Incidental carcinoma in multinodular goiter: risk factors.
The aim of the study was to analyze the frequency of incidental thyroid carcinoma (unknown tumor smaller than or equal to 10 mm) in a consecutive series of 462 total thyroidectomies for multinodular goiter and to investigate the clinical risk factors for this type of malignancy. A retrospective, single-center study of outcome data collected from patients with preoperative diagnosis of multinodular goiter who underwent total thyroidectomy at the General Surgery Unit of Pavia (Italy) between January 2000 and December 2008 was performed. Possible risk factors for malignancy were: gender, age, time of evolution of goiter, presence of a dominant nodule in multinodular goiter, hyperthyroidism, history of radiation to the neck, residence in an area of endemic goiter, prior thyroid surgery, calcifications in the goiter detected by neck ultrasound or chest X-rays, and a family history of thyroid diseases. In a 9-year period, 462 patients underwent total thyroidectomy. We found 41 cases of incidental thyroid carcinoma; the most common histopathological type was papillary. The multivariable analysis demonstrated that the clinical variables associated with occult carcinoma were a personal history of radiation therapy to the neck, the presence of calcifications detected by ultrasound or neck X-rays, and a family history of thyroid diseases; residence in an area of endemic goiter was a protective factor. A personal history of radiation to the neck, detection of calcifications by ultrasound or by neck X-rays, and a family history of thyroid diseases should be considered clinical risk factors for malignancy in multinodular goiter.


[Diagnosis and management of visceral arteries aneurysms].
Visceral arteries aneurysms appear to be of particular clinical importance in surgical practice. Approximately 22% of the reported cases of visceral arterial aneurysms are complicated by a rupture with a high risk of an eventually lethal outcome. Endovascular embolization of the aneurysmal cavity and closure of the arterial wall defect by means of stent-grafts are increasingly gaining ground in surgical practice, which may reasonably be attributed to the minimally invasive nature of the procedure as compared with the conventional and routinely performed surgical intervention. The review deals with the analysis of the Russian and foreign literature pertaining to the problem concerned, covering the aetiology, incidence, localization of aneurysms, and clinical manifestations thereof, also pointing out diagnostic possibilities of instrumental methods of study. To this was added the description of therapeutic modalities using both an open operation, and with the help of endovascular interventions. Also, a comparative assessment of efficacy and safety of various therapeutic techniques is presented herein.


Relative contribution of aortic and carotid baroreflexes to heart rate control in man during steady state and dynamic increases in arterial pressure.
We studied the contribution of carotid vs. extracarotid baroreceptors in control of heart rate in normal humans. We measured heart interval (HI) and arterial pressure during steady-state infusion of phenylephrine (PE). PE increased mean arterial pressure (MAP) by 13 +/- 2 mmHg (mean +/- SEM; n = 10) and thus stimulated both carotid and aortic baroreceptors. Neck pressure (NP) was applied during PE infusion to counter the increase in transmural carotid sinus pressure, thus leaving only aortic baroreceptors stimulated by the increase in arterial pressure. PE infusion alone prolonged HI by 230 +/- 24 ms (P less than 0.05). Application of NP attenuated the HI response to 65 +/- 22 ms above control (P less than 0.05 vs. PE alone). During these steady-state increases in arterial pressure, elimination of the carotid baroreflex contribution reduced the HI prolongation by 41-70% in five subjects and by greater than 93% in five subjects. We also measured the HI response to dynamic ramp elevation of systolic arterial pressure (SAP) using bolus administrations of PE. Baroreflex control was calculated from the slope of the regression correlating SAP to succeeding HI for PE alone (carotid and aortic baroreceptor activation) and for PE plus superimposed dynamic NP at levels equal to the increases in SAP (aortic baroreceptor activation). During PE alone, the baroreflex slope was 20.2 +/- 2.9 ms/mmHg (n = 10). During PE plus NP, the baroreflex slope was reduced by 30% to 14.1 +/- 2.8 ms/mmHg (P less than 0.02 vs. during PE alone). Thus, during dynamic increases in arterial pressure, eliminating the carotid baroreflex contribution reduced the HI response by 30%. These studies indicate that extracarotid (presumably aortic) and carotid baroreflexes both participate in control of heart rate in humans. Extracarotid (aortic) baroreflexes appear to have the greater role in control of heart rate during dynamic increases in arterial pressure.


Status inequalities, perceived discrimination, and eudaimonic well-being: do the challenges of minority life hone purpose and growth?
Considerable prior research has investigated links between racial/ethnic status and diverse aspects of mental functioning (e.g. psychological disorders, quality of life, self-esteem), but little work has probed the connections between minority status and eudaimonic well-being. Derived from existential and humanistic perspectives, eudaimonia describes engagement in life challenges and is operationalized with assessments of purpose in life, personal growth, autonomy, environmental mastery, self-acceptance, and positive relations with others. Using Midlife in the United States (MIDUS), a national survey of Americans aged 25-74, plus city-specific samples of African Americans in New York City and Mexican Americans in Chicago, minority status was found to be a positive predictor of eudaimonic well-being, underscoring themes of psychological strength in the face of race-related adversity. Perceived discrimination was found to be a negative predictor of eudaimonic well-being, although such effects were gender-specific: it was women, both majority and minority, with high levels of discrimination in their daily lives whose sense of growth, mastery, autonomy, and self-acceptance was compromised.


All solid photonic bandgap fiber based on an array of oriented rectangular high index rods.
We report the fabrication, characterization and modeling of an all-solid photonic bandgap fiber (PBGF) based on an array of oriented rectangular rods. Observed near-field patterns of cladding modes clearly identify the cut-off rod modes at the bandgap edges. The bend losses in this fiber depend on the bend direction, and can be understood by the directional coupling properties of the different rod modes and the modeled density of cladding states.


Bonding rearrangements in organometallic reactions: from orbitals to curly arrows.
Reaction mechanisms include a description of both the nuclear and electronic rearrangements along the energetically most favourable pathway. Extracting the nuclear rearrangements from the outcome of quantum chemical calculations is straightforward, while it is more intricate for the electronic rearrangements. This is particularly true when changes in the bonding pattern are of interest, just as in the arrow-pushing formalism used in chemical schemes. Here, we report on our use of a simple and highly visual procedure to recover the bonding rearrangements along a reaction pathway from DFT calculations and to draw curly arrows. We show that the procedure allows us discern among mechanistic proposals in the context of organometallic reactions featuring the forming and breaking of bonds.


The role of Mycobacterium leprae phenolic glycolipid I (PGL-I) in serodiagnosis and in the pathogenesis of leprosy.
PGL-I (phenolic glycolipid I) emerged in the early 1980s on the one hand as part of intensive efforts to define the typing antigens of a host of Mycobacterium spp. and also from characterisation of the lipids of skin biopsies from highly bacillary positive lepromatous leprosy patients. PGL-I, despite its extreme lipophilicity due to its inherent phthiocerol dimycocerosyl component, is highly antigenic evoking high titre IgM antibodies in lepromatous leprosy patients, attributable largely to the unique 3,6-di-O-methyl-beta-D-glucosyl entity at the non-reducing terminus of its trisaccharide. PGL-I itself or in the form of semisynthetic neoglycoproteins containing the synthetic terminal disaccharide or the whole trisaccharide chemically conjugated to such as bovine or human serum albumin, has found its greatest utility in the serological diagnosis, confirmation and management of lepromatous leprosy. PGL-I has also been implicated in the tropism of M. leprae for Schwann cells, through specific binding to laminin, and to play an important role in downregulation of the inflammatory immune response and inhibition of dendritic cell maturation and activation, thereby facilitating the persistence of M. leprae/leprosy.


Causes, consequences and biomarkers of stress in swine: an update.
In recent decades there has been a growing concern about animal stress on intensive pig farms due to the undesirable consequences that stress produces in the normal physiology of pigs and its effects on their welfare and general productive performance. This review analyses the most important types of stress (social, environmental, metabolic, immunological and due to human handling), and their biological consequences for pigs. The physio-pathological changes associated with stress are described, as well as the negative effects of stress on pig production. In addition an update of the different biomarkers used for the evaluation of stress is provided. These biomarkers can be classified into four groups according to the physiological system or axis evaluated: sympathetic nervous system, hypothalamic-pituitary-adrenal axis, hypothalamic-pituitary-gonadal axis and immune system. Stress it is a process with multifactorial causes and produces an organic response that generates negative effects on animal health and production. Ideally, a panel of various biomarkers should be used to assess and evaluate the stress resulting from diverse causes and the different physiological systems involved in the stress response. We hope that this review will increase the understanding of the stress process, contribute to a better control and reduction of potential stressful stimuli in pigs and, finally, encourage future studies and developments to better monitor, detect and manage stress on pig farms.


Biflavonoid fraction from Garcinia kola seed ameliorates hormonal imbalance and testicular oxidative damage by anti-tuberculosis drugs in Wistar rats.
Tuberculosis (TB) is a global health problem. The effects of anti-TB drugs on male reproductive system have not been properly evaluated. We investigated the effects of anti-TB drugs on testicular antioxidant indices, sperm characteristics and hormonal levels in rats, and the protective role of kolaviron (KV), a biflavonoid from Garcinia kola seed. Twenty-eight male Wistar rats were assigned into four groups and orally treated with corn oil (control), anti-TB drugs [4-Tabs=isoniazid (5 mg/kg), rifampicin (10 mg/kg), pyrazinamide (15 mg/kg) and ethambutol (15 mg/kg) in combination], anti-TB drugs +KV and KV alone (200 mg/kg). Anti-TB drugs and KV were given three times per week for 8 weeks. In vitro, reducing power, inhibition of lipid peroxidation (LPO), diphenyl-1-picrylhydrazyl (DPPH) and hydroxyl radical scavenging effects of KV were examined. KV at 10, 20, 50 and 100 μg/mL showed strong reducing potential and effectively scavenged DPPH and OH radicals in a concentration-dependent manner. Furthermore, KV significantly inhibited LPO in rats' liver homogenate. In vivo, administration of 4-Tabs caused a significant (p<0.05) decrease in body weight gain and weight of testis of rats. Body weight gain and weight of testis decreased by 45% and 36%, respectively, in the 4-Tabs-treated rats. Also, 4-Tabs increased testicular lipid peroxidation by 82%, with a concomitant decrease in antioxidant indices. Testicular reduced glutathione, superoxide dismutase and glutathione peroxidase decreased by 2.2-, 1.9- and 1.6-folds, respectively. Likewise, 4-Tabs markedly decreased sperm count, motility, luteinizing hormone and testosterone. Co-administration of KV with 4-Tabs normalized body weight, enhanced antioxidant system and improved sperm characteristics. Kolaviron protects male reproductive system from oxidative damage by anti-tuberculosis drugs via the antioxidative mechanism.


