Rare "Inverted" Verrucous Carcinoma (Carcinoma Cuniculatum) of the Sacrogluteal Region: Case Report and Literature Review.
A 49-year-old woman with a past history of several infundibular cysts in the head and neck region presented with a 6-month history of a nonhealing perianal abscess on a background of 13 years of chronic sacral-buttock abscesses and discharging sinuses as part of hidradenitis suppurativa. After 2 surgical procedures and inadequate healing, a wide local excision was performed. The surgical specimen revealed an extensive, infiltrating, cystic and deeply penetrating, dermal and subcutaneous neoplasm with multiple fistulous tracts extending to the skin surface. The histopathology was consistent with carcinoma cuniculatum, a rare, slow growing, verucciform variant of squamous cell carcinoma. An entirely subcutaneous verrucous carcinoma of the sacrogluteal region is exceptionally rare, and this represents the first documentation of such a case in a female.


Methodological considerations for a psychosocial illness survey in general practice.
A survey of psychosocial morbidity in general practice was undertaken in a rural West Australian community. Twenty-two general practitioners collected information on 487 patients in a period of 5 weeks. The information comprised the socio-demographic characteristics of the patients, their illness profile and patterns of treatment and referral. The methodological issues considered for such a survey related to the selection of participating doctors, the identification of appropriate cases, the acceptability of a diagnostic classification and the definition of the population at risk. The methodology assessment established the plausibility of the findings compared to other studies, and hence the adequacy of the methodology used. The patterns of distribution of the psychosocial illness in relation to sex, age, diagnostic category, chronicity, the level of reporting of morbidity and treatment and referral were consistent with the findings of other studies.


Analyzing sentiments and themes on cannabis in Canada using 2018 to 2020 Twitter data.
The Canadian Cannabis Act came into effect on October 17, 2018, which allowed Canadian adults to consume cannabis for non-medical purposes (Government of Canada, Cannabis regulations (SOR/2018-144). Cannabis Act, (2018a); Parliament of Canada, C-45: an Act respecting cannabis and to amend the Controlled Drugs and Substances Act, the Criminal Code and other Acts, 2018). With this major policy change, it is unknown how the attitude of the public changed and how information on cannabis changed. Social media platforms, including Twitter, are significant venues for studying emerging patterns in social issues such as cannabis legalization. This study aimed to examine sentiments, themes and contents of cannabis-related tweets by suppliers (both licensed and unlicensed) and general tweets in Canada. To our knowledge, this is the first analysis that mixes sentiment analysis and thematic analysis of Canadians' cannabis-related Twitter data. A sample of Canadian cannabis-related tweets was collected from January 2018 to August 2020 through the Twitter Application Programming Interface (API). Using a standard access token and the Twitter Standard Search API, tweets were extracted based on Twitter handles to capture the content of both licensed and unlicensed cannabis retailers in Canada, as well as relevant cannabis-related keywords to capture public content. We conducted sentiment and positive polarity analyses, and content analysis to identify attitudes and themes around cannabis use in Canada. This study gathered and analyzed a total of 44,970 tweets in the sentiment analysis and a total of 1035 tweets in the thematic analysis. Descriptive analysis showed that monthly tweets peaked prior to legalization in October 2018 and again during the initial wave of the COVID-19 pandemic in February and March 2020. The data showed an overall positive sentiment polarity with a high of + 0.24 in April 2019 and a low of + 0.14 in March 2020. Thematic analysis revealed the themes: (i) education/information, (ii) uses of cannabis, (iii) cannabis products including packing, quality, price, types, and sources, (iv) cannabis policies including regulations and public safety, (v) access, (vi) social issues include gender and stigma, and (vii) COVID-19 impact. This study combined the power of big data collection and analysis with manual coding and analysis methods to extract rich content from large data using social media communications on issues related to cannabis in Canada. The findings of this study may inform policies on advertising cannabis products and highlighted some patterns related to education, access, and safety that deserve further investigation.


Common genetic polymorphisms in moyamoya and atherosclerotic disease in Europeans.
Moyamoya is the most common cerebrovascular disease in children in Japan. The disease's etiology is still widely unknown. Several publications describe histopathological changes in the walls of affected vessels similar to those seen in atherosclerosis. In this study, we analyzed the DNA of European patients with Moyamoya disease for single nucleotide polymorphisms associated with atherosclerotic changes. We genotyped 17 SNPs in or adjacent to 11 genes (ELN, LIMK1, CDKN2A/B, CXCL12, Pseudogene ENSG00000197218, PSRC1, MTHFD1L, SMAD3, MIA3, PDGF-B, TIMP2) comparing 40 DNA samples of Moyamoya disease patients to 68 healthy controls from central Europe. The mean age of onset of Moyamoya disease (MMD)-related symptoms was 15.4 years of age. Genotyping was performed by sequencing the SNP containing genetic regions with custom-made primers. We found strong association of one SNP (rs599839 [A/G], OR = 2.17, 95% CI = 1.17, 4.05; p = 0.01) with the risk allele G located in the 3' UTR region of the PSRC-1 gene. Three further SNPs (rs8326, rs34208922, rs501120) in or adjacent to the genes ELN and CXCL12 showed tendencies towards risk alleles with p values between 0.1 and 0.2 but did not reach statistical significance in our cohort. Our results indicate a possible parallel of common processes in the genesis of Moyamoya disease and atherosclerotic disease. Further analyses in larger European cohorts and replication in patients of different ethnicity may lead to possible early detection of patients at risk for developing MMD and subsequently to future causative therapies.


