Genome-Scale Imaging of the 3D Organization and Transcriptional Activity of Chromatin.
The 3D organization of chromatin regulates many genome functions. Our understanding of 3D genome organization requires tools to directly visualize chromatin conformation in its native context. Here we report an imaging technology for visualizing chromatin organization across multiple scales in single cells with high genomic throughput. First we demonstrate multiplexed imaging of hundreds of genomic loci by sequential hybridization, which allows high-resolution conformation tracing of whole chromosomes. Next we report a multiplexed error-robust fluorescence in situ hybridization (MERFISH)-based method for genome-scale chromatin tracing and demonstrate simultaneous imaging of more than 1,000 genomic loci and nascent transcripts of more than 1,000 genes together with landmark nuclear structures. Using this technology, we characterize chromatin domains, compartments, and trans-chromosomal interactions and their relationship to transcription in single cells. We envision broad application of this high-throughput, multi-scale, and multi-modal imaging technology, which provides an integrated view of chromatin organization in its native structural and functional context.


Six-month outcomes following an emergency hospital admission for older adults with co-morbid mental health problems indicate complexity of care needs.
two-thirds of older patients admitted as an emergency to a general hospital have co-existing mental health problems including delirium, dementia and depression. This study describes the outcomes of older adults with co-morbid mental health problems after an acute hospital admission. a follow-up study of 250 patients aged over 70 admitted to 1 of 12 wards (geriatric, medical or orthopaedic) of an English acute general hospital with a co-morbid mental health problem and followed up at 180 days. twenty-seven per cent did not return to their original place of residence after the hospital admission. After 180 days 31% had died, 42% had been readmitted and 24% of community residents had moved to a care home. Only 31% survived without being readmitted or moving to a care home. However, 16% spent >170 of the 180 days at home. Significant predictors for poor outcomes were co-morbidity, nutrition, cognitive function, reduction in activities of daily living ability prior to admission, behavioural and psychiatric problems and depression. Only 42% of survivors recovered to their pre-acute illness level of function. Clinically significant behavioural and psychiatric symptoms were present at follow-up in 71% of survivors with baseline cognitive impairment, and new symptoms developed frequently in this group. the variable, but often adverse, outcomes in this group implies a wide range of health and social care needs. Community and acute services to meet these needs should be anticipated and provided for.


The GAA*TTC triplet repeat expanded in Friedreich's ataxia impedes transcription elongation by T7 RNA polymerase in a length and supercoil dependent manner.
Large expansions of the trinucleotide repeat GAA*TTC within the first intron of the X25 (frataxin) gene cause Friedreich's ataxia, the most common inherited ataxia. Expansion leads to reduced levels of frataxin mRNA in affected individuals. Here we show that GAA*TTC tracts, in the absence of any other frataxin gene sequences, can reduce the amount of GAA-containing transcript produced in a defined in vitro transcription system. This effect is due to an impediment to elongation that forms in the GAA*TTC tract during transcription, a phenomenon that is exacerbated by both superhelical stress and increased tract length. On supercoiled templates the major truncations of the GAA-containing transcripts occur in the distal (3') end of the GAA repeat. To account for these observations we present a model in which an RNA polymerase advancing within a long GAA*TTC tract initiates the transient formation of an R*R*Y intramolecular DNA triplex. The non-template (GAA) strand folds back creating a loop in the template strand, and the polymerase is paused at the distal triplex-duplex junction.


Anaesthesia, surgery, and life-threatening allergic reactions: management and outcomes in the 6th National Audit Project (NAP6).
Anaphylaxis during anaesthesia is a serious complication for patients and anaesthetists. There is little published information on management and outcomes of perioperative anaphylaxis in the UK. The 6th National Audit Project of the Royal College of Anaesthetists (NAP6) collected and reviewed 266 reports of Grade 3-5 anaphylaxis from all UK NHS hospitals over 1 yr. Quality of management was assessed against published guidelines. Appropriately senior anaesthetists resuscitated all patients. Immediate management was 'good' in 46% and 'poor' in 15%. Recognition and treatment of anaphylaxis were prompt in 97% and 83% of cases, respectively. Epinephrine was administered i.v. in 76%, i.m. in 14%, both in 6%, and not at all in 11% of cases. A catecholamine infusion was administered in half of cases. Cardiac arrests (40 cases; 15%) were promptly treated but cardiac compressions were omitted in half of patients with unrecordable BP. The surgical procedure was abandoned in most cases, including 10% where surgery was urgent. Of 54% admitted to critical care, 70% were level 3, with most requiring catecholamine infusions. Ten (3.8%) patents (mostly elderly with cardiovascular disease) died from anaphylaxis. Corticosteroids and antihistamines were generally administered early. We found no clear evidence of harm or benefit from chlorphenamine. Two patients received vasopressin and one glucagon. Fluid administration was inadequate in 19% of cases. Treatment included sugammadex in 19 cases, including one when rocuronium had not been administered. Adverse sequelae (psychological, cognitive, or physical) were reported in one-third of cases. Management of perioperative anaphylaxis could be improved, especially with respect to administration of epinephrine, cardiac compressions, and i.v. fluid. Sequelae were common.


Fish Ontology framework for taxonomy-based fish recognition.
Life science ontologies play an important role in Semantic Web. Given the diversity in fish species and the associated wealth of information, it is imperative to develop an ontology capable of linking and integrating this information in an automated fashion. As such, we introduce the Fish Ontology (FO), an automated classification architecture of existing fish taxa which provides taxonomic information on unknown fish based on metadata restrictions. It is designed to support knowledge discovery, provide semantic annotation of fish and fisheries resources, data integration, and information retrieval. Automated classification for unknown specimens is a unique feature that currently does not appear to exist in other known ontologies. Examples of automated classification for major groups of fish are demonstrated, showing the inferred information by introducing several restrictions at the species or specimen level. The current version of FO has 1,830 classes, includes widely used fisheries terminology, and models major aspects of fish taxonomy, grouping, and character. With more than 30,000 known fish species globally, the FO will be an indispensable tool for fish scientists and other interested users.


Shark Spotters: Successfully reducing spatial overlap between white sharks (Carcharodon carcharias) and recreational water users in False Bay, South Africa.
White sharks (Carcharodon carcharias) are apex predators that play an important role in the structure and stability of marine ecosystems. Despite their ecological importance and protected status, white sharks are still subject to lethal control to reduce the risk of shark bites for recreational water users. The Shark Spotters program, pioneered in Cape Town, South Africa, provides a non-lethal alternative for reducing the risk of human-shark conflict. In this study we assessed the efficacy of the Shark Spotters program in reducing overlap between water users and white sharks at two popular beaches in False Bay, South Africa. We investigated seasonal and diel patterns in water use and shark presence at each beach, and thereafter quantified the impact of different shark warnings from shark spotters on water user abundance. We also assessed the impact of a fatal shark incident on patterns of water use. Our results revealed striking diel and seasonal overlap between white sharks and water users at both beaches. Despite this, there was a low rate of shark-human incidents (0.5/annum) which we attribute partly to the success of the Shark Spotters program. Shark spotters use visual (coloured flags) and auditory (siren) cues to inform water users of risk associated with white shark presence in the surf zone. Our results showed that the highest risk category (denoted by a white flag and accompanying siren) caused a significant reduction in water user abundance; however the secondary risk category (denoted by a red flag with no siren) had no significant effect on water users. A fatal shark incident was shown to negatively impact the number of water users present for at least three months following the incident. Our results indicate that the Shark Spotters program effectively reduces spatial overlap between white sharks and water users when the risk of conflict is highest.


Social and Psychological Predictors of Body Mass Index among South Africans 15 Years and Older: SANHANES-1.
This study investigated how psychological distress and the proxies for social position combine to influence the risk of both underweight and overweight in South Africans aged 15 years and older. This was a cross-sectional study that included 2254 men and 4170 women participating in the first South African National Health and Nutrition Examination Survey (SANHANES-1). An analysis exploring the associations of social and mental health characteristics with body mass index (BMI) was conducted using binary and multinomial logistic regressions. Results suggested that, overall, women had a higher risk of overweight/obesity compared to men (age-adjusted odds ratio [AOR] 4.65; 95% confidence intervals [CI] 3.94-5.50). The gender effect on BMI was smaller in non-African participants (AOR 3.02; 95% CI 2.41-3.79; p-value for interaction = 0.004). Being employed and having a higher level of education were associated with higher risks of overweight and obesity and a lower risk of underweight. Being single or without a spouse and poor mental health were found to increase the odds of being underweight, especially in men. To conclude, there are strong social gradients and important gender and ethnic differences in how BMI is distributed in the South African population.


Differential regulation of SP-A1 and SP-A2 genes by cAMP, glucocorticoids, and insulin.
In the human fetal lung, surfactant protein A (SP-A) is encoded by two highly similar genes, SP-A1 and SP-A2, which are developmentally and hormonally regulated. Using primer extension analysis, we evaluated the levels of SP-A1 and SP-A2 mRNA transcripts in human fetal lung explants and in a human adult lung adenocarcinoma cell line (H441 cells) cultured in the absence or presence of either dibutyryladenosine 3',5'-cyclic monophosphate (DBcAMP, 1 mM), dexamethasone (10(-7) M), or insulin (2.5 micrograms/ml). In the human fetal lung explants, the content of SP-A1 mRNA was approximately four times that of SP-A2 mRNA. DBcAMP increased SP-A1 mRNA levels by 100% and SP-A2 mRNA levels by 500%, thus reducing the ratio of SP-A1 mRNA to SP-A2 mRNA to approximately 1:1. Dexamethasone inhibited all of the SP-A1 and SP-A2 mRNA transcripts to the same extent, by approximately 70%, whereas insulin inhibited all SP-A mRNA transcripts by approximately 60%. The ratio of SP-A1 to SP-A2 mRNA in dexamethasone- or insulin-treated explants was the same as the ratio observed in controls. In the H441 cells, SP-A1 mRNA levels were approximately 1.5 times that of SP-A2 mRNA levels. DBcAMP increased both SP-A1 and SP-A2 mRNA levels by 100%. Dexamethasone inhibited SP-A1 mRNA levels in the cell line by 60%, whereas SP-A2 mRNA levels were not significantly affected. Insulin inhibited SP-A1 mRNA levels in the cell line by 40% without affecting SP-A2 mRNA levels. These findings suggest that the two human SP-A genes are regulated differently in the two model systems.


