD for each second of increase. Only few procedure-specific studies have examined the impact of FTS for colorectal cancer on POD. This is the first study to investigate the risk factors for POD, in a vulnerable octogenarian oncogeriatric population submitted to FTS surgery and frailty stratification.


Eribulin mesylate, a novel microtubule inhibitor in the treatment of breast cancer.
Microtubule-targeted agents are one of the most common classes of chemotherapeutic drug for the treatment of breast cancer. Limitations of current microtubule-targeted agents such as primary or secondary resistance of cancer cells and side effects like neuropathy prompted the discovery and introduction of newer more effective drugs. This review aims to provide a summary of the novel halichondrin B analog eribulin mesylate (E7389) and illustrate where it is placed in the treatment arena versus other agents that are approved or are currently in various stages of clinical development. Preclinical and clinical trial (phases I-III) data for eribulin were obtained from scientific journals and meeting abstracts, posters, and oral presentations. The use of current and other emerging microtubule inhibiting agents in breast cancer was also surveyed and briefly reviewed. Eribulin mesylate at a dose of 1.4 mg/m(2) given on days 1 and 8 of a 21-day cycle increased overall survival in patients with metastatic breast cancer (MBC). Neutropenia, fatigue, alopecia, nausea and anemia were common adverse events (AEs) associated with eribulin in clinical studies. A low incidence of peripheral neuropathy was also associated with eribulin in clinical studies (21-26%). Other emerging microtubule targeted agents, such as vinflunine and larotaxel, also reported efficacy in patients with MBC who had received prior chemotherapy, with grade 3/4 neutropenia being the most common AEs for both agents. Eribulin mesylate offers clinical activity in advanced breast cancer through improved overall survival, its favorable side-effect profile and convenience of preparation and administration.


Self-assembled nanoscale DNA-porphyrin complex for artificial light harvesting.
Mimicking green plants' and bacteria's extraordinary ability to absorb a vast number of photons and harness their energy is a longstanding goal in artificial photosynthesis. Resonance energy transfer among donor dyes has been shown to play a crucial role on the overall transfer of energy in the natural systems. Here, we present artificial, self-assembled, light-harvesting complexes consisting of DNA scaffolds, intercalated YO-PRO-1 (YO) donor dyes and a porphyrin acceptor anchored to a lipid bilayer, conceptually mimicking the natural light-harvesting systems. A model system consisting of 39-mer duplex DNA in a linear wire configuration with the porphyrin attached in the middle of the wire is primarily investigated. Utilizing intercalated donor fluorophores to sensitize the excitation of the porphyrin acceptor, we obtain an effective absorption coefficient 12 times larger than for direct excitation of the porphyrin. On the basis of steady-state and time-resolved emission measurements and Markov chain simulations, we show that YO-to-YO resonance energy transfer substantially contributes to the overall flow of energy to the porphyrin. This increase is explained through energy migration along the wire allowing the excited state energy to transfer to positions closer to the porphyrin. The versatility of DNA as a structural material is demonstrated through the construction of a more complex, hexagonal, light-harvesting scaffold yielding further increase in the effective absorption coefficient. Our results show that, by using DNA as a scaffold, we are able to arrange chromophores on a nanometer scale and in this way facilitate the assembly of efficient light-harvesting systems.


MtDNA mutation pattern in tumors and human evolution are shaped by similar selective constraints.
Multiple human mutational landscapes of normal and cancer conditions are currently available. However, while the unique mutational patterns of tumors have been extensively studied, little attention has been paid to similarities between malignant and normal conditions. Here we compared the pattern of mutations in the mitochondrial genomes (mtDNAs) of cancer (98 sequences) and natural populations (2400 sequences). De novo mtDNA mutations in cancer preferentially colocalized with ancient variants in human phylogeny. A significant portion of the cancer mutations was organized in recurrent combinations (COMs), reaching a length of seven mutations, which also colocalized with ancient variants. Thus, by analyzing similarities rather than differences in patterns of mtDNA mutations in tumor and human evolution, we discovered evidence for similar selective constraints, suggesting a functional potential for these mutations.


Destruction and solubilization of supported phospholipid bilayers on silica by the biosurfactant surfactin.
The lipopeptide surfactin from Bacillus subtilis strains exhibits strong surface and biological activity, the latter probably because of its interaction with biological membranes. We have investigated the interaction of aqueous solutions of surfactin with supported bilayers of diphosphatidylcholine (DPPC) on silica using neutron reflectometry. We have also used small-angle neutron scattering (SANS) to study the solubilized aggregates formed as a result of the destruction of the supported membrane by surfactin. Although surfactin on its own does not attach to the silica supporting surface, it is taken up from solution by the membrane, confirming that there is an attractive interaction between DPPC and surfactin. The surfactin concentration in the layer can reach up to about 20 mol % relative to DPPC. The membrane is stable provided that the surfactin concentration is below its critical micelle concentration (cmc, 5 x 10(-5) M). Above the cmc, however, the membrane is solubilized and removed from the surface, though not always completely, over a period of hours. There are signs that there is an induction period while the surfactin concentration builds up in the membrane. This would be consistent with the need for a threshold concentration of surfactin in the bilayer. The presence of a surfactin correlation peak in the SANS showed that in the bulk solution, at the same concentrations as used for the deposition, surfactin forms aggregates that must be localized in the DPPC multilamellar vesicles at a separation of about 160 A. The structure could be fitted with an approximate model where the surfactin has an aggregation number of 50 +/- 10 with a radius of about 27 A. Given the very small water thicknesses in the DPPC lamellar aggregates, the surfactin must exist as aggregates in the phospholipid bilayer, and these structures are responsible for solubilizing the DPPC.


First record of the genus Colosmittia Andersen & Saether (Chironomidae: Orthocladiinae) from the neotropical region.
Colosmittia brasileira sp. n. from São Paulo state, Brazil, is described and illustrated based on a male imago. The genus Colosmittia Andersen & Saether was described based on a single species, C. clavata Andersen & Saether, from the West Usambara Mountains, Tanzania, East Africa. The discovery of the new species shows that Colosmittia has an Afro-Brazilian distribution pattern.


Sphingolipid-mediated restoration of Mitf expression and repigmentation in vivo in a mouse model of hair graying.
Recent advances in the identification and characterisation of stem cell populations has led to substantial interest in understanding the precise triggers that would operate to induce activation of quiescent stem cells. Melanocyte stem cells (MSCs) reside in the bulge region of the hair follicles and are characterised by reduced expression of the microphthalmia-associated transcription factor (Mitf) and its target genes implicated in differentiation. Vitiligo is characterised by progressive destruction of differentiated melanocytes. However, therapies using UV irradiation therapy can induce a degree of repigmentation, suggesting that MSCs may be activated. As Mitf is implicated in control of proliferation, we have explored the possibility that inducing Mitf expression via lipid-mediated activation of the p38 stress-signalling pathway may represent a re-pigmentation strategy. Here we have isolated from placental extract a C18:0 sphingolipid able to induce Mitf and tyrosinase expression via activation of the p38 stress-signalling pathway. Strikingly, in age-onset gray-haired C57BL/6J mice that exhibit decaying Mitf expression, topical application of placental sphingolipid leads to increased Mitf in follicular melanocytes and fresh dense black hair growth. The results raise the possibility that lipid-mediated activation of the p38 pathway may represent a novel approach to an effective vitiligo therapy.


Incidental finding and successful management of Larrey's hernia during laparoscopic cholecystectomy: Case report.
Larrey hernias (LH) are birth defects causing abdominal viscera to protrude into the thoracic cavity. With an incidence of 2-4 %, they are exceptional in adults. A 65-year-old female patient was admitted for an elective laparoscopic cholecystectomy. During history intake, besides biliary colic, no additional symptoms were reported. Physical examination yielded normal results. Chest-X ray did not reveal any anomalies. Intraoperatively, an inspection of the diaphragm revealed a 3 cm defect in the left-sided sternocostal triangle, with the omentum protruding through the thorax. After performing cholecystectomy, the content of the LH was cautiously reduced. The hernia sac was not resected, to prevent potential injury to the neighboring anatomical structures. The defect was closed using non-resorbable interrupted sutures. The postoperative course was uneventful. No recurrence was detected during follow-up. LH diagnosis is challenging due to its unspecific symptoms. Only 10 % of patients are asymptomatic. CT imaging establishes a positive diagnosis and identifies acute complications requiring emergency management. Asymptomatic LH cases mandate surgery. Laparoscopic management is safe and efficient. The trans-abdominal approach offers easier access to hernia content. Hernia sac resection is still debatable. The selection of defect closure technique hinges on the quality and elasticity of the tissue, as well as the size of the defect, all under the unwavering banner of the tension-free principle. Literature remains conflicting on mesh use.


Flexible planar supercapacitors by straightforward filtration and laser processing steps.
There is ever increasing demand for flexible energy storage devices due to the development of wearable electronics and other small electronic devices. The electrode flexibility is best provided by a special set of nanomaterials, but the required methodology typically consists of multiple steps and are designed just for the specific materials. Here, a facile and scalable method of making flexible and mechanically robust planar supercapacitors with interdigital electrode structure made of commercial carbon nanomaterials and silver nanowires is presented. The capacitor structure is achieved with vacuum filtration through a micropatterned contact mask and finished with simple laser processing steps. A maximum specific capacitance of 4 F cm-3 was measured with cyclic voltammetry at scan rate of 5 mV s-1. The reliability and charge transfer properties of devices were further investigated with galvanostatic charge-discharge measurements and electrochemical impedance spectroscopy, respectively. Furthermore, mechanical bending tests confirmed the devices have excellent mechanical integrity, and the deformations have no adverse effects on the electrochemical charge-discharge behavior and stability.