Chromosome-Scale Genome Assemblies of Aphids Reveal Extensively Rearranged Autosomes and Long-Term Conservation of the X Chromosome.
Chromosome rearrangements are arguably the most dramatic type of mutations, often leading to rapid evolution and speciation. However, chromosome dynamics have only been studied at the sequence level in a small number of model systems. In insects, Diptera and Lepidoptera have conserved genome structure at the scale of whole chromosomes or chromosome arms. Whether this reflects the diversity of insect genome evolution is questionable given that many species exhibit rapid karyotype evolution. Here, we investigate chromosome evolution in aphids-an important group of hemipteran plant pests-using newly generated chromosome-scale genome assemblies of the green peach aphid (Myzus persicae) and the pea aphid (Acyrthosiphon pisum), and a previously published assembly of the corn-leaf aphid (Rhopalosiphum maidis). We find that aphid autosomes have undergone dramatic reorganization over the last 30 My, to the extent that chromosome homology cannot be determined between aphids from the tribes Macrosiphini (Myzus persicae and Acyrthosiphon pisum) and Aphidini (Rhopalosiphum maidis). In contrast, gene content of the aphid sex (X) chromosome remained unchanged despite rapid sequence evolution, low gene expression, and high transposable element load. To test whether rapid evolution of genome structure is a hallmark of Hemiptera, we compared our aphid assemblies with chromosome-scale assemblies of two blood-feeding Hemiptera (Rhodnius prolixus and Triatoma rubrofasciata). Despite being more diverged, the blood-feeding hemipterans have conserved synteny. The exceptional rate of structural evolution of aphid autosomes renders them an important emerging model system for studying the role of large-scale genome rearrangements in evolution.


For protection from HIV-1 infection, more might not be better: a systematic analysis of HIV Gag epitopes of two alleles associated with different outcomes of HIV-1 infection.
A subset of women in the Pumwani Sex Worker Cohort, established in 1985 in Nairobi, Kenya, remains uninfected despite repeated high-risk exposure (HIV-exposed, seronegative [HESN]) through active sex work. This HESN phenotype is associated with several alleles of human leukocyte antigens (HLAs) and specific CD8(+) and CD4(+) T cell responses to HIV-1. The associations of HLA alleles with differential HIV-1 infection are most likely due to their different abilities to present antigen and the different immune responses they induce. The characteristics of epitopes of HLA alleles associated with different outcomes of HIV-1 infection might therefore point to a vital clue for developing an effective vaccine. In this study, we systematically analyzed HIV-1 clade A and D Gag CD8(+) T cell epitopes of two HLA class I alleles associated with different outcomes of HIV-1 infection. Binding affinity and off-rates of the identified epitopes were determined. Gamma interferon (IFN-γ) enzyme-linked immunospot (ELISpot) assays with patient peripheral blood mononuclear cells (PBMCs) validated the epitopes. Epitope-specific CD8(+) T cells were further phenotyped for memory markers with tetramer staining. Our study showed that the protective allele A*01:01 recognizes only three Gag epitopes. By contrast, B*07:02, the allele associated with susceptibility, binds 30 epitope variants. These two alleles differ most importantly in the spectrum of Gag epitopes they can present and not in affinity, off-rates, the location of the epitopes, or epitope-specific Tem/Tcm frequencies. The binding of more epitopes and strong IFN-gamma ELISpot responses are associated with susceptibility to HIV-1 infection, while more focused antigen recognition of multiple subtypes is protective. Rational vaccine design should take these observations into account.


[On demand analgesia: new concepts for treatment of acute pain].
Intravenous demand analgesia is introduced as a possible way to optimize the treatment of acute pain. Within certain limits patients are allowed to self-administer small doses of analgesics as often as they need; microprocessors are used to control safe operation and to document individual drug consumption. Literature is reviewed with respect to previous experience with patient activated analgesia, and new data are presented from a pilot study with 11 analgesic drugs administered on demand during the early postoperative period. Demand analgesia is described not only as an effective therapeutic concept but also as an interesting tool for pain research (influences on pain perception, comparison of analgesic potencies etc.). It is strongly suggested from the results that treatment of acute pain ought to be more individualized than it is now in routine practice.


Chronic procrastination among Turkish adults: exploring decisional, avoidant, and arousal styles.
The authors examined the prevalence of chronic procrastination (decisional, avoidant, and arousal styles) as functions of demographic variables among 354 Turkish adults (148 men, 206 women; M age = 38.7 years, SD = 8.26 years). Prevalence analyses showed that among Turkish participants, 17.5% were indecisive procrastinators, 13.8% were avoidant procrastinators, and 14.7% were arousal procrastinators. Results did not yield significant differences for gender or age on any forms of procrastination, which is consistent with other international samples. However, significant differences emerged depending on the number of children such that Turkish adults who had more than 3 children claimed to be more indecisive than they claimed to be arousal or avoidant procrastinators. Respondents with less than a graduate degree reported higher rates of indecision than did respondents with at least a graduate degree.


[Computed tomographic diagnosis and differential diagnosis of leiomyosarcoma of the inferior vena cava].
The computer tomographic appearances of the rare leiomyosarcoma of the inferior vena cava are described and illustrated by one case. CT is particularly informative and the differential diagnosis from caval thrombosis and extension of tumour thrombus into the cava is discussed.