[Peripheral disorders of intraventricular conduction in ischemic cardiopathy].
The complex question of peri-infarction blocks is examined. Whereas this term was once used for conduction disturbances now interpreted as fascicular blocks, a distinction is drawn here between these and parietal, post-Hisian blocks and infarctual blocks. Their vectorcardiographic picture are described, along with the possible expression of segmentary blocks at the peripheral branches of the posterior fascicle of the left branch. These electrogenetic interpretations are discussed in the light of data obtained by phonomechanographic methods in cases of parietal block.


Altered gene expression during cold acclimation of spinach.
Exposure of spinach (Spinacia oleracea L.) plants to a constant 5 degrees C induced a greater tolerance to extracellular freezing. The metabolic basis of this cold acclimation response in plants is not understood. In this study we tested the hypothesis that cold acclimation derives from altered gene transcription. We found that exposure of plants to low temperature resulted in a rapid and stable change in the translatable poly(A)+ RNA populations extracted from leaves, as determined by a cell-free in vitro translation assay. The initial appearance of mRNAs for two high molecular weight translation products correlated with an increase in freezing tolerance. Cold acclimation of plants for 8 days resulted in further qualitative changes in mRNA populations. At least four additional mRNAs increased in concentration upon continued exposure of spinach to 5 degrees C, whereas three other mRNAs present in 20 degrees C-grown leaves decreased. We also tested the possibility that the low temperature-induced mRNAs might encode heat shock proteins. We studied heat shock-induced protein synthesis by in vivo labeling techniques and found that spinach synthesized at least eight distinctive heat shock proteins during exposure to 40 degrees C. Most polypeptides induced by exposure to low temperature, however, appeared not to be heat shock proteins. Thus, the change in mRNAs induced by low temperature is a separate response from that induced by high temperature.


Effect of wearable chair on gait, balance, and discomfort of new users during level walking with anterior loads.
Walking with anterior loads is common in industrial scenarios, but as exoskeletons are increasingly used in work environments to alleviate musculoskeletal disorders (MSDs), this new "human-robot" system composed of the human body and exoskeleton may be associated with new risks and harm that warrant further investigation. Therefore, this study will discuss the effect of a wearable chair on the gait, balance, and discomfort of new users with different weights of anterior loads during level walking. Twenty-two healthy subjects (sex balanced) participated in the experiment. Each exposure comprised one of two exoskeleton states (with/without) and four load conditions: No carried load, carrying an empty box (0.3 kg), 5%Body Weight (BW), and 10%BW. The order of exoskeleton states and load conditions was randomly assigned. Using an eight-camera motion capture system to record the entire movement. And the subjective discomfort and perceived balance after each exposure were recorded on an 11-point numeric rating scale, respectively. Using SPSS 26.0 software (IBM Inc., Chicago) to conduct statistical analyses. Level walking with a wearable chair in different load conditions significantly affected gait parameters (like cadence) and gait balance. The perceived balance decreased with the exoskeleton, consistent with objective results. For subjective discomfort, wearing the exoskeleton significantly impacted global discomfort. Also, it increased the local discomfort of the shoulders, waist, thighs, shanks, and feet/ankles. For new users, the risk of losing balance or falling may be increased when wearing an exoskeleton for non-target task behaviors (level walking/anterior load), and caution is recommended when the anterior load exceeds 5% BW. The proposed strategy for assessing human gait, balance, and discomfort in wearable chairs may be applied during the iterative design of the product. These controls will help develop training programs and implementation guidelines for this exoskeleton type.


Selective targeting of tumor associated macrophages in different tumor models.
Tumor progression largely depends on the presence of alternatively polarized (M2) tumor-associated macrophages (TAMs), whereas the classical M1-polarized macrophages can promote anti-tumorigenic immune responses. Thus, selective inhibition of M2-TAMs is a desirable anti-cancer approach in highly resistant tumor entities such as hepatocellular carcinoma (HCC) or breast cancer. We here examined whether a peptide that selectively binds to and is internalized by in vitro-differentiated murine M2 macrophages as compared to M1 macrophages, termed M2pep, could be used to selectively target TAMs in HCC and breast carcinoma. We confirmed selectivity of M2pep for in vitro M2 polarized macrophages. Upon incubation of suspended mixed 4T1 tumor cells with M2pep, high amounts of the TAMs were found to be associated with M2pep, whereas in mixed tumor cell suspensions from two HCC mouse models, M2pep showed only low-degree binding to TAMs. M2pep also showed low-degree targeting of liver macrophages. This indicates that the TAMs in different tumor entities show different targeting of M2pep and that M2pep is a very promising approach to develop selective M2-TAM-targeting in tumor entities containing M2-TAMs with significant amounts of the so far elusive M2pep receptor(s).


The impact of socio-economic status on all-cause mortality after percutaneous coronary intervention: an observational cohort study of 13,770 patients.
The relation between socio-economic status (SES) and outcomes after percutaneous coronary intervention (PCI) has not been established. We sought to determine whether or not socio-economic status impacts on prognosis after PCI. This was an observational cohort study of 13,770 consecutive patients who underwent PCI at a single centre between 2005 and 2011. Patient socio-economic status was defined by the English Index of Multiple Deprivation (IMD) score, according to residential postcode. Patients were analysed by quintile of IMD score (Q1, least deprived; Q5, most deprived). Median follow-up was 3.7 (IQR: 2.0-5.1) years and the primary outcome was all-cause mortality. Patients in Q5 (most deprived) were younger, more commonly South Asian, and had higher rates of smoking, diabetes mellitus, renal impairment, previous MI, and previous PCI than patients in Q1. Rates of long-term mortality increased progressively across the five quintiles of IMD score in a linear fashion (p=0.0004), as did rates of recurrent MI, target vessel revascularisation, and CABG. The difference in mortality rates persisted after adjustment for other potential confounding factors after multivariate analysis (Q5 vs. Q1: HR 1.93, 95% CI: 1.38-2.69). In this large contemporary cohort of patients receiving PCI, socio-economic status was associated with prognosis in a linear fashion.


Biodiversity and Enzyme Activity of Marine Fungi with 28 New Records from the Tropical Coastal Ecosystems in Vietnam.
The coastal marine ecosystems of Vietnam are one of the global biodiversity hotspots, but the biodiversity of marine fungi is not well known. To fill this major gap of knowledge, we assessed the genetic diversity (ITS sequence) of 75 fungal strains isolated from 11 surface coastal marine and deeper waters in Nha Trang Bay and Van Phong Bay using a culture-dependent approach and 5 OTUs (Operational Taxonomic Units) of fungi in three representative sampling sites using next-generation sequencing. The results from both approaches shared similar fungal taxonomy to the most abundant phylum (Ascomycota), genera (Candida and Aspergillus) and species (Candida blankii) but were different at less common taxa. Culturable fungal strains in this study belong to 3 phyla, 5 subdivisions, 7 classes, 12 orders, 17 families, 22 genera and at least 40 species, of which 29 species have been identified and several species are likely novel. Among identified species, 12 and 28 are new records in global and Vietnamese marine areas, respectively. The analysis of enzyme activity and the checklist of trophic mode and guild assignment provided valuable additional biological information and suggested the ecological function of planktonic fungi in the marine food web. This is the largest dataset of marine fungal biodiversity on morphology, phylogeny and enzyme activity in the tropical coastal ecosystems of Vietnam and Southeast Asia. Biogeographic aspects, ecological factors and human impact may structure mycoplankton communities in such aquatic habitats.


[Hemodynamic function of patients with diffuse suppurative peritonitis].
A complex examination of central hemodynamics and contracting function of the heart was performed in 85 patients in the preoperative period. It was established that the toxic phase of peritonitis is characterized by the disturbed central hemodynamics and worse contracting function of the myocardium which are found to aggravate the process in the terminal phase and to require intensive prophylactic and curative measures. The authors consider that the shock index and coefficient of the functional state of central hemodynamics can be used in urgent cases for the assessment of the functional state of blood circulation.


A novel estrogen-enhanced transcript identified in the rat uterus by differential display.
Estrogen exerts its physiological effects in the uterus by inducing a cascade of transcriptional events; however, the number of genes known to be directly activated by estrogen in the uterus is small. In this study, immature ovariectomized rats were treated with estrogen or vehicle, and 3 h later the uterine horns were flushed to extract epithelial RNA. This RNA was used in the differential display technique to search for estrogen-responsive genes. Products of reverse transcriptase-PCR, made with pairs of arbitrary and oligo-deoxythymidine primers, were separated on denaturing polyacrylamide gels; candidate bands were excised and reamplified to produce probes for use in Northern blot analysis and screening of a lambda gt10 complementary DNA library made from rat uterus. A novel estrogen-enhanced transcript, designated EET-1, was identified from a differential display band, and the estrogen sensitivity of its expression was verified in Northern analysis. Characterization of EET-1 expression in the uterus showed that estrogen treatment resulted in a rapid and transient increase in EET-1 messenger RNA; steady state levels peaked between 2-3 h, returning to basal levels by 6 h. This increase was not abolished by pretreatment with cycloheximide, indicating that induction of EET-1 is a primary response to estrogen. Induction was specific to estrogen when extracts of whole uterus were examined; in the epithelium, there was also a slight response to progesterone. Expression of the gene was found in all organs surveyed; however, hormonal regulation was observed only in tissues of the reproductive tract and in the kidney. Analysis of cloned EET-1 complementary DNA revealed a 2008-base sequence that showed 61% identity with a reported transcript that encodes a protein that plays a role in phorbol ester-induced regulation of the tumor necrosis factor-alpha gene. Potential casein kinase-2 and protein kinase C phosphorylation sites and a cysteine-rich region were identified in the amino acid sequence deduced from EET-1. Thus, it appears that EET-1 represents a primary estrogen response gene that may code for a phosphorylated protein involved in gene regulation through a protein kinase C-activated pathway.