A collaborative computer aided diagnosis (C-CAD) system with eye-tracking, sparse attentional model, and deep learning.
Computer aided diagnosis (CAD) tools help radiologists to reduce diagnostic errors such as missing tumors and misdiagnosis. Vision researchers have been analyzing behaviors of radiologists during screening to understand how and why they miss tumors or misdiagnose. In this regard, eye-trackers have been instrumental in understanding visual search processes of radiologists. However, most relevant studies in this aspect are not compatible with realistic radiology reading rooms. In this study, we aim to develop a paradigm shifting CAD system, called collaborative CAD (C-CAD), that unifies CAD and eye-tracking systems in realistic radiology room settings. We first developed an eye-tracking interface providing radiologists with a real radiology reading room experience. Second, we propose a novel algorithm that unifies eye-tracking data and a CAD system. Specifically, we present a new graph based clustering and sparsification algorithm to transform eye-tracking data (gaze) into a graph model to interpret gaze patterns quantitatively and qualitatively. The proposed C-CAD collaborates with radiologists via eye-tracking technology and helps them to improve their diagnostic decisions. The C-CAD uses radiologists' search efficiency by processing their gaze patterns. Furthermore, the C-CAD incorporates a deep learning algorithm in a newly designed multi-task learning platform to segment and diagnose suspicious areas simultaneously. The proposed C-CAD system has been tested in a lung cancer screening experiment with multiple radiologists, reading low dose chest CTs. Promising results support the efficiency, accuracy and applicability of the proposed C-CAD system in a real radiology room setting. We have also shown that our framework is generalizable to more complex applications such as prostate cancer screening with multi-parametric magnetic resonance imaging (mp-MRI).


Impact of thermal stress on placental function and fetal physiology.
In ruminants, prolonged exposure to high ambient temperatures negatively affects placental development and function. The pursuing limitations in placental oxygen and nutrient supply between the mother and fetus slow fetal growth lowering birth weights and postnatal performance. The pregnant ewe is a long-standing animal model for the study of maternal- fetal interactions and is susceptible to naturally occurring heat stress, which causes fetal growth restriction. In the pregnant ewe, studies show that the fetus adapts to hyperthermia-induced placental insufficiency to preserve placental transport capacity of oxygen and nutrients. These adaptive responses are at the expense of normal fetal development and growth. Enlarged transplacental gradient for oxygen and glucose facilitates diffusion across the placenta, but develops by lowering fetal blood oxygen and glucose concentrations. Fetal hypoxemia and hypoglycemia slow growth and alter their metabolic and endocrine profiles. Deficits in amino acids transport across the placenta are present but are overcome by reduced fetal clearance rates, likely due to fetal hypoxemia or endocrine responses to hypoxic stress. Here, we provide an overview of the performance limitations observed in ruminants exposed to heat stress during pregnancy, but we focus our presentation on the sheep fetus in pregnancies complicated by hyperthermia-induced placental insufficiency. We define the characteristics of placental dysfunction observed in the fetus of heat stressed ewes during pregnancy and present developmental adaptations in organogenesis, metabolism, and endocrinology that are proposed to establish maladaptive situations reaching far beyond the perinatal period.


Links between nonshared friendship experiences and adolescent siblings' differences in aspirations.
Using a sibling design, this study examined the association between adolescents' friendship experiences and their aspirations for self-acceptance, affiliation, and financial success. We hypothesized that adolescent siblings would differ in their aspirations and that unique experiences in friendships would be associated with these differences. Within our sample of 102 same-sex sibling pairs (mean age older sibling 16 years, younger sibling 14 years), only a small degree of sibling similarity was found for aspirations as well as friendship experiences. Self-acceptance and affiliation were positively linked to general friendship positivity as well as to positive features of the adolescents' closest friend. Bivariate model-fitting techniques revealed that nonshared processes (i.e., unique to each child in the family) explained these links between friendship experiences and aspirations. The results indicate that growing up in one home and being socialized by the same parents does not make adolescent siblings similar in their aspirations but rather that nonshared experiences like those with close friends are related to aspiration dissimilarity of siblings.


The reference transcriptome of the adult female biting midge (Culicoides sonorensis) and differential gene expression profiling during teneral, blood, and sucrose feeding conditions.
Unlike other important vectors such as mosquitoes and sandflies, genetic and genomic tools for Culicoides biting midges are lacking, despite the fact that they vector a large number of arboviruses and other pathogens impacting humans and domestic animals world-wide. In North America, female Culicoides sonorensis midges are important vectors of bluetongue virus (BTV) and epizootic hemorrhagic disease virus (EHDV), orbiviruses that cause significant disease in livestock and wildlife. Libraries of tissue-specific transcripts expressed in response to feeding and oral orbivirus challenge in C. sonorensis have previously been reported, but extensive genome-wide expression profiling in the midge has not. Here, we successfully used deep sequencing technologies to construct the first adult female C. sonorensis reference transcriptome, and utilized genome-wide expression profiling to elucidate the genetic response to blood and sucrose feeding over time. The adult female midge unigene consists of 19,041 genes, of which less than 7% are differentially expressed during the course of a sucrose meal, while up to 52% of the genes respond significantly in blood-fed midges, indicating hematophagy induces complex physiological processes. Many genes that were differentially expressed during blood feeding were associated with digestion (e.g. proteases, lipases), hematophagy (e.g., salivary proteins), and vitellogenesis, revealing many major metabolic and biological factors underlying these critical processes. Additionally, key genes in the vitellogenesis pathway were identified, which provides the first glimpse into the molecular basis of anautogeny for C. sonorensis. This is the first extensive transcriptome for this genus, which will serve as a framework for future expression studies, RNAi, and provide a rich dataset contributing to the ultimate goal of informing a reference genome assembly and annotation. Moreover, this study will serve as a foundation for subsequent studies of genome-wide expression analyses during early orbivirus infection and dissecting the molecular mechanisms behind vector competence in midges.


[Variability of the cytogenetic structure of Apodemus peninsula (Rodentia, Muridae) population from the West Sayans region].
Karyological investigations of East-Asiatic mice (28 animals) from 5 catching points in the region of West Sayans revealed the presence of 1-12 B-chromosomes in these animals. Nearly all the mice had their individual variant of B-chromosomes system, including combinations of two-shoulder-like chromosomes of different size (from 1 to 5), and also small acrocentric (from 0 to 1) and dot-like B-chromosomes (from 0 to 9). Most frequent were the mice with 5 and 6 (21%) B-chromosomes. The catching points were 120 kilometers from each other, and clinical changes were observed between these points in the direction from the South to the North.


Clinical history and management of bicuspid aortic valve in children and adolescents.
Bicuspid aortic valve (BAV) is one of the most common congenital heart defects in children, adolescents and adults. BAV can occur as an isolated lesion or in association with other congenital heart defects, such as coarctation of the aorta or genetic syndromes like Turner syndrome. Although the majority of long term complications associated with BAV manifest later in life, children and adolescents may present with early onset valvular dysfunction or dilation of the aorta. BAV is a heterogeneous disease with a wide array of presentations at various ages, depending on the degree of aortic valve dysfunction, aortic dilation and presence of associated lesions. Aortic valve stenosis and/or regurgitation are the primary indications for intervention in children and adolescents with BAV. Although a majority of young patients with BAV also have some aortic dilation, interventions on the aorta are very rare during this time frame. Children and adolescents with BAV benefit from comprehensive assessment of their risk profile to determine follow-up surveillance intervals, sports recommendations, and timing of surgical intervention. The morphologic phenotype of BAV is important to identify, as it may predict future complications and prognosis.


Perceived barriers to diabetic eye care: qualitative study of patients and physicians.
To address inadequate retinopathy screening at a largely indigent clinic and to explore perceived barriers, using qualitative techniques. Responses were analyzed from structured focus groups of patients and key informant interviews of primary diabetic physicians and ophthalmologists at the Medical Center of Louisiana in New Orleans. The number of diabetic patients screened at the center from 2000 to 2002 was obtained by quantitative analysis of an administrative database. Participants cited finances as the major barrier, while physicians cited inadequate patient education. Patients largely believed that diabetic education was adequate, yet there was a gap between patient education provided and their understanding. All sources agreed that poor access to care, particularly the 1-year wait for an appointment, was a barrier. No respondent mentioned constraints of the system to provide eye care to the number of diabetic patients as a possible barrier, despite the 1-year wait for an eye appointment and a 29% increase in eye examinations within 2 years. Perceptions of barriers to diabetic eye care differed among physicians and patients, although both groups agreed that access to care was a barrier. A gap exists between educational material provided to patients and what patients understand. A large unrecognized workload stresses the capacity of the current system.