Hybridogenesis in the Water Frogs from Western Russian Territory: Intrapopulation Variation in Genome Elimination.
Hybridogenesis in an interspecific hybrid frog is a coupling mechanism in the gametogenic cell line that eliminates the genome of one parental species with endoduplication of the remaining genome of the other parental species. It has been intensively investigated in the edible frog Pelophylax kl. esculentus (RL), a natural hybrid between the marsh frog P. ridibundus (RR) and the pool frog P. lessonae (LL). However, the genetic mechanisms involved remain unclear. Here, we investigated the water frogs in the western Russian territory. In three of the four populations, we genetically identified 16 RL frogs living sympatrically with the parental LL species, or with both parental species. In addition, two populations contained genome introgression with another species, P. bedriagae (BB) (a close relative of RR). In the gonads of 13 RL frogs, the L genome was eliminated, producing gametes of R (or R combined with the B genome). In sharp contrast, one RL male eliminated the L or R genome, producing both R and L sperm. We detected a variation in genome elimination within a population. Based on the genetic backgrounds of RL frogs, we hypothesize that the introgression of the B genome resulted in the change in choosing a genome to be eliminated.


Physical properties of collective motion in suspensions of bacteria.
A suspension of microswimmers, the simplest realization of active matter, exhibits novel material properties: the emergence of collective motion, reduction in viscosity, increase in diffusivity, and extraction of useful energy. Bacterial dynamics in dilute suspensions suggest that hydrodynamic interactions and collisions between the swimmers lead to collective motion at higher concentrations. On the example of aerobic bacteria Bacillus subtilis, we report on spatial and temporal correlation functions measurements of collective state for various swimming speeds and concentrations. The experiments produced a puzzling result: while the energy injection rate is proportional to the swimming speed and concentration, the correlation length remains practically constant upon small speeds where random tumbling of bacteria dominates. It highlights two fundamental mechanisms: hydrodynamic interactions and collisions; for both of these mechanisms, the change of the swimming speed or concentration alters an overall time scale.


Neuroprotective effect of Lycium barbarum on retina of Royal College of Surgeons (RCS) rats: a preliminary study.
Hereditary retinal dystrophy usually leads to blindness. Using Royal College of Surgeons (RCS) rats as a hereditary retinal dystrophy model, we investigated the possible neuroprotective effects of the aqueous extract of dried Lycium barbarum (LBA). Sixty postnatal RCS rats were selected and randomly divided into a control group (CG, thirty rats) and an experimental group (EG). Ten days after birth, EG rats were treated by 1 mg/kg of LBA per day, and CG rats were normally fed. These rats were killed at postnatal day (P) 25, P35 and P50, and retinal tissue was prepared for analysis. Photoreceptor cells were assessed by hematoxylin and eosin (HE) staining, TUNEL detection and Caspase-2 protein expression. We found that in rats at P25, the outer nuclear layer (ONL) of EG was thicker and more photoreceptor cells survived. Meanwhile, the TUNEL expression in EG was obviously reduced compared with CG. The Caspase-2 positive cells were found in the ganglion cell layer and inner nuclear layer in both CG and EG at 25-50 postnatal days, but the expression in EG rats was significantly lower than in CG at P25. The results demonstrated that LBA might have a neuroprotective role on the retinal tissue of RCS rats at the early stage by protecting photoreceptors and inhibiting apoptosis involving Caspase-2 protein.


Early surgery and neurodevelopmental outcomes of children born extremely preterm.
To (1) compare the neurodevelopmental outcomes at 8 years of age of children born extremely preterm (EP) who underwent surgical procedures during the course of their initial hospital admission with those who did not and (2) compare the outcomes across eras, from 1991 to 2005. Prospective observational cohort studies conducted over three different eras (1991-1992, 1997 and 2005). Surviving EP children, who required surgical intervention during the primary hospitalisation, were assessed for general intelligence (IQ) and neurosensory status at 8 years of age. Major neurosensory disability comprised any of moderate/severe cerebral palsy, IQ less than -2 SD relative to term controls, blindness or deafness. Overall, 29% (161/546) of survivors had surgery during the newborn period, with similar rates in each era. Follow-up rates at 8 years were high (91%; 499/546), and 17% (86/499) of survivors assessed had a major neurosensory disability. Rates of major neurosensory disability were substantially higher in the surgical group (33%; 52/158) compared with those who did not have surgery (10%; 34/341) (OR 4.28, 95% CI 2.61 to 7.03). Rates of disability in the surgical group did not improve over time. After adjustment for relevant confounders, no specific surgical procedure was associated with increased risk of disability. Major neurosensory disability at 8 years was higher in children born EP who underwent surgery during their initial hospital admission compared with those who did not. The rates of major neurosensory disability in the surgical cohort are not improving over time.


Resonance Raman studies of Co-O2 and O-O stretching vibrations in oxy-cobalt hemes.
Strong evidence suggests that the stretching vibration of the bound oxygen can be perturbed by an accidentally degenerate porphyrin ring mode, resulting in two split frequencies. In the Co(II)(TpivPP) (pyridine) (18)O(2) complex, we demonstrate that the nu((18)O-(18)O) mode, after being shifted from its nu((16)O-(16)O) value at 1,156 cm(-1), undergoes a resonance interaction with the 1,080 cm(-1) porphyrin mode, giving rise to two lines at 1,067 and 1,089 cm(-1). In the O(2) complex of Co(II) mesoporphyrin IX-substituted sperm whale myoglobin, we observed a dramatic intensity increase at 1,132 cm(-1) upon (16)O(2) --> (18)O(2) substitution, which is due to the reappearance of the 1,132-cm(-1) porphyrin mode after the removal of resonance conditions. A decrease in O(2) binding affinity, caused by the proximal base tension, corresponds to an increase in the Co-O(2) stretching frequency. The nu(Co-O(2)) at 527 cm(-1) for the low affinity Co(II)(TpivPP)(1,2-Me(2)Im) O(2) complex is 11 cm(-1) higher than the 516-cm(-1) value for the high affinity complex (with N-MeIm replacing 1,2-Me(2)Im). However, in the corresponding iron complexes the reverse behavior is observed, i.e., the nu(Fe-O(2)) decreases for the (1,2-Me(2)Im) complex. There is a 24-cm(-1) difference in the Co-O(2) stretching frequencies between Co(II)(TpivPP)(N-MeIm)O(2) (at 516 cm(-1)) and oxy meso CoMb (at 540 cm(-1)), suggesting a protein induced distortion of the Co-O-O linkage. However, the values for nu(Fe-O(2)) are nearly identical between Fe(II)(TpivPP)(N-MeIm)O(2) (at 571 cm(-1)) and oxy Mb (at 573 cm(-1)), indicating that O(2) binds to myoglobin in the same manner as in the sterically unhindered "picket fence" complex. Evidence is presented that suggests the presence of two dioxygen stretching frequencies due to two different conformers in each of the N-MeIm and 1,2-Me(2)Im complex of oxy Co(II)(TpivPP).