Superacid-Mediated Functionalization of Hydroxylated Cucurbit[n]urils.
Herein we report a facile transformation of hydroxylated cucurbit[n]uril (CB[n], n = 6 and 7) to other functionality-conjugated CB[n]s by nucleophilic substitution of the hydroxyl group with a wide range of nitriles and alcohols. The reaction proceeds efficiently via generation of a superelectrophilic carbocation on the CB framework from hydroxylated CB[n]s under superacidic conditions. One of the resulting CB[n] derivatives with reactive functionality, monocarboxylated CB[7], is efficiently conjugated to an enzyme (horseradish peroxidase, HRP) by amide coupling. This provides a CB[7]-conjugated functional biomaterial (CB[7]-HRP) that selectively detects proteins labeled with a guest, adamantylammonium (AdA), based on bioorthogonal high-affinity host-guest interactions between CB[7] and AdA. We demonstrated the potential of overcoming the limitations in preparing reactive functional CB[n] derivatives, enabling the exploration of novel bioapplications of CB[n]-based host-guest chemistry with new CB[n]-conjugated functional materials.


Independent effects on cellular and humoral immune responses underlie genotype-by-genotype interactions between Drosophila and parasitoids.
It is common to find abundant genetic variation in host resistance and parasite infectivity within populations, with the outcome of infection frequently depending on genotype-specific interactions. Underlying these effects are complex immune defenses that are under the control of both host and parasite genes. We have found extensive variation in Drosophila melanogaster's immune response against the parasitoid wasp Leptopilina boulardi. Some aspects of the immune response, such as phenoloxidase activity, are predominantly affected by the host genotype. Some, such as upregulation of the complement-like protein Tep1, are controlled by the parasite genotype. Others, like the differentiation of immune cells called lamellocytes, depend on the specific combination of host and parasite genotypes. These observations illustrate how the outcome of infection depends on independent genetic effects on different aspects of host immunity. As parasite-killing results from the concerted action of different components of the immune response, these observations provide a physiological mechanism to generate phenomena like epistasis and genotype-interactions that underlie models of coevolution.


If you build it, will they come? Evaluation of a co-located exercise clinic and cancer treatment centre using the RE-AIM framework.
Employ the Reach, Effectiveness, Adoption, Implementation, Maintenance framework to evaluate the effectiveness of a co-located exercise clinic model in increasing access to exercise for people undergoing cancer treatment in a private clinic in Western Australia. This retrospective evaluation utilised a mixed-method approach to gather feedback from key stakeholder groups involved with the exercise clinic. Questionnaires and workout summary sheets were gathered from 237 exercise clinic participants over the 50-month evaluation period. These were supplemented by survey results from 119 patients who received cancer treatment at the facility, and semi-structured interviews from seven radiation oncologists, eight nurses, and three accredited exercise physiologists involved with the exercise clinic. The co-located clinic demonstrated positive outcomes related to effectiveness and adoption. Participant feedback indicated satisfaction with the exercise programming (effectiveness), and clinicians were receptive to referring patients to the clinic (adoption). However, no clear implementation or maintenance plan was employed and overall reach (12%) remained suboptimal throughout the evaluation period. Co-locating an exercise clinic into a treatment facility does not in itself overcome the logistical challenges of providing integrated exercise services to people during cancer treatment. To enhance its utilisation, an implementation plan needs to accompany the intervention.


Digital-resolution and highly sensitive detection of multiple exosomal small RNAs by DNA toehold probe-based photonic resonator absorption microscopy.
Small noncoding RNAs (snRNA) have been emerging as promising diagnostic biomarkers for detecting early stage cancer. Currently existing methods for snRNA detection, including northern blot, reverse transcription-polymerase chain reaction, microarrays and RNA-Seq, are limited to time-consuming, low sensitivity, expensive instrumentation or complex analysis of data. Herein, we present a rapid quantitative analysis of multiple liver cancer-associated exosomal snRNA by a nucleic acid toehold probe-based photonic resonator absorption microscopy (PRAM) assay, with digital resolution and high sensitivity. The assay relies on the use of three toehold probe-encoded gold nanoparticles (AuNPs) and addressable photonic crystal (PC) sensing chips. The presence of target snRNA will initiate toehold-mediated strand displacement reactions that trigger the capture of gold particles onto the PC surface, which is subsequently imaged by PRAM for digital counting of detected snRNA molecules. We achieved highly sensitive and selective detection of three snRNA targets in buffer with a 30 min assay protocol, with detection limits of 4.56 fM, 4.68 fM and 0.69 pM. Having confirmed our assay's performance for detection of snRNA targets spiked into exosomal RNA extracts, we demonstrated its capability for quantitative detection of the same targets from patient blood plasma samples. The approach offers a rapid, simple workflow that operates at room temperature with a single step without enzymatic amplification, while the detection instrument can be implemented as a low-cost portable system for point of care environments.


Induction and inhibition of aromatase (CYP19) activity by natural and synthetic flavonoid compounds in H295R human adrenocortical carcinoma cells.
Flavonoids and related structures (e.g., flavones, isoflavones, flavanones, catechins) exert various biological effects, including anticarcinogenic, antioxidant and (anti-)estrogenic effects, and modulation of sex hormone homeostasis. A key enzyme in the synthesis of estrogens from androgens is aromatase (cytochrome P450 19; CYP19). We investigated the effects of various natural and synthetic flavonoids on the catalytic activity and promoter-specific expression of aromatase in H295R human adrenocortical carcinoma cells. Natural flavones were consistently more potent inhibitors than flavanones. IC(50) values for 7-hydroxyflavone, chrysin, and apigenin were 4, 7, and 20 microM, respectively; for the flavanones 7-hydroxyflavanone and naringenin the IC(50) values were 65 and 85 microM, respectively. The steroidal aromatase inhibitor (positive control) 4-hydroxyandrostenedione had an IC(50) of 20 nM. The inhibition by apigenin and naringenin coincided with some degree of cytotoxicity at 100 microM. The natural flavonoid derivative rotenone (IC(50) 0.3 microM) was the most potent aromatase inhibitor tested. Several synthetic flavonoid and structurally related quinolin-4-one analogs inhibited aromatase activity. The most potent inhibitor was 4'-tert-butyl-quinolin-4-one (IC(50) 2 microM), followed by two 2-pyridinyl-substituted alpha-naphthoflavones (IC(50)s 5 and >30 microM). The two 2-pyridinyl-substituted gamma-naphthoflavones consistently produced biphasic concentration-response curves, causing about 1.5-fold aromatase induction at concentrations below 1 microM and inhibition above that level (IC(50)s 7 and >30 microM). The natural flavone quercetin and isoflavone genistein induced aromatase activity 4- and 2.5-fold induction, respectively, at 10 microM. This coincided with increased intracellular cAMP concentrations and increased levels of the cAMP-dependent pII and to a lesser extent 1.3 promoter-specific aromatase transcripts. These results shed light on the structure-activity relationships for aromatase inhibition as well as mechanisms of induction in human H295R cells.


Community- and genome-based views of plant-associated bacteria: plant-bacterial interactions in soybean and rice.
Diverse microorganisms are living as endophytes in plant tissues and as epiphytes on plant surfaces in nature. Questions about driving forces shaping the microbial community associated with plants remain unanswered. Because legumes developed systems to attain endosymbioses with rhizobia as well as mycorrhizae during their evolution, the above questions can be addressed using legume mutants relevant to genes for symbiosis. Analytical methods for the microbial community have recently been advanced by enrichment procedures of plant-associated microbes and culture-independent analyses targeting the small subunit of rRNA in microbial ecology. In this review, we first deal with interdisciplinary works on the global diversity of bacteria associated with field-grown soybeans with different nodulation genotypes and nitrogen application. A subpopulation of Proteobacteria in aerial parts of soybean shoots was likely to be regulated through both the autoregulation system for plant-rhizobium symbiosis and the nitrogen signaling pathway, suggesting that legumes accommodate a taxonomically characteristic microbial community through unknown plant-microbe communications. In addition to the community views, we then show multiphasic analysis of a beneficial rice endophyte for comparative bacterial genomics and plant responses. The significance and perspectives of community- and genome-based approaches are discussed to achieve a better understanding of plant-microbe interactions.


Paracetamol availability in pharmacy and non-pharmacy outlets in Dublin, Ireland.
In 2004, there were 11,092 presentations to Irish hospitals with deliberate self-harm, including 7,933 cases of drug overdose, of which 31% involved paracetamol. Limiting the availability of paracetamol reduces morbidity and mortality associated with paracetamol overdose. The present study aimed to determine the level of compliance with statutory regulations governing the sale of paracetamol in Ireland. Researchers visited pharmacy (n = 20) and non-pharmacy outlets (newsagents, mini-markets and supermarkets) (n = 50) in Dublin city and attempted to purchase amounts of paracetamol that exceeded the statutory limits for a single transaction. Amounts of paracetamol in excess of statutory limits for a single transaction were purchased in 50.0% of pharmacies, 81.8% of newsagents/mini-markets and 20.0% of supermarkets. One year later, we again visited pharmacy (n = 20) and non-pharmacy outlets (n = 50) in Dublin city and purchased amounts of paracetamol in excess of statutory limits in 50.0% of pharmacies, 52.3% of newsagents/mini-markets and 10.0% of supermarkets. We recommend that (a) notwithstanding the improvement in compliance rates in newsagents/mini-markets, the sale of paracetamol in these outlets should be discontinued; (b) the sale of paracetamol in supermarkets should continue, although automated checkout tills should be appropriately re-programmed; and (c) there should be greater efforts to ensure compliance with statutory regulations in pharmacies.


A HF Loaded Lewis-Acidic Aluminium Chlorofluoride for Hydrofluorination Reactions.
The very strong Lewis acid aluminium chlorofluoride (ACF) was loaded with anhydrous HF. The interaction between the surface of the catalyst and HF was investigated using a variety of characterization methods, which revealed the formation of polyfluorides. Moreover, the reactivity of the HF-loaded ACF towards the hydrofluorination of alkynes was studied.


