Synthesis of 64Cu-labeled magnetic nanoparticles for multimodal imaging.
Complementary imaging modalities provide more information than either method alone can yield and we have developed a dual-mode imaging probe for combined magnetic resonance (MR) and positron emission tomography (PET) imaging. We have developed dual-mode PET/MRI active probes targeted to vascular inflammation and present synthesis of (1) an aliphatic amine polystyrene bead and (2) a novel superparamagnetic iron oxide nanoparticle targeted to macrophages that were both coupled to positron-emitting copper-64 isotopes. The amine groups of the polystyrene beads were directly conjugated with an amine-reactive form (isothiocyanate) of aza-macrocycle 1,4,7,10-tetraazacyclo-dodecane-1,4,7,10-tetraacetic acid (DOTA). Iron oxide nanoparticles are dextran sulfate coated, and the surface was modified to contain aldehyde groups to conjugate to an amine-activated DOTA. Incorporation of chelated Cu-64 to nanoparticles under these conditions, which is routinely used to couple DOTA to macromolecules, was unexpectedly difficult and illustrates that traditional conjugation methods do not always work in a nanoparticle environment. Therefore, we developed new methods to couple Cu-64 to nanoparticles and demonstrate successful labeling to a range of nanoparticle types. We obtained labeling yields of 24% for the amine polystyrene beads and 21% radiolabeling yield for the anionic dextran sulfate iron oxide nanoparticles. The new coupling chemistry can be generalized for attaching chelated metals to other nanoparticle platforms.


Time of day accounts for overnight improvement in sequence learning.
The theory that certain skills improve with a night of sleep has received considerable interest in recent years. However, because sleep typically occurs at the same time of day in humans, it is difficult to separate the effects of sleep from those of time of day. By using a version of the Serial Response Time Task, we assessed the role of sleep in implicit sequence learning while controlling for possible time-of-day effects. We replicated the apparent benefit of sleep on human participants. However, our data show that sleep does not affect implicit sequence learning; rather, time of day affects the ability of participants to express what they have learned.


Oxidative stress in endometrial hyperplasia.
Reactive oxygen species seem to be involved in the onset and promotion of carcinogenesis. In 80% of cases of endometrial adenocarcinoma type I, a clear association exists with endometrial hyperplasia, which is considered a key factor in the endometrial oncological spectrum. The presence or absence of atypical cells determines oncological potential. This study explored the behavior of oxidative stress (catalase and malondialdehyde) in endometrial hyperplasia (with or without atypical cells) by comparing it with the oxidative stress existing in both the proliferative and secretory phases. Endometrial specimens from 55 women were used, 32 of which were histologically diagnosed as physiological (17 proliferative and 15 secretory endometria) and 23 as endometrial hyperplasia (18 nonatypical and 5 atypical endometrial hyperplasia). Significant differences were found in the malondialdehyde variable between the proliferative endometrium and the endometrium with atypical hyperplasia (P = 0.0208) and between both types of endometrial hyperplasia (P = 0.0441). The other comparisons were not statistically significant. No changes in catalase activity were observed. Our findings seem to suggest that the presence of atypical cells in endometrial hyperplasia induces a reduction in lipid peroxidation, which could permit survival and growth of these cells. This possible decrease in lipid peroxidation does not seem to be mediated by an increase in endometrial catalase activity.


Neutrophil gelatinase-associated lipocalin reflects the severity of renal impairment in subjects affected by chronic kidney disease.
Neutrophil gelatinase-associated lipocalin (NGAL) is a small 25-kDa protein released from kidney tubular cells after harmful stimuli. It represents one of the most promising future biomarkers in the diagnostic field of acute kidney injury (AKI), as the increase in NGAL levels is a good predictor of a brief-term onset of AKI, notably anticipating the resulting increase in serum creatinine. However, recent studies also suggest a possible role for NGAL in chronic kidney disease (CKD). For this reason we evaluated serum (sNGAL) and urinary NGAL (uNGAL) in a cohort of CKD patients in order to verify the relationship with the severity of renal impairment. In CKD patients sNGAL, uNGAL and the fractional excretion of this protein were notably increased as compared to controls. Furthermore both sNGAL and uNGAL were correlated with serum creatinine and, inversely, with residual glomerular filtration rate (GFR): this last relationship was found to be even closer than that found between GFR and serum creatinine. Multivariate models validate these correlations as independent, confirming that in these patients NGAL is a better predictor of GFR than serum creatinine. The results confirm NGAL as an important biomarker in clinical nephrology, extending to CKD the pathophysiological role of this protein in tubular adaptations to renal damage.


Oxygen status of lung granulomas in Mycobacterium tuberculosis-infected mice.
It is often assumed that Mycobacterium tuberculosis (Mtb)-induced granulomatous lesions, particularly those undergoing central caseation, are anoxic, and that the survival of Mtb in these lesions requires the integrity of its non-oxidative respiratory pathways. Using the hypoxia marker pimonidazole, we now provide immunohistochemical evidence that in the most frequently used animal model system of inbred mice Mtb-induced granulomas, even after more than one year of aerogenic infection, are not severely hypoxic. In contrast, chronic aerosol infection with M. avium strain TMC724 was associated with hypoxia surrounding necrotizing granuloma centres. Direct measurements of oxygen tension with a flexible microelectrode in mouse lungs chronically infected with Mtb disclosed a wide range of oxygen partial pressures in different parts of the lungs which, however, rarely approached the anoxic conditions consistently found in necrotizing tumours. We further show that an Mtb mutant, defective in nitrate reductase (narG) necessary for survival under anaerobic conditions in vitro, can persist in the lungs of chronically infected mice to a similar extent as wild-type Mtb. These findings have important implications for the use of the mouse model of Mtb infection in developing eradication chemotherapy and for evaluating putative mechanisms of chronic persistence and latency of Mtb.


Acute Epiglottitis in the Immunocompromised Host: Case Report and Review of the Literature.
We present a case of acute epiglottitis in a 16-year-old with severe aplastic anemia. He was admitted with a history suggestive of a severe upper airway infection and an absolute neutrophil count of 0 per cubic millimeter. Despite his immunocompromised state, he presented with the classical signs and symptoms of epiglottitis. We review here the presentation and comorbidities of immunocompromised patients with epiglottitis. In addition, the appropriate choice of empirical antibiotic therapy is important for the management of epiglottitis in immunocompromised patients, especially in the post-Haemophilus influenza type B vaccination era. In our patient, Enterobacter cloacae was isolated from endoscopically directed throat cultures, and treatment was successful without the need for intubation. The current literature suggests that in immunocompromised patients, particularly those who are neutropenic, there is a potentially wide range of organisms, both bacterial and fungal, that may play a role in the pathology of acute epiglottitis.


Porous Structured Ni-Fe-P Nanocubes Derived from a Prussian Blue Analogue as an Electrocatalyst for Efficient Overall Water Splitting.
Exploring nonprecious metal electrocatalysts to replace the noble metal-based catalysts for full water electrocatalysis is still an ongoing challenge. In this work, porous structured ternary nickel-iron-phosphide (Ni-Fe-P) nanocubes were synthesized through one-step phosphidation of a Ni-Fe-based Prussian blue analogue. The Ni-Fe-P nanocubes exhibit a rough and loose porous structure on their surface under suitable phosphating temperature, which is favorable for the mass transfer and oxygen diffusion during the electrocatalysis process. As a result, Ni-Fe-P obtained at 350 °C with poorer crystallinity offers more unsaturated atoms as active sites to expedite the absorption of reactants. Additionally, the introduction of nickel improved the electronic structure and then reduced the charge-transfer resistance, which would result in a faster electron transport and an enhancement of the intrinsic electrocatalytic activities. Benefiting from the unique porous nanocubes and the chemical composition, the Ni-Fe-P nanocubes exhibit excellent hydrogen evolution reaction and oxygen evolution reaction activities in alkaline medium, with low overpotentials of 182 and 271 mV for delivering a current density of 10 mA cm-2, respectively. Moreover, the Ni-Fe-P nanocubes show outstanding stability for sustained water splitting in the two-electrode alkaline electrolyzer. This work not only provides a facile approach for designing bifunctional electrocatalysts but also further extends the application of metal-organic frameworks in overall water splitting.


β-Cryptoxanthin ameliorates metabolic risk factors by regulating NF-κB and Nrf2 pathways in insulin resistance induced by high-fat diet in rodents.
The aim of this experiment was to determine the effects of β-cryptoxanthin (BCX) on the cardiometabolic health risk factors and NF-κB and Nrf2 pathway in insulin resistance induced by high-fat diet (HFD) in rodents. Twenty-eight Sprague-Dawley rats were allocated into four groups: (1) Control, rats fed a standard diet for 12 weeks; (2) BCX, rats fed a standard diet and supplemented with BCX (2.5 mg/kg BW) for 12 weeks; (3) HFD, rats fed a HFD for 12 weeks, (4) HFD + BCX, rats fed a HFD and supplemented with BCX for 12 weeks. BCX reduced cardio-metabolic health markers and decreased inflammatory markers (P < 0.001). Rats fed a HFD had the lower total antioxidant capacity and antioxidant enzymes activities and higher MDA concentration than control rats (P < 0.001 for all). Comparing with the HFD group, BCX in combination with HFD inhibited liver NF-κB and TNF-α expression by 22% and 14% and enhanced liver Nrf2, HO-1, PPAR-α, and p-IRS-1 by 1.43, 1.41, 3.53, and 1.33 fold, respectively (P < 0.001). Furthermore, in adipose tissue, BCX up-regulated Nrf2, HO-1, PPAR-α, and p-IRS-1 expression, whereas, down-regulated NF-κB and TNF-α expression. In conclusion, BCX decreased visceral fat and cardiometabolic health risk factors through modulating expressions of nuclear transcription factors.


Chilo suppressalis heat shock proteins are regulated by heat shock factor 1 during heat stress.
Heat shock factor 1 (HSF1) functions to maintain cellular and organismal homeostasis by regulating the expression of target genes, including those encoding heat shock proteins (HSPs). In the present study, the gene encoding HSF1 was cloned from the rice pest Chilo suppressalis, and designated Cshsf1. The deduced protein product, CsHSF1, contained conserved domains typical of the HSF1 family, including a DNA-binding domain, two hydrophobic heptad repeat domains, and a C-terminal transactivation domain. Real-time quantitative PCR showed that Cshsf1 was highly expressed in hemocytes. Expression analysis in different developmental stages of C. suppressalis revealed that Cshsf1 was most highly expressed in male adults. RNAi-mediated silencing of Cshsf1 expression reduced C. suppressalis survival at high temperatures. To investigate the regulatory interactions between Cshsf1 and Cshsps, the promoters and expression patterns of 18 identified Cshsps in C. suppressalis were analysed; four types of heat shock elements (HSEs) were identified in promoter regions including canonical, tail-tail, head-head, and step/gap. The expression of Cshsp19.0, Cshsp21.7B, Cshsp60, Cshsp70 and Cshsp90 was positively regulated by Cshsf1; however, Cshsp22.8, Cshsp702, Cshsp705 and Cshsp706 gene expression was not altered. This study provides a foundation for future studies of HSF1 in insects during thermal stress.