Intraoperative collection of autologous platelet-rich plasma from the cardiopulmonary bypass circuit upon initiation of extracorporeal circulation.
The aim of this study is to evaluate the possibility of the autologous platelet-rich plasma (PRP) collection from the cardiopulmonary bypass (CPB) circuit and to evaluate its effect on the aggregative function. For seventy-two patients undergoing cardiac surgery with CPB, an autologous PRP was prepared using the Haemonetics Component Collection System® by drawing blood from the CPB circuit immediately after CPB was established. The blood samples were taken at three points for examination, A: beginning of surgery, B: immediately after heparin reversal with protamine following discontinuation of CPB, C: after the collected autologous PRP was returned to the patient. Platelet count and platelet aggregation ability were analyzed. The mean platelet count in autologous PRP was 5.5 (range: 3-14) units. Platelet count decreased by 115.0 (±27.3) × 1000/μl from A to B and increased by 27.3 ± 17.2 (× 1000/μl) from B to C. When platelet aggregation was measured by Adenosine Diphosphate (ADP) 3.0 μM, it decreased by 42.6% ± 12.1% from A to B and increased by 8.7% ± 7.4% from B to C. Autologous PRP can be safely collected by drawing blood from the CPB circuit, platelet count and aggregation ability significantly decreased after CPB including autologous PRP collection. Some improvement was detected in the number of the platelets count and platelet aggregation ability by administrating an autologous PRP even if autologous PRP is collected from CPB circuit. UMI-CTR, UMIN000023776 . Registered 1 October 2016.


Tuning stamp surface energy for soft lithography of polar molecules to fabricate bioactive small-molecule microarrays.
Soft-lithography-based techniques are widely used to fabricate microarrays. Here, the use of microcontact insertion printing is described, a soft-lithography method specifically developed for patterning at the dilute scales necessary for highly selective biorecognition. By carefully tuning the polar surface energy of polymeric stamps, problems associated with patterning hydrophilic tether molecules inserted into hydrophilic host self-assembled monolayers (SAMs) are surmounted. Both prefunctionalized tethers and on-chip functionalization of SAMs patterned by microcontact insertion printing enable the fabrication of small-molecule microarrays. Substrates patterned with the neurotransmitter precursor 5-hydroxytryptophan selectively capture a number of different types of membrane-associated receptor proteins, which are native binding partners evolved to recognize free serotonin. These advances provide new avenues for chemically patterning small molecules and fabricating small molecule microarrays with highly specific molecular recognition capabilities.


Barley and oat cultivars with diverse carbohydrate composition alter ileal and total tract nutrient digestibility and fermentation metabolites in weaned piglets.
An experiment was conducted to evaluate the effects of cereal carbohydrate form (isolated v. cereal matrix) and level, especially mixed-linked β-glucan (hereafter referred to as β-glucan) and starch amylase/amylopectin ratio on nutrient digestibility and fermentation parameters in the intestines of weaned pigs. Four hulless barley cultivars containing varying β-glucan levels (41 to 84 g/kg) were compared with hulled barley, supplemented or not with a β-glucan concentrate (BBG; 270 g/kg β-glucan) and two oat cultivars for digestibility and fermentation metabolites. Seventy-two weaned piglets (BW = 12.8 ± 1.9 kg) were assigned to one of nine diets composed of 815 g/kg cereal, 60 g/kg whey, 90 g/kg soy protein isolate and 35 g/kg minerals. After 15 days, the pigs were killed, and digesta collected from ileum and colon were analyzed for proximate nutrients, short-chain fatty acids (SCFAs), lactic acid (LA) and ammonia. Ileal and total tract digestibility of proximate nutrients and non-starch polysaccharides (NSPs) were determined using HCl-insoluble ash as a marker. Organic matter (OM) ileal digestibility was greater (P < 0.05) for diets based on hulless barley (77% ± 1.1% on average), as compared with hulled barley (64% ± 1.4%) and oat (58% ± 1.5%). Similar trends were found for total tract OM digestibility, varying from 90% ± 0.3% for hulless barley to 67% ± 0.4% for oat, on average. NSP digestibility differed (P < 0.05) within and between cereal types, ranging from 20% (hulled barley plus 163 g/kg BBG or 40 g/kg β-glucan) to 51% (SB94893 hulless barley cultivar with high β-glucan and high amylose ratio) at the ileum and from 44% (hulled barley) to 84% (SB94893 cultivar) at the total tract level. No dietary effect (P > 0.05) was found for SCFA concentration in ileal contents, whereas in colonic contents, SCFA was lower in pigs fed oat (P < 0.001). LA concentration was greater (P < 0.001) in the colon of pigs fed hulless barley than in pigs fed hulled barley and oat. Expressed per kg carbohydrate (NSP + starch) fermented, the ammonia concentration at the colon was lowest for hulled barley diets (supplemented with β-glucan) and the highest for oat diets. In conclusion, the interaction of both form and level of β-glucan impacted nutrient digestibility and fermentation. Hulless barleys with high soluble NSP such as β-glucan and resistant starch yielded, in general higher SCFA and LA and lower ammonia. Hulless barleys may, therefore, have potential for use in feeding strategies designed to improve gut health in pigs.