Effects of yoga interventions on fatigue in cancer patients and survivors: a systematic review of randomized controlled trials.
Fatigue is one of the most frequently reported, distressing side effects reported by cancer survivors and often has significant long-term consequences. Research indicates that yoga can produce invigorating effects on physical and mental energy, and thereby may improve levels of fatigue. The objective of this systematic review was to examine the literature that reports the effects of randomized, controlled yoga interventions on self-reported fatigue in cancer patients and survivors. The online electronic databases, PubMed and PsycINFO, were used to search for peer-reviewed research articles studying the effects of yoga interventions on fatigue in cancer survivors. Combinations of yoga, cancer, and fatigue-related search terms were entered simultaneously to obtain articles that included all three elements. Studies were included if they met the following inclusion criteria: participants were male or female cancer patients or survivors participating in randomized, controlled yoga interventions. The main outcome of interest was change in fatigue from pre- to post-intervention. Interventions of any length were included in the analysis. Risk of bias using the format of the Cochrane Collaboration's tool for assessing risk of bias was also examined across studies. Ten articles met inclusion criteria and involved a total of 583 participants who were predominantly female, breast cancer survivors. Four studies indicated that the yoga intervention resulted in significant reductions in self-reported fatigue from pre- to post-intervention. Three of the studies reported that there were significant reductions of fatigue among participants who attended a greater number of yoga classes. Risk of bias was high for areas of adequate selection, performance, detection, and patient-reported bias and mixed for attrition and reporting bias. Risk of bias was uniformly low for other forms of bias, including financial conflicts of interest. Results of the studies included in this review suggest that yoga interventions may be beneficial for reducing cancer-related fatigue in women with breast cancer; however, conclusions should be interpreted with caution as a result of levels of bias and inconsistent methods used across studies. More well-constructed randomized controlled trials are needed to determine the impact of yoga interventions on fatigue in cancer patients and survivors.


Relative Density of Away from Home Food Establishments and Food Spend for 24,047 Households in England: A Cross-Sectional Study.
Eating away from home is a risk factor for poor diet quality and obesity. With an ever-increasing proportion of household food spend directed toward eating out, the proliferation of these food establishments may contribute to their use, a potential precursor to less healthy food choices and low overall diet quality. However few studies are conducted at the national level and across a range of away from home food sources. The purpose of this study was to examine the association between the density of away from home food establishments (e.g., restaurants, fast food outlets and cafés) and household spend on away from home food within a nationally representative sample for England, UK. A cross-sectional analysis of data from Wave 1 of the UK Household Longitudinal Survey (n = 24,047 adults aged ≥19y) was conducted. Exposure was characterised as the density of away from home food establishments to all other food sources within 1 mile of the home, divided into quintiles (Q1 as lowest exposure and Q5 as highest exposure). The primary outcome included households with a high away from home equivalised monthly food spend (≥25% of total food spend). Logistic regression was used to estimate associations between away from home food establishment exposure and high away from home food spend. Away from home food establishment density was significantly associated with a greater odds of high monthly food spend (Q3: OR = 1.18, 95% CI = 1.07, 1.30; Q4: OR = 1.30, 95% CI = 1.18, 1.43; and Q5: OR = 1.52, 95% CI = 1.37, 1.68) with attenuation after controlling for known socioeconomic confounders (Q4: OR = 1.13, 95% CI = 1.02, 1.25; and Q5: OR = 1.16, 95% CI = 1.04, 1.30) compared to those least exposed (Q1). Those most exposed to away from home food establishments had a 16% greater odds of allocating more than 25% of household food spend on away from home food sources. This study provides one of the first analyses at the national level to examine the role of the local food environment in relation to household food spend, a potential precursor to diet quality and health.


Fluoride-releasing sealant and caries-like enamel lesion formation in vitro.
The aim of this laboratory study was to evaluate the effects of a fluoride-releasing pit and fissure sealant (FS) and a conventional non-fluoride-containing pit and fissure sealant (CS) on caries-like lesion formation in enamel. Twelve extracted, macroscopically caries-free human molar teeth underwent fluoride-free prophylaxis and were sectioned into toothquarters. Cavity preparations were placed in buccal and lingual surfaces of the toothquarters, acid-etched and filled with sealant material (per the manufacturer's instructions) as follows: 1) mesiobuccal and mesiolingual quarters--FS (Fissurit-F, VocoChemie); and 2) distobuccal and distolingual quarters--CS (Fissurit, VocoChemie). Prior to caries formation in an acidified gel, the toothquarters were thermocycled (500 cycles) in artificial saliva. Sections were taken following caries initiation (6 week gel exposure) and caries progression (9 week gel exposure), and examined by polarized light microscopy to determine mean primary surface lesion depth and presence or absence of wall lesions. Mean surface lesion depths were significantly different between FS and CS groups following caries initiation (FS = 119 microns; CS = 157 microns, p < 0.05, paired t-test) and progression (FS = 169 microns; CS = 221 microns, p < 0.05, paired t-test). Wall lesions were reduced in FS (14% initiation; 25% progression) when compared with CS (19% initiation; 35% progression); however, this was not significantly different (p > 0.05, paired t-test). A pit and fissure sealant containing releasable fluoride provided a caries inhibiting effect with a significant reduction in lesion depth in the surface enamel adjacent to the fluoride-releasing sealant and a tendency toward reduction in the frequency of wall lesions. Fluoride release by pit and fissure sealants may provide additional protection against caries formation in cuspal incline enamel and smooth surfaces adjacent to sealed pits and fissures, and act as a fluoride reservoir with long-term release of fluoride into the immediately adjacent oral environment.


Herpes zoster ophthalmicus and the immunocompromised host: a case report and review.
Herpes zoster is the secondary form of varicella zoster virus disease, caused by the reactivation of the dormant virus in the sensory ganglia. It manifests as a unilateral cutaneous dermatitis with a prodromal fever and malaise. Herpes zoster ophthalmicus occurs when the ophthalmic division of the trigeminal nerve becomes afflicted. This case represents a middle-aged female with breast carcinoma. Cancer radiotherapy and chemotherapy created an immunosuppressed state, which allowed the development of herpes zoster ophthalmicus. Most patients who manifest zoster are immunocompetent. However, with the increased incidence of immunodeficient states (e.g., chemotherapy, organ transplantation and acquired immunodeficiency syndrome), clinicians are faced with a greater number of cases of zoster. In the immunodeficient population, especially, dissemination of the zoster and potentially damaging complications can occur. In the light of these facts, clinicians must be well versed in all aspects of herpes zoster disease, including the clinical and laboratory diagnosis, as well as the incidence and presentation of herpes zoster. Current treatments, such as the use of famciclovir, acyclovir, valcyclovir, and prednisone, must also be understood.


Reduced folate carrier polymorphism (80A-->G) and neural tube defects.
Transport of folates in mammalian cells occurs by a carrier-mediated mechanism. The human folate carrier (RFC-1) gene has been isolated and characterized. Within this gene, a common polymorphism, 80A-->G, changing a histidine to an arginine in exon 2 (H27R), was recently identified. Defects in folate metabolism, such as defective carrier molecules, could be implicated in the etiology of neural tube defects (NTDs). In the present case-control study, we recruited 174 Italian probands with nonsyndromic NTD, 43 mothers, 53 fathers and 156 control individuals and evaluated the impact of RFC-1 variant on NTD risk. A statistically significant risk was calculated for the 80GG genotype of the NTD cases (OR=2.35; 95% CI 1.21-4.58) and mothers (OR=2.74; 95% CI 0.92-8.38). On the contrary, the heterozygous genotype of the mothers and both heterozygous and homozygous genotypes of the fathers did not seem to be significant NTD risk factors. Furthemore, according to the multifactorial inheritance of NTDs, we demonstrated that the combined genotypes for MTHFR 1298A-->C and RFC-1 80A-->G polymorphisms of cases resulted in greater NTD risk than heterozygosity or homozygosity for RFC-1 80A-->G variant alone. Conversely, our data provide no evidence for an association between NTD phenotype and combined MTHFR C677T/RFC-1 A80G genotypes. Moreover, here we describe the combinations of the two MTHFR polymorphic sites (677CT and 1298AC) with RFC-1 genotypes. We found that both patients and controls could have at most quadruple-mutation combinations. Interestingly, 27% (7/26) of the mothers and 18.75% (30/160) of the cases genotyped presented four mutant alleles in comparison with 8.5% (11/129) of the controls. Finally, the frequency of NTD cases and mothers carrying combined heterozygosity for the two MTHFR polymorphisms and RFC-1 80GG homozygosity (677CT/1298AC/80GG) (cases=11.3%; mothers 11.5%) was increased compared with controls (1.6%). Altogether, our findings support the hypothesis that RFC-1 A80G variant may contribute to NTD susceptibility in the Italian population.


Effects of bifunctional linker on the performance of P3HT/CdSe quantum dot-linker-ZnO nanocolumn photovoltaic device.
We study the effects of bifunctional linker on the photovoltaic properties of P3HT/CdSe quantum dot-linker-ZnO nanocolumn heterostructure. The CdSe quantum dots are bound on the surface of ZnO nanocolumns through either aliphatic linker of 3-aminopropyl trimethoxysilane(APS) or aromatic linker of p-aminophenyl trimethoxysilane(APhS) using simple solution process. As compared to CdSe bound by aliphatic linker(APS), while CdSe is bound by aromatic linker(APhS), more than one fold increase of short circuit current density (J(SC)) of the device obtained under irradiance, which is attributed to a more efficient charge transfer dynamics at interface. In addition, the ZnO-APhS-CdSe/P3HT devices possess about 4.8 folds in power conversion efficiency as compared to ZnO/P3HT device as the results of reduction in shunt loss and interfacial recombination.