Epidermal Growth Factor Pathway in the Age-Related Decline of Oligodendrocyte Regeneration.
Oligodendrocytes (OLs) are specialized glial cells that myelinate CNS axons. OLs are generated throughout life from oligodendrocyte progenitor cells (OPCs) via a series of tightly controlled differentiation steps. Life-long myelination is essential for learning and to replace myelin lost in age-related pathologies such as Alzheimer's disease (AD) as well as white matter pathologies such as multiple sclerosis (MS). Notably, there is considerable myelin loss in the aging brain, which is accelerated in AD and underpins the failure of remyelination in secondary progressive MS. An important factor in age-related myelin loss is a marked decrease in the regenerative capacity of OPCs. In this review, we will contextualize recent advances in the key role of Epidermal Growth Factor (EGF) signaling in regulating multiple biological pathways in oligodendroglia that are dysregulated in aging.


Anesthesia with halothane and nitrous oxide alters protein and amino acid metabolism in dogs.
General anesthesia in combination with surgery is known to result in negative nitrogen balance. To determine whether general anesthesia without concomitant surgery decreases whole body protein synthesis and/or increases whole body protein breakdown, two groups of dogs were studied: Group 1 (n = 6) in the conscious state and Group 2 (n = 8) during general anesthesia employing halothane (1.5 MAC) in 50% nitrous oxide and oxygen. Changes in protein metabolism were estimated by isotope dilution techniques employing simultaneous infusions of [4,53H]leucine and alpha-[1-14C]-ketoisocaproate (KIC). Total leucine carbon flux was unchanged or slightly increased in the anesthetized animals when compared to the conscious controls, indicating only a slight increase in the rate of proteolysis. However, leucine oxidation was increased (P less than 0.001) by more than 80% in the anesthetized animals when compared with their conscious controls, whereas whole body nonoxidative leucine disappearance, an indicator of whole body protein synthesis, was decreased. The ratio of leucine oxidation to the nonoxidative rate of leucine disappearance, which provides an index of the catabolism of at least one essential amino acid in the postabsorptive state, was more than twofold increased (P less than 0.001) in the anesthetized animals regardless of the tracer employed. These studies suggest that the administration of anesthesia alone, without concomitant surgery, is associated with a decreased rate of whole body protein synthesis and increased leucine oxidation, resulting in increased leucine and protein catabolism, which may be underlying or initiating some of the protein wasting known to occur in patients undergoing surgery.


Handedness and 23 Early Life Characteristics in 37,495 Dutch Twins.
In studies of singletons, a range of early-life characteristics have been reported to be associated with handedness, but some of these associations have failed to replicate. We examined associations between 23 early life characteristics with handedness in a large sample of 37,495 5-year-old twins. We considered three definitions of handedness: left-handedness (LH), mixed-handedness (MH), and non-right-handedness (NRH). Our main aim was to test whether the associations with sex, birth weight, gestational age, and season of birth - as reported in singletons - replicate in twins, and to examine twin-specific variables, including zygosity, chorionicity, birth order, and intertwin delivery time. Compared to previously published data from adults born as singletons (7.23%), the prevalence of NRH was higher in both twins (16.19%) and their parents (15.09%). In the twins, LH and NRH were associated with parents' LH. Male sex and lower gestational age were associated with NRH, and LH was associated with not being breastfed. MH was related to neurodevelopmental delays and higher externalizing problems later in childhood. Other previously reported associations were not replicated, and no twin-specific characteristics were related to handedness. These results emphasize the importance of considering multiple definitions of handedness and indicate a small number of replicated associations across studies.


The aging farm population and rural aging research.
This article explores the potential and the promise of convergence between gerontological and occupational health researchers to better understand challenges faced by aging farmers including declining economic viability of family farms, the aging of the population of working farmers, and probability of work-related injury or disability among older farmers. Although the need for research seems obvious, the economic, demographic, and psychosocial dynamics of continued work among aging farmers is under-studied in the occupational health literature and absent in the gerontological literature. Following examination of studies of aging farmers drawn from the occupational health literature, we review studies of rural aging in the gerontological literature. First, we compare varying definitions of rural across federal agencies that impact the ability of researchers using these data to examine variability across rural places. Next, we review studies based upon primary data that include rural residence among their independent variables. We describe different definitions of rural residence across federal agencies with an eye toward their methodological and conceptual impact on the rural aging literature. Then we describe inadequate and incomplete definition and measurement of rural residence across published studies of primary data. Following discussion of the implications of these shortcomings for rural aging research including farmers and others engaged in extractive activities, we discuss the potential for joint work among gerontologists and occupational health researchers to better understand the significance of aging for transition in the agricultural economy and the viability of family farms. We recommend attention to the definition and measurement of rural residence to include variability in rural farm and non-farm populations and refocusing the occupational health literature on aging farmers to include a life course perspective from gerontological theory applied through longitudinal research designs.


Isolation and characterization of multipotent mesenchymal stem cells in nasal polyps.
Mesenchymal stem cells (MSCs) are multipotent progenitor cells in adult tissues. This study aimed to investigate nasal polyp (NP) tissues as a potential new source of multipotent MSCs that maintain their stemness and differentiation potential following multiple rounds of passaging. NP tissues were obtained from 10 patients during endoscopic sinus surgery. After isolating and culturing NP-derived MSCs (npMSCs), the expression levels of the surface markers CD34, CD44, CD45, CD73, CD90, CD105, CD106, CD146 and human leukocyte antigens-class II DR antigen (HLA-DR) were estimated by flow cytometry. NpMSCs were cultured in chondrogenic, osteogenic, adipogenic, or neurogenic differentiation medium. The differentiation potential of npMSCs was analyzed by Alcian blue, alizarin red S, oil red O, and immunocytochemical staining and reverse transcription-polymerase chain reaction. The clonogenic potential of npMSCs was measured using a colony-forming unit assay. Cell proliferation of npMSCs was measured using the 3-(4,5-Dimethylthiazol-2-yl)-2,5-Diphenyltetrazolium Bromide (MTT) assay. Flow cytometry analysis revealed that npMSCs were negative for hematopoietic lineage markers (CD34, CD45, and HLA-DR) and positive for MSC markers (CD44, CD73, CD90, and CD105). The npMSCs differentiated into osteogenic, adipogenic, chondrogenic, and neurogenic lineages, respectively. Chondrogenically differentiated npMSCs were stained with Alcian blue, osteogenically differentiated npMSCs were stained with alizarin red S, and adipogenically differentiated npMSCs were stained with oil red O. Real-time polymerase chain reaction results showed that the differentiated npMSCs expressed the respective differentiation markers (Sox 9 and Col2A for chondrogenesis, Runx2 and osteocalcin for osteogenesis, fatty acid-binding protein 4 and peroxisome proliferator-activated receptor γ for adipogenesis, TuJ1, neurofilament light chain, and neurofilament heavy chain for neurogenesis). There were no significant differences in the clonogenic potential and proliferation rate between early and late passage npMSCs. These results show that npMSCs possess the characteristics of MSCs in terms of morphology, multipotent differentiation capacity, cell surface marker expression, and clonogenicity. Thus, npMSCs may represent an alternative source of MSCs.


Repair of congenital tracheal stenosis.
We have used six different techniques in 61 operations performed at Children's Memorial Hospital (Chicago, IL) between 1982 and 2001 on 54 infants with complete tracheal rings and primary or recurrent tracheal stenosis. Short-term and long-term outcomes are reviewed for all techniques including pericardial tracheoplasty, tracheal autograft, tracheal resection, cartilage tracheoplasty, slide tracheoplasty, and aortic homograft patch tracheoplasty. Patients' ages ranged from 7 days to 72 months; mean age at operation was 6 months. There were 33 boys and 21 girls. Associated pulmonary artery sling was present in 19 of 54 patients (35%). Significant associated intracardiac anomaly was present in 13 of 54 patients (24%). The number of complete tracheal rings involved ranged from two to 18 rings (mean, 14+/-5). All procedures were performed with the use of cardiopulmonary bypass. Simultaneous repair of pulmonary artery sling and cardiac abnormalities was undertaken. There were three early deaths, two after pericardial tracheoplasty and one after tracheal autograft. There were eight late deaths, five after pericardial tracheoplasty, one after tracheal autograft, one after slide tracheoplasty, and one after tracheal resection. Median length of hospital stay was 60 days for pericardial tracheoplasty, 28 days for tracheal autograft, 14 days for tracheal resection, and 18 days for the slide tracheoplasty. Follow-up is complete in all patients. Tracheal autograft is currently our procedure of choice for patients with long-segment tracheal stenosis because of its use of all-autologous material, technical ease of performance, already-present epithelial lining of the autograft, intrinsic maintenance of the cartilage contour, potential for growth, and ready availability. We limit the use of tracheal resections to patients with eight or less rings of tracheal stenosis.


A Network Pharmacology Approach to Uncover the Potential Mechanism of Yinchensini Decoction.
To predict and explore the potential mechanism of Yinchensini decoction (YCSND) based on systemic pharmacology. TCMSP database was searched for the active constituents and related target proteins of YCSND. Cytoscape 3.5.1 was used to construct the active ingredient-target interaction of YCSND and network topology analysis, with STRING online database for protein-protein interaction (PPI) network construction and analysis; and collection from the UniProt database of target protein gene name, with the DAVID database for the gene ontology (GO) functional analysis, KEGG pathway enrichment analysis mechanism and targets of YCSND. The results indicate the core compounds of YCSND, namely, kaempferol, 7-Methoxy-2-methyl isoflavone, and formononetin. And its core targets are prostaglandin G/H synthase 2, estrogen receptor, Calmodulin, heat shock protein HSP 90, etc. PPI network analysis shows that the key components of the active ingredients of YCSND are JUN, TP53, MARK1, RELA, MYC, and so on. The results of the GO analysis demonstrate that extracellular space, cytosol, and plasma membrane are the main cellular components of YCSND. Its molecular functions are mainly acting on enzyme binding, protein heterodimerization activity, and drug binding. The biological process of YCSND is focused on response to drug, positive regulation of transcription from RNA polymerase II promoter, the response to ethanol, etc. KEGG results suggest that the pathways, including pathways in cancer, hepatitis B, and pancreatic cancer, play a key role in YCSND. YCSND exerts its drug effect through various signaling pathways and acts on kinds of targets. By system pharmacology, the potential role of drugs and the mechanism of action can be well predicted.