Neonatal mortality and perinatal risk factors in rural southwestern Nigeria: a community-based prospective study.
Reliable data on births and deaths particularly at the community level are scarce yet they are urgently needed to inform policy and assess the improvements which may have occurred with recent interventions. To determine neonatal mortality rate and identify perinatal risk factors associated with neonatal deaths. In a community based prospective study, baseline data on births and deaths were collected as they occurred in a rural community of Southwest Nigeria from 1993 to 1998. Data on births and deaths were collected for the period. There were 972 live births and 64 infant deaths giving an infant mortality rate of 65.8 per 1000. Neonatal deaths accounted for a half of all infant deaths (32) giving a neonatal mortality rate of 32.9 per 1000. Twelve (37.5%) of neonatal deaths occurred on the first day of life; half of all neonatal deaths occurred within two days of birth, 21(65.6%) occurred during the first seven days of life and only 11 (34.4%) occurred over the last three weeks of the first month. The commonest known cause of death was associated with low birth weight (LBW) which was responsible for eight (25%) of deaths, while sepsis and fever and maternal deaths and failure to thrive were responsible for four (12.5%) and three (9.4%) deaths respectively. Asphyxia accounted for 3(9.4%) deaths; neonatal tetanus, congenital abnormality and diarrhoea were responsible for one (3.1%) death each. Cause of death was unclassified in many early neonatal deaths particularly those which occurred at home. Predictors of neonatal death included LBW, RR of 4.7; delivery outside a health facility, RR of 3.6; lack of attendant at delivery, RR of 5.01; and Traditional Birth Attendant (TBA) delivering the baby, RR of 2.7. Effect of sex of the neonate, mother and fathers ages were not significant at the 5% level in the model. Neonatal deaths contribute significantly to the high infant mortality in this rural community. Services provided by TBAs are not optimal but appear to be better than having no one in attendance at delivery. TBAs therefore need to be trained to identify at risk neonates and refer. Obstetric and public health services have to be available and made more accessible at the grass root level.


Water quality monitoring records for estimating tap water arsenic and nitrate: a validation study.
Tap water may be an important source of exposure to arsenic and nitrate. Obtaining and analyzing samples in the context of large studies of health effects can be expensive. As an alternative, studies might estimate contaminant levels in individual homes by using publicly available water quality monitoring records, either alone or in combination with geographic information systems (GIS). We examined the validity of records-based methods in Washington State, where arsenic and nitrate contamination is prevalent but generally observed at modest levels. Laboratory analysis of samples from 107 homes (median 0.6 microg/L arsenic, median 0.4 mg/L nitrate as nitrogen) served as our "gold standard." Using Spearman's rho we compared these measures to estimates obtained using only the homes' street addresses and recent and/or historical measures from publicly monitored water sources within specified distances (radii) ranging from one half mile to 10 miles. Agreement improved as distance decreased, but the proportion of homes for which we could estimate summary measures also decreased. When including all homes, agreement was 0.05-0.24 for arsenic (8 miles), and 0.31-0.33 for nitrate (6 miles). Focusing on the closest source yielded little improvement. Agreement was greatest among homes with private wells. For homes on a water system, agreement improved considerably if we included only sources serving the relevant system (rho = 0.29 for arsenic, rho = 0.60 for nitrate). Historical water quality databases show some promise for categorizing epidemiologic study participants in terms of relative tap water nitrate levels. Nonetheless, such records-based methods must be used with caution, and their use for arsenic may be limited.


Is specific antibody determination diagnostic for asthma attributable to low-molecular-weight agents?
It is important to understand a medical testís performance characteristics, so that it can be used appropriately. Performance characteristics of tests for antibodies specific to low-molecular-weight (LMW) agents in predicting asthma caused by these agents differ in the study population. In general, currently published data supporting the use of tests to detect specific IgE and IgG to LMW agents in the diagnosis of occupational asthma is limited and inconclusive. However, a few general statements can be made. The most promising results have been achieved for agents such as acid anhydrides and platinum salts, where specific IgE responses appear to play a significant pathogenic role in causing occupational asthma. Results have been less promising for agents such as isocyanates and plicatic acid, for which antibody responses do not appear to underlie the development of asthma in most individuals. In the case of isocyanates, determination of antigen-specific IgG might have some utility as a biomarker of exposure.