Frequency of Hypoplasia of the Vertebral Body at L5, and Its Relationship with Degeneration in Patients with Low Back Pain.
To explain the association between vertebral body hypoplasia and degenerative changes in the discovertebral complex and facet joints, and to assess the incidence of hypoplasia of the vertebral body at the L5 level. A retrospective analysis was made of 3,100 patients aged 20?50 years who underwent lumbar MRI with a complaint of back pain, of which 55 were identified with vertebral body hypoplasia. Intervertebral disc degeneration was evaluated in the study using the Pfirrmann and Modified Pfirrmann classification systems, while degenerative changes in the vertebrae endplate were assessed using the Modic classification system. Osteoarthritis of the facet joint was graded at the L4-5 level, and spondylolysis and spondylolisthesis rates were compared between the control group and the hypoplasic group. The incidence of hypoplasia of the vertebral body at the L5 level was found to be 1.8% in the population with back pain in the 20?50-year age group. In the hypoplasia group, disc degeneration was detected at a higher rate than in the control group (p < 0.001). The distribution of Modic signal changes in the superior and inferior endplates of the vertebrae differed significantly between the hypoplasia and control groups (p < 0.001).The rate of spondylolysis was 7.7% in the control group and 65.5% in the hypoplasia group (p < 0.001), and spondylolisthesis was significantly more common in the hypoplasia group (18.4%, p < 0.001). In addition, facet joint degeneration was identified more frequently in the hypoplasia group. Degenerative findings were detected in 74.5% of the right posterior intervertebral joints, and in 70.9% of the left posterior intervertebral joints in the hypoplasia group. Vertebral body hypoplasia is a predisposing factor for disc degeneration, facet osteoarthritis and degeneration in the vertebral endplates, and has also been associated with spondylolysis and spondylolisthesis.


Highly Efficient Spatially-Temporally Synchronized Construction of Robust Li3PO4-rich Solid-Electrolyte Interphases in Aqueous Li-ion Batteries.
Solid electrolyte interphase (SEI) makes the electrochemical window of aqueous electrolytes beyond the thermodynamics limitation of water. However, achieving the energetic and robust SEI is more challenging in aqueous electrolytes because the low SEI formation efficiency (SFE) only contributed from anion-reduced products, and the low SEI formation quality (SFQ) negatively impacted by the hydrogen evolution, resulting in a high Li loss to compensate for SEI formation. Herein, we propose a highly efficient strategy to construct Spatially-Temporally Synchronized (STS) robust SEI by the involvement of synergistic chemical precipitation-electrochemical reduction.In this case, a robust Li3PO4-rich SEI enables intelligent inherent growth at the active site of the hydrogen by the chemical capture of the OH- stemmed from the HER to trigger the ionization balance of dihydrogen phosphate (H2PO4-) shift to insoluble solid Li3PO4. It is worth highlighting that the Li3PO4 formation does not extra-consume lithium derived from the cathode but makes good use of the product of HER (OH-), prompting the SEI to achieve 100% SFE and pushing the HER potential into -1.8 V vs. Ag/AgCl. This energetic and robust SEI offers a new way to achieve anion/concentration-independent interfacial chemistry for the aqueous batteries.


Ventral tegmental area leptin receptor neurons specifically project to and regulate cocaine- and amphetamine-regulated transcript neurons of the extended central amygdala.
Leptin acts via its receptor (LepRb) to regulate neural circuits in concert with body energy stores. In addition to acting on a number of hypothalamic structures, leptin modulates the mesolimbic dopamine (DA) system. To determine the sites at which LepRb neurons might directly influence the mesolimbic DA system, we examined the distribution of LepRb neurons and their projections within mesolimbic brain regions. Although the ventral tegmental area (VTA) contains DA LepRb neurons, LepRb neurons are absent from the amygdala and striatum. Also, LepRb-EGFPf mice (which label projections from LepRb neurons throughout the brain) reveal that few LepRb neurons project to the nucleus accumbens (NAc). In contrast, the central amygdala (CeA) and its rostral extension receive copious projections from LepRb neurons. Indeed, LepRb-specific anterograde tracing demonstrates (and retrograde tracing confirms) that VTA LepRb neurons project to the extended CeA (extCeA) but not the NAc. Consistently, leptin promotes cAMP response element-binding protein phosphorylation in the extCeA, but not NAc, of leptin-deficient animals. Furthermore, transgenic mice expressing the trans-synaptic tracer wheat germ agglutinin in LepRb neurons reveal the innervation of CeA cocaine- and amphetamine-regulated transcript (CART) neurons by LepRb neurons, and leptin suppresses the increased CeA CART expression of leptin-deficient animals. Thus, LepRb VTA neurons represent a subclass of VTA DA neurons that specifically innervates and controls the extCeA; we hypothesize that these neurons primarily modulate CeA-directed behaviors.


Transoral protrusion of a peritoneal catheter: a case report and literature review.
Transoral protrusion of a peritoneal catheter is rare. Only two cases have been reported in the English literature. We now report the case of a 5-year-old girl who presented with a catheter that had been inserted 4 years previously, protruding from her mouth. Signs of cerebrospinal fluid infection or peritonitis were absent. The peritoneal catheter was cut and externalized at the chest. The distal portion, which had perforated the stomach wall, was removed using endoscopic procedures. After 3 weeks of antibiotic treatment, a new shunt was inserted. Analysis of 50 cases of bowel perforation extracted from the English literature showed that among the suggested factors such as age, gender, nutritional state, history of abdominal surgery, and length and type of the catheter, age was the only predisposing factor. In the treatment of bowel perforation by a peritoneal catheter, suspected shunt infection should be managed properly and contamination be minimized during removal of the peritoneal catheter.


Antiproliferative effects of artemisinin on human breast cancer cells requires the downregulated expression of the E2F1 transcription factor and loss of E2F1-target cell cycle genes.
Artemisinin, a sesquiterpene phytolactone derived from Artemisia annua, is a potent antimalarial compound with promising anticancer properties, although the mechanism of its anticancer signaling is not well understood. Artemisinin inhibited proliferation and induced a strong G1 cell cycle arrest of cultured MCF7 cells, an estrogen-responsive human breast cancer cell line that represents an early-stage cancer phenotype, and effectively inhibited the in-vivo growth of MCF7 cell-derived tumors from xenografts in athymic nude mice. Artemisinin also induced a growth arrest of tumorigenic human breast cancer cell lines with preneoplastic and late stage cancer phenotypes, but failed to arrest the growth of a nontumorigenic human mammary cell line. Concurrent with the cell cycle arrest of MCF7 cells, artemisinin selectively downregulated the transcript and protein levels of the CDK2 and CDK4 cyclin-dependent kinases, cyclin E, cyclin D1, and the E2F1 transcription factor. Analysis of CDK2 promoter-luciferase reporter constructs showed that the artemisinin ablation of CDK2 gene expression was accounted for by the loss of CDK2 promoter activity. Chromatin immunoprecipitation revealed that artemisinin inhibited E2F1 interactions with the endogenous MCF7 cell CDK2 and cyclin E promoters. Moreover, constitutive expression of exogenous E2F1 prevented the artemisinin-induced cell cycle arrest and downregulation of CDK2 and cyclin E gene expression. Taken together, our results demonstrate that the artemisinin disruption of E2F1 transcription factor expression mediates the cell cycle arrest of human breast cancer cells and represents a critical transcriptional pathway by which artemisinin controls human reproductive cancer cell growth.


A Cross-Cultural Study on Attachment and Adjustment Difficulties in Adolescence: The Mediating Role of Self-Control in Italy, Spain, China, and Poland.
From a socio-ecological perspective, individuals are influenced by the interplay of individual, relational, and societal factors operating as a broader system. Thereby, to support youth adjustment during the critical adolescence period, the interplay between these factors should be investigated. This study aimed to investigate cross-cultural differences in adolescents' maternal and paternal attachment, adolescents' adjustment difficulties and self-control, and in their association. N = 1000 adolescents (mean (M) age = 16.94, SD = 0.48; 45.90% males) from China, Italy, Spain, and Poland participated by completing self-report measures. Results showed cross-country similarities and differences among the considered variables and their associative pattern. Moreover, conditional process analysis evaluating the association between maternal vs. paternal attachment and adjustment difficulties, mediated by self-control, and moderated by country, was performed. Maternal attachment directly, and indirectly through greater self-control, influenced adjustment difficulties in all four countries. This association was stronger among Spaniards. Paternal attachment influenced directly, and indirectly through self-control, on adolescents' adjustment difficulties only in Italy, Spain, and Poland, and was stronger among Polish adolescents. For Chinese adolescents, paternal attachment solely associated with adjustment difficulties when mediated by self-control. Thus, results highlighted both similarities and differences across countries in the interplay between maternal vs. paternal attachment and self-control on adolescents' adjustment difficulties. Implications are discussed.


A New Technique for the Surgical Treatment of Atlantoaxial Instability: C1 Lateral Mass and C2-3 Transfacet Screwing.
Atlantoaxial instability is a special entity that may be caused by many disorders such as trauma, tumor, arthritis, congenital malformation and infection. Atlantoaxial fixation is needed to provide stability, prevent neurological deficits and correct deformity. The objective of this study is to introduce an alternative technique for the treatment of atlantoaxial instability in patients who have vertebral artery anomaly, anomalous C2 or osteoporosis. C1-2-3 fixation was performed in a 50-years-old, male patient with atlantoaxial instability due to os odontoideum. C1 lateral masses identified and screw placement was performed. C2 facet joints were identified bilaterally. Superior margin of junction of pedicle and the lamina was used as the entry point and 3.5x22 mm screws were inserted from C2 facet joint to the C3 facet joint in mediolateral and craniocaudal direction under fluoroscopic guidance with caution. The posterior fixation screws are interconnected with two rods. Finally, autologous grafts were placed posterolaterally to encourage the fusion. Patient's complaints relieved after the surgery. C1-C2 instability wasn't seen in the postoperative radiological examinations. In the surgical treatment of C1-2 instability, our technique could help to reduce the possibility of vertebral artery injury in patients who have a vertebral artery course anomaly or when it is difficult to place C2 pedicle screws due to anomalous C2 pedicles and osteoporosis. High fusion rate could be achived with this technique due to passing through the four cortical surfaces. No wire or allograft was required. Thus, the instrumentation cost could be reduced.


Cementing techniques for hip resurfacing arthroplasty: development of a laboratory model.
Hip resurfacing is extremely technique-sensitive, yet scientific investigations into cementing techniques are lacking. In this study, we tested open-cell, reticulated, carbon-foam materials in comparison with paired human femoral heads to validate a laboratory cementing model for resurfacing arthroplasty. Paired human femoral heads prepared for resurfacing were compared with thirty and sixty-pore-per-inch fat-filled foam specimens. Two different cementing techniques were analyzed: manual application of high-viscosity cement, and half component-filling with low-viscosity cement. Real-time measurements were made of cement pressure and temperature. Cement penetration areas and depths were quantified. We found no significant differences between the human femoral heads and the fat-filled thirty-pore-per-inch foam models in all measured variables (pressures at the top, chamfer and outer wall, temperature at the 5-mm and 15-mm subsurface). There was no significant difference in the cement penetration of the human femoral heads and the fat-filled thirty-pore-per-inch foam models. There were a number of significant differences between the human femoral heads and the sixty-pore-per-inch foam models with use of the low-viscosity cement technique. The differences between the cementing techniques were greater than those between the three materials for most of the measurements. Fat-filling (to emulate bone marrow) of lower-density carbon foam more closely simulates the cement penetration resistance and thermal properties of human femoral heads than does the denser (unfilled) material. This model is sensitive to differences in cementing technique.