Formulation and evaluation of taste-masked oral disintegrating tablet containing tolterodine-loaded montmorillonite.
The present study aimed to obtain a taste-masked oral disintegrating tablet (ODT) containing tolterodine tartrate (TT) intercalated into montmorillonite (MMT). The TT-MMT hybrid was prepared by ion exchange reaction. The effect of the initial concentration of TT, MMT, temperature, and pH on the encapsulation efficiency (EE) % of the drug in MMT was evaluated. The selected TT-MMT hybrid was characterized by X-ray diffraction (XRD), Fourier transforms infrared (FTIR), differential scanning calorimetry (DSC), and scanning electron microscopy (SEM). Then, the optimized TT-MMT hybrid was incorporated in the ODT prepared by direct compression method and taste-masking assessment performed by a human test panel. The EE% of TT was in the range of 22.67 to 71.06% in different formulations. It was found that increases in MMT concentration significantly increased EE%. DSC and XRD studies indicated that the TT was intercalated in the MMT interlayer space in an amorphous or molecular state. In-vitro release studies at pH 6.8 showed that the amount of the drug released from the TT-MMT hybrid was negligible for the first 3 min. The post-compression of ODT also showed satisfactory results in terms of friability, hardness, disintegration time, and taste. MMT-ODT could be a suitable vehicle for the taste masking of TT, with the potential for use in patients with swallowing problems.


Dynactin enhances the processivity of kinesin-2.
Kinesin-2 is a major microtubule-based motor in most cell types. Its in vitro motile properties have been analyzed extensively and been found to differ considerably from kinesin-1. Although recombinant kinesin-2 heterodimers exhibit processive movement, the processivity of the native kinesin-2 holoenzyme has never been evaluated. Kinesin-2 can interact with dynactin, a 'processivity factor' for cytoplasmic dynein, which may alter its motile properties. In this study, we analyze the in vitro motility of single native kinesin-2 molecules and determine the effects of dynactin on motor processivity. We find that individual native kinesin-2 molecules travel processively. Dynactin has no effect on velocity but significantly increases the run length of kinesin-2 movements. These results show that the interaction with dynactin has important functional consequences on the activity of the kinesin-2 motor.


The immunology of asthma.
Asthma is a common disease that affects 300 million people worldwide. Given the large number of eosinophils in the airways of people with mild asthma, and verified by data from murine models, asthma was long considered the hallmark T helper type 2 (TH2) disease of the airways. It is now known that some asthmatic inflammation is neutrophilic, controlled by the TH17 subset of helper T cells, and that some eosinophilic inflammation is controlled by type 2 innate lymphoid cells (ILC2 cells) acting together with basophils. Here we discuss results from in-depth molecular studies of mouse models in light of the results from the first clinical trials targeting key cytokines in humans and describe the extraordinary heterogeneity of asthma.


Evaluation of the Gram stain as a screening tool for maternal carriage of group B beta-hemolytic streptococci. The Vaginal Infections and Prematurity Study Group.
To determine the usefulness of the vaginal Gram stain as a screen for maternal group B streptococcal carriage, we compared the presence of gram-positive cocci on Gram stain with a cervicovaginal culture in 7755 women at 23-26 weeks' gestation and in 1452 women at delivery. Group B streptococci were isolated from 18.4% of women at 23-26 weeks and 14.9% of women at delivery. The sensitivity, specificity, positive predictive value, and negative predictive value of the Gram stain were 28, 69, 17, and 81%, respectively, in mid-gestation and 34, 72, 18, and 86%, respectively, at delivery. The presence of gram-positive cocci on Gram stain was strongly associated with the isolation of Gardnerella vaginalis and with the presence of bacterial vaginosis. We conclude that most gram-positive cocci seen on Gram stain are probably anaerobes or micrococci and that the vaginal Gram stain is neither sensitive nor specific enough to be of use as a tool in the diagnosis of maternal group B streptococcal carriage.


Release of 2-thiobarbituric acid reactive products from glutamate, deoxyuridine or DNA during autoxidation of dopamine in the presence of copper ions.
Cytotoxic effects of catecholamine are thought to be caused by the formation of 0-semiquinone and superoxide radicals. Dopamine in the presence of copper ions releases aldehydic products from glutamate, deoxyuridine or DNA capable of reacting with 2-thiobarbituric acid (TBA). The formation of TBA reactive products (TBAR) was concentration dependent of both dopamine and copper ion. Complete inhibition of formation of TBAR from glutamate, deoxyuridine or DNA was observed in the presence of thiourea and catalase. Mannitol, albumin and superoxide dismutase offered substantial protection. The present data indicate that dopamine in the presence of copper ions can lead to the formation of reactive hydroxyl radicals which can release aldehydic products from glutamate, deoxyuridine or DNA capable of reacting with TBA.


Exploring factors related to the anger superiority effect in children with Autism Spectrum Disorder.
Despite face and emotion recognition deficits, individuals with Autism Spectrum Disorder (ASD) appear to experience the anger superiority effect, where an angry face in a crowd is detected faster than a neutral face. This study extended past research to examine the impacts of ecologically valid photographic stimuli, gender and anxiety symptoms on the anger superiority effect in children with and without ASD. Participants were 81, 7-12year old children, 42 with ASD matched on age, gender and perceptual IQ to 39 typically developing (TYP) children. The photographic stimuli did not impact on task performance in ASD with both groups exhibiting the anger superiority effect. There were no gender differences and no associations with anxiety. Age was associated with the effect in the TYP but not ASD group. These findings confirm a robust effect of speeded detection of threat in ASD which does not appear to be confounded by gender or anxiety, but may have different underlying age-associated mechanisms.


Molecular and biochemical screening for the diagnosis and management of medullary thyroid carcinoma in multiple endocrine neoplasia type 2A.
Patients with Multiple Endocrine Neoplasia (MEN) type 2A are at risk for early medullary thyroid carcinoma (MTC). We performed different screening tests for MTC--a recently reported biochemical screening test using omeprazole-induced calcitonin (CT) stimulation and DNA analysis--in fifteen members of two non-consanguineous Brazilian families with MEN 2A. RET proto-oncogene analysis was carried out by direct DNA sequencing of PCR-amplified products for exons 10 and 11. Family 1 showed a germline mutation (C634Y) in three individuals; a sister and a brother with symptomatic MTC; the former also presented with pheochromocytoma and hyperparathyroidism, and her son was a nine-year-old boy of previously unknown status. Family 2 showed the C634R mutation only in the index case, who presented with cutaneous lichen amyloidosis in addition to MTC, pheochromocytoma and hyperparathyroidism. Neither her parents nor her four brothers showed this genetic abnormality, suggesting a de novo RET proto-oncogene mutation in this patient. The controls and patients presented normal basal gastrin levels and a significant increase after omeprazole. Basal CT levels were elevated in patients with MTC and undetectable in control and asymptomatic family members. No subject showed any increase in CT levels after omeprazole treatment. In conclusion, the two most frequent RET proto-oncogene mutations in MEN 2A are present in Brazilian families. In addition, the specificity of basal and omeprazole-stimulated calcitonin is rather limited, and the efficacy of the omeprazole test still needs to be systematically examined. Therefore, RET proto-oncogene analysis must be the first choice for a screening procedure to identify gene carriers in MEN 2A family members and to permit early prophylactic treatment of MTC.


Prevention of renal ischemic injury by silencing the expression of renal caspase 3 and caspase 8.
Apoptotic pathways mediated by caspases play a critical role in renal ischemia-reperfusion injury (IRI). Downregulation of the caspase cascade, using small interfering RNA (siRNA) to silence the expression of caspase 3 and caspase 8, may have substantial therapeutic potential for limiting renal injury. IRI was induced in mice by clamping of the renal vein and artery for 25 or 35 min at 37 degrees C. Caspase 3 and caspase 8 (caspase 3/8) siRNA was administrated by hydrodynamic injection. Quantitative polymerase chain reaction (PCR) and immunohistochemistry were used to analyze the gene silencing efficacy, and the therapeutic effects of siRNA were evaluated by renal function analysis, histological examination, and overall survival of mice suffering from IRI. In this study, we have shown, using quantitative PCR, that IRI is associated with increased levels of renal caspase 3/8 mRNA. Mice treated with caspase 3/8 siRNA showed a significant down-regulation in kidney expression of caspase 3/8 at both, transcriptional and protein levels. Kidney function in IRI was protected by siRNA therapy, as levels of blood urea nitrogen and creatinine were significantly reduced in mice treated with siRNA. Histological examination demonstrated that tissue injury caused by IRI was significantly reduced as a result of caspase 3/8 siRNA treatment. Furthermore, survival data showed that more than 70% of mice in siRNA-treated groups survived until the end of the eight-day observation period. Herein, we have demonstrated the therapeutic potential of using siRNA to knock down the expression of caspases and prevent acute renal injury.


Clinical application of marrow mesenchymal stem cells for hard tissue repair.
Human marrow mesenchymal stem cells were cultured in a medium containing glycerophosphate, ascorbic acid, and dexamethasone (Dex) on alumina ceramic discs and on tissue culture polystyrene (TCPS) dishes. Cell proliferation followed by osteogenic differentiation was observed to be equal on both culture substrata. The differentiation resulted in the appearance of bone-forming osteoblasts, which fabricated mineralized matrices on these substrata. Stem cells kept at 4 degrees C for 24 h outside a CO2 incubator maintained a viability level of more than 90%. The regenerative cultured bone outside the incubator also maintained high alkaline phosphatase activity for several hours. These results verified that cultured bone fabricated at a cell processing center can be transported to distant hospitals for use in hard tissue repair. To date, the tissue engineered cultured bone formed on alumina ceramics in this environment have already been used in clinical situations, such as total ceramic ankle replacements.


Molecular characterization of human impacted third molars: diversification of compartments.
To gain more insight into the development of human teeth, we characterized different compartments of impacted third molars at two developmental stages by assessing expression levels of a set of genes. We considered genes known to be essential for the development of teeth and ectomesenchyme as well as genes covering characteristic features of stemness. Molars were divided into the operculum, periodontal ligament, developing pulp and, using a new approach, the pad-like tissue beneath the developing pulp. Markers for ectomesenchyme and tooth development known from rodents were assayed by semiquantitative PCR and every compartment was assigned its own signature of gene expression. The expression of markers characteristic of stem cells pointed to multipotent features. The expression patterns found shift in the course of development underscoring the relevance of these genes involved in human tooth development. The results suggest an inherent asymmetry between the developing pulp and pad-like tissue established early in tooth development. A microarray analysis of cells derived from pad-like tissue and pulp proper was performed to obtain cues regarding the consequences of tissue diversification. Both sets of data support the validity of our new approach to the subdivision of the developing tooth, by indicating a compartment-dependent commitment of isolated cells probably due to the postulated asymmetry within the developing tooth germ.