Structural analyses of the Group A flavin-dependent monooxygenase PieE reveal a sliding FAD cofactor conformation bridging OUT and IN conformations.
Group A flavin-dependent monooxygenases catalyze the cleavage of the oxygen-oxygen bond of dioxygen, followed by the incorporation of one oxygen atom into the substrate molecule with the aid of NADPH and FAD. These flavoenzymes play an important role in many biological processes, and their most distinct structural feature is the choreographed motions of flavin, which typically adopts two distinct conformations (OUT and IN) to fulfill its function. Notably, these enzymes seem to have evolved a delicate control system to avoid the futile cycle of NADPH oxidation and FAD reduction in the absence of substrate, but the molecular basis of this system remains elusive. Using protein crystallography, size-exclusion chromatography coupled to multi-angle light scattering (SEC-MALS), and small-angle X-ray scattering (SEC-SAXS) and activity assay, we report here a structural and biochemical characterization of PieE, a member of the Group A flavin-dependent monooxygenases involved in the biosynthesis of the antibiotic piericidin A1. This analysis revealed that PieE forms a unique hexamer. Moreover, we found, to the best of our knowledge for the first time, that in addition to the classical OUT and IN conformations, FAD possesses a "sliding" conformation that exists in between the OUT and IN conformations. This observation sheds light on the underlying mechanism of how the signal of substrate binding is transmitted to the FAD-binding site to efficiently initiate NADPH binding and FAD reduction. Our findings bridge a gap currently missing in the orchestrated order of chemical events catalyzed by this important class of enzymes.


Two components of a velvet-like complex control hyphal morphogenesis, conidiophore development, and penicillin biosynthesis in Penicillium chrysogenum.
Penicillium chrysogenum is the industrial producer of the antibiotic penicillin, whose biosynthetic regulation is barely understood. Here, we provide a functional analysis of two major homologues of the velvet complex in P. chrysogenum, which we have named P. chrysogenum velA (PcvelA) and PclaeA. Data from array analysis using a DeltaPcvelA deletion strain indicate a significant role of PcVelA on the expression of biosynthesis and developmental genes, including PclaeA. Northern hybridization and high-performance liquid chromatography quantifications of penicillin titers clearly show that both PcVelA and PcLaeA play a major role in penicillin biosynthesis in a producer strain that underwent several rounds of UV mutagenesis during a strain improvement program. Both regulators are further involved in different developmental processes. While PcvelA deletion leads to light-independent conidial formation, dichotomous branching of hyphae, and pellet formation in shaking cultures, a DeltaPclaeA strain shows a severe impairment in conidiophore formation under both light and dark conditions. Bimolecular fluorescence complementation assays provide evidence for a velvet-like complex in P. chrysogenum, with structurally conserved components that have distinct developmental roles, illustrating the functional plasticity of these regulators in genera other than Aspergillus.


Absolute sphericity measurement.
Several conventional methods for absolute sphericity testing of optical surfaces are known. One method has been used previously for real time interferometry, but a detailed investigation has not been carried out so far. In this work the known conventional methods are reviewed and assessed for suitability in real time interferometry. One method has been applied to phase stepping interferometry and examined. Adjustment peculiarities, experimental results of deviation measurements on normal surfaces, and application of normals are reported. Measuring errors, especially coherent noise, are analyzed and a special subsequent digital spatial filtering technique for diminution of noise is described.


Comparative performance of two polyp detection systems on CT colonography.
The purpose of our study was to evaluate two current automatic polyp detection systems to determine their sensitivity and false-positive rate in patients who have undergone CT colonography and subsequent endoscopy. We evaluated two polyp detection systems--Polyp Enhanced Viewing (PEV) and the Summers computer-aided detection (CAD) system (National Institutes of Health [NIH]) using a unique cohort of CT colonography examinations: 31 examinations with true-positive lesions identified by radiologists and 34 examinations with false-positive lesions incorrectly identified by radiologists. All patients had reference-standard colonoscopy within 7 days of CT. Candidate lesions were compared with the endoscopic reference standard and prospective radiologist interpretation. The sensitivity and false-positive rates were calculated for each system. The NIH system had a higher sensitivity than the PEV tool for polyps > or = 1 cm (22/23, 96%; 78-99%, 95% CI vs 14/23, 61%; 38-81%, 95% CI; p = 0.008, respectively). There was no significant difference in the detection of medium-sized polyps 6-9 mm in size (8/13 vs 6/13, p = 0.68, respectively). The PEV tool had an average of 1.18 false-positive detections per patient, whereas the NIH tool had an average of 5.20 false-positive detections per patient, with the PEV tool having significantly fewer false-positive detections in both patient groups (p < 0.001). One polyp detection system tended to operate with a higher sensitivity, whereas the other tended to operate with a lower false-positive rate. Prospective trials using polyp detection systems as a primary or secondary means of CT colonography interpretation appear warranted.


Irradiation of a primary tumor, unlike surgical removal, enhances angiogenesis suppression at a distal site: potential role of host-tumor interaction.
Changes in distal angiogenesis in response to irradiation of primary tumors are not known. To this end, PC-3, a human prostate carcinoma, and FSA-II, a murine fibrosarcoma, were grown in the gastrocnemius muscles of male nude mice. Distal angiogenesis was measured in gel containing human recombinant basic fibroblast growth factor placed in the cranial windows of these mice. PC-3-bearing mice showed inhibition of distal angiogenesis, as compared with non-tumor-bearing controls. Surgical removal of tumors tended to accelerate distal angiogenesis; in comparison, after irradiation of the PC-3 primary tumor, rates of angiogenesis in the cranial window were retarded. Irradiation of the non-tumor-bearing leg or of non-tumor-bearing animals showed no measurable effect on rate of growth of vessels in the cranial window. Similar results were found with the FSA-II tumors, with slowed distal angiogenesis in tumor-bearing animals and further suppression in animals with irradiated tumors. These results demonstrate that the effect of irradiation of a primary tumor on angiogenesis at a distal site may differ from the effect of surgical removal of the primary tumor. Unlike surgery, irradiation of a tumor may enhance angiogenic suppression at a distal site, and this difference may involve host-tumor interaction.