Intravitreal anti-VEGF therapy blocks inflammatory cell infiltration and re-entry into the circulation in retinal angiogenesis.
Anti-VEGF-A antibody (Ab) (e.g., bevacizumab, ranibizumab) is widely used as a treatment against retinal angiogenesis and edema. The purpose of this study was to evaluate whether intravitreal anti-VEGF Ab injection modulates inflammatory cells in retinal angiogenesis. To investigate whether intravitreal bevacizumab injections affect the number of inflammatory cells in proliferative diabetic retinopathy (PDR) membranes in patients, immunohistochemical staining with CD45 Ab (pan-leukocyte marker) was performed using the surgically obtained membranes in pars plana vitrectomy with or without pretreatment with bevacizumab. To check whether anti-VEGF-A Ab affects leukocytes going in and out of blood vessels during retinal angiogenesis, the authors performed their novel leukocyte transmigration assay and CD45 immunostaining in a mouse model of oxygen-induced retinopathy (OIR). The authors' new imaging approach revealed that intravitreal injection of anti-VEGF-A Ab blocks leukocyte infiltration as well as angiogenesis. The Ab injection inhibited leukocyte transmigration before affecting the angiogenenic area. CD45 staining showed no significant difference in the leukocyte number in the angiogenic retina or the human PDR membranes between the anti-VEGF-A Ab injected group and the control group. Furthermore, VEGF-A inhibition also affected leukocytes going out from the retina. Intravitreal injection of anti-VEGF-A Ab could inhibit leukocyte trafficking in the retina, suggesting that anti-VEGF-A therapy could serve as a treatment in retinal inflammation.


[Efficacy and safety of cefozopran (CZOP) monotherapy and combination therapy with CZOP and amikacin (AMK) for infections accompanying hematological diseases].
We evaluated efficacy and safety of monotherapy with CZOP (1-2 g x 2/day) and combination therapy with CZOP (1-2 g x 2/day) and AMK (200 mg x 2/day) for infections in patients with hematological diseases. Efficacy was evaluated in 71 patients of monotherapy group and 70 patients of combination therapy group. Underlying diseases were mostly leukemia and lymphoma. Infections included sepsis, suspected sepsis, pneumonia and so on. Efficacy in CZOP monotherapy was excellent in 21 patients (31.3%), good in 23 patients (34.3%), fair in 5 patients (7.5%) and the efficacy rate was 65.7%. On the other hand, in combination therapy, each was 14 patients (21.2%), 23 patients (34.8%), 12 patients (18.2%) and the efficacy rate was 56.1%. Side effects such as eruption were noted in 2 patients. Abnormal laboratory findings were noted in 9 patients. All side effects as well as abnormal laboratory findings were minimal. It was concluded that CZOP monotherapy was effective in the treatment of various infections accompanying hematological diseases.


The Effects of Implementation Quality of a School-Based Social and Emotional Well-Being Program on Students' Outcomes.
School-based social and emotional learning (SEL) programs can be effective in producing positive outcomes for students. However, when the implementation quality is poor, these programs often lose their effectiveness and fail to produce the expected positive outcomes. The current study evaluates a school-based SEL program for 15-18-year-olds in Ireland by determining the impact of implementation quality on program outcomes. The study also examines the effects on outcomes of different implementation dimensions including Dosage, Adherence, Quality of Delivery, and Participant Responsiveness. Employing a cluster randomized controlled trial design, this study collected student outcome data (n = 675) from 32 disadvantaged schools across three time points (pre-, post-, 12-month follow-up) and compared these data across three treatment groups (high-implementation, low-implementation, and control). Linear mixed models (LMM) were used to determine the relationships between the implementation data and student outcome data longitudinally. The findings revealed that the positive effects of the program were only observed with the high-, but not the low-implementation group (reduced suppression of emotions (p = 0.049); reduced avoidance coping (p = 0.006); increased social support coping (p = 0.009); reduced levels of stress (p = 0.035) and depressive symptoms (p = 0.025). The comparison of implementation dimensions revealed that only Quality of Delivery had a significant effect on all of the tested outcomes. This study highlights the importance of high-quality implementation in producing positive outcomes and supports the need to evaluate implementation using multiple dimensions.


Nonlinear spectroscopy.
Although nonlinear spectroscopy evolved slowly in its initial stages, it is now becoming an important new branch of atomic and molecular spectroscopy. A variety of phenomena are being observed for the first time, either in steady state or in transient behavior. In a sense, the methods of microwave and nuclear magnetic resonance spectroscopy are now being reproduced in the optical region, and with the same precision and detail.


Immunochemical characterization and radioimmunometric detection of molecules shed by human ovarian cancer.
Monoclonal antibodies (MAbs) OC125, MOv2 and MOv8 recognize the CA125, CAMOv2 and CAMOv8 epitopes, respectively, which are associated with human ovarian carcinomas and are shed by these tumors. The biochemical analysis of the recognized antigens and epitopes has been performed to investigate the possibility of exploiting their expression, if any, on the same molecules. Cross-competition experiments clearly indicated that the 3 epitopes are distinct. Biochemical analysis was performed on a cyst fluid from an ovarian cystadenoma. Heat treatment and periodate oxidation indicated that CAMOv2 and CAMOv8 are saccharidic and suggested that CA125 is a conformational epitope to which both saccharides and the protein backbone could contribute. By gel-filtration chromatography CA125 activity was eluted into 2 peaks of high molecular weight, whereas CAMOv2 and CAMOv8 activities were associated with a single broad peak which included CA125-positive fractions. Isopycnic centrifugation showed that CA125, CAMOv2 and CAMOv8 carrying molecules had the same high density (1.46 g/ml) in the first peak, whereas CA125 molecules had a lower density (1.41 g/ml) in the second peak. Double-determinant immunoradiometric assays, carried out using different combinations of the MAbs, indicated that in the cyst fluid molecules expressing both CAMOv2 and CAMOv8 could be detected, whereas CA125 was carried by different molecules. CAMOv2 and CA125 could however be expressed on the same molecule in 2 out of 9 ascitic fluids from ovarian carcinoma patients. Taken together, these data indicate that CA125 and CAMOv2-CAMOv8 were only occasionally expressed on the same molecules. Therefore, the use of the CA125-CAMOv2 combination could not increase the sensitivity achievable by using each respective simultaneous immunoradiometric assay.


Expression of transforming growth factors alpha and beta-1 messenger RNA in the bovine mammary gland during different stages of development and lactation.
It is now widely accepted that the mammary gland is under interconnected hormonal and local control. Growth factors are involved in the intercellular signalling of the gland. Our aim was the detection of transforming growth factors alpha (TGF-alpha) and beta 1 (TGF-beta 1) messenger RNA during mammogenesis, lactogenesis, galactopoiesis and involution in the bovine mammary gland (total n = 27). During these stages the RNA was assessed by means of ribonuclease protection assay and reverse transcription-polymerase chain reaction (RT-PCR). To study possible influences of oestrogen, progesterone and prolactin on growth factor expression, mammary RNA was obtained from heifers after induced mammogenesis and lactogenesis, with and without additional prolactin inhibition (total n = 20). Very low levels of TGF-alpha and TGF-beta 1 expression were detected during lactogenesis and galactopoiesis, increasing levels during mammogenesis of primigravid heifers, and highest levels during mammogenesis of virgin heifers and during involution. TGF-alpha expression after induced mammogenesis was greater than after induced lactogenesis or physiological mammogenesis during pregnancy. Furthermore, TGF-alpha mRNA contents increased after prolactin inhibition. TGF-beta 1 expression was almost equal after induced mammogenesis and lactogenesis, but greater than during the physiological mammogenesis and lactogenesis. In conclusion, it can be assumed that growth promoting TGF-alpha and growth inhibiting TGF-beta 1 are co-expressed in the bovine mammary gland. Higher mRNA contents of both factors during mammogenesis and involution may indicate autocrine or paracrine functions for these growth factors during proliferation and reorganisation of the mammary tissue.


Cloning, characterization and expression of complete coding sequences of three IgE binding Malassezia furfur allergens, Mal f 7, Mal f 8 and Mal f 9.
Malassezia furfur, formerly known as Pityrosporum orbiculare or P. ovale, is a yeast that colonizes human skin. Normally, this yeast is nonpathogenic but under the influence of predisposing factors it may induce IgE reactivity in patients with atopic dermatitis. Approximately 40-65% of atopic dermatitis patients have IgE antibodies and/or skin reactivity against M. furfur and a higher T-cell response against this yeast is found in atopic dermatitis patients than in healthy individuals. By making a cDNA library displayed on a phage surface, we previously cloned five different IgE-binding proteins, Mal f 5, Mal f 6, MF 7, MF 8 and MF 9, from this yeast. The cDNAs encoding these allergens were sequenced and expressed in Escherichia coli. The sequences of MF 7, MF 8 and MF 9 were not full length (missing their 5'-ends) giving only partial gene products. To obtain complete cDNA sequences, we performed RACE-PCR to amplify the 5'-ends of each cDNA. These PCR products were sequenced and analyzed. The coding sequences of Mal f 7, Mal f 8 and Mal f 9 encode proteins with ORFs of 141 (16.2 kDa), 179 (19.2 kDa) and 126 (14.0 kDa) amino-acid residues, respectively. None of the putative proteins showed significant sequence homology with other known proteins in the searched database. The proteins encoded by the complete cDNA sequences were expressed in E. coli as recombinant proteins. Immunoblotting and radioallergosorbant test data showed that all of the expressed recombinant proteins have the ability to bind serum IgE from atopic dermatitis patients and furthermore, the M. furfur extract could specifically inhibit this IgE binding.