Identification of the key genes implicated in the transformation of OLP to OSCC using RNA-sequencing.
Oral lichen planus (OLP) is a chronic inflammatory disease that may transform to oral squamous cell carcinoma (OSCC), while its carcinogenesis mechanisms are not entirely clear. This study was designed to identify the important genes involved in the malignant transformation of OLP to OSCC. After RNA-sequencing, the differently expressed genes (DEGs) in OLP vs. normal and OSCC vs. normal groups, respectively, were identified by limma package in R language, and then clustering analysis were conducted by Pheatmap package in R language. Weighed gene co-expression network analysis (WGCNA) was performed for the DEGs to screen disease-associated modules. Using Cytoscape software, co-expression networks were constructed for the genes involved in the modules. Enrichment analysis was conducted for the genes involved in the co-expression networks using GOstat package in R language. Finally, quantitative real-time PCR (qRT-PCR) experiments were conducted to validate the key genes. There were, respectively, 223 and 548 DEGs in OLP vs. normal and OSCC vs. normal groups. WGCNA identified the blue modules for the DEGs in the two groups as disease-associated modules. Moreover, 19 common DEGs (including upregulated BCL9L, PER2 and TSPAN33, and downregulated GMPS and HES1) associated with both OLP and OSCC were identified. In the co-expression networks, BCL9L, HES1, PER2 and TSPAN33 might function in OLP via interactions (such as BCL9L-TSPAN33 and HES1-PER2). qRT-PCR analysis showed that BCL9L, PER2 and TSPAN33 were significantly upregulated, and GMP and HES1 were downregulated. These findings indicated that BCL9L, GMPS, HES1, PER2 and TSPAN33 affected the transformation of OLP to OSCC.


Integrated care pathway for co-occurring major depressive and alcohol use disorders: Outcomes of the first two years.
Major Depressive Disorder (MDD) and Alcohol Use Disorder (AUD) are highly prevalent, comorbid, and have significant impact on morbidity, mortality, and socioeconomic burden in Canada. Combined psycho- and pharmacotherapies for both conditions promise better outcomes than treatment as usual (TAU). At the Centre for Addiction and Mental Health, Toronto, Canada, we developed and implemented an Integrated Care Pathway (ICP) specifically for treatment of concurrent MDD and AUD. The goal of the study is to assess the clinical effectiveness of the ICP approach in comparison to TAU. Non-randomized design, clinical chart review, Chi-square and t-tests, Cohen's d, Linear Mixed Effects Models, Kaplan-Meier, and log-rank analyses. Eighty-one ICP patients were included, matched to 81 controls by age, sex, severity of depressive symptoms, and patterns of drinking. ICP cohort had a significantly lower dropout rate (18.5% vs 69.1%, p < .001; at 16 weeks of treatment, respectively), both cohorts demonstrated significant reduction in the number of heavy drinking days (β = .01, p < .001) and standard drinks per week (β = .15, p < .001) with a significantly higher reduction of both indicators over time in the ICP cohort. Significant reduction in depressive symptoms severity (QIDS: 14.6 vs 10.0, p < .001; BDI: 26.3 vs 16.2, p < .001) was observed in ICP cohort (no data for TAU cohort). The ICP patients demonstrated improvements on several levels including depressive symptoms, and changes in alcohol drinking patterns. The study demonstrated the overall effectiveness of the ICP and apparent advantage over TAU, which must be corroborated through a randomized clinical trial. (Am J Addict 2017;26:602-609) SCIENTIFIC SIGNIFICANCE: This study is one of the first works showing the outcomes of an ICP developed in the mental health area and for co-occurring disorders. Despite the limitations, the relative advantage of the ICP methodology warrants future research in this area.


COVID-19 and Global Distributive Justice: 'Health Diplomacy' of India and South Africa for the TRIPS waiver.
The second wave of the COVID-19 pandemic had left heart-wrenching impacts on all facets of life in general and the availability, accessibility, and affordability of medicines and vaccines in particular. Rather, the world has been divided into two groups regarding access to medicine and vaccines as haves and have-nots. The rich countries had pre-ordered the vaccines of COVID-19 along with the holding of the same. The pandemic situation was further worsened, given the Trade-Related Intellectual Property Rights (TRIPS) in practice and restrictions on sharing technology of vaccines, medicines, and life-saving equipment. In this context, India and South Africa have proposed the joint proposal and garnered support for waiving off TRIPS to ensure equity, accessibility, and affordability of vaccines and the same as public goods. In this review, we emphasize that global justice is one of the important elements of normative international theories, which focus on all the moral obligations from the world's rich to the world's poor. The paper also questions and argues that if the rich countries fail to go by the principles of global justice, can the Indian and South African (SA) patent diplomacy play a catalyst role in global justice? The review concludes with an emphasis on global solidarity, and the acceptance of joint India-South Africa's "patent diplomacy" for TRIPS waiver would result in mass production and fair distribution, making the COVID-19 medicines and technologies available to everyone regardless of their poor-rich status.


Alexia Without Agraphia: A Rare Entity.
Pure alexia refers to an acquired disorder associated with the damage to medial occipitotemporal gyrus in the dominant hemisphere, which is also known as visual word form area (VWFA). VWFA is involved in rapid word recognition and fluent reading. Alexia without agraphia is a disconnection syndrome that occurs when the splenium is also damaged with the occipital lobe on a dominant side. We report a case of a 72-year-old right-handed male who presented with alexia without agraphia accompanied by right homonymous hemianopia resulting from acute infarct of the left occipital lobe, the splenium of the corpus callosum and posterior thalamus that probably occurred on the previous day. During the evaluation, he exhibited marked impairment in the ability to read with the vision being grossly normal. Magnetic resonant imaging (MRI) revealed an acute infarct of the left occipital lobe, the splenium of the corpus callosum and posterior thalamus. A computerized tomography angiogram (CTA) revealed left posterior cerebral artery (PCA) territory infarct without any evidence of hemorrhagic conversion. Infarction of the occipital lobe on the dominant side (left) in a right-handed individual may cause a disruption in the visual word form area and is manifested by an inability to read with no abnormalities in visual acuity.


Network analysis reveals why Xylella fastidiosa will persist in Europe.
The insect vector borne bacterium Xylella fastidiosa was first detected in olive trees in Southern Italy in 2013, and identified as the main culprit behind the 'olive quick decline syndrome'. Since then, the disease has spread rapidly through Italy's main olive oil producing region. The epidemiology of the outbreak is largely unstudied, with the list of X. fastidiosa hosts and vectors in Europe likely incomplete, and the role humans play in dispersal unknown. These knowledge gaps have led to management strategies based on general assumptions that require, among others, local vector control and, in certain areas, the destruction of infected plants and healthy ones around them in an attempt to eradicate or halt the spreading pest. Here we show that, regardless of epidemiological uncertainties, the mere distribution of olive orchards in Southern Italy makes the chances of eradicating X. fastidiosa from the region extremely slim. Our results imply that Southern Italy is becoming a reservoir for X. fastidiosa. As a consequence, management strategies should keep the prevalence of X. fastidiosa in the region as low as possible, primarily through vector control, lest the pathogen, that has also been detected in southern France and the island of Mallorca (Spain), continues spreading through Italy and Europe.


MicroRNA-17-92 Regulates the Transcription Factor E2F3b during Myogenesis In Vitro and In Vivo.
Myogenic differentiation, which occurs during muscle development, is a highly ordered process that can be regulated by E2F transcription factors. Available data show that E2F3b, but not E2F3a, is upregulated and required for myogenic differentiation. However, the regulation of E2F3b expression in myogenic differentiation is not well understood. To investigate whether E2Fb expression is controlled by miRNAs, we used bioinformatics to combine the database of microRNAs downregulated during myogenesis and those predicted to target E2F3. This identified miR-17 and miR-20a as miRNAs potentially involved in E2F3 regulation. We found that miR-17-92 controls the expression of E2F3b in C2C12 cells during myogenic differentiation. Moreover, we confirmed that miR-20a regulates the expression of E2F3b proteins in vivo using a muscle regeneration model.


Parotid tuberculosis.
Tuberculosis of the parotid gland is a rare condition. We describe a case of tuberculosis of right parotid gland in a 17-year-old male patient. Diagnosis was made by early suspicion and confirmed by demonstration of epitheloid granulomas on fine needle aspiration cytology (FNAC). Patient was successfully treated with daily regimen of four drugs (rifampicin, isoniazid, pyrazinamide, ethambutol) for first two months followed by two drugs (rifampicin and isoniazid) for last four months.


Body weight loss during lactation in relation to energy and protein metabolism in standard-fed primiparous sows.
After 5 weeks of lactation 14 standard-fed primiparous sows were divided into a low weight-loss group (L-gr, loss < 25 kg, n = 7) and a high weight-loss group (H-gr, loss > or = 25 kg, n = 7). Body weights of the sows and their litters were recorded on days 2, 7, 14, 21, 28 and 35 of lactation. Blood samples were collected before the morning feeding on each weighing day. Samples were analysed to determine concentrations of insulin, glucagon, glucose, triglycerides, non-esterified fatty acids (NEFA), urea and creatinine. The H-gr sows lost weight throughout lactation, whereas the L-gr sows gained weight during the last week. Weight loss was higher in the H-gr than in the L-gr during weeks 2, 3 and 5 of lactation. Litter size and litter weight gain were higher in the H-gr than in the L-gr. Significant changes in levels of insulin, glucagon, glucose, triglycerides and creatinine were observed over lactation. No significant differences in concentrations of any of the parameters were found between the two groups, except for insulin and cholesterol which were higher in the L-gr. Catabolism of adipose tissue and muscle protein was observed in both groups during the first week of lactation. This catabolic state was more pronounced and tended to be prolonged in the H-gr. Concentrations of all parameters seemed to be stable in both groups during the last two weeks of lactation.