GDP release preferentially occurs on the phosphate side in heterotrimeric G-proteins.
After extra-cellular stimulation of G-Protein Coupled Receptors (GPCRs), GDP/GTP exchange appears as the key, rate limiting step of the intracellular activation cycle of heterotrimeric G-proteins. Despite the availability of a large number of X-ray structures, the mechanism of GDP release out of heterotrimeric G-proteins still remains unknown at the molecular level. Starting from the available X-ray structure, extensive unconstrained/constrained molecular dynamics simulations were performed on the complete membrane-anchored Gi heterotrimer complexed to GDP, for a total simulation time overcoming 500 ns. By combining Targeted Molecular Dynamics (TMD) and free energy profiles reconstruction by umbrella sampling, our data suggest that the release of GDP was much more favored on its phosphate side. Interestingly, upon the forced extraction of GDP on this side, the whole protein encountered large, collective motions in perfect agreement with those we described previously including a domain to domain motion between the two ras-like and helical sub-domains of G(α).


Cooperative anion binding and electrochemical sensing by modular podands.
A series of podands based on two or three hydrogen bonding "arms" situated in mutually ortho, meta, or para relationships about an aryl core have been prepared, and their affinities for simple inorganic anions were measured. Of the two-arm hosts the meta compound and to a lesser extent the ortho host exhibit a cooperative anion binding effect. The two arms function essentially independently in the para derivative. The mutually meta three-arm host shows dramatically enhanced cooperative binding. Conformational changes within the meta two-arm host result in significantly enhanced electrochemical anion sensing compared with the more conformationally rigid three-arm host.


Infant formula, past and future: opportunities for improvement.
Infant formulas provide nutritional support to health infants that promotes growth and development equivalent to that in healthy infants fed human milk. Formula-fed infants are not as well protected against infections, and there remain infants whose health, growth, and development may not be supported optimally by either the formulas currently available or human milk. Some infants may be better supported by genetically engineered formulas that contain immunity-enhancing antibodies or antigens. Formulas that contain cytokines promoting epithelial cell growth and integrity may be protective against necrotizing enterocolitis. Formulas containing proteins with genetically excluded allergenic epitopes or formulas with tolerogenic peptides may be useful in treating allergic diseases of suppressing the development of autoimmune disorders later in life. Formulas with genetically engineered biologically active substances might increase the absorption of nutrients in infants with compromised absorption or digestion, enhance host immunity and mucosal integrity, and, potentially militate or protect against the risk of disease.


Individual differences in nonverbal number discrimination correlate with event-related potentials and measures of probabilistic reasoning.
The current study investigated the neural activity patterns associated with numerical sensitivity in adults. Event-related potentials (ERPs) were recorded while adults observed sequentially presented display arrays (S1 and S2) of non-symbolic numerical stimuli (dots) and made same/different judgments of these stimuli by pressing a button only when numerosities were the same (target trials). The main goals were to contrast the effects of numerical distance (close, medium, and far) and change direction (increasing, decreasing) between S1 and S2, both in terms of behavior and brain activity, and to examine the influence of individual differences in numeracy on the effects of these manipulations. Neural effects of distance were found to be significant between 360 and 600 ms after the onset of S2 (greater negativity-wave activity for closer numerical distances), while direction effects were found between 320 and 440 ms (greater negativity for decreasing direction). ERP change direction effects did not interact with numerical distance, suggesting that the two types of information are processed independently. Importantly, subjects' behavioral Weber fractions (w) for the same/different discrimination task correlated with distance-related ERP-activity amplitudes. Moreover, w also correlated with a separate objective measure of mathematical ability. Results thus draw a clear link between brain and behavior measures of number discrimination, while also providing support for the relationship between nonverbal magnitude discrimination and symbolic numerical processing.


Learning, specialization, efficiency and task allocation in social insects.
One of the most spectacular features of social insect colonies is their division of labor. Although individuals are often totipotent in terms of the labor they might perform, they might persistently work as scouts, fighters, nurses, foragers, undertakers or cleaners with a repetitiveness that might resemble an assembly line worker in a factory. Perhaps because of this apparent analogy, researchers have often assumed a priori that such labor division must be efficient, but empirical proof is scarce. New work on Themnothorax ants shows that there might be no link between an individual's propensity to perform a task, and their efficiency at that task, nor are task specialists more efficient than generalists. Here we argue that learning psychology might provide the missing link between social insect task specialization and efficiency: just like in human societies, efficiency at a job specialty is only partially a result of "talent", or innate tendency to engage in a job: it is much more a result of perfecting skills with experience, and the extent to which experience can be carried over from one task to the next (transfer), or whether experience at one task might actually impair performance at another (interference). Indeed there is extensive circumstantial evidence that learning is involved in almost any task performed by social insect workers, including food type recognition and handling techniques, but also such seemingly basic tasks as nest building and climate control. New findings on Cerapachys ants indicate that early experience of success at a task might to some extent determine the "profession" an insect worker chooses in later life.


Advancing Proficiencies for Health Professionals in the Treatment of Tobacco Use Among Marginalized Communities: Development of a Competency-Based Curriculum and Virtual Workshop.
Tobacco-related disparities are a leading contributor to health inequities among marginalized communities. Lack of support from health professionals is one of the most cited barriers to tobacco cessation reported by these communities. Improving the proficiencies with which health professionals incorporate social and cultural influences into therapeutic interactions has the potential to address this critical barrier. In general, training to improve these proficiencies has shown promise, but the specific proficiencies required for treating tobacco use among marginalized communities are unknown. This project aimed to develop a competency-based curriculum to improve these proficiencies among health professionals with experience and training in the evidence-based treatment of tobacco use, and then pilot test the content delivered via an expert review of a virtual, self-paced workshop. We used the Delphi Technique to systematically identify the specific competencies and corresponding knowledge and skill sets required to achieve these proficiencies. Educational content was developed to teach these competencies in a virtual workshop. The workshop was evaluated by 11 experts in the field by examining pre- and post-training changes in perceived knowledge, skill, and confidence levels and other quantitative and qualitative feedback. Repeated measures analysis of variance and paired sample t-tests were used to examine pre-post training differences. Six competencies and corresponding skill sets were identified. After exposure to the virtual workshop, the experts reported significant increases in the overall proficiency for each competency as well as increases in nearly all levels of knowledge, skill, and confidence within the competency skill sets. Qualitative and quantitative findings indicate that content was relevant to practice. These findings provide preliminary support for 6 competencies and skills sets needed to improve therapeutic interpersonal interactions that recognize the importance of social and cultural influences in the treatment of tobacco use.


A novel technique of adjusting segmentation boundary layers to achieve comparability of retinal thickness and volumes between spectral domain and time domain optical coherence tomography.
The quantitative assessment of retinal thickness and volume varies according to the optical coherence tomography (OCT) machine used due to differences in segmentation lines. We describe a novel method of adjusting the segmentation lines of spectral-domain OCT (SD-OCT) to enable comparison with time-domain OCT (TD-OCT), and assess factors affecting its accuracy. In a prospective study, SD-OCT (Spectralis OCT) and TD-OCT (Stratus OCT) were sequentially performed on 200 eyes of 100 healthy individuals. Central retinal thickness (CRT), central point thickness (CPT), and 1-mm volume of the Early Treatment Diabetic Retinopathy Study grid were compared between the two machines. The segmentation lines on SD-OCT were manually adjusted by a trained operator and the parameters compared again with TD-OCT. The mean CRTs of Spectralis and Stratus were significantly different (268.2 μm vs. 193.9 μm, P < 0.001). After adjustment of segmentation lines, the mean adjusted Spectralis CRT was 197.3 μm, with the difference between SD-OCT and TD-OCT measurements decreasing from 74.3 μm to 3.4 μm (P < 0.001). The difference between the adjusted Spectralis and Stratus CRTs was smallest for high myopes (≤ -6.0 diopters [D]) compared with those with moderate and low myopia (1.5 μm vs. 3.5 μm and 4.6 μm, respectively; P < 0.001). Similar trends were obtained for central 1-mm volumes and CPT. Interoperator and intraoperator repeatability for adjustment of the segmentation lines were good, with an intraclass correlation of 0.99 for both. Manual adjustment of SD-OCT segmentation lines reliably achieves retinal thickness and volume measurements that are comparable to that of TD-OCT. This is valuable to allow comparisons in multicenter clinical trials where different OCT machines may be used.


A literature review of spirituality in coping with early-stage Alzheimer's disease.
This paper presents a literature review focusing on the use of spirituality in coping by older persons with early-stage Alzheimer's disease from their perspectives. The purpose of this literature review is to examine the existing body of knowledge about spirituality in coping with Alzheimer's disease and to apply a spiritual framework of coping in organizing the literature to identify themes and gaps in knowledge. Despite the abundance of Alzheimer's disease research, little is known about how older persons with this devastating disease cope with the consequential losses. Maintaining a sense of normalcy and preserving self-worth are coping strategies reported by older persons with early-stage Alzheimer's disease. As spirituality is an effective coping resource for older persons with numerous psychological and personal losses in their lives, it may be an important coping resource for person with Alzheimer's disease. A literature search was conducted to find research published between 1990-2006 aimed at understanding spirituality in coping with early-stage Alzheimer's disease. Six research studies were reviewed. Findings suggest that persons with early-stage Alzheimer's disease draw from their spirituality and faith to find meaning and courage in facing the challenges of cognitive losses. Furthermore, they are able to provide rich information about their spirituality and the psychosocial aspects of living with Alzheimer's disease. Limited empirical knowledge compels the need for future research to explore how spirituality is utilized in coping with early-stage Alzheimer's disease. Enhancing persons' abilities to cope effectively with their diseases is an important goal of nursing care. Understanding how older persons with Alzheimer's disease cope with their memory loss is critical to the development of evidence-based interventions to minimize the stress of living with this disease.