Trade-offs between cold protection and air pollution-induced mortality of China's heating policy.
The winter heating policy in northern China was designed to safeguard households from the harsh subfreezing temperatures. However, it has inadvertently resulted in seasonal spikes in air pollution levels because of the reliance on coal as an energy source. While the loss of life years attributable to mortality from air pollution caused by winter heating has been estimated, the beneficial effect of protection from cold temperatures has not been assessed, primarily due to a lack of individual-level data linking these variables. Our study aims to address this research gap. We provide individual-level empirical evidence that quantifies the impact of protection from cold temperatures and air pollution on mortality, studying 5,334 older adults living around the Huai River during the period between 2000 and 2018. Our adjusted Cox-proportional hazard models show that winter heating was associated with a 22% lower mortality rate (95% CI: 16-28%). Individuals residing in areas without access to winter heating are subjected to heightened mortality risks during periods of cold temperatures. The protective effect is offset by a 27.8% rise attributed to elevated PM2.5 levels. Our results imply that the equilibrium between the effects of these two factors is achieved when PM2.5 concentration exceeds 24.3 µg/m3 (95% CI: 18.4-30.2). Our research suggests that while the existing winter heating policy significantly mitigates winter mortality by lessening the detrimental effects of cold temperatures, future air pollution reduction could provide further health benefits.


α-Linolenic acid attenuates doxorubicin-induced cardiotoxicity in rats through suppression of oxidative stress and apoptosis.
Doxorubicin (DOX), a widely used anti-tumor drug, can give rise to severe cardiotoxicity by oxidative stress and cell apoptosis, which restricts its clinical application. α-Linolenic acid (ALA) has been shown to serve as a potent cardioprotective agent. The aim of this study was to explore the protective effects of ALA on DOX-induced cardiotoxicity and the underlying molecular mechanisms for this cardioprotection in rats. Rats were randomly divided into four groups and administrated with normal saline, ALA (500 µg/kg), DOX (2.5 mg/kg), or ALA (500 µg/kg) plus DOX (2.5 mg/kg) for 17 days. The results showed that DOX treatment significantly increased the heart weight/body weight, liver wet weight (WW)/dry weight (DW), lung WW/DW, serum levels of brain natriuretic peptide, creatine kinase-MB, lactate dehydrogenase, and cardiac troponin I, myocardial necrosis and myocardial malondialdehyde content, and induced the mRNA expression of Nrf2 in the nucleus, cleaved caspase-3, Bax, and superoxide dismutase (SOD). In addition, DOX led to a significant decrease in left ventricular end-diastolic volume, stroke volume, ejection fraction, SOD, glutathione-peroxidase, catalase, as well as the expression of Kelch-like ECH-associated protein 1 (Keap1) in the cytoplasm, phospho-AKT, phospho-ERK, and Bcl-2. Co-treatment with ALA significantly eliminated these changes induced by DOX except further reduction of Keap1 and elevation of Nrf2 and SOD mRNA. These results showed the cardioprotective effects of ALA on DOX-induced cardiotoxicity in rats. The mechanisms might be associated with the enhancement of antioxidant defense system through activating Keap1/Nrf2 pathway and anti-apoptosis through activating protein kinase B/extracellular signal regulated kinase pathway. Our results suggested a promising future of ALA-based preventions and therapies for myocardial damage after administration of DOX.


Association of ATP-binding cassette transporter A1 gene polymorphisms with plasma lipid variability and coronary heart disease risk.
Our study aimed to investigate the association of ABCA1 polymorphisms with plasma lipid variability and CHD risk in the Chinese Han population. 754 CHD patients and 760 controls were included in this case-control study. Three SNPs (rs363717, rs4149339, and rs4149338) in ABCA1 3'UTR and one nonsynonymous SNP (rs2230808) in ABCA1 exon 35 were selected and genotyped. The analysis of genetic data was performed using the SNPstats program and the SPSS17.0 software. Significant associations were observed between SNP rs363717 and CHD risk under different genetic models before or after Bonferroni corrections (codominant model: OR = 0.70, P = 0.003 for AG vs. AA; dominant model: OR = 0.71, P = 0.003 for GG + AG vs. AA). The nonsynonymous SNP rs2230808 was associated with higher total cholesterol levels (P = 0.047). The GCC haplotype (consisting of alleles of SNPs rs363717, rs4149339, and rs4149338) was associated with a decreased risk of CHD (OR = 0.8, P = 0.027). Three ABCA1 SNPs interacted with high triglyceride levels to increase CHD risk (P values of interactions were 0.010 for rs363717, 0.010 for rs4149339, and 0.020 for rs4149338, respectively). Our results suggest that ABCA1 polymorphisms influence plasma lipid variability and CHD risk. ABCA1 polymorphisms could also modify the effects of plasma lipids on CHD risk.


Cooperative plasminogen recruitment to the surface of Streptococcus canis via M protein and enolase enhances bacterial survival.
Streptococcus canis is a zoonotic pathogen capable of causing serious invasive diseases in domestic animals and humans. Surface-exposed M proteins and metabolic enzymes have been characterized as major virulence determinants in various streptococcal species. Recently, we have identified SCM, the M-like protein of S. canis, as the major receptor for miniplasminogen localized on the bacterial surface. The present study now characterizes the glycolytic enzyme enolase as an additional surface-exposed plasminogen-binding protein. According to its zoonotic properties, purified S. canis enolase binds to both human and canine plasminogen and facilitates degradation of aggregated fibrin matrices after activation with host-derived urokinase-type plasminogen activator (uPA). Unlike SCM, which binds to the C terminus of human plasminogen, the S. canis enolase interacts N terminally with the first four kringle domains of plasminogen, representing angiostatin. Radioactive binding analyses confirmed cooperative plasminogen recruitment to both surface-exposed enolase and SCM. Furthermore, despite the lack of surface protease activity via SpeB in S. canis, SCM is released and reassociated homophilically to surface-anchored SCM and heterophilically to surface-bound plasminogen. In addition to plasminogen-mediated antiphagocytic activity, reassociation of SCM to the bacterial surface significantly enhanced bacterial survival in phagocytosis analyses using human neutrophils. Streptococcal infections are a major issue in medical microbiology due to the increasing spread of antibiotic resistances and the limited availability of efficient vaccines. Surface-exposed glycolytic enzymes and M proteins have been characterized as major virulence factors mediating pathogen-host interaction. Since streptococcal infection mechanisms exert a subset of multicombinatorial processes, the investigation of synergistic activities mediated via different virulence factors has become a high priority. Our data clearly demonstrate that plasminogen recruitment to the Streptococcus canis surface via SCM and enolase in combination with SCM reassociation enhances bacterial survival by protecting against phagocytic killing. These data propose a new cooperative mechanism for prevention of phagocytic killing based on the synergistic activity of homophilic and heterophilic SCM binding in the presence of human plasminogen.


Can excreted thiocyanate be used to detect cyanide exposure in live reef fish?
Cyanide fishing, where a solution of sodium or potassium cyanide is used to stun reef fish for easy capture for the marine aquarium and live fish food trades, continues to be pervasive despite being illegal in many countries and destructive to coral reef ecosystems. Currently, there is no easy, reliable and universally accepted method to detect if a fish has been exposed to cyanide during the capture process. A promising non-invasive technique for detecting thiocyanate ions, the metabolic byproduct excreted by exposed fish, has been reported in the literature. In an effort to validate this method, four cyanide exposure studies on Amphiprion ocellaris (common clownfish) were carried out over three years. Fish were either exposed to the same (25 ppm) or twice the concentration (50 ppm) as the previsouly published method. Over 100 water samples of fish exposed to cyanide were analyzed by reverse phase HPLC with a C30 column treated with polyethylene glycol and UV detector operating at 220 nm. No thiocyanate was detected beyond the analytical standards and positive controls prepared in seawater. As an alternate means of detecting thiocyanate, water samples and thiocyanate standards from these exposures were derivatized with monobromobimane (MBB) for LC-MS/MS analysis. Thiocyanate was detected in standards with concentrations as low as 0.6 μg/L and quantified to 1 μg/L, but thiocyanate could not be detected in any of the water samples from fish exposed to cyanide with this method either, confirming the HPLC results. Further, we calculated both the mass balance of thiocyanate and the resultant plausible dosage of cyanide from the data reported in the previously published method. These calculations, along with the known lethal dosage of cyanide, further suggests that the detection of thiocyanate in aquarium water is not a viable method for assessing fish exposure to cyanide.


The effect of peer education model on sexual myths of Turkish university students: An interventional study.
The research was conducted to determine the effects of peer education model on sexual myths of Turkish university students. This is an interventional study. Peer educators were asked to perform educational activities for the intervention group. The participants in the control group were not subjected to any interventions. Data collection tools were simultaneously administered to all students in the intervention (n = 646) and control groups ( n = 532). The Peer Education Program Pertaining to Sexual Myths applied to the interventon group by peer educators is effective in reducing sexual myths and increasing sexual knowledge level. Peer education model should be integrated into the health education programs by nurses to improve the sexual health and reproductive health of young people.


Influenza A virus alters pneumococcal nasal colonization and middle ear infection independently of phase variation.
Streptococcus pneumoniae (pneumococcus) is both a widespread nasal colonizer and a leading cause of otitis media, one of the most common diseases of childhood. Pneumococcal phase variation influences both colonization and disease and thus has been linked to the bacteria's transition from colonizer to otopathogen. Further contributing to this transition, coinfection with influenza A virus has been strongly associated epidemiologically with the dissemination of pneumococci from the nasopharynx to the middle ear. Using a mouse infection model, we demonstrated that coinfection with influenza virus and pneumococci enhanced both colonization and inflammatory responses within the nasopharynx and middle ear chamber. Coinfection studies were also performed using pneumococcal populations enriched for opaque or transparent phase variants. As shown previously, opaque variants were less able to colonize the nasopharynx. In vitro, this phase also demonstrated diminished biofilm viability and epithelial adherence. However, coinfection with influenza virus ameliorated this colonization defect in vivo. Further, viral coinfection ultimately induced a similar magnitude of middle ear infection by both phase variants. These data indicate that despite inherent differences in colonization, the influenza A virus exacerbation of experimental middle ear infection is independent of the pneumococcal phase. These findings provide new insights into the synergistic link between pneumococcus and influenza virus in the context of otitis media.