Expression and regulation of miR-17a and miR-430b in zebrafish ovarian follicles.
MicroRNAs (miRNAs) are small noncoding RNAs that post-transcriptionally regulate gene expression and control many developmental and physiological processes. Oocyte maturation in fish is mainly regulated by luteinizing hormone (LH) and maturation-inducing hormone (MIH). In addition, growth factors, including members of the transforming growth factor β (TGF-β) superfamily, have also been shown to play important roles in regulating oocyte maturation. In this study, we determined the expression and regulation of two miRNAs, miR-17a and miR-430b, which potentially target signalling molecules in the TGF-β pathway, in zebrafish ovarian follicles. Using real-time PCR, we observed that miR-17a and miR-430b levels in follicular cells were significantly lower in late vitellogenic and full grown follicles than in early vitellogenic follicles. Treatment with a LH analog, human chorionic gonadotropin, significantly down-regulated miR-17a and miR-430b expression in follicular cells but had no effect on their expression in oocytes. Forskolin also inhibited follicular cell miR-430b expression; however, no significant changes in miR-17a levels were observed after Forskolin treatment. Finally, MIH did not affect the expression of these miRNAs either in follicular cells or oocytes at the time points tested. These findings suggest that miR-17a and miR-430b may be involved in the regulation of follicle development and oocyte maturation in zebrafish.


Effectiveness of MVA-BN vaccination in a population at high-risk of mpox: a Spanish cohort study.
With over 7,500 cases notified since April 2022, Spain has experienced the highest incidence of mpox in Europe. From July 12th onwards, the Modified Vaccinia Ankara-Bavaria Nordic (MVA-BN) smallpox vaccine was offered as pre-exposure prophylaxis for individuals at high-risk of mpox, including those receiving pre-exposure prophylaxis for HIV (HIV-PrEP). Our aim was to assess the effectiveness of one dose of MVA-BN vaccine as pre-exposure against mpox virus (MPXV) infection in persons on HIV-PrEP. We conducted a national retrospective cohort study between July 12 and December 12, 2022. Individuals ≥18 years, receiving HIV-PrEP as of July 12 and with no previous MPXV infection or vaccination were eligible. Each day, we matched individuals receiving a first dose of MVA-BN vaccine and unvaccinated controls of the same age group and region. We used a Kaplan-Meier estimator and calculate risk ratios (RR) and vaccine effectiveness (VE = 1-RR). We included 5,660 matched pairs, with a median follow-up of 62 days (interquartile range 24-97). Mpox cumulative incidence was 5.6 per 1,000 (25 cases) in unvaccinated and 3.5 per 1,000 (18 cases) in vaccinated. No effect was found during days 0-6 post-vaccination (VE -38.3; 95% confidence interval (95%CI): -332.7; 46.4), but VE was 65% in ≥7 days (95%CI 22.9; 88.0) and 79% in ≥14 days (95%CI 33.3; 100.0) post-vaccination. One dose of MVA-BN vaccine offered protection against mpox in a most-at-risk population shortly after the vaccination. Further studies need to assess the VE of a second dose and the duration of protection over time.


Early diagnosis and evidence-based care of surgical sepsis.
Sepsis continues to be a common and serious problem among surgical patients. It is a leading cause of both morbidity and mortality in the perioperative period. The early identification of sepsis and the early implementation of evidence-based care can improve outcomes. This focused review will identify ways to improve the early identification of sepsis and discuss the current evidence-based guidelines for the early management of sepsis, severe sepsis, and septic shock in the surgical patients.


Second Case of Deceased Donor Liver Transplantation in a Patient Co-infected with HIV and HCV in Japan: Special Reference to the Management of Complicated Coagulopathy Due to a Diverse Spectrum of Preformed Anti-HLA Antibodies.
We report the second case of deceased donor liver transplantation in a patient co-infected with human immunodeficiency virus (HIV) and hepatitis C virus (HCV) in Japan. A 48-year-old patient with hemophilia A was infected with HIV and HCV through contaminated factor VIII concentrate in his childhood and developed cirrhosis and hepatocellular carcinoma. The patient was on the transplant list for a deceased donor liver. The patient had broad spectrum anti-HLA class I and II antibodies, which may be attributed to repeated whole blood transfusions in the past. Catastrophic coagulopathy during the surgery was predicted because of the underlying hemophilic status and severe thrombocytopenia requiring HLA-matched platelet products, which are difficult to obtain quickly. To maintain adequate platelet counts (> 5 × 104/µL) while awaiting liver transplantation, a thrombopoietin receptor agonist and rituximab were administered. During surgery, factor VIII concentrate was administered according to a previously planned protocol. Adequate hemostasis was obtained, and the operation was completed without uncontrollable coagulopathy. The postoperative course was uneventful, and the patient was discharged on postoperative day 41. Detailed planning is required for surgical patients with hemophilia and HIV/HCV cirrhosis, especially for those with a diverse spectrum of anti-HLA antibodies.


Level of Toll-like receptor agonist exposure differentially determines chemokine production in humans.
Toll-like receptor (TLR) agonists, ubiquitously present in the environment, are key players in activating synthesis of cytokines and chemokines that control normal and pathophysiological processes, including multiple inflammatory diseases. TLR2 and TLR4 respond to bacterial cell wall products. We examined the impact of TLR activation on human immune capacity using stimuli ranging from the low levels seen in most environments to the high concentrations widely used for in vitro studies. Peripheral blood mononuclear cells from 117 healthy children were activated with lipopolysaccharide (TLR4 ligand) or peptidoglycan (TLR2 ligand) over a million-fold range of concentrations. Resulting interleukin-6, CCL2, and CCL22 production were quantified by ELISA. The intensity of cytokine production elicited was linearly related to the intensity of the stimulus up to maximal responses. In marked contrast, chemokine production was not linearly related to agonist concentration. Responses rose with increasing stimulation, and then were markedly reduced (40%-100%, p < 0.0001) in response to the high levels of TLR stimulation most commonly cited. Thus, the levels of TLR4 and TLR2 agonists typically used for in vitro interrogation of immune capacity yield results clearly distinct from those obtained using commonly occurring environmental levels of TLR ligands. These findings demonstrate the importance of utilizing TLR ligands at concentrations more closely mimicking environmental levels when assessing immune capacity.


Morphological and phylogenetic features of the Crimean population of Juniperus deltoides R.P. Adams.
Juniperus deltoides is a relict species from the Tertiary Period. It is a typical representative of the Mediterranean group of the section Juniperus. It is included in the Red Books of the Republic of Crimea and the city of Sevastopol. Until recently, it was believed that a population of J. oxycedrus grew in Crimea. Currently, J. deltoides is described as a cryptic species, morphologically difficult to distinguish from J. oxycedrus. As a result, it became necessary to conduct a series of detailed studies to determine the morphological and phylogenetic features of the Crimean cryptic population in order to identify it as being one of the species of the cryptic pair. The studies were carried out in two stages: at the first stage, the morphological features of the vegetative and generative organs and their difference from J. oxycedrus were determined; the second stage included genetic research. The length of the needles of the Crimean population is 12.94 ± 0.19 mm, which corresponds to the Eastern Italian population of J. deltoides. At the same time, the width of the needles is 1.39 ± 0.02 mm, which is typical of the Portuguese population of J. oxycedrus. The dimensions of the cones are d1 (conditional height) = 7.54 ± 0.14 mm, and d2 (conditional width) = 9.11 ± 0.09 mm, which is more in line with J. deltoides. The shapes of the cones are very diverse. Some individuals have cones, the covering scales of which are visually indistinguishable, and their tops are completely fused. A similar phenomenon is characteristic of the Western Mediterranean populations of J. oxycedrus. Morphological analysis of the vegetative and generative organs of J. deltoides showed that when these two traits are combined, it is not possible to reliably distinguish between J. deltoides and J. oxycedrus individuals. Nuclear (ITS internal transcribed spacer) and chloroplast (petN-psbM, trnS-trnG) non-coding regions of the genome were used for genetic analysis. Studies have shown that the nuclear regions of genes have greater variability than chloroplast regions. The sequences obtained in this work formed a clade with J. deltoides samples 9430 and 9431 (BAYLU) growing in Turkey, which makes it possible to assign the samples studied to J. deltoides.


Deconjugation of N-glucuronide conjugated metabolites with hydrazine hydrate--biomarkers for exposure to the food-borne carcinogen 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP).
The metabolism of the carcinogen 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) has been investigated in rabbit liver S9. Two phase I metabolites, N(2)-OH-PhIP and 4'-OH-PhIP were identified based on UV and mass spectra and co-elution with reference standards. Fortification of the incubation with UDGPA resulted in a complete glucuronidation of PhIP and N(2)-OH-PhIP, while 4'-OH-PhIP was only partly glucuronidated. Also, the PhIP metabolite 5-OH-PhIP was completely glucuronidated by rabbit liver S9, while 5-OH-PhIP was a poor substrate for CYP mediated hydroxylation. The glucuronic acid conjugates of PhIP metabolites were unsusceptible to treatment with beta-glucuronidase indicating that these are N-glucuronides. Treatment of the conjugates with hydrazine hydrate, however, resulted in complete hydrolysis of the glucuronic acid conjugates as well as in reduction to the parent amine of metabolites hydroxylated in the exocyclic amino group. Urine was collected from a male volunteer following consumption of fried chicken. Treatment of the urine with beta-glucuronidase/sulfatase resulted in release of 4'-OH-PhIP, while treatment with hydrazine hydrate in addition resulted in release of substantial amounts of PhIP and 5-OH-PhIP. The data show that hydrazine hydrate can hydrolyse N-glucuronides of metabolites of PhIP, glucuronides that are unsusceptible to enzymatic hydrolysis. In addition the data indicate that humans metabolise a large fraction of ingested PhIP to genotoxic metabolites. The chemical hydrolysis of glucuronide conjugates of PhIP metabolites with hydrazine hydrate observed in this study may also be a useful approach in the development of biomarkers for exposure and effect of other xenobiotics.


A comparison of self-reported health status and perceptual responses toward environmental noise in rural, suburban, and urban regions in Canada.
Health Canada, in collaboration with Advanis, conducted the Canadian Perspectives on Environmental Noise Survey (CPENS) to investigate expectations and attitudes toward environmental noise in rural and non-rural Canada. The CPENS, a 26-item questionnaire, was completed online by 6647 randomly selected Canadians, age 18 y and older between April and May 2021. The prevalence of reporting their area as often or always calm, quiet, and relaxing was 76.8%, 64%, and 48.4% in rural/remote, suburban, and urban, respectively. A high expectation of quiet was less prevalent yet followed the same pattern: rural/remote (58.2%), suburban (37.4%), and urban (21.8%). Self-reported health status and noise sensitivity were unrelated to geographic region. A high magnitude of non-specific sleep disturbance over the previous 12 months was reported by 7.8% overall; highest among urban dwellers (9.8%), followed by suburban (7.2%) and rural/remote (5.5%) dwellers (p < 0.01). High annoyance toward road traffic noise was 8.5% overall, and significantly higher in urban (10.5%), relative to suburban (7.9%) and rural/remote (6.6%) areas (p < 0.0001). Annoyance toward noise from rail, aircraft, mining, industry, marine activity, construction, wind turbines, and landscaping equipment is reported. The analysis also explores potential differences between Indigenous Peoples of Canada and non-Indigenous Canadians in their attitudes and expectations toward environmental noise.