Hepatopathy following irradiation and chemotherapy for Wilms' tumor.
Two children being treated with combination chemotherapy and irradiation for localized, rightsided Wilms' tumor developed sudden enlargement of the liver with defects on liver scintigram resembling liver metastases. One child also developed pancytopenia. When chemotherapy was temporarily withheld in both children, hepatomegaly and scintigram abnormalities resolved. The planned courses of chemotherapy were subsequently completed without complications. The clinical course in our patients is compared to previously published experiences. Awareness of this complication could prevent the mistaken diagnosis of metastatic disease and emphasizes the care necessary when administering cytotoxic drugs to children receiving irradiation to all or a portion of the liver.


[Down's syndrome risk assessment in Denmark--secondary publication].
In 2004 The Danish National Board of Health introduced a new guideline regarding prenatal screening. All pregnant women are now offered a Down's syndrome risk assessment. The new guideline has had an impact on the number of invasive early prenatal procedures. The number of procedures fell by 50% from 2000 to 2006. 90% of the foetuses with Down's syndrome are detected prenatally. Denmark is one of the first countries in the world in which risk assessment for Down's syndrome has been successfully implemented at a national level.


Low-dimensional learned feature spaces quantify individual and group differences in vocal repertoires.
Increases in the scale and complexity of behavioral data pose an increasing challenge for data analysis. A common strategy involves replacing entire behaviors with small numbers of handpicked, domain-specific features, but this approach suffers from several crucial limitations. For example, handpicked features may miss important dimensions of variability, and correlations among them complicate statistical testing. Here, by contrast, we apply the variational autoencoder (VAE), an unsupervised learning method, to learn features directly from data and quantify the vocal behavior of two model species: the laboratory mouse and the zebra finch. The VAE converges on a parsimonious representation that outperforms handpicked features on a variety of common analysis tasks, enables the measurement of moment-by-moment vocal variability on the timescale of tens of milliseconds in the zebra finch, provides strong evidence that mouse ultrasonic vocalizations do not cluster as is commonly believed, and captures the similarity of tutor and pupil birdsong with qualitatively higher fidelity than previous approaches. In all, we demonstrate the utility of modern unsupervised learning approaches to the quantification of complex and high-dimensional vocal behavior.


Fast Distributed Dynamics of Semantic Networks via Social Media.
We investigate the dynamics of semantic organization using social media, a collective expression of human thought. We propose a novel, time-dependent semantic similarity measure (TSS), based on the social network Twitter. We show that TSS is consistent with static measures of similarity but provides high temporal resolution for the identification of real-world events and induced changes in the distributed structure of semantic relationships across the entire lexicon. Using TSS, we measured the evolution of a concept and its movement along the semantic neighborhood, driven by specific news/events. Finally, we showed that particular events may trigger a temporary reorganization of elements in the semantic network.


Overview of the Pediatric Endoscopy Quality Improvement Network Quality Standards and Indicators for Pediatric Endoscopy: A Joint NASPGHAN/ESPGHAN Guideline.
Pediatric-specific quality standards for endoscopy are needed to define best practices, while measurement of associated indicators is critical to guide quality improvement. The international Pediatric Endoscopy Quality Improvement Network (PEnQuIN) working group was assembled to develop and define quality standards and indicators for pediatric gastrointestinal endoscopic procedures through a rigorous guideline consensus process. The Appraisal of Guidelines for REsearch and Evaluation (AGREE) II instrument guided PEnQuIN members, recruited from 31 centers of various practice types representing 11 countries, in generating and refining proposed quality standards and indicators. Consensus was sought via an iterative online Delphi process, and finalized at an in-person conference. Quality of evidence and strength of recommendations were rated according to the GRADE (Grading of Recommendation Assessment, Development, and Evaluation) approach. Forty-nine quality standards and 47 indicators reached consensus, encompassing pediatric endoscopy facilities, procedures, endoscopists, and the patient experience. The evidence base for PEnQuIN standards and indicators was largely adult-based and observational, and downgraded for indirectness, imprecision, and study limitations to "very low" quality, resulting in "conditional" recommendations for most standards (45/49). The PEnQuIN guideline development process establishes international agreement on clinically meaningful metrics that can be used to promote safety and quality in endoscopic care for children. Through PEnQuIN, pediatric endoscopists and endoscopy services now have a framework for auditing, providing feedback, and ultimately, benchmarking performance. Expansion of evidence and prospective validation of PEnQuIN standards and indicators as predictors of clinically relevant outcomes and high-quality pediatric endoscopic care is now a research priority.


ZnO based heterojunctions and their application in environmental photocatalysis.
As an alternative to TiO2 photocatalysts, ZnO exhibits a large potential for photocatalytic (PC) applications in environmental treatments, such as degradation of wastewater, sterilization of drinking water, and air cleaning. However, the efficiency achieved with ZnO to date is far from that expected for commercialization, due to rapid charge recombination, photo-corrosion as well as poor utilization of solar energy. Fortunately, in recent years, a great number of breakthroughs have been achieved in PC performance (including activity and stability) of micro-/nano- structured ZnO by forming heterojunctions (HJs) with metal nanoparticles (NPs), carbon nanostructures and other semiconductors. In most cases, the improvement of PC performance was ascribed to the better charge separation at the interfaces between ZnO and the other components. Sometimes, the formation of hybrids is also in favor of visible light harvesting. This review summarizes recent advances in the fields of environmental photocatalysis by ZnO based HJs, and especially emphasizes their abilities in degradation of organic pollutants or harmful substances in water. We aim to reveal the mechanism underlying the enhanced PC performance by constructing HJs, and extend the potential of ZnO HJ photocatalysts for future trends, and practical, large-scale applications in environment-related fields.