Clinicopathologic findings in the Bannayan-Riley-Ruvalcaba syndrome.
The term Bannayan-Riley-Ruvalcaba syndrome has been proposed to reflect the clinical overlap of 3 conditions previously described as separate entities, each inherited in an autosomal dominant fashion. They are the Riley-Smith, Bannayan-Zonana, and Ruvalcaba-Myhre-Smith syndromes. We studied 2 kindreds with the Bannayan-Riley-Ruvalcaba syndrome. Characteristic cutaneous findings included multiple subcutaneous lipomas and vascular malformations, lentigines of the penis and vulva, verrucae, and acanthosis nigricans. Macrocephaly with normal ventricular size, mental retardation, central nervous system vascular malformations, intestinal polyposis, skeletal abnormalities, and thyroid tumors were the most common systemic featues. A striking clinical finding in 1 patient was widespread verrucous changes of both lips that histologically showed epidermal hyperplasia with papillomatosis and hyperkeratosis. Biopsy specimens of facial papules demonstrated the histological features of both syringomas and trichilemmomas. Lentiginous hyperplasia of the epidermis with increased pigment in the basal layer and a slight increase in the number of melanocytes were seen in biopsy specimens of the penile lentigines. The histologic findings of both the facial lesions and the pigmented macules of the penis in the Bannayan-Riley-Ruvalcaba syndrome have not, to our knowledge, been reported previously. The similarities between the Bannayan-Riley-Ruvalcaba syndrome and Cowden disease raise the possibility of a common genetic pathogenesis for these 2 diseases.


The effects of brain lateralization on motor control and adaptation.
Lateralization of mechanisms mediating functions such as language and perception is widely accepted as a fundamental feature of neural organization. Recent research has revealed that a similar organization exists for the control of motor actions, in that each brain hemisphere contributes unique control mechanisms to the movements of each arm. The authors review present research that addresses the nature of the control mechanisms that are lateralized to each hemisphere and how they impact motor adaptation and learning. In general, the studies suggest an enhanced role for the left hemisphere during adaptation, and the learning of new sequences and skills. The authors suggest that this specialization emerges from a left hemisphere specialization for predictive control-the ability to effectively plan and coordinate motor actions, possibly by optimizing certain cost functions. In contrast, right hemisphere circuits appear to be important for updating ongoing actions and stopping at a goal position, through modulation of sensorimotor stabilization mechanisms such as reflexes. The authors also propose that each brain hemisphere contributes its mechanism to the control of both arms. They also discuss the potential advantages of such a lateralized control system.


Serodiagnostics for Severe Acute Respiratory Syndrome-Related Coronavirus 2 : A Narrative Review.
Accurate serologic tests to detect host antibodies to severe acute respiratory syndrome-related coronavirus 2 (SARS-CoV-2) will be critical for the public health response to the coronavirus disease 2019 pandemic. Many use cases are envisaged, including complementing molecular methods for diagnosis of active disease and estimating immunity for individuals. At the population level, carefully designed seroepidemiologic studies will aid in the characterization of transmission dynamics and refinement of disease burden estimates and will provide insight into the kinetics of humoral immunity. Yet, despite an explosion in the number and availability of serologic assays to test for antibodies against SARS-CoV-2, most have undergone minimal external validation to date. This hinders assay selection and implementation, as well as interpretation of study results. In addition, critical knowledge gaps remain regarding serologic correlates of protection from infection or disease, and the degree to which these assays cross-react with antibodies against related coronaviruses. This article discusses key use cases for SARS-CoV-2 antibody detection tests and their application to serologic studies, reviews currently available assays, highlights key areas of ongoing research, and proposes potential strategies for test implementation.


Understanding decision-making processes for sugar consumption in adolescence.
The mechanisms by which adolescents make food choices are not clear. The interaction and combination of the many social and psychological factors must be considered when examining adolescents' decision-making processes for sound food choices. The aim of this investigation is to examine one specific food choice, namely, the use of sucrose in hot drinks. One hundred and eighty-seven adolescents in their 16th year completed a questionnaire on the consumption of sugar using the method developed by AJZEN & FISHBEIN in their 'Theory of Reasoned Action'. The group was randomly divided into two groups so that decision-making processes with respect to two behavioural intentions-adding sugar to tea and coffee and excluding it-could be examined. The findings suggest that the immediate pleasurable taste of sugar outweighed and deferred the recognition of dangers associated with its consumption. Past dental health experiences, behaviours and education together with the role of parental figures acted as important influences. An awareness of these factors should assist dental health professionals to highlight the importance of sound food choices when negotiating dental health goals with adolescents.


Neurological injury during cardiopulmonary bypass in the rat.
Cerebral injury is a well-known complication of cardiac surgery. Investigations of both injury mechanisms and neuroprotective strategies have partially been limited by the lack of an adequate preclinical model of small animal cardiopulmonary bypass (CPB). We sought to determine if neurological injury could be demonstrated in a recovery model of complete CPB in the rat. Rats (n = 5) underwent 45 min of normothermic CPB followed by 24 h of recovery. Compared to sham-operated rats (n = 5), the CPB group showed a worse neurological outcome score (median, 25-75th percentile) compared to controls (5, 4-7 vs 9, 8-9, p = 0.016). This rat model of CPB may allow for the study of CPB-associated neurological injury.


Reconstruction of axial tomographic high resolution data from confocal fluorescence microscopy: a method for improving 3D FISH images.
Fluorescent confocal laser scanning microscopy allows an improved imaging of microscopic objects in three dimensions. However, the resolution along the axial direction is three times worse than the resolution in lateral directions. A method to overcome this axial limitation is tilting the object under the microscope, in a way that the direction of the optical axis points into different directions relative to the sample. A new technique for a simultaneous reconstruction from a number of such axial tomographic confocal data sets was developed and used for high resolution reconstruction of 3D-data both from experimental and virtual microscopic data sets. The reconstructed images have a highly improved 3D resolution, which is comparable to the lateral resolution of a single deconvolved data set. Axial tomographic imaging in combination with simultaneous data reconstruction also opens the possibility for a more precise quantification of 3D data. The color images of this publication can be accessed from http://www.esacp.org/acp/2000/20-1/heintzmann.++ +htm. At this web address an interactive 3D viewer is additionally provided for browsing the 3D data. This java applet displays three orthogonal slices of the data set which are dynamically updated by user mouse clicks or keystrokes.


[Chiral capillary gas chromatography for the separation of the enantiomers of 4-chloromethyl-2,2-dimethyl-1,3-dioxolane].
Chiral compounds play an important role in the pharmaceutical industry owing to their unique biological activities. The enantiomers must be separated because they can exhibit different pharmacological activities. Thus, the development of chiral separation methods is essential to determine the purity of enantiomers. 4-Chloromethyl-2,2-dimethyl-1,3-dioxolane is an important chiral pharmaceutical intermediate. In this context, a method based on chiral capillary gas chromatography was established for the separation and determination of the enantiomers of 4-chloromethyl-2,2-dimethyl-1,3-dioxolane. The separation of (R)- and (S)-4-chloromethyl-2,2-dimethyl-1,3-dioxolane was initially investigated using two conventional stationary-phase capillary columns: SH-I-5Sil MS and SH-WAX. The stationary phase of SH-I-5Sil MS consisted of 5% phenyl and 95% polymethylsiloxane, whereas the stationary phase of SH-WAX consisted of 100% crosslinked polyethylene glycol. Neither of the columns exhibited chiral selectivity, so they both were unable to separate the enantiomers of 4-chloromethyl-2,2-dimethyl-1,3-dioxolane. Subsequently, the separation of (R)- and (S)-4-chloromethyl-2,2-dimethyl-1,3-dioxolane was investigated using four chiral columns: Rt-bDEXm, Rt-bDEXsm, Rt-bDEXse, and InertCap CHIRAMIX. Among the chiral columns, Rt-bDEXse, which used a stationary phase composed of 2,3-di-O-ethyl-6-O-tert-butyl dimethylsilyl β-cyclodextrin added to 14% cyanopropyl phenyl and 86% dimethyl polysiloxane, achieved the best separation of (R)- and (S)-4-chloromethyl-2,2-dimethyl-1,3-dioxolane. Thus, this column was selected as the analytical column for further method optimization. Detection was performed using a hydrogen flame ionization detector. The effects of various gas chromatographic parameters, such as linear velocity, initial column temperature, column heating rate, and solvent type, on the separation of (R)- and (S)-4-chloromethyl-2,2-dimethyl-1,3-dioxolane were investigated. The optimal chromatographic conditions included a linear velocity of 70 cm/s, an initial column temperature of 70 ℃, and a column heating rate of 2.0 ℃/min. The final column oven temperature was 150 ℃. Methanol, ethanol, ethyl acetate, n-hexane, dichloromethane, and dimethyl sulfoxide were selected as solvents. The results showed that dimethyl sulfoxide interfered with the peaks of the target compounds, whereas the other solvents had no significant effect on the peak shape and separation of (R)- and (S)-4-chloromethyl-2,2-dimethyl-1,3-dioxolane. Methanol was finally selected as the solvent in this study. Further experiments revealed that (R)- and (S)-4-chloromethyl-2,2-dimethyl-1,3-dioxolane could be rapidly separated within 10 min, with a resolution greater than 1.5. A good linear relationship was observed in the range of 0.5-50.0 mg/L, with a linear correlation coefficient greater than 0.998. The limits of detection for (R)- and (S)-4-chloromethyl-2,2-dimethyl-1,3-dioxolane were 0.07 and 0.08 mg/L, respectively, and the corresponding limits of quantification were 0.22 and 0.25 mg/L, respectively. Spiked recovery tests were performed at three spiked levels of 0.5, 2.0, and 10.0 mg/L using methanol as the blank to determine the accuracy of the proposed method. The recoveries for (R)- and (S)-4-chloromethyl-2,2-dimethyl-1,3-dioxolane were 94.0%-99.1% and 96.0%-98.8%, respectively, with relative standard deviations (RSDs) of 1.26%-4.87% and 1.51%-4.46%, respectively. The established method is efficient and reliable; thus, it can serve as a reference for the separation of the enantiomers of 4-chloromethyl-2,2-dimethyl-1,3-dioxolane. It can also potentially be applied to evaluate the enantiomeric purity of other chiral compounds in the pharmaceutical industry and produce chiral drugs and other related compounds.


Swarm Robotic Behaviors and Current Applications.
In swarm robotics multiple robots collectively solve problems by forming advantageous structures and behaviors similar to the ones observed in natural systems, such as swarms of bees, birds, or fish. However, the step to industrial applications has not yet been made successfully. Literature is light on real-world swarm applications that apply actual swarm algorithms. Typically, only parts of swarm algorithms are used which we refer to as basic swarm behaviors. In this paper we collect and categorize these behaviors into spatial organization, navigation, decision making, and miscellaneous. This taxonomy is then applied to categorize a number of existing swarm robotic applications from research and industrial domains. Along with the classification, we give a comprehensive overview of research platforms that can be used for testing and evaluating swarm behavior, systems that are already on the market, and projects that target a specific market. Results from this survey show that swarm robotic applications are still rare today. Many industrial projects still rely on centralized control, and even though a solution with multiple robots is employed, the principal idea of swarm robotics of distributed decision making is neglected. We identified mainly following reasons: First of all, swarm behavior emerging from local interactions is hard to predict and a proof of its eligibility for applications in an industrial context is difficult to provide. Second, current communication architectures often do not match requirements for swarm communication, which often leads to a system with a centralized communication infrastructure. Finally, testing swarms for real industrial applications is an issue, since deployment in a productive environment is typically too risky and simulations of a target system may not be sufficiently accurate. In contrast, the research platforms present a means for transforming swarm robotics solutions from theory to prototype industrial systems.