Involvement of JunB Proto-Oncogene in Tail Formation During Early Xenopus Embryogenesis.
Integration of signaling pathways is important for the establishment of the body plan during embryogenesis. However, little is known about how the multiple signals interact to regulate morphogenesis. Here, we show that junb is expressed in the posterior neural plate and the caudal fin during Xenopus embryogenesis and that overexpression of wild-type JunB induces small head phenotypes and ectopic tail-like structures. A mutant form of JunB that lacked GSK3 and MAPK phosphorylation sites showed stronger tail-like structure-inducing activity than wild-type JunB. Moreover, the mutant JunB induced expression of tailbud and neural marker genes, but not somite and chordoneural hinge (CNH) marker genes in ectopic tail-like structures. In ectodermal explants of Xenopus embryos, overexpression of JunB increased the expression of tailbud and posterior marker genes including fgf3, xbra (t) and wnt8. These results indicate that JunB is capable of inducing the ectopic formation of tissues similar to the tailbud, and that the tailbud-inducing activity of JunB is likely to be regulated by FGF and Wnt pathways. Overall, our results suggest that JunB is a regulator of tail organization possibly through integration of several morphogen signaling pathways.


The Mediating Role of Place Attachment Dimensions in the Relationship Between Local Social Identity and Well-Being.
Well-functioning communities provide a range of material and psychological resources that enhance well-being. The degree to which individuals see themselves as part of the local social group, or local social identity, i.e., the social identification with the community of the place where people are living, may play an important role in enhancing happiness and well-being, as well as relationships of people with their own living environment, i.e., place attachment. We hypothesized that local social identity influences well-being via specific components of place attachment to the residential city/town, i.e., place identity, social relations, and lack of resources (which is the opposite of place dependence). We measured local social identity, individual well-being, interdependent happiness, and place attachment in a sample of N = 375 participants. We tested our hypotheses by conducting a series of mediation analyses with local social identity as an independent variable, individual well-being and interdependent happiness as dependent variables, and place attachment subfactors, i.e., place identity, social relations, and lack of resources, as mediators. Results showed that the relation between local social identity and both individual well-being and interdependent happiness was positively mediated by place identity and social relations, while the lack of resources emerged as a negative mediator only in the relation between local social identity and individual well-being (not for interdependent happiness). Practical implications and future developments are discussed.


Anomalous origin of the right coronary artery from pulmonary artery in an adult presenting with rapid atrial fibrillation: a case report.
An anomalous origin of the right coronary artery from pulmonary artery (ARCAPA) is a very rare coronary anomaly. A 56-year-old man, presenting haemodynamically unstable due to very rapid atrial fibrillation, was found to have ARCAPA by coronary computed tomography angiography. He had normal left ventricular ejection fraction and without reversible ischaemia on an adenosine stress rubidium positron emission tomography. He was treated solely with betablockers and has been well since. Numerous case reports on ARCAPA have previously been published, but no previous reports have found rapid atrial fibrillation to be the primary symptom of presentation. Current evidence level concerning the treatment is low; nevertheless, surgical intervention should always be considered to prevent sudden cardiac death. The patient in this case was offered surgical intervention but declined.


Anatase titania nanorods as an intercalation anode material for rechargeable sodium batteries.
For the first time, we report the electrochemical activity of anatase TiO2 nanorods in a Na cell. The anatase TiO2 nanorods were synthesized by a hydrothermal method, and their surfaces were coated by carbon to improve the electric conductivity through carbonization of pitch at 700 °C for 2 h in Ar flow. The resulting structure does not change before and after the carbon coating, as confirmed by X-ray diffraction (XRD). Transmission electron microscopic images confirm the presence of a carbon coating on the anatase TiO2 nanorods. In cell tests, anodes of bare and carbon-coated anatase TiO2 nanorods exhibit stable cycling performance and attain a capacity of about 172 and 193 mAh g(-1) on the first charge, respectively, in the voltage range of 3-0 V. With the help of the conductive carbon layers, the carbon-coated anatase TiO2 delivers more capacity at high rates, 104 mAh g(-1) at the 10 C-rate (3.3 A g(-1)), 82 mAh g(-1) at the 30 C-rate (10 A g(-1)), and 53 mAh g(-1) at the 100 C-rate (33 A g(-1)). By contrast, the anode of bare anatase TiO2 nanorods delivers only about 38 mAh g(-1) at the 10 C-rate (3.3 A g(-1)). The excellent cyclability and high-rate capability are the result of a Na(+) insertion and extraction reaction into the host structure coupled with Ti(4+/3+) redox reaction, as revealed by X-ray absorption spectroscopy.


Effect of surgical revascularization in patients with coronary artery disease and ventricular tachycardia or fibrillation in the Antiarrhythmics Versus Implantable Defibrillators (AVID) Registry.
Patients who undergo resuscitation from near-fatal ventricular arrhythmias often have significant coronary artery disease, and revascularization has been shown to reduce myocardial ischemia and cardiac arrest episodes in this patient population. The magnitude of benefit attributed to revascularization has varied by study, and the use of adjunct implantable cardioverter defibrillator (ICD) therapy has not been well-characterized. The Antiarrhythmics Versus Implantable Defibrillators (AVID) registry included 3117 patients with life-threatening ventricular arrhythmias, of whom 2321 (77%) had documented coronary artery disease and 281 (17%) underwent a coronary artery bypass grafting revascularization procedure after the index event. Patients who underwent a revascularization procedure were younger, had a lower incidence rate of prior myocardial infarction and ventricular arrhythmia, had a higher left ventricular ejection fraction, had less congestive heart failure, and were more likely to have had ventricular fibrillation as the presenting arrhythmia. Patients who underwent revascularization had a better survival rate than did those who did not undergo such a procedure after the index event, and adjustment for differing baseline patient covariates did not alter the relative survival rate benefit. Further, ICD implantation offered a similar survival rate advantage to those patients in the AVID registry with coronary artery disease independent of revascularization. Coronary revascularization in the AVID registry patients with coronary artery disease effected a survival rate benefit that was not attributable to differences in baseline patient characteristics. The benefit of ICD on patient survival rate was not attenuated by a revascularization procedure.


Terahertz time-domain spectroscopy as a tool to monitor the glass transition in polymers.
We demonstrate the suitability of terahertz time-domain spectroscopy as a non-destructive, contact-free tool to monitor the glass transition in polymers--a core feature of the amorphous phase. Below the glass transition temperature T(g), segmental motions along the polymer chain are frozen due to the lack of free volume between neighboring macromolecules. We show that this transition also reflects in the temperature dependence of the refractive index at terahertz frequencies. Two domains can be identified, which differ in their sensitivity to temperature changes. To verify the proposed approach, we determine the glass transition temperature T(g) of semi-crystalline poly(oxymethylene) (POM) with terahertz time-domain spectroscopy and validate the results by destructive differential scanning calorimetry (DSC) measurements.


Erectile failure following pelvic trauma: a review of pathophysiology, evaluation, and management, with particular reference to the penile prosthesis.
Twenty-five inflatable and two semi-rigid rod type penile prostheses have been implanted in 27 patients with erectile failure following pelvic trauma. Reoperation was required in 13 patients in the inflatable prosthesis group but ultimate success and satisfaction were achieved in 92%. The etiology of erectile failure following various types of trauma is reviewed, as well as the approach to the evaluation of erectile failure in such a patient. Where etiology-specific corrective therapy is not possible, the penile prosthesis has proven to be an acceptable form of substitution therapy.


Application of Response Surface Methodology (RSM) for the Optimization of Ultrasound-Assisted Extraction (UAE) of Moringa oleifera: Extraction Yield, Content of Bioactive Compounds, and Biological Effects In Vitro.
This study optimized ultrasound-assisted extraction conditions to maximize the extraction yield, total flavonoid content (TFC), total phenolic content (TPC), and DPP IV enzyme inhibitory activity from Moringa oleifera. The four UAE factors, solvent ratio (A), solvent-solid ratio (B), extraction temperature (C), and extraction time (D), were optimized using response surface methodology (RSM). A Box-Behnken design was used for the experimental design. The optimal conditions were found to be a 50% v/v solvent ratio, a 30% v/w solvent-solid ratio, 35 °C extraction temperature, and 45 min extraction time. The experimental value of extraction yield (R1), TFC (R2), TPC (R3), and DPP IV enzyme inhibitory activity (R4) (87.99% w/w, 56.63 mg QE/g extract, 97.26 mg GAE/g extract, and 93.32% inhibition, respectively) agreed with those predicted by RSM models (88.10% w/w, 56.61 mg QE/g extract, 97.16 mg GAE/g extract, and93.38% inhibition, respectively), thus demonstrating the appropriateness of the model used and the ability of the RSM to optimize the extraction conditions. Excellent DPP IV enzyme inhibitory activity was exhibited by M. oleifera compared with the standard, sitagliptin. While the modeled equation fits the data, the t-test is not significant, suggesting that the experimental values agree with those predicted by the RSM-BBD.


Risk factors associated with Tuberculosis (TB) among people living with HIV/AIDS: A pair-matched case-control study in Guangxi, China.
As one of the poorest provinces in China, Guangxi has a high HIV and TB prevalence, with the annual number of TB/HIV cases reported by health department among the highest in the country. However, studies on the burden of TB-HIV co-infection and risk factors for active TB among HIV-infected persons in Guangxi have rarely been reported. To investigate the risk factors for active TB among people living with HIV/AIDS in Guangxi Zhuang autonomous region, China. A surveillance survey was conducted of 1 019 HIV-infected patients receiving care at three AIDS prevention and control departments between 2013 and 2015. We investigated the cumulative prevalence of TB during 2 years. To analyze risk factors associated with active TB, we conducted a 1:1 pair-matched case-control study of newly reported active TB/HIV co-infected patients. Controls were patients with HIV without active TB, latent TB infection or other lung disease, who were matched with the case group based on sex and age (± 3 years). A total of 1 019 subjects were evaluated. 160 subjects (15.70%) were diagnosed with active TB, including 85 clinically diagnosed cases and 75 confirmed cases. We performed a 1:1 matched case-control study, with 82 TB/HIV patients and 82 people living with HIV/AIDS based on surveillance site, sex and age (±3) years. According to multivariate analysis, smoking (OR = 2.996, 0.992-9.053), lower CD 4+ T-cell count (OR = 3.288, 1.161-9.311), long duration of HIV-infection (OR = 5.946, 2.221-15.915) and non-use of ART (OR = 7.775, 2.618-23.094) were independent risk factors for TB in people living with HIV/AIDS. The prevalence of active TB among people living with HIV/AIDS in Guangxi was 173 times higher than general population in Guangxi. It is necessary for government to integrate control planning and resources for the two diseases. Medical and public health workers should strengthen health education for TB/HIV prevention and treatment and promote smoking cessation. Active TB case finding and early initiation of ART is necessary to minimize the burden of disease among patients with HIV, as is IPT and infection control in healthcare facilities.