Composite resections for oral cancers--experience with 97 consecutive cases.
A retrospective study was carried out from the evaluable records of all (N = 97) patients who underwent composite resections in unit 'Head & Neck 'C' - Tata Memorial Hospital, over the years 1980, 81, 82, for a variety of oral cancers. The purpose of this study was to assess the true value of radical ablation. Tobacco addiction was observed in all patients with adequate documentation of habits. The vast majority of operations were performed for lesions of the buccal mucosa (N = 48) and lower alveolus (20); and squamous carcinoma was the predominant histologic type. Most patients presented with advanced T3 and T4 lesions. Nodal findings revealed a conspicuous disparity between clinical and pathological findings; and the final 'N' status was the most significant prognostic determinant. The results of reconstructive methods have also been reviewed. The majority of recurrences occurred within 12 months of surgery, local recurrence being commonest.


Risk of periprosthetic femoral neck fracture after hip resurfacing arthroplasty: valgus compared with anatomic alignment. A biomechanical and clinical analysis.
Early clinical results of hip resurfacing arthroplasty have led to the recommendation to achieve a neck-shaft angle of 140 degrees when inserting the femoral component. In addition, the idea of adhering to an absolute angle when inserting instrumentation in hips with excessive anatomic varus or valgus neck-shaft angles has raised concern. A biomechanical analysis was completed in order to determine if the achieved valgus orientation of the femoral component reduced the risk of periprosthetic fracture. Twenty fresh-frozen cadaveric femora were blindly assigned to be implanted with a neutral or valgus-oriented hip-resurfacing femoral component. Bone mineral density scans were acquired for all femora. All specimens were loaded axially to failure at a rate of 0.21 mm per second. Radiographs of the specimens were measured in order to determine the relative valgus orientation of the femoral components and the change in offset. There was a significant increase in the ultimate failure load for the valgus-oriented components. While the bone density scans revealed that the bone mineral densities measured in the neutral and valgus-oriented femoral components were almost identical, the ultimate failure load was found to be significantly increased for the valgus-oriented components (6955 N) compared with the neutral-oriented components (5254 N). For the valgus-oriented femoral components, two had failure at the subcapital level, seven had vertical shear fractures, and one had an anterior shear fracture. For the neutral-oriented components, five subcapital fractures and five vertical shear failures were observed. The study suggests that a valgus orientation decreases the risk of periprosthetic femoral neck fracture following hip resurfacing. It also brings into question the use of an absolute angle for all patients. Obtaining the maximum possible valgus angle, while avoiding notching, may in fact provide the optimum protection from periprosthetic femoral neck fractures.


Comparison of the centering ability of Wave·One and Reciproc nickel-titanium instruments in simulated curved canals.
The aim of this study was to evaluate the shaping ability of newly marketed single-file instruments, Wave·One (Dentsply-Maillefer) and Reciproc (VDW GmbH), in terms of maintaining the original root canal configuration and curvature, with or without a glide-path. According to the instruments used, the blocks were divided into 4 groups (n = 10): Group 1, no glide-path / Wave·One; Group 2, no glide-path / Reciproc; Group 3, #15 K-file / Wave·One; Group 4, #15 K-file / Reciproc. Pre- and post-instrumented images were scanned and the canal deviation was assessed. The cyclic fatigue stress was loaded to examine the cross-sectional shape of the fractured surface. The broken fragments were evaluated under the scanning electron microscope (SEM) for topographic features of the cross-section. Statistically analysis of the data was performed using one-way analysis of variance followed by Tukey's test (α = 0.05). The ability of instruments to remain centered in prepared canals at 1 and 2 mm levels was significantly lower in Group 1 (p < 0.05). The centering ratio at 3, 5, and 7 mm level were not significantly different. The Wave·One file should be used following establishment of a glide-path larger than #15.


The Affinity of Sterols for Different Phospholipid Classes and Its Impact on Lateral Segregation.
Cholesterol is an essential molecule in the membranes of mammalian cells. It is known to be distributed heterogeneously within the cells, between the bilayer leaflets, as well as between lateral domains within the bilayer. However, we do not know exactly how cholesterol is distributed and what forces drive this sorting process because it extremely difficult to study using currently available methods. To further elucidate this distribution, we measured how cholesterol partitions between different phospholipid (PL) environments using different methods based on cholesterol, TopFluor-cholesterol, and cholesta-5,7,9(11)-triene-3-β-ol. Based on the obtained relative partition coefficients, we made predictions regarding how cholesterol would be distributed between lateral domains and between the inner and outer leaflets of the plasma membrane. In addition, using a trans-parinaric acid fluorescence-based method, we tested how cholesterol could influence lateral segregation through its interaction with unsaturated PLs with different headgroups. The results showed that the lower the affinity of cholesterol was for the different unsaturated PLs, the more cholesterol stimulated lateral segregation in a ternary bilayer of unsaturated PL/N-palmitoyl-D-erythro-sphingomyelin and cholesterol. Overall, the results indicate that both the distribution of cholesterol between different lipid environments and the impact of cholesterol on lateral segregation can be predicted relatively accurately from determined relative partition coefficients.


A novel comparative pattern analysis approach identifies chronic alcohol mediated dysregulation of transcriptomic dynamics during liver regeneration.
Liver regeneration is inhibited by chronic ethanol consumption and this impaired repair response may contribute to the risk for alcoholic liver disease. We developed and applied a novel data analysis approach to assess the effect of chronic ethanol intake in the mechanisms responsible for liver regeneration. We performed a time series transcriptomic profiling study of the regeneration response after 2/3rd partial hepatectomy (PHx) in ethanol-fed and isocaloric control rats. We developed a novel data analysis approach focusing on comparative pattern counts (COMPACT) to exhaustively identify the dominant and subtle differential expression patterns. Approximately 6500 genes were differentially regulated in Ethanol or Control groups within 24 h after PHx. Adaptation to chronic ethanol intake significantly altered the immediate early gene expression patterns and nearly completely abrogated the cell cycle induction in hepatocytes post PHx. The patterns highlighted by COMPACT analysis contained several non-parenchymal cell specific markers indicating their aberrant transcriptional response as a novel mechanism through which chronic ethanol intake deregulates the integrated liver tissue response. Our novel comparative pattern analysis revealed new insights into ethanol-mediated molecular changes in non-parenchymal liver cells as a possible contribution to the defective liver regeneration phenotype. The results revealed for the first time an ethanol-induced shift of hepatic stellate cells from a pro-regenerative phenotype to that of an anti-regenerative state after PHx. Our results can form the basis for novel interventions targeting the non-parenchymal cells in normalizing the dysfunctional repair response process in alcoholic liver disease. Our approach is illustrated online at http://compact.jefferson.edu .


Long-term antibacterial properties of a nanostructured titanium alloy surface: An in vitro study.
The demand for joint replacement and other orthopedic surgeries involving titanium implants is continuously increasing; however, 1%-2% of surgeries result in costly and devastating implant associated infections (IAIs). Pseudomonas aeruginosa and Staphylococcus aureus are two common pathogens known to colonise implants, leading to serious complications. Bioinspired surfaces with spike-like nanotopography have previously been shown to kill bacteria upon contact; however, the longer-term potential of such surfaces to prevent or delay biofilm formation is unclear. Hence, we monitored biofilm formation on control and nanostructured titanium disc surfaces over 21 days following inoculation with Pseudomonas aeruginosa and Staphylococcus aureus. We found a consistent 2-log or higher reduction in live bacteria throughout the time course for both bacteria. The biovolume on nanostructured discs was also significantly lower than control discs at all time points for both bacteria. Analysis of the biovolume revealed that for the nanostructured surface, bacteria was killed not just on the surface, but at locations above the surface. Interestingly, pockets of bacterial regrowth on top of the biomass occurred in both bacterial species, however this was more pronounced for S. aureus cultures after 21 days. We found that the nanostructured surface showed antibacterial properties throughout this longitudinal study. To our knowledge this is the first in vitro study to show reduction in the viability of bacterial colonisation on a nanostructured surface over a clinically relevant time frame, providing potential to reduce the likelihood of implant associated infections.


Giant retinal tear as a complication of attempted removal of intravitreal lens fragments during cataract surgery.
To report giant retinal tear and retinal detachment as a complication of attempted removal of intravitreal lens fragments at the time of cataract surgery and to evaluate the anatomic and visual acuity outcomes of pars plana vitrectomy and retinal reattachment surgery. Retrospectively, 10 patients with giant retinal tear, retinal detachment, and intravitreal lens fragments in 10 eyes were reviewed. In 10 eyes, retrieval of intravitreal lens fragments using the limbal approach by deep vitrectomy, copious vitreous cavity irrigation, or deep vitreous cavity phacoemulsification had been attempted by the anterior segment surgeon at the time of cataract surgery in each patient. The average interval from cataract surgery to the initial vitreoretinal consultation was 8 days. Each of the 10 eyes had a giant retinal tear involving the inferior retina: in four eyes, of between 90 degrees and 180 degrees; in four, equal to 180 degrees; and in two, of greater than 180 degrees. After pars plana vitrectomy and retinal detachment repair, nine (90%) of 10 eyes had retinal reattachment, but seven patients required more than one operation. One eye had persistent retinal detachment, and one eye had corneal graft failure. Seven (70%) of the 10 eyes had best-corrected final visual acuity of 20/200 or better; three eyes had light-perception, hand-motion, and counting-fingers vision. Aggressive attempts at intravitreal lens fragment retrieval from a limbal-based approach should be avoided because these procedures may result in serious retinal complications, such as formation of a giant retinal tear.


[Role of the geneticist in prenatal diagnosis].
Medical geneticists, assisted by genetic counselors, are one of the main actors of prenatal diagnostic centers. They are involved at all stages of pregnancy: when there is an upstream project and a specific parental history, during pregnancy in case of accidental discovery of anomalies in fetal ultrasound, but also after a medical termination of pregnancy to clarify the subsequent genetic counseling. If possible, genetic counseling should be done before conception, as a first step in accurate diagnosis is often necessary. The results of some sophisticated tests will be known only after several months.


Photoinduced Charge Accumulation and Prolonged Multielectron Storage for the Separation of Light and Dark Reaction.
The utilization of solar energy is restricted by the intermittent nature of solar influx. We present novel noble-metal free complexes that can be photochemically charged in the presence of sacrificial electron donors and remain stable in its charged form for over 14 h. This allows the doubly reduced Cu(I) 4H-imidazolate complex to be stored after photochemical charging and used as a reagent in dark reactions, such as the reduction of methyl viologen or oxygen. Combined UV-vis/EPR spectroelectrochemistry indicates that a two-electron reduction is induced by introducing sacrificial electron donors that facilitate proton-coupled electron transfer. Repeated photochemical reduction and chemical oxidation reveals that the complex retained a charging capacity of 72% after four cycles. We demonstrate a chemical system that can decouple photochemical processes from the day-night cycle, which has been a barrier to realizing utilization of solar energy in photochemical processes on a global scale.