A single-molecule FRET sensor for monitoring DNA synthesis in real time.
We developed a versatile DNA assay and framework for monitoring polymerization of DNA in real time and at the single-molecule level. The assay consists of an acceptor labelled DNA primer annealed to a DNA template that is labelled on its single stranded, downstream overhang with a donor fluorophore. Upon extension of the primer using a DNA polymerase, the overhang of the template alters its conformation from a random coil to the canonical structure of double stranded DNA. This conformational change increases the distance between the donor and the acceptor fluorophore and can be detected as a decrease in the Förster resonance energy transfer (FRET) efficiency between both fluorophores. Remarkably, the DNA assay does not require any modification of the DNA polymerase and albeit the simple and robust spectroscopic readout facilitates measurements even with conventional fluorimeters or stopped-flow equipment, single-molecule FRET provides additional access to parameters such as the processivity of DNA synthesis and, for one of the three DNA polymerases tested, the detection of binding and dissociation of the DNA polymerase to DNA. We furthermore demonstrate that primer extensions by a single base can be resolved.


Fusiform aneurysms of anterior cerebral artery: center experience and systematic literature review.
Fusiform aneurysms of the anterior cerebral artery (ACA) are uncommon, and the natural history of this entity is poorly characterized. Along with our center experience, we conducted a systematic literature review to help shed light on the clinical course of ACA fusiform aneurysms. We queried our institutional database to identify cases with fusiform aneurysms of ACA. In addition, following the PRISMA algorithm, we identified all reported cases published in the English literature from the inception of PubMed until December 2022. We categorized clinical presentations into three categories: (i) traumatic/iatrogenic, (ii) spontaneous symptomatic ruptured/unruptured, and (iii) spontaneous asymptomatic aneurysms. We utilized descriptive statistics. We identified seven cases from our center along with 235 patients from published literature. Blunt trauma was responsible for the development of 19 aneurysms. Sixty-three percent of these aneurysms tend to rupture within 2 weeks from the initial trauma, and despite treatment, only 74% of these patients had good clinical outcomes. Spontaneous symptomatic presentation occurred in 207 patients and was often associated with previous/concomitant ACA dissection. Subarachnoid hemorrhage from ruptured aneurysms was the most common presentation. Spontaneous symptomatic fusiform aneurysm is rapidly evolving lesions, and treatment is necessary. Three of our own cases were treated with an endovascular flow diverter (pipeline) stenting with good outcomes. Spontaneous asymptomatic aneurysms were reported in nine patients. These lesions are often associated with other vascular abnormalities. Treatment included surgical clipping with good clinical outcomes. Instead, four patients from our center database were managed conservatively with equally good outcomes. Our study demonstrates good clinical outcomes when fusiform aneurysms of ACA, especially when symptomatic, are treated promptly with either reconstructive or deconstructive therapies.


Treatment with 5-lipoxygenase inhibitor VIA-2291 (Atreleuton) in patients with recent acute coronary syndrome.
Production of leukotrienes by 5-lipoxygenase (5-LO) has been linked to unstable atherosclerotic plaques and cardiovascular events. VIA-2291 is a potent 5-LO inhibitor. In a double-blinded study, 191 patients were randomly assigned 3 weeks after an acute coronary syndrome to receive 25, 50, or 100 mg VIA-2291 or placebo daily for 12 weeks. The primary study end point, whole blood stimulated leukotriene LTB4 at trough drug level, was reduced in all VIA-2291 groups (P<0.0001) in a dose-dependent fashion, with approximately 80% inhibition in >90% of patients in the 100-mg group. A significant reduction of urine leukotriene LTE4 was obtained in all dose groups. No serious adverse events were considered related to study drug. A subset of 93 patients who had undergone a 64-slice coronary CT examination at baseline continued on study medication for a total of 24 weeks and underwent a repeat scan. Five of these patients withdrew or were noncompliant and 28 had nonevaluable scans. Among the 60 remaining patients, new coronary plaques were observed in 5 of 18 (27.8%) placebo-treated patients and in 2 of 42 (4.8%) VIA-2291-treated patients (P=0.01). A reduction in noncalcified plaque volume at 24 weeks versus placebo was observed in VIA-2291-treated groups in the 34 of these 60 patients in whom this end point was analyzable (P<0.01). VIA-2291 reduces leukotriene production at 12 weeks after an acute coronary syndrome. Preliminary data from the CT substudy suggest that such a reduction in leukotriene production may influence atherosclerosis; however, this requires confirmation in a larger study. Clinical Trial Registration- URL: http://www.clinicaltrials.gov. Unique identifier: NCT00358826.


Negative signaling via FcgammaRIIB1 in B cells blocks phospholipase Cgamma2 tyrosine phosphorylation but not Syk or Lyn activation.
Crosslinking of the B cell antigen receptor surface immunoglobulin induces tyrosine phosphorylation and activation of the Src family and Syk tyrosine protein kinases, tyrosine phosphorylation of phospholipase Cgamma2 (PLCgamma2) and increases in intracellular second messengers inositol phosphates and Ca2+. These activation events, in conjunction with other pathways, culminate in the induction of B cell proliferation and differentiation. In contrast, co-crosslinking surface Ig with the B cell IgG Fc receptor prevents many of these activation events, including B cell proliferation and differentiation. The precise nature of the negative signal(s) derived from Fc receptors that prevent B cell activation is not known. Here, early activation events were examined in B cells stimulated via the antigen receptor alone or under co-crosslinking conditions. The data indicated a selective block in the tyrosine phosphorylation and activation of PLCgamma2 but not in activation of the upstream kinases, Syk and Lyn, under co-crosslinking conditions. We conclude that the negative signal acts directly on PLCgamma2 and is consistent with recent studies describing an activation-induced association of a phosphotyrosine phosphatase with tyrosine-phosphorylated B cell Fc receptor.


The metabolism of high-molecular-weight ribonucleic acid including polyadenylated species, in the developing rat brain.
High-molecular-weight RNA was isolated from rat brain at various times after the intracranial administration of [32P]Pi. The synthesis of 28S and 18S rRNA could be detected within 1h of the injection of the radioactive precursor and appeared to be more pronounced, relative to other high-molecular-weight RNA, in the brains of older rats compared with those of newborn rats. Polyadenylated RNA, representing most mRNA and their precursors, was isolated by chromatography on oligo(dT)-cellulose. The contribution of this polyadenylated RNA to total RNA synthesis was investigated in the cerebral cortex and the phylogenetically older brain stem at different stages in the development of the rats by using a 5h period of labelling as an arbitrary index of transcription. In the brain stem the proportion of labelled polyadenylated RNA comprised 27-30% of the total RNA. The corresponding values for the cortex decreased from 34% in newborn rats to 23% in 40-150-day-old rats. These data indicated that proportionately more polyadenylated RNA is synthesized in the cortex of the newborn than in the adult rat and that there is a progressive decrease in the synthesis of polyadenylated RNA relative to rRNA during development.


Detection, evaluation, and treatment of renovascular hypertension. Final report. Working Group on Renovascular Hypertension.
Careful interpretation of clinical clues continues to provide valuable information to identify patients in whom further evaluation for renovascular hypertension (RVH) is needed. Newer diagnostic techniques such as intravenous digital subtraction angiography and computer-generated renal flow scans have helped to more accurately identify patients in whom renal arteriography is indicated. More sensitive and specific tests are still needed to establish the hemodynamic significance of renal artery lesions. New classes of antihypertensive drugs, particularly beta-blockers and angiotensin-converting enzyme inhibitors, have enabled the control of blood pressure in most patients with RVH but do not assure preservation of renal function. An aggressive search for and correction of coexisting risk factors, and improved surgical techniques, have resulted in lower surgical mortality. The development of percutaneous transluminal renal angioplasty has provided an invasive, nonsurgical method for managing RVH in selected patients.


Cholinergic regulation of guinea pig duodenal bicarbonate secretion.
Although it is well known that vagal stimulation induces duodenal HCO3- secretion, there is presently no information about the nature of the cholinoceptor and the intracellular signals involved. In a series of experiments performed in a guinea pig duodenal loop model in situ, intravenous carbachol, atropine, pirenzepine, and hexamethonium were used to determine the extent of cholinergic stimulation and the types of cholinoceptors. Carbachol (2 micrograms.kg-1.5 min-1) stimulated HCO3- secretion threefold, and atropine (0.1 mg.kg-1.5 min-1) and pirenzepine (1 mg.kg-1.5 min-1) both abolished this effect. In addition, hexamethonium (0.3 mg.kg-1.5 min-1) inhibited carbachol-stimulated duodenal HCO3- secretion. Vasoactive intestinal peptide (VIP, 5 micrograms.kg-1.5 min-1) stimulated duodenal HCO3- secretion, and this action was partly inhibited by atropine (0.1 mg.kg-1.5 min-1) but not by pirenzepine (1 mg.kg-1.5 min-1). [4Cl-D-Phe6,Leu17]VIP (3.3 mg/kg), an antagonist to VIP, reduced basal, VIP-stimulated, and carbachol-stimulated HCO3- secretion. To examine the role of Ca2+ in this process, Ca2+ ionophore A23187, verapamil, and nifedipine were employed. A23187 (5, 50, 500 micrograms.kg-1.5 min-1) stimulated duodenal HCO3- secretion, an effect blocked by the VIP antagonist, and modestly augmented the effect of carbachol. Verapamil (0.2 mg.kg-1.5 min-1) and nifedipine (1.7 mg.kg-1.5 min-1) stopped the effect of carbachol on duodenal HCO3- secretion. These results suggest, that in cholinergic regulation of duodenal HCO3- secretion, the M-cholinoceptor pathway, Ca2+, and VIP are involved.