Pretargeted Imaging with Gallium-68-Improving the Binding Capability by Increasing the Number of Tetrazine Motifs.
The inverse electron-demand Diels-Alder reaction between 1,2,4,5-tetrazine (Tz) and trans-cyclooct-2-ene (TCO) has gained increasing attraction among extensive studies on click chemistry due to its exceptionally fast reaction kinetics and high selectivity for in vivo pretargeting applications including PET imaging. The facile two-step approach utilizing TCO-modified antibodies as targeting structures has not made it into clinics yet. An increase in the blood volume of humans in comparison to mice seems to be the major limitation. This study aims to show if the design of multimeric Tz-ligands by chelator scaffolding can improve the binding capacity and may lead to enhanced PET imaging with gallium-68. We utilized for this purpose the macrocyclic siderophore Fusarinine C (FSC) which allows conjugation of up to three Tz-residues due to three primary amines available for site specific modification. The resulting mono- di- and trimeric conjugates were radiolabelled with gallium-68 and characterized in vitro (logD, protein binding, stability, binding towards TCO modified rituximab (RTX)) and in vivo (biodistribution- and imaging studies in normal BALB/c mice using a simplified RTX-TCO tumour surrogate). The 68Ga-labelled FSC-based Tz-ligands showed suitable hydrophilicity, high stability and high targeting specificity. The binding capacity to RTX-TCO was increased according to the grade of multimerization. Corresponding in vivo studies showed a multimerization typical profile but generally suitable pharmacokinetics with low accumulation in non-targeted tissue. Imaging studies in RTX-TCO tumour surrogate bearing BALB/c mice confirmed this trend and revealed improved targeting by multimerization as increased accumulation in RTX-TCO positive tissue was observed.


Effects of rokitamycin on phagocytosis and release of oxidant radicals of human polymorphonuclear leukocytes.
A rational choice of an antimicrobial agent must take into account not only the activity against the specific pathogen but also any possible negative or positive effects on the host defense system. Rokitamycin (RKM) is an orally active 16-membered-ring macrolide; there are no reports of specific investigations of these activities in the literature. Polymorphonuclear neutrophils (PMNs) from healthy adult donors were incubated in medium alone or in medium containing increasing concentrations (1, 10, 50, 100 micrograms/ml) of RKM. In unwashed PMNs phagocytosis was unaffected by RKM, while luminol-amplified chemiluminescence (LACL) was significantly reduced by 50 and 100 micrograms/ml. When PMNs were washed after incubation phagocytosis was not modified but LACL was significantly restored. These characteristics of RKM were similar to those of roxithromycin and can be put in correlation with the cellular/extracellular ratio (30.5 for PMNs and 120 for macrophages) that was similar to that of roxithromycin but higher than of other macrolides. The molecular mechanisms by which high concentrations of these two macrolides produce such an impairment of LACL are still unclear. RKM has no unwanted effects on PMNs because the serum concentrations that can be obtained with the highest doses administered to man are lower than the concentrations which did not affect PMN functions in our study.


Influence of functional interleukin 10/tumor necrosis factor-alpha polymorphisms on interferon-alpha, IL-10, and regulatory T cell population in patients with systemic lupus erythematosus receiving antimalarial treatment.
As interleukin 10 (IL-10)/tumor necrosis factor-alpha (TNF-alpha) polymorphisms have been shown to influence TNF-alpha inhibition and clinical response to antimalarial treatment in patients with systemic lupus erythematosus (SLE), we investigated involvement of these variants in antimalarial effects on cytokine serum levels and regulatory T cell population (Treg). The alleles present at -308 TNF-alpha and -1082 IL-10 genes; serum concentrations of interferon-alpha (IFN-alpha), IL-10 and TNF-alpha; and size and function of CD4+CD25(high) (Treg) population were determined in SLE patients and in healthy controls. These data were related to treatment and clinical manifestations. Patients were observed to have increased IFN-alpha serum levels that did not correlate with any treatment. Among patients receiving antimalarial drugs, high IL-10/low TNF-alpha producers presented higher levels of IFN-alpha and IL-10 than carriers of other genotypes. In contrast, patients with the converse, low IL-10/high TNF-alpha genotype who were receiving antimalarial treatment presented increased size and function of Treg population. The percentage of CD4+CD25(high) cells was inversely correlated to TNF-alpha levels. Our findings suggest that the beneficial effect of antimalarials in low IL-10/high TNF-alpha patients with SLE may be partially attributable to the increase in Treg activity, whereas patients with the converse genotype did not show this phenomenon, yet did have significantly upregulated levels of IFN-alpha and IL-10, 2 cytokines that have been associated with SLE activity.


Measuring pretest-posttest change with a Rasch Rating Scale Model.
When measures are taken on the same individual over time, it is difficult to determine whether observed differences are the result of changes in the person or changes in other facets of the measurement situation (e.g., interpretation of items or use of rating scale). This paper describes a method for disentangling changes in persons from changes in the interpretation of Likert-type questionnaire items and the use of rating scales (Wright, 1996a). The procedure relies on anchoring strategies to create a common frame of reference for interpreting measures that are taken at different times and provides a detailed illustration of how to implement these procedures using FACETS.


The effects of mGlu₇ receptor modulation in behavioural models sensitive to antidepressant action in two mouse strains.
There is increasing evidence suggesting a role of the neurotransmitter glutamate in depression. The metabotropic glutamate (mGlu) receptors are G-protein coupled receptors, which mediate a slow modulatory response to glutamate signalling. mGlu₇ receptor is a presynaptic inhibitory autoreceptor showing great promise as a potential therapeutic target for the treatment of depression. Selective pharmacological modulators of mGlu₇ receptor have been developed; the positive allosteric modulator AMN082 and the negative modulator 6-(4-methoxyphenyl)-5-methyl-3-(4-pyridinyl)-isoxazolo[4,5-c]pyridin-4(5H)-one hydrochloride (MMPIP). They remain to be extensively characterized in behavioural models sensitive to antidepressant action. Therefore, we assessed the effects of these compounds on behaviour in two different mouse strains using several preclinical tests sensitive to antidepressant pharmacological action. AMN082 (6 mg/kg) reduced immobility in the forced swim test and tail suspension test (TST) in both C57BL/6j and CD1 mice. In CD1 mice, MMPIP (10 and 30 mg/kg) significantly increased the time spent immobile in the TST, whereas this effect was restricted to a dose of 30 mg/kg in C57BL/6j mice. Administration of MMPIP with AMN082 partially attenuated the antidepressant-like effect of AMN082 in C57BL/6j mice in the forced swim test and the TST. However, this effect was absent from the CD1 strain. This further adds to the growing corpus of data promoting the targeting of mGlu₇ receptor with the aim of achieving an antidepressant effect.


Variability of aflatoxin and cyclopiazonic acid production by Aspergillus section flavi from different substrates in Argentina.
Aspergillus section flavi strains isolated from peanuts, wheat and soybean grown in Argentina were screened for aflatoxins (type B and G) and cyclopiazonic acid (CPA) production. Aspergillus flavus was the predominant species in all substrates, although there was almost the same proportion of A. flavus and Aspergillus parasiticus in peanuts. Aspergillus nomius was not found. Incidence of aflatoxigenic A. flavus strains was higher in peanuts (69%) than in wheat (13%) or soybeans (5%) while the ratio of CPA producers A. flavus isolated from all substrates was very high (94% in peanuts, 93% in wheat and 73% in soybeans). Isolates of A. flavus able to produce simultaneously aflatoxins type B and CPA were detected in all substrates, suggesting the possibility of co-occurrence of these toxins. Almost all isolates of A. parasiticus resulted aflatoxins (type B and G) producers but did not produce CPA. Five of sixty-seven strains isolated from peanuts showed an unusual pattern of mycotoxin production (aflatoxins type B and G simultaneously with CPA). These strains also produced numerous small sclerotia like S strains of A. flavus detected in cottonseed in Arizona and in soils of Thailand and West Africa. The atypical strains are not widely distributed in Argentina and were found uniquely in peanuts.


Comparison of Hamilton Depression Rating Scale and Montgomery-Åsberg Depression Rating Scale: Baked Straight From a Randomized Study.
The symptoms of major depressive disorder (MDD) are nowadays being assessed with the Hamilton and Montgomery-Åsberg Depression Rating Scales. However, there are few studies on the comparison of these two scales. Our study aimed to determine the correlation between the Hamilton Depression Rating Scale (HDRS) and Montgomery-Åsberg Depression Rating Scale (MADRS) scores at baseline through 12 weeks. An ongoing randomized, open-label, three-arm study's interim analysis is portrayed here. The participants were assessed with HDRS and MADRS at baseline, four, eight, and 12 weeks after receiving oral tablets of either vilazodone (20-40 mg/d), escitalopram (10-20 mg/d), or vortioxetine (5-20 mg/d). This study is prospectively registered with the Clinical Trial Registry, India (CTRI/2022/07/043808). Of 71 recruited individuals, 49 (69%) completed the 12-week visit. At baseline, the three groups' median HDRS scores were 30.0, 29.5, and 29.0 (p=0.76), and at 12 weeks, they reduced to 19.5, 19.5, and 18.0 (p=0.18). At baseline, the group-wise median MADRS scores were 36, 36, and 36 (p=0.79); at 12 weeks, they were 24, 24, and 23 (p=0.03). The Pearson correlation revealed that the association between the changes in scores from baseline was strongest for escitalopram (r=0.70, p=0.002) followed by vortioxetine (r=0.59, p=0.01) and vilazodone (r=0.59, p=0.02). The Bland-Altman analysis showed that the mean difference between the scores was 5.11 (95% CI: 3.08-7.14). According to this interim study, HDRS and MADRS scores declined after 12 weeks of therapy. Both scores had strong positive correlation, and the difference between the scores reduced with time.