The effects of long-term regular exercise on endothelial functions, inflammatory and thrombotic activity in middle-aged, healthy men.
As studying with population carrying no classical cardiovascular risk factors seems to be an advantage in isolating effects of regular exercise on endothelial functions, inflammatory and thrombotic activity; the present study was designed to evaluate the clear effects of long-term regular exercise in middle-aged, healthy men. A total of 32 regularly exercising (three times per week, 12.8 ± 6.8 years) men (Group I, mean age = 53.2 ± 6. 1 yrs) and 32 sex- and age-matched sedentary subjects (Group II, mean age = 51.0 ± 7.7 yrs) were involved in the study. All participants were non-smokers and with no history of hypertension and diabetes. During one day preceding tests, the subjects refrained from training and maintained their normal diet. In all subjects, body mass index (BMI), percentage of body fat (% BF) and maximal oxygen uptake (VO2max) were calculated. Serum uric acid, glucose, HbA1c, lipids, high-sensitive C-reactive protein (hs-CRP), fibrinogen levels, white blood cell (WBC) and platelet count were measured. Resting heart rates and blood pressures were recorded and standard exercise stress test was applied using the modified Bruce protocol. Flow-mediated and nitrate-induced dilatation (FMD and NID) of the brachial artery and carotid intima-media thickness (cIMT) were evaluated as markers of endothelial functions and early atherosclerosis. Mean BMI, % BF, systolic and diastolic blood pressures, WBC and platelet count, HbA1c, total and LDL cholesterol, hs-CRP and fibrinogen levels were similar between the groups. Group I had significantly lower serum glucose, uric acid and triglyceride (p < 0.05, p < 0.005 and p < 0.05, respectively) and higher HDL cholesterol levels (p < 0.0001) than in Group II. FMD values were significantly higher in Group I than in Group II (p < 0.005) while there were no significant differences in NID and cIMT measures between the groups. VO2max and cIMT showed a negative correlation in Group I (r = -0.463, p < 0.0001). Negative correlations also existed between VO2max and fibrinogen levels in both Group I and II (r = -0.355, p < 0.05 and r = -0.436, p < 0.05, respectively). These results are concordant with the concept of favorable effects of regular physical exercise on cardiovascular health based on enhancement of endothelial functions even in subjects who have low cardiovascular risk profile. Key PointsThe present study results suggest that regular exercise is effective on endothelial functions even in subjects who have low risk for cardiovascular disease.Therefore, regular exercise is feasible in improving endothelial functions independently from cardiovascular risk profile.


Couples' catastrophizing and co-rumination: Dyadic diary study of patient fatigue after cancer.
Fatigue is a prevalent and long-lasting symptom among patients with cancer that is known to be worsened by patients' catastrophizing thoughts about their fatigue. Spouses are also burdened by patient fatigue, which may lead them to catastrophize as well. Based on the dyadic coping literature, this study hypothesized that patient and spouse catastrophizing translate into worse fatigue through co-rumination-couples' communications dwelling on the negative aspects of fatigue (H1). While maladaptive for fatigue, co-rumination also was expected to foster couple relationship satisfaction (H2). Posttreatment patients with cancer and their spouses (n = 101 dyads) completed daily diaries for 14 days. Patients reported on their momentary fatigue severity. Both couple members reported on their catastrophizing about the patients' fatigue, co-rumination, and their momentary relationship satisfaction. Multilevel structural equation modeling was applied to test within-person actor- and partner-effects between catastrophizing, co-rumination, and changes in fatigue (H1) and between co-rumination and changes in relationship satisfaction (H2). Whereas patient catastrophizing was directly related to their fatigue (b = 0.52, 95% credibility interval [CI] [0.09, 0.95]), as hypothesized, the effect of spouse catastrophizing on patient fatigue was mediated through co-rumination (indirect effect = 0.32, 95% CI [0.07, 0.60]). Unexpectedly, patient- and spouse-reported co-rumination were unrelated to both couple members' relationship satisfaction. Spouse catastrophizing contributes to patient fatigue severity through couples' ruminative communications. Co-rumination was not related to relationship satisfaction. Reducing patient and spouse catastrophizing and fostering adaptive dyadic communication in daily life could be targets for future interventions aiming to relieve fatigue in patients after completion of cancer treatment. (PsycINFO Database Record (c) 2019 APA, all rights reserved).


Multiple Myeloma Index for Risk of Infection.
Based on our earlier research into the main characteristics and risk factors for infections in hospitalized patients with multiple myeloma, we created the numerical Multiple Myeloma Index for Risk of Infection (MMIRI) to predict infection in myeloma patients. The included factors that could influence the pathogenesis and incidence of infections were sex, performance status, Durie Salmon stage of disease, International Staging System, serum creatinine level, immune paresis, neutropenia, serum ferritin level, the presence of any catheters, disease duration, stable/progressive disease, and type of therapy. For each of these parameters, the strength of association with infection was statistically estimated and specific number of points was assigned to each of these parameters, proportional to the strength of the association. When designing the MMIRI, we included only those parameters that we determined were pathophysiologically associated with the infection. After further statistical analysis, we identified an optimal cutoff score of 6 or above as indicating a significant risk for infection, with a sensitivity of 93.2% and specificity of 80.2%. The scoring system in the retrospective receiver operating characteristic analysis showed an area under the curve of 0.918. The potential value of the MMIRI is the possibility of identifying those patients who would benefit from the prophylactic administration of antibiotics and other anti-infective measures while minimizing the contribution to antibiotic resistance related to the overuse of these drugs. As far as we know, this index represents the first attempt to create such an instrument for predicting the occurrence of infections in myeloma patients.


Cortical capacity constraints for visual working memory: dissociation of fMRI load effects in a fronto-parietal network.
Working memory (WM) capacity limitations and their neurophysiological correlates are of special relevance for the understanding of higher cognitive functions. Evidence from behavioral studies suggests that restricted attentional resources contribute to these capacity limitations. In an event-related functional magnetic resonance imaging (fMRI) study, we probed the capacity of the human visual WM system for up to four complex nonnatural objects using a delayed discrimination task. A number of prefrontal and parietal areas bilaterally showed increased blood oxygen level-dependent activity, relative to baseline, throughout the task when more than one object had to be held in memory. Monotonic increases in response to memory load were observed bilaterally in the dorsolateral prefrontal cortex (DLPFC) and the presupplementary motor area (pre-SMA). Conversely, activity in the frontal eye fields (FEFs) and in areas along the intraparietal sulcus (IPS) peaked when subjects had to maintain only two or three objects and decreased in the highest load condition. This dissociation of memory load effects on cortical activity suggests that the cognitive operations subserved by the IPS and FEF, which are most likely related to attention, fail to support visual WM when the capacity limit is approached. The correlation of brain activity with performance implies that only the operations performed by the DLPFC and pre-SMA, which support an integrated representation of visual information, helped subjects to maintain a reasonable level of performance in the highest load condition. These results indicate that at least two distinct cortical subsystems are recruited for visual WM, and that their interplay changes when the capacity limit is reached.


Influence of elastase on alanine-rich peptide hydrogels.
The self-assembly of the alanine-rich amphiphilic peptides Lys(Ala)6Lys (KA6K) and Lys(Ala)6Glu (KA6E) with homotelechelic or heterotelechelic charged termini respectively has been investigated in aqueous solution. These peptides contain hexa-alanine sequences designed to serve as substrates for the enzyme elastase. Electrostatic repulsion of the lysine termini in KA6K prevents self-assembly, whereas in contrast KA6E is observed, through electron microscopy, to form tape-like fibrils, which based on X-ray scattering contain layers of thickness equal to the molecular length. The alanine residues enable efficient packing of the side-chains in a beta-sheet structure, as revealed by circular dichroism, FTIR and X-ray diffraction experiments. In buffer, KA6E is able to form hydrogels at sufficiently high concentration. These were used as substrates for elastase, and enzyme-induced de-gelation was observed due to the disruption of the beta-sheet fibrillar network. We propose that hydrogels of the simple designed amphiphilic peptide KA6E may serve as model substrates for elastase and this could ultimately lead to applications in biomedicine and regenerative medicine.


Large and persistent subnational inequalities in reproductive, maternal, newborn and child health intervention coverage in sub-Saharan Africa.
Subnational inequalities have received limited attention in the monitoring of progress towards national and global health targets during the past two decades. Yet, such data are often a critical basis for health planning and monitoring in countries, in support of efforts to reach all with essential interventions. Household surveys provide a rich basis for interventions coverage indicators on reproductive, maternal, newborn and child health (RMNCH) at the country first administrative level (regions or provinces). In this paper, we show the large subnational inequalities that exist in RMNCH coverage within 39 countries in sub-Saharan Africa, using a composite coverage index which has been used extensively by Countdown to 2030 for Women's, Children's and Adolescent's Health. The analyses show the wide range of subnational inequality patterns such as low overall national coverage with very large top inequality involving the capital city, intermediate national coverage with bottom inequality in disadvantaged regions, and high coverage in all regions with little inequality. Even though nearly half of the 34 countries with surveys around 2004 and again around 2015 appear to have been successful in reducing subnational inequalities in RMNCH coverage, the general picture shows persistence of large inequalities between subnational units within many countries. Poor governance and conflict settings were identified as potential contributing factors. Major efforts to reduce within-country inequalities are required to reach all women and children with essential interventions.