Continuous measurement of enzymatic kinetics in droplet flow for point-of-care monitoring.
Droplet microfluidics is ideally suited to continuous biochemical analysis, requiring low sample volumes and offering high temporal resolution. Many biochemical assays are based on enzymatic reactions, the kinetics of which can be obtained by probing droplets at multiple points over time. Here we present a miniaturised multi-detector flow cell to analyse enzyme kinetics in droplets, with an example application of continuous glucose measurement. Reaction rates and Michaelis-Menten kinetics can be quantified for each individual droplet and unknown glucose concentrations can be accurately determined (errors <5%). Droplets can be probed continuously giving short sample-to-result time (∼30 s) measurement. In contrast to previous reports of multipoint droplet measurement (all of which used bulky microscope-based setups) the flow cell presented here has a small footprint and uses low-powered, low-cost components, making it ideally suited for use in field-deployable devices.


The distribution of 51Cr-labeled lymphocytes into antigen-stimulated mice. Lymphocyte trapping.
The localization of syngeneic (51)Cr-labeled lymph node cells was investigated in CBA/J mice previously challenged with sheep erythrocytes, Salmonella H antigen, keyhole limpet hemocyanin, C57BL/6J skin, or rat skin. The effect of time, dose, and route of antigen administration on lymphocyte migration was studied in both primary and secondary responses. When the distribution pattern of lymphocytes was examined after 20-24 hr, it was found that increased localization of labeled cells occurred in spleen after intravenous or intraperitoneal antigen injection, and in draining lymph nodes after subcutaneous antigen injection or skin grafting. Increased localization (trapping) of lymphocytes was antigen dose dependent and could be demonstrated when 1-6 hr had elapsed between intravenous antigen administration, or when 24 hr had elapsed between subcutaneous antigen administration and intravenous cell infusion. Trapping was transient, lasting approximately 24 hr. Maximal trapping of lymphocytes in the draining nodes occurred 9 days after skin grafting in the first-set allograft response, and 3 days after grafting in the second-set allograft and first-set xenograft responses. The cell type trapped, the specificity and mechanism of action of the trap, and the role of lymphocyte trapping in the initiation of immune responses are discussed.


Prevalence of antitumor antibodies in laying hen model of human ovarian cancer.
Antitumor antibodies are associated with tumors in human cancers. There is relatively little information on the timing and progression of antibody response to tumors. The objective of the study was to determine if spontaneous ovarian cancer in the egg-laying hen is associated with antitumor antibodies. Antibodies were detected by immunoassay and immunoblotting using proteins from normal ovary and ovarian tumors. Candidate antigens were identified by mass spectrometry of immunoreactive spots cut from 2-dimensional gels and Western blot. Antitumor (serum reacting against tumor ovarian extract) and antiovarian (serum reacting against normal ovarian extract) antibodies were significantly associated with ovarian cancer (67%; P <or= 0.001) compared with normal control hens. Hens with abnormal histology but no gross tumor had antitumor antibodies (63%; P <or= 0.025) but not antiovarian antibodies. There were common as well as different immunoreactions against normal ovary and homologous and heterologous tumor proteins in 2-dimensional Western blots. The candidate antigens included those commonly associated with human cancers and other diseases such as vimentin, apolipoprotein A1, Annexin II, enolase, DJ-1, and so on. The results suggest that antitumor antibodies are associated with ovarian cancer in hens, similar to human ovarian cancer. The egg-laying hen may be a model for understanding the antitumor humoral immune response, particularly at early tumor stages that are not readily accessible in human ovarian cancer.


Witness of intimate partner violence in childhood and perpetration of intimate partner violence in adulthood.
At least half a million women are victims of intimate partner violence in the United States annually, resulting in substantial harm. However, the etiology of violence to intimate partners is not well understood. Witnessing such violence in childhood has been proposed as a principal cause of adulthood perpetration, yet it remains unknown whether the association between witnessing intimate partner violence and adulthood perpetration is causal. We conducted a propensity-score analysis of intimate partner violence perpetration to determine whether childhood witnessing is associated with perpetration in adulthood, independent of a wide range of potential confounding variables, and therefore might be a causal factor. We used data from 14,564 U.S. men ages 20 and older from the 2004-2005 wave of the National Epidemiologic Survey on Alcohol and Related Conditions. Nearly 4% of men reported violent behavior toward an intimate partner in the past year. In unadjusted models, we found a strong association between childhood witnessing of intimate partner violence and adulthood perpetration (for witnessing any intimate partner violence, risk ratio [RR] = 2.6 [95% confidence interval = 2.1-3.2]; for witnessing frequent or serious violence, 3.0 [2.3-3.9]). In propensity-score models, the association was substantially attenuated (for witnessing any intimate partner violence, adjusted RR = 1.6 [1.2-2.0]; for witnessing frequent or serious violence, 1.6 [1.2-2.3]). Men who witness intimate partner violence in childhood are more likely to commit such acts in adulthood, compared with men who are otherwise similar with respect to a large range of potential confounders. Etiological models of intimate partner violence perpetration should consider a constellation of childhood factors.


ABCG2 dysfunction increases serum uric acid by decreased intestinal urate excretion.
ATP-binding cassette transporter G2 (ABCG2), also known as breast cancer resistance protein (BCRP), is identified as a high-capacity urate exporter and its dysfunction has an association with serum uric acid (SUA) levels and gout/hyperuricemia risk. However, pathophysiologically important pathway(s) responsible for the ABCG2-mediated urate excretion were unknown. In this study, we investigated how ABCG2 dysfunction affected the urate excretion pathways. First, we revealed that mouse Abcg2 mediates urate transport using the membrane vesicle system. The export process by mouse Abcg2 was ATP-dependent and not saturable under the physiological concentration of urate. Then, we characterized the excretion of urate into urine, bile, and intestinal lumen using in vivo mouse model. SUA of Abcg2-knockout mice was significantly higher than that of control mice. Under this condition, the renal urate excretion was increased in Abcg2-knockout mice, whereas the urate excretion from the intestine was decreased to less than a half. Biliary urate excretion showed no significant difference regardless of Abcg2 genotype. From these results, we estimated the relative contribution of each pathway to total urate excretion; in wild-type mice, the renal excretion pathway contributes approximately two-thirds, the intestinal excretion pathway contributes one-third of the total urate excretion, and the urate excretion into bile is minor. Decreased intestinal excretion could account for the increased SUA of Abcg2-knockout mice. Thus, ABCG2 is suggested to have an important role in extra-renal urate excretion, especially in intestinal excretion. Accordingly, increased SUA in patients with ABCG2 dysfunction could be explained by the decreased excretion of urate from the intestine.


Design, synthesis, and antimycobacterial activity of novel ciprofloxacin derivatives.
Tuberculosis is the deadliest infectious disease affecting humankind with a death toll of approximately 1.7 million people in 2016. The increasing prevalence of multidrug-resistant strains of the causative pathogen, Mycobacterium tuberculosis (Mtb) which results in reduced effectiveness of the current therapies, underscores the urgent need for the development of new antitubercular drugs. In the search for such drugs, we investigated two series of ciprofloxacin (CPX) derivatives (analogues and hybrids). We herein report the design, synthesis, and biological activity of these series against the human virulent Mtb H37Rv strain in vitro. The small propionyl analogue 11 (MIC90 1.6 μM; SI > 61) and the large cholesteryl hybrid 32 (MIC90 2.0 μM; SI > 6) were the most active derivatives, comparable to CPX (MIC90 1.8 μM). However, the slightly less active but non-cytotoxic para-fluorobenzyl hybrid 28 (MIC90 3.7 μM; SI 27) was more selective toward bacteria than 32. Thus, the CPX derivatives 11 and 28 were identified as preferred antitubercular hits for further investigation including distribution, metabolism and pharmacokinetic parameters determination and in vivo activity assessment in animal models.