Determinants of Plasma 25-Hydroxyvitamin D Concentrations among Breast Cancer Survivors in Korea.
We identified demographic, lifestyle, and clinical factors associated with vitamin D status among breast cancer survivors. The vitamin D prediction model may be a useful surrogate of circulating 25-hydroxvitamin D (25(OH)D) concentrations when this measure was not available. We included a total of 216 Korean breast cancer survivors aged 21-79 years who had been diagnosed with stage I to III primary breast cancer and had breast cancer surgery at least 6 months before enrolment. We used linear and logistic regressions to identify determinants for the plasma 25(OH)D concentrations and vitamin D insufficiency (plasma 25(OH)D concentration < 50 nmol/L). We observed that 48.85% of breast cancer survivors had a plasma 25(OH)D concentration less than 50 nmol/L. We identified the following determinants for plasma 25(OH)D concentrations: time since diagnosis (β = -0.005 for 1 month increment), supplementary vitamin D intake (β = 0.06 for 10 μg/day increment), season of the blood draw (β = 0.35 for summer; β = 0.32 for fall; β = 0.26 for winter vs. spring), smoking status (β = 0.28 for former vs. never), use of any supplement (β = -0.35 for non-use vs. use), and the parity number (β = -0.30 for three or more vs. one) were associated with the plasma 25(OH)D concentrations. In addition to the aforementioned variables, body mass index (BMI) was associated with the prevalence of vitamin D insufficiency. We identified the determinants for the plasma 25(OH)D concentrations among Korean breast cancer survivors. Future studies are needed to investigate the role of vitamin D in the progression of breast cancer among Korean breast cancer survivors.


Analysis of Selected Lymphocyte (CD45+) Subset Distribution in Capillary Blood of Young Soccer Players.
Nowak, R, Kostrzerwa-Nowak, D, and Buryta, R. Analysis of selected lymphocyte (CD45+) subset distribution in capillary blood of young soccer players. J Strength Cond Res 35(8): 2279-2286, 2021-Mechanisms responsible for increasing athletes' physical capacity and induction of exercise-induced immunosuppression processes are not fully understood. The aim of the study was to monitor changes in percentages of lymphocyte subsets: T, Th, Tc, B, and NK cells in capillary blood of junior soccer players. Ten subjects median aged 18 years (range 17-19 years) were recruited form young soccer players. Capillary blood was collected 24 hours after each soccer match during the 8 weeks of the final phase of Central Junior League competition, and white blood cell (WBC) phenotyping was performed to determine the percentages of B lymphocytes, NK cells, and T-lymphocyte subsets. Cumulative match-time (a sum of time spend playing the game by each athlete during the observation period) was also calculated. Significant changes in the percentage of total lymphocytes (p = 0.00005) and T cells (p = 0.00006) were observed. The slight increases in lymphocytes' and Th cells' median percentages correlated with increasing cumulative match-time of studied subjects, although the correlation was not strong (R = 0.24; p = 0.0205 and R = 0.30; p = 0.0035, for lymphocytes and Th cells, respectively). It seems that the exercise bouts are among considerable factors influencing the changes in WBC subsets, especially in CD3+ cells, among young soccer players. Regarding the number of games played and training loads, they are more susceptible to immunosuppression and subsequent infections and thus should be monitored regarding WBC phenotype assessment.


Role of the microcirculation in ethanol-induced mucosal injury in the dog.
The aim of the present study was to assess the role of the intestinal microcirculation in the mucosal injury induced by intraenteric ethanol. Mucosal injury was assessed histologically in the ileum and jejunum and quantitated in the ileum by measuring clearance of albumin (37 A, radius) and beta-lactoglobulin A (27 A, radius). A steady-state analysis of the forces and flows governing transcapillary fluid movement was performed in autoperfused segments of jejunum and ileum. In the jejunum and ileum ethanol induced the formation of subepithelial blisters in 10%-40% of the villi. In the ileum, ethanol (5%, vol/vol) increased the clearance of both proteins but the ratio of lactoglobulin to albumin clearance decreased, indicating that the selectivity of the mucosal membrane was diminished. In both the jejunum and ileum ethanol produced similar alterations in the forces governing transcapillary fluid exchange. Ethanol increased the filtration coefficient (35%-40%), but did not alter the osmotic reflection coefficient of intestinal capillaries, indicating that surface area increased whereas vascular permeability was not affected. Capillary pressure increased (2-3 mmHg) whereas interstitial (lymph) protein concentration decreased resulting in an increase in the transcapillary oncotic pressure gradient (1-2 mmHg). The net result of the alterations in the forces governing transcapillary movement was only a doubling of the transcapillary filtration rate (lymph flow). It is concluded that the ethanol-induced increase in mucosal permeability to macromolecules cannot be explained solely on the basis of alterations in the forces and flows governing transcapillary fluid exchange in the small intestine.


Coronary involvement in infants with Kawasaki disease treated with intravenous gamma-globulin.
To analyze the clinical spectrum and the incidence of coronary involvement in infants with typical Kawasaki's disease (KD). A retrospective study was performed on children one year of age or younger diagnosed from February 1992 to January 2006 with typical KD. Children with incomplete forms of the disease were not included. Twenty-five infants were diagnosed with KD during the study period. The median age of the patients was 10 months (range, 4-12 months). All children but one received intravenous gammaglobulin (IVIG), 84% before the 10th day of disease. Seven patients (28%) required the administration of more than one dose of IVIG, because persistence of fever. Coronary artery disease (CAD) was recorded in 6 cases (24%), five of them being boys. All patients with CAD were treated with ASA plus IVIG and 84% of them received this therapy within the first 10 days of the KD onset. In spite of the exclusion of our study of incomplete presentations and of an early administration of IVIG in our patients, we have observed a high rate of infants who developed CAD, which is similar to the one reported in children who do not receive IVIG.


Acrobeads test as a predictor of fertilization in vitro.
To determine whether the results of the Acrobeads test, which measures the expression of the complement regulator molecule CD46 on the inner acrosomal membrane following the acrosome reaction, accurately identifies semen specimens that will exhibit reduced or failed fertilization following conventional IVF insemination. The Acrobeads test was performed on semen specimens from 97 consecutive patients preparing to undergo an IVF cycle utilizing a standardized insemination protocol. Motile sperm populations were examined at 6 h and 24 h post-isolation for sperm-bead agglutination. Results of the Acrobeads test were compared to that of TRITC-PSA staining in matched specimens to directly measure the spontaneous loss of acrosome content. The percentages of TRITC-PSA-negative sperm were determined in freshly isolated motile populations and in duplicate aliquots incubated 18 to 20 h under sperm capacitating conditions. The relationship between the results of both analyses estimating spontaneous acrosome reactions and the rate of fertilization of metaphase II oocytes was examined. The Acrobeads score did not correlate significantly with the rate of fertilization by insemination at 6 h or at 24 h. The negative predictive value of this test was 21.4%. There was no correlation between the Acrobeads score and the percentage of sperm undergoing a spontaneous acrosome reaction as detected by TRITC-PSA labeling. In contrast, the increment increase in the percentage of spontaneous acrosome reactions as quantified by TRITC-PSA staining was correlated with the fertilization rate. Contrary to previous reports, our prospective, double-blinded study failed to demonstrate that the Acrobeads test can accurately predict fertilization outcome in IVF. Therefore, the routine use of this test to screen patients prior to an IVF cycle in order to select appropriate treatment (i.e., ICSI) cannot be recommended.


Chronic candidal meningitis: an uncommon manifestation of candidiasis.
Chronic meningitis is an uncommon manifestation of candidiasis. We present the case of an elderly woman who had symptoms such as headache, malaise, and fever for 8 months and was found to have Candida albicans meningitis, and we review 17 similar cases. An underlying illness or risk factor for candidiasis was present in only 13 (72%) of the 18 patients. Headache, fever, and nuchal rigidity were the predominant clinical findings. Analysis of CSF showed either mononuclear or neutrophilic pleocytosis, an elevated protein level, and a decreased level of glucose. Only 17% of CSF smears were positive, and only 44% of initial CSF cultures yielded Candida species. In four cases, Candida species grew only after special techniques were used; in three cases, CSF cultures remained negative. The overall mortality associated with candidal meningitis was 53%, but among 12 patients who were treated and followed, the rate was 33%. In addition to acute meningitis seen with disseminated infection, Candida species can cause chronic meningitis that mimics tuberculosis and the more common fungal meningitides, such as cryptococcosis.


Colonoscopy and sedation in Romania: early experience using a balanced propofol regimen.
The aim of this study was to evaluate if the sedation during colonoscopy is correctly performed in our patients, especially because it is usually performed by residents in anesthesiology. we retrospectively evaluated sedation in all the colonoscopies performed in our Endoscopy Department in 2007, by analyzing the sedation scheme that was used. 974 colonoscopies were evaluated. The following sedation schemes were used in the majority of cases: midazolam+propofol+fentanyl-507 patients (52.1%) and diazepam+propofol+fentanyl-258 patients (26.5%). Propofol (in combination with one or more other agents) was used for sedation in 96.9% of cases. The mean doses of drugs were: propofol 125.2+/-67.7 mg, midazolam 2.29+/-0.84 mg (or diazepam 3.4+/-1.4 mg) and fentanyl 59+/-10 microg. The following complications were observed during sedation for colonoscopy: 6 patients (0.6%) developed hypoxemia, which was managed successfully with supplemental oxygen administration or flumazenil injection; 1 patient (0.1%) suffered a cardiac arrest that was successfully managed. There were no deaths or other complications. Propofol, combined with an opioid and a benzodiazepine, was used in approximately 97% of cases. The rate of significant oxygen desaturation was low (0.6%). No fatal complications occurred. The mean doses of propofol used were higher than those from published data, while the doses of midazolam and fentanyl were similar.


Inhibition of estrogen-dependent breast cancer growth by a reaction product of alpha-fetoprotein and estradiol.
Reaction of picomolar quantities of human or rodent alpha-fetoprotein (AFP) with nanomolar quantities of 17 beta-estradiol (E2) generates a product of unknown structure, designated AFP/E2, that inhibits estrogen-stimulated growth of mouse uterus. We describe herein the effect of rodent AFP/E2 on the in vivo growth of two estrogen-dependent breast cancers, the MCF-7 human breast cancer and the MTW9A rat mammary cancer. Both cancers were grown as xenografts under the kidney capsule of cyclosporine-immunosuppressed male BDF1 mice. In addition, the MTW9A tumor was grown as a homograft in syngeneic ovariectomized Wistar-Furth female rats. Estrogen support was provided by s.c. Silastic E2 implants. Injecting AFP/E2 that was generated by incubating 1.0 microgram of AFP with 0.5 microgram of E2 for 1 h at room temperature resulted in cessation of growth and, in most cases, regression of MCF-7 tumor xenografts. It also produced regression of MTW9A tumor homografts and significantly inhibited growth of MTW9A xenografts. Treatment with AFP alone or E2 alone did not inhibit growth of these tumors. The data suggest that AFP/E2 has a unique property which causes attenuation or shut-down of the biochemical reactions through which estrogen-dependent tumor growth is mediated.