Hydrologic influence on stability of organic phosphorus in wetland detritus.
Accretion of organic matter in wetlands provides long-term storage for nutrients and other contaminants. Water-table fluctuations and resulting alternate flooded and drained conditions may substantially alter the stability of stored materials including phosphorus (P). To study the effects of hydrologic fluctuation on P mobilization in wetlands, recently accreted detrial material (derived primarily from Typha spp.) was collected from the Everglades Nutrient Removal Project (ENRP), a constructed wetland used to treat agricultural drainage water in the northern Everglades. The detrital material was subjected to different periods of drawdown and consecutive reflooding under laboratory conditions. The 31P nuclear magnetic resonance (31P NMR) spectroscopy analysis revealed that sugar phosphate, glycerophosphate, polynucleotides, and phospholipids (glycerophosphoethanolamine and glycerophosphocholine) were the major forms of P in the detrital material. After 30 d of drawdown, polynucleotides were reduced to trace levels, whereas sugar phosphate, glycerophosphate, and phospholipids remained the major fractions of organic P. Microorganisms seemed to preferentially utilize nucleic acid P, perhaps to obtain associated nutrients including carbon and nitrogen. At the end of the 30-d reflooding period, cumulative P flux from detritus to water column accounted for 3% of the total P (< or = 15 d of drawdown) and further decreased to 2% at 30 d of drawdown, but increased to 8% at 60 d of drawdown. The drawdown (< or = 30 d) not only reduced P flux to the water column, but also increased the humification and microbial immobilization of P. Excessive drawdown (60 d), however, triggered the release of P into the water column as the water content of detritus decreased from 95 to 11%.


Chapter 9: Benign sinonasal neoplasms.
Benign sinonasal neoplasms are a heterogeneous group of tumors that present with similar symptoms including nasal obstruction, anosmia, rhinorrhea, and epistaxis. The proper workup and accurate diagnosis is essential for these tumors so that the appropriate treatment plan can be established. In this article of benign sinonasal neoplasms, we discuss their typical clinical presentation, histological and radiographic findings, and treatment options.


Coronavirus MHV-JHM mRNA 5 has a sequence arrangement which potentially allows translation of a second, downstream open reading frame.
The sequence of a 5'-proximal region of mRNA 5 of coronavirus MHV-JHM was determined by chain-terminator sequencing of cDNA subcloned in M13. The sequence contained two long open reading frames of 321 bases and 264 bases, overlapping by five bases but in different frames. Both open reading frames are initiated by AUG codons in sequence contexts that are relatively infrequently used as initiator codons. The smaller, downstream open reading frame encoded a neutral protein (mol. wt. 10200) with a hydrophobic amino terminus. The larger, 5'-proximal open reading frame encoded a basic protein (mol. wt. 12400) which lacks internal methionine residues. With the exception of the AUG codon initiating the downstream open reading frame, no internal AUG codons were found within the sequence covered by the upstream open reading frame. These results suggest that the MHV-JHM mRNA 5 is translated to produce two proteins by a mechanism involving internal initiation of protein synthesis. Preliminary evidence is presented showing that the downstream open reading frame is functional in vivo.


Fragile X-associated tremor/ataxia syndrome (FXTAS): pathology and mechanisms.
Since its discovery in 2001, our understanding of fragile X-associated tremor/ataxia syndrome (FXTAS) has undergone a remarkable transformation. Initially characterized rather narrowly as an adult-onset movement disorder, the definition of FXTAS is broadening; moreover, the disorder is now recognized as only one facet of a much broader clinical pleiotropy among children and adults who carry premutation alleles of the FMR1 gene. Furthermore, the intranuclear inclusions of FXTAS, once thought to be a CNS-specific marker of the disorder, are now known to be widely distributed in multiple non-CNS tissues; this observation fundamentally changes our concept of the disease, and may provide the basis for understanding the diverse medical problems associated with the premutation. Recent work on the pathogenic mechanisms underlying FXTAS indicates that the origins of the late-onset neurodegenerative disorder actually lie in early development, raising the likelihood that all forms of clinical involvement among premutation carriers have a common underlying mechanistic basis. There has also been great progress in our understanding of the triggering event(s) in FXTAS pathogenesis, which is now thought to involve sequestration of one or more nuclear proteins involved with microRNA biogenesis. Moreover, there is mounting evidence that mitochondrial dysregulation contributes to the decreased cell function and loss of viability, evident in mice even during the neonatal period. Taken together, these recent findings offer hope for early interventions for FXTAS, well before the onset of overt disease, and for the treatment of other forms of clinical involvement among premutation carriers.


Assessment of the Second Mesiobuccal Root Canal in Maxillary First Molars: A Cone-beam Computed Tomographic Study.
The purpose of this study was to investigate the incidence and location of the second mesiobuccal (MB2) root canal of the maxillary first molar and the relationship between the presence of an MB2 canal and the distribution of canal orifices on the pulpal floor with the aid of cone-beam computed tomographic (CBCT) technology. A total of 1008 maxillary first molars (548 patients) were randomly selected and analyzed through CBCT imaging. The association between the incidence of MB2 canals and potential impacting factors including sex, side, age, and the distribution of the main root canal orifices on the pulpal floor was explored. The interorifice distances (ie, the length of a line between the center point of any 2 orifices) at the pulpal floor level were measured using Mimics 10.01 software (ImageWorks, Materialise, Belgium). The majority of 3-rooted maxillary first molars showed 2 root canals (85.4%) in the mesiobuccal root. The incidence of MB2 canals had no statistically significant difference between the left and right sides (P > .05) but had a significant association with the patients' sex and age (P < .05). Receiver operating characteristic curve analysis showed a high diagnostic accuracy (the area under the receiver operating characteristic curve = 0.92) of using the distance ratio of the interorifice distance between the main mesiobuccal and the palatal root canal orifices to the interorifice distance between the distobuccal and the palatal root canal orifices to predict the presence of an MB2 canal. A larger distance ratio (>1.26) indicated a highly probable existence of an MB2 canal. In this study, no molar presented an MB2 canal with a distance ratio of less than 1.16, whereas all molars with a ratio greater than 1.37 presented an MB2 canal without exception. A Bland-Altman scatterplot showed great agreement between the distances of the main mesiobuccal and the distobuccal canal orifices and the second mesiobuccal and the distobuccal canal orifices. Understanding the incidence of MB2 canals and the distribution pattern of canal orifices on the pulpal floor may help clinicians to quickly identify and locate MB2 canals.


HTLV-1 associated adult T-cell leukemia/lymphoma in Israel: report of two patients of Romanian origin.
Human T-lymphotropic virus type 1 (HTLV-1) was the first human oncovirus isolated by Gallo et al. in 1980 and established as an etiological agent for adult T-cell leukemia/ lymphoma (ATL). Although more than 15 million individuals are infected by HTLV-1 through the world, the spread of the virus is highly endemic. The HTLV-1 infection is prevailing in southwestern Japan, inter-tropical Africa, Central and South America. In Kyushu district, Japan, the seroprevalence reaches >30% in the adult population. In the US, Europe and the Middle East the HTLV-1 infection is very rare, and cases of ATL have been reported sporadically. We describe here acute ATL in two patients of Jewish- Romanian origin. The epidemiological anamnesis and screening indicate that both patients acquired the HTLV-1 from their mothers leaving in Romania.


Comparison of 2 high-throughput spectral techniques to predict differences in diet composition of grazing sheep and cattle.
Diet composition can be estimated in free-ranging animals by the use of n-alkane and long-chain fatty alcohol concentrations in feces. However, this technique involves relatively laborious and costly analytical techniques. Two spectroscopy techniques were investigated as a way of determining whether dietary differences are likely, thus indicating whether the more expensive and labor-intensive techniques for more detailed analysis are justified. Fourier-transform infrared spectroscopy (FTIR) and front-face fluorescence emission spectroscopy (lambda(excitation) = 380 nm, lambda(emission) = 600 to 760 nm) were used to analyze fecal samples collected from 2 different breeds of cattle and sheep (4 groups in total, n = 6 per group) grazing moorland plants in 2 grazing sessions. These fecal samples were also analyzed for alkane and alcohol concentrations. Fourier-transform infrared spectra, particularly in the alkane regions, demonstrated clear separation between animal species. Fluorescence emission spectra showed similar separation; fluorophores were most likely chlorophylls and their derivatives. Multivariate analysis of all 3 data sets showed similar variation within and between groups of cattle and sheep, indicating differences in diet selection particularly between species, but also between breed and grazing session. Both spectroscopy methods showed utility in suggesting differences in diet composition that would be worth investigating using more detailed chemical analyses. Of the 2 techniques, the FTIR spectroscopy gave the better comparative results, being able to detect differences in sampling months that were detected with alkanes and alcohols that the fluorescence emission spectroscopy did not detect.


Using the Independent Monitoring for Quality Program to Examine Longitudinal Outcomes for People With Intellectual and Developmental Disabilities.
The purpose of this study is to lay a foundation for illustrating the importance of longitudinal data collection by sharing the results of the Independent Monitoring for Quality (IM4Q) program in Pennsylvania designed to collect data over time on the quality of services for adults with intellectual and developmental disabilities. In this article, we report on the history and characteristics of the IM4Q program, describe the key variables of interest, and highlight the trends in the key variables over 3 years of data collection (2013, 2016, and 2019). The descriptive results indicate mixed trends for the three areas of focus: comparable rates of people employed in community-based settings, less support-related choice, and better everyday choice-making outcomes.


[Comprehensiveness in practice (or, on the practice of comprehensiveness)].
This article reflects on the manifestations or signs of comprehensiveness in health practice, seeking to facilitate recognition of experiences that are advancing in this direction and allowing them to be analyzed subsequently. The article is also intended to spawn increasing involvement by actors in practices based on comprehensiveness. The point of departure is the principle that what characterizes comprehensiveness is an expanded grasp of the needs and ability to recognize the adequacy of the health care supply in the specific context where the subject meets the health team; in addition, to foster comprehensiveness means defending the notion that health actions be attuned to the specific context of each encounter.


Characteristics of granular sludge in a single upflow sludge blanket reactor treating high levels of nitrate and simple organic compounds.
Simultaneous denitrification and methanogenesis were accomplished in a single upflow sludge blanket (USB) reactor. More than 99% and 95% of nitrate and chemical oxygen demand (COD) removal rates were obtained at a loading of 600 mg NO3-N/L x d and 3,300 mg COD/L x d, respectively. The specific denitrification rate (SDR) increased as COD/NO3-N ratios decreased. Maximum SDR with acetate could reach 1.05 g NO3-N/gVSS x d. Significant sludge flotation was observed at the top of the reactor due to the change of microbial composition and the formation of hollow granules. Granules became fluffy and buoyant due to the growth of denitrifiers. Microscopic examination showed that granules exhibited layered structure and they were mainly composed of Methanosarcina sp., Pseudomonas sp., and rod-shaped bacteria.