Minimally Invasive Video-Assisted Total Thyroidectomy (mi V.A.T.T.) - Case Series of 48 Patients.
The first report of miVATT was published in 1998 by Miccoli, leading to a revolution in the field of thyroid surgery. This prospective study aims to evaluate the technique with regard to our department's experience over a four-year period. Between September 2009 and October 2013, 48 adult patients (37 females, 11 males) with a mean age of 41.3 (± 11.6) years underwent scheduled miVATT for benign thyroid lesions. Selection criteria included thyroid volume <15 ml and nodules not exceeding 3.5 cm of diameter. Thyroiditis, previous neck surgery and previous irradiation, mediastinal goiter and involvement in another clinical study constituted the exclusion criteria. The procedure we performed was miVATT as described by Miccoli with the only additions being the use of the Harmonic Scalpel and the fixation of the endoscope on a holding device. Also, no drains were applied. No conversions to open surgery were needed. Operation time for total thyroidectomy was 71.23 min (± 23.81) with a mean hospitalization of 1.14 days (± 0.4). Five patients (10.4%) exhibited transient hypocalcemia, whereas there were no recurrent laryngeal nerve palsies. Post-operative pain was mild and the final aesthetic result was considered excellent by the patients. miVATT is a safe and feasible alternative to the conventional thyroidectomy when performed in carefully selected patients by experienced surgeons.


A role for poly(dA)poly(dT) tracts in directing activity of the Plasmodium falciparum calmodulin gene promoter.
Expression of the Plasmodium falciparum calmodulin gene (pfcam) is developmentally regulated throughout the blood-stage cycle. The promoter lies within approximately 1 kb of intergenic sequence that separates the pfcam open reading frame (ORF) from an upstream inverted ORF encoding a product homologous to the co-chaperone STI1. Using the oligo-capping method, which selectively reverse-transcribes cDNA from only full-length, capped transcript, we have mapped multiple transcription-initiation sites for both genes. Transcription of the pfSTI1 gene initiates over a 150 bp region centred approximately 350 bp upstream of the ORF. The pfcam transcription start sites cluster into four approximately 30 bp regions lying within 180 bp upstream of the pfcam ORF, generating transcripts with 5' untranslated regions (UTR) of 3-173 nucleotides in length. Remarkably, splicing was found to be related to UTR length, with apparent preferential splicing of longer transcripts. Activity of the pfcam promoter diminished in a linear fashion to undetectable levels upon step-wise removal of sequence between 625 and 230 bp upstream of the start ATG. Electromobility-shift assays demonstrated nuclear factor binding to eight oligonucleotide probes spanning 657 bp of the pfcam ORF proximal upstream sequence. The degree of binding correlated with the density of poly(dA)poly(dT) tracts within the probes, and in all cases could be inhibited by excess synthetic poly(dA)poly(dT), but not by poly(dAdT)poly(dAdT). The multiple transcription-initiation sites of both pfSTI1 and pfcam genes lie just downstream of 25 bp-long poly(dA)poly(dT) tracts, and the intergenic region contains over 20 poly(dA)poly(dT) tracts of 4 bp or more. Our results suggest that the basal pfcam promoter is situated between approximately -300 and -230 bp upstream of the pfcam ORF and that the P. falciparum transcription-initiation complex has a low degree of sequence-specificity for the sites of initiation but preferentially acts downstream of long poly(dA)poly(dT) tracts.


Differences in Suicidal Thoughts and Behaviors Among Three Racial Groups.
Background: Despite being a major public health concern, it is unclear how suicidal thoughts and behaviors differentially impact separate racial groups. Aims: The aim of the current study was to examine the occurrence of nonlethal suicide events, in addition to suicide attempt characteristics and factors contributing to suicide attempts. Method: A final sample of 7,094 undergraduates from a large northeastern university, identifying as members of three racial groups (White [67.30%], Black [17.30%], and Asian [15.40%]), completed online questionnaires. Results: White participants reported increased likelihood of endorsing lifetime suicidal ideation and plan, whereas Black participants reported decreased likelihood of these events; no differences were found in rates of lifetime suicide attempts. Black participants' suicidal behavior may involve greater ambivalence of intent. A higher proportion of Asian participants endorsed interpersonal factors as contributing to their suicide attempts, whereas a greater percentage of White participants reported internal contributing factors. Limitations: Findings are limited by the sample size and assessment of lifetime suicidal thoughts and behaviors. Conclusion: The findings present a more nuanced look at attitudes and actions related to suicidal thoughts and behaviors that may inform future research and risk assessment procedures.


Influence of immunization schedule on immunization coverage.
The infant immunization coverage for triple antigen (DPT) from 1968 and trivalent oral polio vaccine (TOPV) from 1972 to 1985 for Peninsular Malaysia are presented. It shows that immunization coverage improved when the recommended age for first dose of DPT was changed from the fourth to the second month of life in 1972 and declined when the recommended age for the first dose of DPT and TOPV was revised again from the second to the third month of life in 1980. The advantages of immunizing children early in life are discussed.


Macrophage-restricted overexpression of glutaredoxin 1 protects against atherosclerosis by preventing nutrient stress-induced macrophage dysfunction and reprogramming.
Deficiency in the thiol transferase glutaredoxin 1 (Grx1) in aging mice promotes, in a sexually dimorphic manner, dysregulation of macrophages and atherogenesis. However, the underlying mechanisms are not known. Here we tested the hypothesis that macrophage-restricted overexpression of Grx1 protects atherosclerosis-prone mice against macrophage reprogramming and dysfunction induced by a high-calorie diet (HCD) and thereby reduces the severity of atherosclerosis. We generated lentiviral vectors carrying cluster of differentiation 68 (CD68) promoter-driven enhanced green fluorescent protein (EGFP) or Grx1 constructs and conducted bone marrow (BM) transplantation studies to overexpress Grx1 in a macrophage-specific manner in male and female atherosclerosis-prone LDLR-/- mice, and fed these mice a HCD to induce atherogenesis. Atherosclerotic lesion size was determined in both the aortic root and the aorta. We isolated BM-derived macrophages (BMDM) to assess protein S-glutathionylation levels and loss of mitogen-activated protein kinase phosphatase 1 (MKP-1) activity as measures of HCD-induced thiol oxidative stress. We also conducted gene profiling on these BMDM to determine the impact of Grx1 activity on HCD-induced macrophage reprogramming. Overexpression of Grx1 protected macrophages against HCD-induced protein S-glutathionylation, reduced monocyte chemotaxis in vivo, limited macrophage recruitment into atherosclerotic lesions, and was sufficient to reduce the severity of atherogenesis in both male and female mice. Gene profiling revealed major sex differences in the transcriptional reprogramming of macrophages induced by HCD feeding, but Grx1 overexpression only partially reversed HCD-induced transcriptional reprogramming of macrophages. Macrophage Grx1 plays a major role in protecting mice atherosclerosis mainly by maintaining the thiol redox state of the macrophage proteome and preventing macrophage dysfunction.


Schistosoma mansoni glyceraldehyde 3-phosphate dehydrogenase is a lung-stage schistosomula surface membrane antigen.
We have previously reported that Schistosoma mansoni larvae emerging from host lung at pH 7.5-7.8 and then fixed with diluted formaldehyde (HCHO) readily bind radiation-attenuated cercariae (RA) vaccine serum antibodies, as assessed by indirect membrane immunofluorescence (IF). Here we show that S. mansoni schistosomula emerging from lung pieces under 5% CO2 (pH < or = 7.3) readily bind RA vaccine serum antibodies, provided they have been incubated for 12 h at pH 7.5-7.8 in foetal calf serum-free RPMI medium, and fixed with diluted HCHO. Ex vivo larvae exposed during incubation to GW4869, a specific inhibitor of tegument-bound, neutral sphingomyelinase (nSMase) displayed significantly diminished binding of RA vaccine serum antibodies, thus suggesting that nSMase activity at pH > or = 7.5 leads to exposure of lung-stage larvae surface membrane antigens to specific antibody detection. More importantly, ex vivo larvae readily bound antibodies directed to dipeptidic multiple antigen peptide constructs, based on S. mansoni-specific sequences in S. mansoni glyceraldehyde 3-phosphate dehydrogenase (SG3PDH). Lung-stage schistosomula IF reactivity was diminished following antiserum absorption with recombinant SG3PDH. The data together indicate that intact ex vivo, as well as, 5-day-old in vitro-grown larvae express SG3PDH on their surface membrane. The findings are discussed in relation to the importance of surface membrane proteins as candidate vaccine antigens.


Using hemoglobin A1c for prediabetes and diabetes diagnosis in adolescents: can adult recommendations be upheld for pediatric use?
The obesity epidemic has resulted in more young people having high-risk profiles for the development of type 2 diabetes. Screening to promote earlier diagnosis and treatment of type 2 diabetes is of significant importance, as untreated disease leads to metabolic, microvascular, and macrovascular complications. However, the choice of screening methodology in adolescents is controversial, and implementation of screening protocols is not uniform. Expert panels have recommended the use of glycated hemoglobin (A1c) for the diagnosis of prediabetes and diabetes, based on the facts that the A1c assay has technical advantages and correlates well with the risk of microvascular diabetes. However, these recommendations are based strictly on data from adult studies and lack any input based on pediatric research. The pediatric research that has been published on the topic indicates that using adult cutoff points for A1c values to predict prediabetes or diabetes significantly underestimates the prevalence of these conditions in the pediatric and adolescent population. Therefore, we call for further investigation of the role of A1c for the diagnosis of prediabetes and diabetes in adolescents before its adoption as a principal diagnostic method in pediatric populations. We contend that a more comprehensive diabetes evaluation, along with A1c, remains necessary for screening adolescents at high risk for prediabetes and type 2 diabetes. Collaborative multicentered studies of prediabetes and type 2 diabetes in the obese pediatric population are especially needed to determine the A1c cutoff points, as well as other diagnostic measures, that best predict diabetes-related comorbid conditions later in life.