Validity of the Mood Disorder Questionnaire in a Brazilian psychiatric population.
OBJECTIVE: Bipolar spectrum disorders are prevalent and frequently underdiagnosed and undertreated. This report describes the development and validation of the Brazilian version of the Mood Disorder Questionnaire, a screening instrument for bipolar spectrum disorders, in an adult psychiatric population. METHOD: A total of 114 consecutive patients attending an outpatient psychiatric clinic completed the Brazilian version of the Mood Disorder Questionnaire. A research psychiatrist, blind to the Mood Disorder Questionnaire results, interviewed patients by means of the mood module of the Structured Clinical Interview for DSM-IV ('gold standard'). RESULTS: The internal consistency of the Brazilian Mood Disorder Questionnaire, evaluated with Cronbach's alpha coefficient was 0.76 (95% CI; 0.69-0.92). Principal component analysis with varimax rotation indicated an 'irritability-racing thoughts' factor and 'energized-activity' factor, which explained 39.1% of variance. On the basis of the SCID, 69 (60.5%) individuals received a diagnosis of bipolar disorders. A Brazilian Mood Disorder Questionnaire screening score of 8 or more items yielded sensitivity of 0.91 (95% CI; 0.85-0.98), specificity of 0.70 (95% CI; 0.62-0.75), a positive predictive value of 0.82 (95% CI; 0.75-0.88) and a negative predictive value of 0.84 (95% CI; 0.77-0.90). CONCLUSION: The present data demonstrate that the Brazilian Mood Disorder Questionnaire is a valid instrument for the screening of bipolar disorders. The instrument needs to be validated in other settings (e.g., in general practice).


The effects of non-invasive brain stimulation on disorder of consciousness in patients with brain injury: A systematic review and meta-analysis of randomized controlled trial.
Disorders of consciousness (DOC) result from neural system injury and manifest as changes in arousal or awareness. This systematic review and meta-analysis aimed to investigate the therapeutic effects of non-invasive brain stimulation (NIBS) techniques, such as transcranial magnetic stimulation (TMS) and transcranial direct current stimulation (tDCS), on consciousness dysfunction in patients with brain disorders. Literature was systematically searched in Medline, Embase, Cochrane database, Web of Science, EBSCO from inception to May 2023. Only randomized controlled trial with NIBS as an intervention and participants with DOC were included. A total of 7 studies with 313 participants were included for meta-analysis. Compared with sham- or placebo-stimulation, NIBS can improve the Coma Recovery Scale-Revised scores significantly (mean difference [MD] = 1.96, 95 % confidence interval [CI] = [1.49; 2.43], P <.0001). NIBS has a significant positive effect in enhancing the symptoms of DOC. Nevertheless, it is imperative for further investigations comprising high-quality research designs and larger sample sizes in order to comprehensively elucidate the effects of NIBS techniques on diverse targets of stimulation within the population of individuals suffering from DOC.


L-phenylalanine ammonia-lyase from French bean (Phaseolus vulgaris L.). Characterization and differential expression of antigenic multiple Mr forms.
L-Phenylalanine ammonia-lyase (PAL; EC 184.108.40.206) purified from suspension-cultured cells of French bean (Phaseolus vulgaris) has been further characterized. A number of techniques, including use of an antiserum and affinity probes, have established that all the antigenic polypeptides represent polymorphic Mr forms of the enzyme. These peptides include an apparently higher-Mr (83,000) form which shows different kinetics of induction from the Mr-77000 forms that have been extensively characterized previously. The larger subunit appeared to be PAL by the following criteria: (a) binding to specific affinity and antibody matrices; (b) peptide mapping; (c) active-site labelling; and (d) amino acid composition. The increased Mr of the larger subunit was not completely attributable to glycosylation, although some sugar residues were detected in this Mr-83000 form but not in the other Mr forms. Mr-83000 subunits were also immunoprecipitated from translations in vitro of mRNA from cells that had been stressed for a long period. They were also detected in leaf tissues that were not yet undergoing an extensive wound response. This form of the enzyme may be constitutive and involved in the low-level accumulation of phenolics in most cell types. By contrast, the Mr-77000 forms of PAL were rapidly induced during elicitor action, wounding or cytokinin-induced xylogenesis as a key regulatory enzyme involved in the synthesis of phenolics under stress conditions or during differentiation.


Professionalism in contemporary medicine: if it is an important academic issue, then surely it is a "hot" issue as well.
Professionalism has been a hot topic in medical education and in medicine in general. Professionalism in medicine embodies the relationship between medicine and society as it forms the basis of patient-physician relationships and the mutual expectations patients and physicians have of each other. Education on professionalism in medicine and professionalism in medical education are two important liasions. Increasing efforts have focused on fostering professionalism in medical education. Medical faculties have long taught the theoretical and technical aspects of medicine, but teaching professionalism in medicine and healing qualities has been a recent trend. The concept of professionalism has evolved over time by a process of exploration and reflection. It seems that medical professionalism has been changing from paternalism to partnership with patients and mutuality, from tribalism to collegiality, and from self-sacrifice to shared responsibility. There is still no consensus on how professionalism in medicine should be defined as and about the best methods for teaching medical professionalism. The aim of this "landscape" review is to promote the complete integration of a culture of professionalism into the educational and research body, including staff, faculty, residents and students.


Dietary supplementation with L-arginine limits cell proliferation in the remnant glomerulus.
One effect of L-arginine is to increase nitric oxide (NO) production by endothelial cells. NO directly reduces endothelin-1 production by endothelial cells and also inhibits platelet-derived growth factor (PDGF) induced cell proliferation. Since subtotal renal ablation is associated with an early phase of cell proliferation in the glomerulus that precedes injury, we examined the effect of dietary supplementation with L-arginine on glomerular cell proliferation and expression of the cytokine endothelin-1 (ET-1). A first group of renal-ablated rats was untreated. A second group of renal-ablated rats received L-arginine (1%) in the drinking water. Two weeks after subtotal ablation renal cortical tissue was snap frozen for immunohistochemical analysis for proliferating cell nuclear antigen (PCNA) expression and ET-1. Protein and total RNA was extracted from sieved glomeruli. mRNA levels were quantitated by co-amplification RT-PCR utilizing specific 5' and 3' primers for rat ET-1 and beta-actin. L-arginine reduced the number of PCNA positive nuclei in remnant glomeruli, and Western blot Analysis of glomerular proteins also showed that L-arginine reduced PCNA expression. Glomerular ET-1 mRNA levels and protein immunostaining declined in the rats receiving L-arginine. We conclude that dietary supplementation with L-arginine reduces early cell proliferation in the remnant glomerulus, an effect that may be mediated, in part, by a decrease in ET-1 production.


Targeting Phosphatases and Kinases: How to Checkmate Cancer.
Metastatic disease represents the major cause of death in oncologic patients worldwide. Accumulating evidence have highlighted the relevance of a small population of cancer cells, named cancer stem cells (CSCs), in the resistance to therapies, as well as cancer recurrence and metastasis. Standard anti-cancer treatments are not always conclusively curative, posing an urgent need to discover new targets for an effective therapy. Kinases and phosphatases are implicated in many cellular processes, such as proliferation, differentiation and oncogenic transformation. These proteins are crucial regulators of intracellular signaling pathways mediating multiple cellular activities. Therefore, alterations in kinases and phosphatases functionality is a hallmark of cancer. Notwithstanding the role of kinases and phosphatases in cancer has been widely investigated, their aberrant activation in the compartment of CSCs is nowadays being explored as new potential Achille's heel to strike. Here, we provide a comprehensive overview of the major protein kinases and phosphatases pathways by which CSCs can evade normal physiological constraints on survival, growth, and invasion. Moreover, we discuss the potential of inhibitors of these proteins in counteracting CSCs expansion during cancer development and progression.


The measurement of biological age.
One of the objectives of gerontological research is to achieve, reproducibly and at will, a verifiable discrepancy between the chronological and biological age of organisms. To accomplish this, the experimenter must be in a position to measure biological age independently. In theory, this can be done in the three ways: by actuarial analysis of large populations, assessment of overall morbidity, or observation of chronic degenerative changes that can be actually measured or graded according to a scale. Of these three approaches, only the last appears to be promising in experimental research. However, not all progressive degenerative changes represent practically useful parameters of biological age. Criteria for their evaluation are presented, and their theoretical prerequisites as well as concrete applications discussed. In a more general way, one has to be aware that biological age is a statistical entity. It cannot be directly observed but only inferred from quantifiable epiphenomena, and is, as such, not measurable like temperature or weight.


Development of a Direct Pulp-capping Model for the Evaluation of Pulpal Wound Healing and Reparative Dentin Formation in Mice.
Dental pulp is a vital organ of a tooth fully protected by enamel and dentin. When the pulp is exposed due to cariogenic or iatrogenic injuries, it is often capped with biocompatible materials in order to expedite pulpal wound healing. The ultimate goal is to regenerate reparative dentin, a physical barrier that functions as a "biological seal" and protects the underlying pulp tissue. Although this direct pulp-capping procedure has long been used in dentistry, the underlying molecular mechanism of pulpal wound healing and reparative dentin formation is still poorly understood. To induce reparative dentin, pulp capping has been performed experimentally in large animals, but less so in mice, presumably due to their small sizes and the ensuing technical difficulties. Here, we present a detailed, step-by-step method of performing a pulp-capping procedure in mice, including the preparation of a Class-I-like cavity, the placement of pulp-capping materials, and the restoration procedure using dental composite. Our pulp-capping mouse model will be instrumental in investigating the fundamental molecular mechanisms of pulpal wound healing in the context of reparative dentin in vivo by enabling the use of transgenic or knockout mice that are widely available in the research community.