Protective school climates and reduced risk for suicide ideation in sexual minority youths.
We examined whether sexual minority students living in states and cities with more protective school climates were at lower risk of suicidal thoughts, plans, and attempts. Data on sexual orientation and past-year suicidal thoughts, plans, and attempts were from the pooled 2005 and 2007 Youth Risk Behavior Surveillance Surveys from 8 states and cities. We derived data on school climates that protected sexual minority students (e.g., percentage of schools with safe spaces and Gay-Straight Alliances) from the 2010 School Health Profile Survey, compiled by the Centers for Disease Control and Prevention. Lesbian, gay, and bisexual students living in states and cities with more protective school climates reported fewer past-year suicidal thoughts than those living in states and cities with less protective climates (lesbians and gays: odds ratio [OR] = 0.68; 95% confidence interval [CI] = 0.47, 0.99; bisexuals: OR = 0.81; 95% CI = 0.66, 0.99). Results were robust to adjustment for potential state-level confounders. Sexual orientation disparities in suicidal thoughts were nearly eliminated in states and cities with the most protective school climates. School climates that protect sexual minority students may reduce their risk of suicidal thoughts.


Bibliometric analysis of research trends and topic areas in traditional Chinese medicine therapy for lymphoma.
Traditional Chinese Medicine (TCM) is effective as a cancer treatment modality. However, this is the first bibliometric analysis of TCM in lymphoma treatment. This study explores the current trends and research topics of TCM in treating lymphoma from 2000 to 2023. We searched within the Web of Science Core Collection (WoSCC) for publications on TCM in lymphoma treatment, spanning 2000 to 2023. Subsequently, we employed a comprehensive approach utilizing CiteSpace software and VOSviewer to visually analyze research trends, authors, institutions, co-cited references, and keywords. From January 1, 2000, to August 31, 2023, annual scientific publications on TCM for lymphoma treatment have steadily increased. Among the leading institutions in this field, the Beijing University of Chinese Medicine and the Fujian Medical University occupied the top positions. Regarding the authors, Jun Peng, Jiumao Lin, and Hongwei Chen emerged as the top three contributors. In the co-citation analysis of references, the top three co-cited references were authored by Hanahan D, Elmore S, and Livak KJ with citations numbered 13, 14, and 17, respectively. In particular, keywords reflecting current emerging trends included 'pathway', 'traditional Chinese medicine', 'oxidative stress', and 'macrophage polarization'. This bibliometric analysis provides a comprehensive overview of TCM for lymphoma treatment. This analysis identified the predominant trends and research topics in the field. The findings are expected to be of significant value for researchers who focus on TCM in lymphoma treatment, helping them better understand the development of this field.


Stomatal Penetration of Wheat Seedlings by Stem and Leaf Rust: Effect of Light and Carbon Dioxide.
Removal of atmospheric carbon dioxide enhanced penetration of seedling wheat by stem rust Puccinia graminis in light and dark but did not materially affect penetration by leaf rust P. recondita. A concentration of 5 percent CO(2) nearly suppressed penetration by P. graminis but not by P. recondita. Thus light may promote penetration by P. graminis through photosynthetic reduction of CO(2) within the leaf and P. recondita may penetrate independently of light because it is relatively insensitive to the effects of CO(2).


Motor rotation is essential for the formation of the periplasmic flagellar ribbon, cellular morphology, and Borrelia burgdorferi persistence within Ixodes scapularis tick and murine hosts.
Borrelia burgdorferi must migrate within and between its arthropod and mammalian hosts in order to complete its natural enzootic cycle. During tick feeding, the spirochete transmits from the tick to the host dermis, eventually colonizing and persisting within multiple, distant tissues. This dissemination modality suggests that flagellar motor rotation and, by extension, motility are crucial for infection. We recently reported that a nonmotile flaB mutant that lacks periplasmic flagella is rod shaped and unable to infect mice by needle or tick bite. However, those studies could not differentiate whether motor rotation or merely the possession of the periplasmic flagella was crucial for cellular morphology and host persistence. Here, we constructed and characterized a motB mutant that is nonmotile but retains its periplasmic flagella. Even though ΔmotB bacteria assembled flagella, part of the mutant cell is rod shaped. Cryoelectron tomography revealed that the flagellar ribbons are distorted in the mutant cells, indicating that motor rotation is essential for spirochetal flat-wave morphology. The ΔmotB cells are unable to infect mice, survive in the vector, or migrate out of the tick. Coinfection studies determined that the presence of these nonmotile ΔmotB cells has no effect on the clearance of wild-type spirochetes during murine infection and vice versa. Together, our data demonstrate that while flagellar motor rotation is necessary for spirochetal morphology and motility, the periplasmic flagella display no additional properties related to immune clearance and persistence within relevant hosts.


Single-Cell Sequencing of Brain Cell Transcriptomes and Epigenomes.
Single-cell sequencing technologies, including transcriptomic and epigenomic assays, are transforming our understanding of the cellular building blocks of neural circuits. By directly measuring multiple molecular signatures in thousands to millions of individual cells, single-cell sequencing methods can comprehensively characterize the diversity of brain cell types. These measurements uncover gene regulatory mechanisms that shape cellular identity and provide insight into developmental and evolutionary relationships between brain cell populations. Single-cell sequencing data can aid the design of tools for targeted functional studies of brain circuit components, linking molecular signatures with anatomy, connectivity, morphology, and physiology. Here, we discuss the fundamental principles of single-cell transcriptome and epigenome sequencing, integrative computational analysis of the data, and key applications in neuroscience.


Contextualizing the Genes Altered in Bladder Neoplasms in Pediatric andTeen Patients Allows Identifying Two Main Classes of Biological ProcessesInvolved and New Potential Therapeutic Targets.
Research on bladder neoplasms in pediatric and teen patients (BNPTP) has described 21 genes, which are variously involved in this disease and are mostly responsible for deregulated cell proliferation. However, due to the limited number of publications on this subject, it is still unclear what type of relationships there are among these genes and which are the chances that, while having different molecular functions, they i) act as downstream effector genes of well-known pro- or anti- proliferative stimuli and/or interplay with biochemical pathways having oncological relevance or ii) are specific and, possibly, early biomarkers of these pathologies. A Gene Ontology (GO)-based analysis showed that these 21 genes are involved in biological processes, which can be split into two main classes: cell regulation-based and differentiation/development-based. In order to understand the involvement/overlapping with main cancer-related pathways, we performed a meta-analysis dependent on the 189 oncogenic signatures of the Molecular Signatures Database (OSMSD) curated by the Broad Institute. We generated a binary matrix with 53 gene signatures having at least one hit; this analysis i) suggests that some genes of the original list show inconsistencies and might need to be experimentally re- assessed or evaluated as biomarkers (in particular, ACTA2) and ii) allows hypothesizing that important (proto)oncogenes (E2F3, ERBB2/HER2, CCND1, WNT1, and YAP1) and (putative) tumor suppressors (BRCA1, RBBP8/CTIP, and RB1-RBL2/p130) may participate in the onset of this disease or worsen the observed phenotype, thus expanding the list of possible molecular targets for the treatment of BNPTP.


Review article: current management of alcoholic liver disease.
Alcoholic liver disease, including acute alcoholic hepatitis and alcoholic cirrhosis, is a major cause of morbidity and mortality in the Western world. Abstinence remains the cornerstone of management of all forms of alcoholic liver disease. Recent research, which has elucidated the mechanisms of alcohol-induced liver injury, offers the prospect of advances in the management of alcoholic liver disease. We review the most recent data on the efficacy of treatment of acute alcoholic injury, including nutritional support, corticosteroids, anti-inflammatory agents and antioxidants, and agents that are directed against the progression to fibrosis, such as colchicines, propylthiouracil and antioxidants. Although these therapies offer a tantalizing glimpse into a future that may include therapies that directly alter the process of injury and repair in the liver, none has been shown consistently to improve the course of alcoholic liver damage. Consequently, liver transplantation remains an ultimate option for selected patients with liver failure due to chronic alcoholic liver damage.


Behavioral correlates of dopaminergic unit activity in freely moving cats.
Single unit activity of dopaminergic neurons in the substantia nigra was recorded in freely moving cats under a variety of conditions. These neurons displayed their highest discharge rate during active waking (3.68 +/- 0.30 spikes/s), which was 20% greater than their discharge rate during quiet waking (3.07 +/- 0.20). Although these cells fired somewhat faster during active waking, their activity displayed no correlation with phasic EMG changes, and, in general, their activity showed little relationship to overt behavioral changes. As the cat progressed from quiet waking through slow-wave sleep and REM sleep there was no significant change in either the rate or pattern of firing of dopaminergic neurons. In addition, no correlation was observed between the activity of these neurons and either sleep spindles or PGO waves. These neurons did respond, however, to the repeated presentation of a click or light flash with excitation followed by inhibition, with no evidence of habituation. One of the most impressive changes in dopaminergic unit activity was a large decrease in association with orienting responses. This was seen in over 50% of the cells in which this relationship was examined. As the behavioral orientation habituated with repeated stimulus presentation, so did the associated dopaminergic unit suppression. In conclusion, dopaminergic neurons maintain a remarkably constant rate and pattern of firing across a variety of behaviors and states. However, this stability can be dramatically altered under special circumstances, such as during and following orienting responses.


The nature of technological hazard.
Technological hazards are evaluated in terms of quantitatively expressed physical, biological, and social descriptors. For each hazard a profile is constructed that considerably extends the conventional definition of risk. The profile, which is termed hazardousness, was understood in pilot experiments on perception and appeared to capture a large fraction of lay people's concern with hazard. It also suggests an orderly method for establishing priorities for the management of hazards.


Current changes in the management and outcome of patients with curable colorectal cancer.
Major changes in the evaluation and treatment of curable colorectal cancer (CRC) have emerged in the last two decades. These changes have led to better patient outcome overtime. To evaluate the impact of these changes as reflected in the difference in long-term outcome of a consecutive group of recently laparoscopically operated curable CRC patients and a consecutive group of patients operated 20 years earlier in the same department. Data of the new group were taken from our prospectively collected data of patients who underwent elective laparoscopic surgery for CRC in recent years. Data regarding patients operated on 20 years ago were retrieved from previous prospectively collected data on the long-term survival of CRC patients operated in the same department. The recently operated group comprised 203 patients and the previous group 199 patients. Perioperative mortality was 0.5% in the new group versus 1.5% in the old group (not significant). There were more early-stage and more proximal tumors in the recently operated group. A Kaplan-Meier 5-year survival analysis revealed no difference between stage I patients of the two groups. However, there was a significant increase in 5-year survival in the new group for stage II (85% vs. 63%, P = 0.004) and for stage III patients (57% vs. 39%, P = 0.01). This trend was maintained after removing the rectal cancer patients from the calculated data. We have demonstrated improved survival for stage II and ILL CRC patients overa 20-year period in the same medical center. This change most likely reflects advances both in imaging techniques leading to more accurate staging and in adjuvant treatments.