Jasmonate perception regulates jasmonate biosynthesis and JA-Ile metabolism: the case of COI1 in Nicotiana attenuata.
CORONATINE INSENSITIVE 1 (COI1) is a well-known key player in processes downstream of jasmonic acid (JA) biosynthesis: silencing COI1 in Nicotiana attenuata (ir-coi1) makes plants insensitive to JA, prevents the up-regulation of JA-mediated defenses and decreases the plant's resistance to herbivores and pathogens. In agreement with previous studies, we observed that regulation of several JA biosynthesis genes elicited by Manduca sexta oral secretions (OS) is COI1 dependent. In response to wounding and application of OS ir-coi1 plants accumulate 75% less JA compared with wild-type plants (WT), resembling JA levels found in plants silenced in the key enzyme in JA biosynthesis LIPOXYGENASE 3 (as-lox). However, while OS-elicited as-lox plants also accumulated lower levels of the JA-conjugate JA-isoleucine (JA-Ile) than did WT plants, JA-Ile accumulation in ir-coi1 was higher, prolonged and peaked with a delay of 30 min. In vivo substrate feeding experiments of N. attenuata demonstrate that the increased and prolonged JA-Ile accumulation pattern in ir-coi1 is not the result of altered substrate availability, i.e. of JA and/or Ile, but is due to an approximately 6-fold decrease in JA-Ile turnover. These results provide the first evidence for a second, novel regulatory feedback function of COI1 in enhancing JA-Ile turnover. Hence, in addition to its control over JA biosynthesis, COI1 might fine-tune the dynamics of the jasmonate response after induction by herbivore elicitors.


Recent Development of Copper-Based Nanozymes for Biomedical Applications.
Copper (Cu), an indispensable trace element within the human body, serving as an intrinsic constituent of numerous natural enzymes, carrying out vital biological functions. Furthermore, nanomaterials exhibiting enzyme-mimicking properties, commonly known as nanozymes, possess distinct advantages over their natural enzyme counterparts, including cost-effectiveness, enhanced stability, and adjustable performance. These advantageous attributes have captivated the attention of researchers, inspiring them to devise various Cu-based nanomaterials, such as copper oxide, Cu metal-organic framework, and CuS, and explore their potential in enzymatic catalysis. This comprehensive review encapsulates the most recent advancements in Cu-based nanozymes, illuminating their applications in the realm of biochemistry. Initially, it is delved into the emulation of typical enzyme types achieved by Cu-based nanomaterials. Subsequently, the latest breakthroughs concerning Cu-based nanozymes in biochemical sensing, bacterial inhibition, cancer therapy, and neurodegenerative diseases treatment is discussed. Within this segment, it is also explored the modulation of Cu-based nanozyme activity. Finally, a visionary outlook for the future development of Cu-based nanozymes is presented.


Growth-Friendly Spine Surgery in Escobar Syndrome.
The aims of this study were to characterize the spinal deformity of patients with Escobar syndrome, describe results of growth-friendly treatments, and compare these results with those of an idiopathic early-onset scoliosis (EOS) cohort to determine whether the axial stiffness in Escobar syndrome limited correction. We used 2 multicenter databases to review the records of 8 patients with EOS associated with Escobar syndrome who had at least 2-year follow-up after initiation of growth-friendly treatment from 1990 to 2016. An idiopathic EOS cohort of 16 patients matched for age at surgery (±1 y), postoperative follow-up (±1 y), and initial curve magnitude (±10 degrees) was identified. A randomized 1:2 matching algorithm was applied (α=0.05). In the Escobar group, spinal deformity involved 7 to 13 vertebrae and ranged from no vertebral anomalies in 3 patients to multiple segmentation defects in 6 patients. Mean age at first surgery was 5 years (range, 1.4 to 7.8 y) with a mean follow-up of 7.5 years (range, 4.0 to 10 y). Mean major curve improved from 76 degrees at initial presentation, to 43 degrees at first instrumentation, to 37 degrees at final follow-up (both P<0.001). Mean pelvic obliquity improved from 16 degrees (range, 5 to 31 degrees) preoperatively to 4 degrees (range, 0 to 8 degrees) at final follow-up (P=0.005). There were no differences in the mean percentage of major curve correction between the idiopathic EOS and Escobar groups at the immediate postoperative visit (P=0.743) or final follow-up (P=0.511). There were no differences between the cohorts in T1-S1 height at initial presentation (P=0.129) or in growth per month (P=0.211). Multiple congenital fusions and spinal curve deformity are common in Escobar syndrome. Despite large areas of congenital fusion, growth-friendly constructs facilitate spinal growth and improve curve correction. These results are comparable to those in idiopathic EOS. Level III-case-control study.


The association of interpersonal trauma with somatic symptom severity in a primary care population with chronic pain: exploring the role of gender and the mental health sequelae of trauma.
Female trauma survivors develop somatic symptoms more frequently than males. We propose a model for somatic symptom development among trauma survivors, focusing on gender. Among 597 urban primary care patients with chronic pain, we examined the association between somatic symptom severity and three interpersonal trauma types: 1) sexual trauma (ST), 2) intimate partner violence (IPV), and 3) childhood trauma history (≥3 adverse childhood experiences (3+ACE)). We developed a structural equation model in which PTSD, depression, and substance abuse were evaluated as potential mediators of the path between trauma exposure and somatic symptom severity, and explored the role of gender in this model. 350 (59%) respondents were female; the mean age was 47. Women reported significantly more somatic symptoms than men, although somatic symptoms were increased among all interpersonal trauma survivors. In models in which the potential intervening variables are considered in aggregate, we did not find a signficant interaction between gender and trauma on somatic symptom severity, with the exception of 3+ACEs. A structural equation model showed depression and substance abuse, for men, and depression, for women, were associated with somatic symptom severity. PTSD was not associated with somatic symptom severity. Paths from trauma exposures to mental health sequelae were stronger for men. Women have more severe somatic symptoms. With the exception of 3+ACEs, the association between trauma and somatic symptoms is amplified in both genders. Structural equation models showed the pathways differed by gender in function and strength of association.


Effects of spinal tractotomy on spatial sequence recognition in macaques.
Five Macaca speciosa monkeys were trained to discriminate between the order of two tactile stimulus presentations (proximal-distal vs. distal-proximal) to the lateral calf. Psychophysical thresholds for tactile sequence recognition were obtained by varying the distance between the spots stimulated. Stabilized preoperative thresholds for stimulation on the lateral calf averaged 10.4 mm, which is comparable to point localization thresholds for sequential contact of the proximal limbs of humans. Complete interruption of the ipsilateral fasciculus gracilis produced elevations of thresholds within the first 3 postoperative weeks to an average of 3.6 times the control values. With training over 6 postoperative months, normal discrimination recovered. In contrast to the effects of dorsal column (DC) lesions, interruption of the lateral and ventral columns ipsilaterally or contralaterally produced no deficit or a mild and transient deficit. Monkeys with isolation of either the ipsilateral dorsolateral column (ILC) or the contralateral ventral quadrant (CVQ) exhibited substantial and enduring deficits. Thresholds were elevated an average of 5 times the control values, and recovery was not observed or was incomplete after months of training. In contrast, isolation of the ipsilateral dorsal column produced little or no threshold elevation. The results of isolating lesions complement the series of primary lesions to each cord sector, showing that spatiotactile sequence recognition for the hindlimb is served more critically by the dorsal columns than by the lateral columns.


Influence of shape and finishing on the corrosion of palladium-based dental alloys.
The purpose of this study was to evaluate the effects of the surface treatment and shape of the dental alloy on the composition of the prosthetic work and its metallic ion release in a corrosive medium after casting. Orion Argos (Pd-Ag) and Orion Vesta (Pd-Cu) were used to cast two crowns and two disks. One of each was polished while the other was not. Two as-received alloys were also studied making a total of 5 specimens per alloy type. The specimens were submersed for 7 days in a lactic acid/sodium chloride solution (ISO standard 10271) and evaluated for surface structure characterization using SEM/EDAX. The solutions were quantitatively analysed for the presence of metal ions using ICP-MS and the results were statistically analysed with one-way ANOVA and a Tukey post-hoc test. Palladium is released from all specimens studied (range 0.06-7.08 µg·cm(-2)·week(-1)), with the Pd-Cu alloy releasing the highest amounts. For both types of alloys, ion release of both disk and crown pairs were statistically different from the as-received alloy except for the Pd-Ag polished crown (P>.05). For both alloy type, disk-shaped pairs and unpolished specimens released the highest amounts of Pd ions (range 0.34-7.08 µg·cm(-2)·week(-1)). Interestingly, in solutions submerged with cast alloys trace amounts of unexpected elements were measured. Shape and surface treatment influence ion release from dental alloys; polishing is a determinant factor. The release rate of cast and polished Pd alloys is between 0.06-0.69 µg·cm(-2)·week(-1), which is close to or exceeding the EU Nickel Directive 94/27/EC compensated for the molecular mass of Pd (0.4 µg·cm(-2)·week(-1)). The composition of the alloy does not represent the element release, therefore we recommend manufacturers to report element release after ISO standard corrosion tests beside the original composition.