Feasibility study of goal setting discussions between older adults and volunteers facilitated by an eHealth application: development of the Health TAPESTRY approach.
In keeping with the changing needs of the Canadian population, primary care systems need to become more person-focused in providing quality care to older adults. As part of Health TAPESTRY, a complex intervention to strengthen primary care for older adults, a goal setting exercise was developed and tested in an initial feasibility study, intended to foster collaboration between patients and providers. Participants-clinic clients-were recruited from the McMaster Family Health Team in Hamilton, Ontario. Five participants took part in the goal setting feasibility study phase I, which tested the functionality of a technology-enabled goal setting exercise between older adults and volunteers. Based on observations and feedback from volunteers, interprofessional team members, and older adults, the exercise was refined to include a guided survey and goals report. The goal setting survey is a list of probing questions designed based on SMART (specific, measurable, attainable, relevant, timely) goal setting strategies and goal attainment scaling (GAS). This was used in phase II, carried out with 16 participants, where the feasibility of goal setting and goal attainment with support from volunteers and interprofessional teams was tested. Volunteers carried out the goal setting survey via a tablet computer, a report of client goals was generated and sent to interprofessional teams, and client goals were discussed during clinic huddles. At 6 months of follow-up, clients self-evaluated their progress using GAS. The goal setting exercise in phase I took an average of 24:45 (SD 11:42) minutes and yielded a diverse set of life and health goals. Goals identified by older adults were primarily focused on the maintenance of a certain level of activity or health state. Phase I work resulted in important changes to the goal setting process (e.g., asking about goal setting later in conversation, changing wording of questions) and development of a summary report of goals sent to the interprofessional team. In phase II, 44 goals were set by 16 participants during an average 7:23 (SD 4:26) minute discussion. Of these goals, 43.9% were characterized as health goals while 63.4% were characterized as life goals. Under the umbrella of Life goals, productivity featured most prominently at 22.9% of all goals. Goal attainment was not measured in phase I. In phase II, clients had an average weighted goal attainment score of 51.5. Considering client preferences for one goal over another, 68.8% of clients, on average, at least partially achieved the goals they had set. Goal setting as part of the Health TAPESTRY approach was feasible and provided interprofessional teams with client narratives that helped improve care management for older adults. The overall intervention-including the refined goal setting component-is being scaled and evaluated in a pragmatic randomized controlled trial.


Paradoxical glomerular filtration of carbon nanotubes.
The molecular weight cutoff for glomerular filtration is thought to be 30-50 kDa. Here we report rapid and efficient filtration of molecules 10-20 times that mass and a model for the mechanism of this filtration. We conducted multimodal imaging studies in mice to investigate renal clearance of a single-walled carbon nanotube (SWCNT) construct covalently appended with ligands allowing simultaneous dynamic positron emission tomography, near-infrared fluorescence imaging, and microscopy. These SWCNTs have a length distribution ranging from 100 to 500 nm. The average length was determined to be 200-300 nm, which would yield a functionalized construct with a molecular weight of approximately 350-500 kDa. The construct was rapidly (t(1/2) approximately 6 min) renally cleared intact by glomerular filtration, with partial tubular reabsorption and transient translocation into the proximal tubular cell nuclei. Directional absorption was confirmed in vitro using polarized renal cells. Active secretion via transporters was not involved. Mathematical modeling of the rotational diffusivity showed the tendency of flow to orient SWCNTs of this size to allow clearance via the glomerular pores. Surprisingly, these results raise questions about the rules for renal filtration, given that these large molecules (with aspect ratios ranging from 100:1 to 500:1) were cleared similarly to small molecules. SWCNTs and other novel nanomaterials are being actively investigated for potential biomedical applications, and these observations-that high aspect ratio as well as large molecular size have an impact on glomerular filtration-will allow the design of novel nanoscale-based therapeutics with unusual pharmacologic characteristics.


Glucagon-like peptides in the CNS of man: localization and possible functional importance.
Glucagon-like peptides in the central nervous system (CNS) of man with the immunofluorescence and the peroxidase-antiperoxidase method were studied. It has been found that there are immunoreactive glucagon cells present in the hypothalamus hippocampus, amygdaloid nuclei cerebral cortex, and medulla oblongata region. The findings confirm earlier investigations from this laboratory performed along this line.


Dental caries prevalence and CPITN of 12-year-old rural schoolchildren in Transkei.
The study investigated the prevalence and pattern of caries with particular reference to tooth and surface type and the CPITN of 12-y-old rural schoolchildren in Engcobo, Transkei. 349 schoolchildren, with a 4:6 male:female ratio were examined. The fluoride content of the water varied from 0-0.5 p.p.m. The results indicate that caries levels are low--47 per cent of the sample was caries-free. Both the median DMFT and DMFS was 1.0 (with a mean 1.7 and 2.8). The D component comprised 89 per cent, the M-10 and F-1 per cent of the total DMFT. Amongst boys, caries was distributed almost equally between the maxillary (112) and mandibular (114) arches whereas for girls more teeth were affected in the mandibular arch. Molar teeth in boys and girls accounted for 90 per cent of all teeth affected with the first molars accounting for 50 per cent and the second molars 40 per cent. In the maxillary and mandibular arch for the total group, a greater number of first molars were affected than the second molars. For girls in both the maxilla and mandible, the second molars were affected more frequently than the first molars. Overall the occlusal surfaces were affected most frequently followed by the buccal, distal, lingual and mesial. Gingival bleeding and calculus were prevalent in most sextants. Less than 6 per cent of the total subjects had no periodontal disease. Calculus was found in over 70 per cent of the children. The vast majority of the sample (94 per cent) needed oral hygiene instruction.


Acute results, complications, and effect of lesion characteristics on outcome with the solid-state, pulsed-wave, mid-infrared laser angioplasty system: final multicenter registry report. Holmium:YAG Laser Multicenter Investigators.
The solid-state, mid-infrared holmium:YAG laser (2.1 microm wavelength) is a relatively new percutaneous device that has recently been evaluated in a multicenter study. Because of its unique wavelength and photoacoustic effects on atherosclerotic plaques, this laser may be useful in treatment of symptomatic patients with coronary artery disease. This study sought to evaluate the safety and efficacy of mid-infrared laser angioplasty in the treatment of coronary artery lesions. Laser angioplasty was performed on 2,038 atherosclerotic lesions in 1,862 consecutive patients with a mean age of 61 +/- 11 years. Clinical indications included unstable angina (69%), stable angina (20%), acute infarction (6%), and positive exercise test (5%). Complex lesion morphology included eccentricity (62%), thrombus (30%), total occlusion (27%), long lesions (14%), and saphenous vein grafts (11%). This laser catheter alone successfully reduced stenosis (>20%) in 87% of lesions. With adjunct balloon angioplasty, 93% procedural success was achieved. The presence of thrombus within the target lesion was a predictor of procedural success (OR = 2.0 [95% confidence interval 2.0, 4.0], P = .04). Bifurcation lesions (OR = 0.5 [95% confidence interval 0.2, 1.0], P = .05) and severe tortuosity of the treated vessel (OR = 0.4 [95% confidence interval 0.2, 0.9], P = .02) were identified as significant predictors of decreased laser success. Calcium within the lesion was associated with reduced procedural success (OR = 0.57 [95% confidence interval 0.34, 0.97], P = .03), and calcified lesions required significantly more energy pulses than noncalcified lesions (119 +/- 91 pulses vs. 101 +/- 86 pulses, respectively, P = .0002). Complications included in-hospital bypass surgery 2.5%, Q-wave myocardial infarction 1.2%, and death 0.8%. Perforation occurred in 2.2% of patients; major dissection in 5.8% of patients, and spasm in 12% of patients. No predictor of major complications was identified. Six-month angiographic restenosis was documented in 54% of patients, and clinical restenosis occurred in 34% of patients. Mid-infrared laser has a safety profile similar to that of other debulking devices. This laser may be useful in select patients presenting with acute ischemic syndromes associated with intracoronary thrombus; however, like other coronary lasers, it is limited by the need for adjunctive balloon angioplasty and/or stenting to achieve adequate final luminal diameter. No beneficial effects on reducing 6-month restenosis rates were observed.


The teleost retina as a model for developmental and regeneration biology.
Retinal development in teleosts can broadly be divided into three epochs. The first is the specification of cellular domains in the larval forebrain that give rise to the retinal primordia and undergo early morphogenetic movements. The second is the neurogenic events within the retina proper-proliferation, cell fate determination, and pattern formation-that establish neuronal identities and form retinal laminae and cellular mosaics. The third, which is unique to teleosts and occurs in the functioning eye, is stretching of the retina and persistent neurogenesis that allows the growth of the retina to keep pace with the growth of the eye and other tissues. The first two events are rapid, complete by about 3 days postfertilization in the zebrafish embryo. The third is life-long and accounts for the bulk of retinal growth and the vast majority of adult retinal neurons. In addition, but clearly related to the retina's developmental history, lesions that kill retinal neurons elicit robust neuronal regeneration that originates from cells intrinsic to the retina. This paper reviews recent studies of retinal development in teleosts, focusing on those that shed light on the genetic and molecular regulation of retinal specification and morphogenesis in the embryo, retinal neurogenesis in larvae and adults, and injury-induced neuronal regeneration.


Should we cure hepatitis C virus in patients with hepatocellular carcinoma while treating cancer?
Direct acting antivirals stabilize or improve liver function in the majority of patients with hepatitis C virus cirrhosis. Hepatic decompensation is the main driver of death of patients with early, successfully treated hepatocellular carcinoma superimposed to cirrhosis. Treatment with direct acting antivirals could improve the prognosis of these subjects, independently from the subsequent course of hepatocellular carcinoma, if the efficacy in obtaining viral clearance is as high as in patients without a history of hepatocellular carcinoma, and if the risk of hepatocellular carcinoma recurrence is unaffected. When dealing with hepatocellular carcinoma patients, direct acting antivirals can be indicated in two different settings: (a) subjects in which hepatocellular carcinoma has been already successfully treated ("cured" hepatocellular carcinoma), or (b) subjects whose hepatocellular carcinoma is still untreated or untreatable ("active" hepatocellular carcinoma). Although there are abundant data on "cured" hepatocellular carcinoma, evidence supporting treatment decisions in patients with "active" hepatocellular carcinoma is at best scarce and controversial, since these patients as well as patients with hepatocellular carcinoma listed for liver transplantation are usually excluded from treatment.


Locked-in state with bilateral internal capsule infarcts.
A posttraumatic patient was tetraplegic and mute (locked-in), but he retained consciousness and communicated by eye movements. CT showed bilateral internal capsule (IC) infarcts involving the posterior limb and caudal part of the genu, sparing the ventral brainstem. This is the first report of the locked-in state caused by infarcts in both IC.