Evaluation of the adverse effects of biological agents used in the treatment of psoriasis: A multicenter retrospective cohort study.
The objective was to reveal and compare the adverse effects of infliximab, etanercept, adalimumab, ustekinumab and secukinumab, and determine possible risk factors. The follow-up files and computer-based records of patients with psoriasis were retrospectively screened between January 2007 and September 2019. The five biological agents were compared in terms of their adverse effects, and factors that might be related to these effects were explored. While there was no statistically significant difference between the agents in terms of the rate of serious adverse effects, when all the adverse effects were evaluated together, the highest rate was seen in the use of infliximab and the lowest in secukinumab (P = .001). The rates of adverse effects and related drug discontinuation were higher in the use of anti-TNF agents compared to interleukin inhibitors (P = .004 and P = .012, respectively). The agent with the highest drug discontinuation rate due to adverse effects was infliximab while the least discontinued agent was ustekinumab (P = .036). There were more side effects with anti-TNF than interleukin inhibitors, but the serious adverse effect rate was similar in both groups. The incidence of certain adverse effects increases depending on age, number of comorbidities, biological agent and its group, concomitant systemic therapy, and use of multiple agents.


The CUSUM chart method as a tool for continuous monitoring of clinical outcomes using routinely collected data.
The lack of robust systems for monitoring quality in healthcare has been highlighted. Statistical process control (SPC) methods, utilizing the increasingly available routinely collected electronic patient records, could be used in creating surveillance systems that could lead to rapid detection of periods of deteriorating standards. We aimed to develop and test a CUmulative SUM (CUSUM) based surveillance system that could be used in continuous monitoring of clinical outcomes, using routinely collected data. The low Apgar score (5 minute Apgar score < 7) was used as an example outcome. A surveillance system based on the Observed minus Expected (O-E) as well as the 2-sided Log-Likelihood CUSUM charts was developed. The Log-Likelihood chart was designed to detect a 50% rise (deterioration) and halving (improvement) in the odds of low Apgar scores. Baseline rates were calculated from data for 2001 to 2004, and were used to monitor deliveries for 2005. Deliveries for nulliparous and multiparous women were monitored separately. All analyses were retrospective. The CUSUM system detected periods of increased rates of low Apgar scores for each of the nulliparous and multiparous cohorts. The overall rate for 2005 was eventually found to be 0.67%, which was higher than the baseline reference rate of 0.44% from 2001 to 2004. CUSUM methods can be used in continuous monitoring of clinical outcomes using routinely collected data. Used prospectively, they could lead to the prompt detection of periods of suboptimal standards.


Preparation and characterization of monoclonal antibody against human B7-H4 molecule.
B7-H4, a member of B7 family, is widely expressed in tumor tissues and plays an important role in the negative regulation of T cell immunity. In this study, we report on the establishment and characterization of a functional anti-human B7-H4 monoclonal antibody (MAb) 5G3 through hybridoma method. Flow cytometry analysis showed that MAb 5G3 specifically bound to B7-H4 molecule. Functional experiments indicated that MAb 5G3 could block the inhibitory role of B7-H4 molecule on A549 cells in and reduce the apoptosis of Jurkat cells, suggesting that MAb 5G3 is an antagonistic antibody and a useful tool for further studies of B7-H4 functions in cancers.


Purple Acid Phosphatase5 is required for maintaining basal resistance against Pseudomonas syringae in Arabidopsis.
Plants have evolved an array of constitutive and inducible defense strategies to restrict pathogen ingress. However, some pathogens still manage to invade plants and impair growth and productivity. Previous studies have revealed several key regulators of defense responses, and efforts have been made to use this information to develop disease resistant crop plants. These efforts are often hampered by the complexity of defense signaling pathways. To further elucidate the complexity of defense responses, we screened a population of T-DNA mutants in Colombia-0 background that displayed altered defense responses to virulent Pseudomonas syringae pv. tomato DC3000 (Pst DC3000). In this study, we demonstrated that the Arabidopsis Purple Acid Phosphatse5 (PAP5) gene, induced under prolonged phosphate (Pi) starvation, is required for maintaining basal resistance to certain pathogens. The expression of PAP5 was distinctly induced only under prolonged Pi starvation and during the early stage of Pst DC3000 infection (6 h.p.i). T-DNA tagged mutant pap5 displayed enhanced susceptibility to the virulent bacterial pathogen Pst DC3000. The pap5 mutation greatly reduced the expression of pathogen inducible gene PR1 compared to wild-type plants. Similarly, other defense related genes including ICS1 and PDF1.2 were impaired in pap5 plants. Moreover, application of BTH (an analog of SA) restored PR1 expression in pap5 plants. Taken together, our results demonstrate the requirement of PAP5 for maintaining basal resistance against Pst DC3000. Furthermore, our results provide evidence that PAP5 acts upstream of SA accumulation to regulate the expression of other defense responsive genes. We also provide the first experimental evidence indicating the role PAP5 in plant defense responses.


Ventricular septal defect: results after repair in infancy.
During the 19 years from 1957 through 1975, there have been 106 patients under age 2 years who have undergone surgery for repair of a large ventricular septal defect at the University of Michigan Medical Center. The majority of the patients had either severe pulmonary hypertension or intractable congestive heart failure. Eighty-three infants survived operation; there has been one late death. The greatest mortality occurred in patients under age 6 months and in those with severe pulmonary hypertension. Surviving infants showed marked symptomatic improvement and change in growth patterns. Complications included the development of complete right bundle branch blodk or left anterior hemiblock in approximately 50 percent of patients and, in one instance, complete atrioventricular block. Forty-five patients have undergone cardiac catheterization 1 to 8 years postoperatively. Although 17 were found to have residual septal defects only 3 of these had a pulmonary to systemic flow ratio of 1.5:1 or more, and reoperation was accomplished without incident in these 3 patients and in 3 others with smaller shunts. With one exception, postoperative pulmonary arterial pressures and pulmonary to systemic vascular resistance ratios were normal or near normal, thus representing a significant contrast with findings in patients operated on after age 2 years. Whereas the complications of surgery appear no greater in the infant than in the older patient, many of the benefits can be realized only with operation at the earlier age.


Effects of ion solvation and volume change of reaction on the equilibrium and morphology in cation-exchange reaction of nanocrystals.
The effects of cation solvation and the volume change (Delta V) of reaction on the equilibrium and the morphology change in the cation-exchange reactions of metal chalcogenide nanocrystals, CdE --> M(x)E(y) (E = S, Se, Te; M = Pd, Pt), were investigated. Since the solvation of cations is an important controllable factor determining the free energy of the reaction, the effect of varying cation solvation conditions on the equilibrium of the reaction was examined. A two-phase solvent environment, where the cations involved in the exchange reaction were preferentially solvated in different phases by using selective cation complexing molecules, was particularly efficient in increasing the thermodynamic driving force. The effect of Delta V of reaction on the morphology of the product nanocrystals was also investigated. Depending on the stress developed in the lattice during the reaction, product nanocrystals underwent varying degrees of morphological changes such as void formation and fragmentation in addition to the preservation of the original morphology of the reactant nanocrystals. The knowledge of the effect of ion solvation and Delta V of reaction on the equilibrium and product morphology provides a new strategy and useful guides to the application of cation-exchange reactions for the synthesis of a broader range of inorganic nanocrystals.


Pediatric-onset Behçet disease in Bahrain: report of nine cases and literature review.
This report studies the clinical features of Behçet disease (BD) in children and compares our results with other international studies. We retrospectively reviewed patient data that included the clinical picture, HLA typing, and treatment in BD cases. This study reviewed data from a total of nine children with BD. Median age at presentation was seven years, with a male to female ratio of 2:1. There was one patient who had Down's syndrome. Oral ulcers were present in all children, while genital ulcers were present in only 66% of cases. Skin manifestation was seen in 88% and uveitis in 55%. There was evidence of gastrointestinal (55%), neurological (55%), and musculoskeletal manifestations (77%). HLA B5 was positive in 66% of cases and 55% had positive family histories. Apart from gastrointestinal symptoms, our results were comparable with other studies. Awareness of BD symptoms in the pediatric age group is crucial for early diagnosis and treatment. The coexistence of BD and Down's syndrome needs further genetic study, which may link these two major disorders.


Factors determining normal adult height in girls with gonadotropin-dependent precocious puberty treated with depot gonadotropin-releasing hormone analogs.
Several factors can affect adult height (AH) of patients with gonadotropin-dependent precocious puberty (GDPP) treated with depot GnRH analogs. Our objective was to determine factors influencing AH in patients with GDPP treated with depot GnRH analogs. A total of 54 patients (45 girls) with GDPP treated with depot GnRH analog who reached AH was included in the study. Univariate and multivariate analyses of the factors potentially associated with AH were performed in all girls with GDPP. In addition, clinical features of the girls who attained target height (TH) range were compared with those who did not. Predicted height using Bayley and Pinneau tables was compared with attained AH. In girls the mean AH was 155.3 +/- 6.9 cm (-1.2 +/- 1 sd) with TH range achieved by 81% of this group. Multiple regression analysis revealed that the interval between chronological age at onset of puberty and at the start of GnRH analog therapy, height sd scores (SDSs) at the start and end of therapy, and TH explained 74% of AH variance. The predicted height at interruption of GnRH therapy, obtained from Bayley and Pinneau tables for average bone age, was more accurate than for advanced bone age in both sexes. In boys the mean AH was 170.6 +/- 9.2 cm (-1 +/- 1.3 SDS), whereas TH was achieved by 89% of this group. The major factors determining normal AH in girls with GDPP treated with depot GnRH analogs were shorter interval between the onset of puberty and start of therapy, higher height SDS at the start and end of therapy, and TH. Therefore, prompt depot GnRH analog therapy in properly selected patients with GDPP is critical to obtain normal AH.