A national survey of computed tomography doses in hybrid PET-CT and SPECT-CT examinations in the UK.
The aim of this study was to conduct a nationwide survey of computed tomography (CT) doses for a wide range of PET-CT and single photon emission computed tomography-computed tomography (SPECT-CT) imaging procedures, with the aim of generating proposed UK national diagnostic reference levels (NDRLs). CT protocol and dosimetry data for three PET-CT and seven SPECT-CT examinations were gathered from centres across the UK. Data were divided according to CT purpose (attenuation correction, localization or diagnostic) and third quartile values of scanner average dose metrics were used to generate suggested NDRLs for a range of examination and CT purpose combinations. Achievable doses were also established from the median of the dose distributions. Data were obtained from 47 centres, allowing suggested NDRLs to be produced for fluorine-18-fluorodeoxyglucose half-body PET-CT, and parathyroid, post-thyroid ablation, meta-iodobenzylguanidine/octreotide, cardiac and bone SPECT-CT examinations.Variations in dose of up to a factor of 35 were observed for a given examination/CT purpose combination. For fluorine-18-fluorodeoxyglucose half-body PET-CT examination dose levels for the three CT purposes overlapped, which highlights the variability in the way in which CT purposes are interpreted across the UK. This lack of standardization is believed to be the largest contributor to the dose variations that were observed. The survey highlighted the need for targeted optimization work in many centres. Suggested UK NDRLs and achievable doses for six common PET-CT and SPECT-CT examinations have been established as a result of this study.


A novel phosphatidylserine-functionalized AuNP for the visual detection of free copper ions with high sensitivity and specificity.
In this paper, we have reported on novel phosphatidylserine-functionalized AuNPs (gold nanoparticles) for the visual detection of Cu2+ by employing phosphatidylserine for Cu2+ recognition and AuNPs for signal generation. The phosphatidylserine (1,2-dioleoyl-sn-glycero-3-phospho-l-serine, DOPS) was covalently assembled on the AuNP surface to obtain DOPS-functionalized AuNPs. It was demonstrated that DOPS-functionalized AuNPs could specifically bind Cu2+ and lead to the aggregation of AuNPs, which gave rise to a colour change from wine-red to blue and a new absorption band around 650 nm. This provides a sensing platform for the simple, rapid and field portable colorimetric detection of Cu2+. By using the sensing platform, a selective and sensitive visual biosensor for the detection of Cu2+ was developed. The proposed biosensor has outstanding analytical advantages such as good stability, relatively high sensitivity, low cost and short analysis time. It can be used to detect concentrations of Cu2+ as low as 30 μM in river water by observation with the naked eye and of 1.55 μM Cu2+ in river water by UV-visible spectrophotometry, within 10 min and with a recovery of 98-103% and a relative standard deviation (RSD) < 4% (n = 6). The proposed biosensor is promising for on-site detection of trace Cu2+ in clinical diagnosis or environmental monitoring.


Understanding Drivers of Coronavirus Disease 2019 Vaccine Hesitancy Among Blacks.
Coronavirus disease 2019 (COVID-19) has disproportionately affected communities of color, with black persons experiencing the highest rates of disease severity and mortality. A vaccine against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has the potential to reduce the race mortality gap from COVID-19; however, hesitancy toward the vaccine in the black community threatens vaccine uptake. We conducted focus groups with black barbershop and salon owners living in zip codes of elevated COVID-19 prevalence to assess their attitudes, beliefs, and norms around a COVID-19 vaccine. We used a modified grounded theory approach to analyze the transcripts. We completed 4 focus groups (N = 24 participants) in July and August 2020. Participants were an average age of 46 years, and 89% were black non-Hispanic. Hesitancy against the COVID-19 vaccine was high due to mistrust in the medical establishment, concerns with the accelerated timeline for vaccine development, limited data on short- and long-term side effects, and the political environment promoting racial injustice. Some participants were willing to consider the vaccine once the safety profile is robust and reassuring. Receiving a recommendation to take the vaccine from a trusted healthcare provider served as a facilitator. Health beliefs identified were similar to concerns around other vaccines and included the fear of getting the infection with vaccination and preferring to improve one's baseline physical health through alternative therapies. We found that hesitancy of receiving the COVID-19 vaccine was high; however, provider recommendation and transparency around the safety profile might help reduce this hesitancy.


Clinical features of canine granulocytic anaplasmosis in 18 naturally infected dogs.
Anaplasma phagocytophilum, the causative agent of canine granulocytic anaplasmosis (CGA), is a Gram-negative intracellular organism transmitted by ixodid ticks. Thus far, only a few clinical studies evaluating dogs with CGA have been published. Evaluation of dogs naturally infected with A. phagocytophilum in which known co-infections were excluded. Eighteen dogs with CGA. Prospective study. The diagnosis of CGA was based on a positive PCR test result; dogs with co-infections were excluded. History, clinical findings, CBC, clinical biochemistry, infectious disease screening, diagnostic imaging, and the course of disease were evaluated. CGA was diagnosed based on a positive PCR test for A. phagocytophilum; 10 dogs also had morulae in neutrophils. Six of 18 dogs were seronegative to A. phagocytophilum, the others were seropositive. All dogs were acutely ill. The most common clinical findings were lethargy, inappetence, fever, and splenomegaly. Abnormal laboratory results included thrombocytopenia, anemia, lymphopenia, hypoalbuminemia, and abnormally high plasma alkaline phosphatase activity. In 6 of 10 dogs tested, the platelet-bound antibody test was positive; Coombs' test was negative in 9 dogs. All dogs were treated with doxycycline and recovered. PCR testing as well as blood smear analysis for morulae were negative in 14 tested dogs 2-8 weeks after beginning treatment. Clinical findings in dogs with CGA were nonspecific. Positive platelet-bound antibody test results suggest immune-mediated platelet destruction as an important pathogenic mechanism. With correct diagnosis and treatment, prognosis is good.


Dose effects of beta-tricalcium phosphate nanoparticles on biocompatibility and bone conductive ability of three-dimensional collagen scaffolds.
Three-dimensional collagen scaffolds coated with beta-tricalcium phosphate (β-TCP) nanoparticles reportedly exhibit good bioactivity and biodegradability. Dose effects of β-TCP nanoparticles on biocompatibility and bone forming ability were then examined. Collagen scaffold was applied with 1, 5, 10, and 25 wt% β-TCP nanoparticle dispersion and designated TCP1, TCP5, TCP10, and TCP25, respectively. Compressive strength, calcium ion release and enzyme resistance of scaffolds with β-TCP nanoparticles applied increased with β-TCP dose. TCP5 showed excellent cell-ingrowth behavior in rat subcutaneous tissue. When TCP10 was applied, osteoblastic cell proliferation and rat cranial bone augmentation were greater than for any other scaffold. The bone area of TCP10 was 7.7-fold greater than that of non-treated scaffold. In contrast, TCP25 consistently exhibited adverse biological effects. These results suggest that the application dose of β-TCP nanoparticles affects the scaffold bioproperties; consequently, the bone conductive ability of TCP10 was remarkable.


The tumorous-head-1 locus affects bristle number of the Drosophila melanogaster cuticle.
The tuh-1 maternal effect locus contains two naturally occurring isoalleles, tuh-1h and tuh-1g. Until recently there has been no possibility to distinguish between the tuh-lh and the tuh-1g maternal effects other than evaluating their effect on the Bithorax-Complex (BXC) Abdominal B (Abd-B) mutant tuh-3. However, in this report we identify a bristle phenotype associated with the tuh-1 locus that has very interesting evolutionary implications. Females homozygous for tuh-1h always produce adult offspring with more bristles than females homozygous or heterozygous for tuh-1g. The effect is global. Increased bristle number occurs in the head, the thorax, and the anterior and posterior abdomen. Females totally deficient for the tuh-1 gene produce offspring with high bristle number. Thus, the bristle phenotype results from the absence of the maternally contributed tuh-1g factor. Genetic evidence shows that the bristle phenotype is caused by the tuh-1 locus and that tuh-1h is completely recessive to tuh-1g. The tuh-1 locus is located at the euchromatin-beta-heterochromatin junction near the centromere of the X chromosome and deficiency analysis places the locus between the lethal genes extra organs (eo) and lethal B20 (lB20). The variance in bristle number attributable to the tuh-1 locus in nature is approximately 10.1%, an indication that the bristle phenotype is most likely a neutral, pleiotrophic side effect of tuh-1.


Effects of antibiotic prophylaxis on women undergoing nonelective cesarean section in a community hospital.
A randomized, double-blind, placebo-controlled study was done of a short course of cefamandole administered intravenously after cord clamping as prophylaxis in women undergoing primary nonelective cesarean section in a community hospital. Duration of labor equal to or more than 14 hours was the only significant risk factor between patients who had postoperative infectious morbidity and those who had none. Four of 43 patients (9.3%) who received cefamandole, as opposed to 13 of 47 (27.7%) who received the placebo, developed infections (p less than 0.05). This difference was reflected totally in the difference in endomyometritis development between the groups. The use of intraoperative culturing predicted infection in 4 of 13 patients in the placebo group who developed infections postoperatively. No adverse side effects were noted, and there were no cases of delayed serious infection.