A cuproptosis-related lncRNA signature-based prognostic model featuring on metastasis and drug selection strategy for patients with lung adenocarcinoma.
Introduction: Lung adenocarcinoma is a common cause of mortality in patients with cancer. Recent studies have indicated that copper-related cell death may not occur in the same way as previously described. Long non-coding RNAs (lncRNAs) play a key role in the occurrence and development of tumors; however, the relationship between cuproptosis and lncRNAs in tumorigenesis and lung adenocarcinoma (LUAD) treatment has not been well established. Our study aimed to construct a model to analyze the prognosis of lung adenocarcinoma in patients using a carcinogenesis-related lncRNA (CR) signature. Methods: The transcriptional profiles of 507 samples from The Cancer Genome Atlas were assessed. Cox regression and co-expression analyses, and the least absolute shrinkage and selection operator (LASSO) were used to filter the CR and develop the model. The expression status of the six prognostic CRs was used to classify all samples into high- and low-risk groups. The overall disease-free survival rate was compared between the two groups. The Gene Ontology and the Kyoto Encyclopedia of Genes and Genomes were used to identify the pathways and mechanisms involved in this model. Subsequently, immunotherapy response, sensitivity, and correlation analyses for several anti-tumor medications were performed. In vitro experiments, including qPCR, were conducted in nine lung adenocarcinoma cell lines and 16 pairs of lung adenocarcinoma and para-carcinoma tissues. Results: After confirmation using the ROC curve, patients in the low-risk category benefited from both overall and disease-free survival. Gene Ontology analysis highlighted cell movement in the model. In the in vitro experiments, qPCR results showed the expression levels of six CRs in 16 pairs of carcinoma and para-carcinoma tissues, which were in accordance with the results of the model. AL138778.1 is a protective factor that can weaken the invasion and migration of A549 cells, and AL360270.1 is a hazardous factor that promotes the invasion and migration of A549 cells. According to this model, targeted treatments such as axitinib, gefitinib, linsitinib, pazopanib, and sorafenib may be more appropriate for low-risk patients. Conclusion: Six CR profiles (AL360270.1, AL138778.1, CDKN2A-DT, AP003778.1, LINC02718, and AC034102.8) with predictive values may be used to evaluate the prognosis of patients with lung adenocarcinoma undergoing therapy.


An unusual presentation of multiple myeloma.
The authors report a case of a 58-year-old woman, ex-smoker, who was referred to the respiratory clinic with a presumed unresolving airspace shadowing in the right lung. Further evaluation of the shadowing with a CT thorax revealed rib lesions, a pancreatic lesion and multiple liver lesions, making the diagnosis of metastatic pancreatic carcinoma most likely. However, further blood investigations and imaging eventually revealed the cause for the shadowing to be multiple myeloma, since the unresolving shadowing was actually a rib lesion.


Challenges and opportunities for eliminating tuberculosis - leveraging political momentum of the UN high-level meeting on tuberculosis.
As demonstrated by the United Nations High-Level Meeting on tuberculosis (TB) held in September 2018, the political momentum for TB has been increasing. The aim of this study was to analyze the current challenges and opportunities for global TB control and, with specific focus on policies surrounding TB control, to reveal what kinds of efforts are needed to accelerate global TB control. We organized two expert meetings with the purposes of assessing the current situation and analyzing challenges regarding TB control. By applying Shiffman and Smith's framework which contains four categories; Actor, Ideas, Political context, and Issue characteristics, we analyzed the challenges and opportunities for global TB control based on the findings from the two expert meetings. In the Actor Category, we found that although there has already been active engagement by non-governmental organizations (NGOs), civil society organizations (CSOs) and private sectors, there still remained an area with room for improvement. In particular, the complexities behind varying drug regulatory and procurement systems per country hindered the active participation of the private sector in this area. As for the Ideas category, due to an increasing threat of antimicrobial resistance and growing number of global migrations, TB is now widely recognized as a health security issue rather than a purely health issue. This makes TB an easier target for political attention. As for the Political category, having the UN High-Level Meeting itself is not enough; such meetings must be followed up by actual commitments from heads of states. Lastly the issue characteristic indicates that the amount of funding for R&D for new drugs, vaccines and diagnostics for TB is not at an adequate level, and investment in childhood TB and missing cases are particularly in need. This study provides important insight into the current status of global efforts toward end TB epidemic. The outcomes from the UN high-level meeting on TB need to be closely monitored will be crucial for the progress towards this goal.


Evolution of oil-producing trichomes in Sisyrinchium (Iridaceae): insights from the first comprehensive phylogenetic analysis of the genus.
Sisyrinchium (Iridaceae: Iridoideae: Sisyrinchieae) is one of the largest, most widespread and most taxonomically complex genera in Iridaceae, with all species except one native to the American continent. Phylogenetic relationships within the genus were investigated and the evolution of oil-producing structures related to specialized oil-bee pollination examined. Phylogenetic analyses based on eight molecular markers obtained from 101 Sisyrinchium accessions representing 85 species were conducted in the first extensive phylogenetic analysis of the genus. Total evidence analyses confirmed the monophyly of the genus and retrieved nine major clades weakly connected to the subdivisions previously recognized. The resulting phylogenetic hypothesis was used to reconstruct biogeographical patterns, and to trace the evolutionary origin of glandular trichomes present in the flowers of several species. Glandular trichomes evolved three times independently in the genus. In two cases, these glandular trichomes are oil-secreting, suggesting that the corresponding flowers might be pollinated by oil-bees. Biogeographical patterns indicate expansions from Central America and the northern Andes to the subandean ranges between Chile and Argentina and to the extended area of the Paraná river basin. The distribution of oil-flower species across the phylogenetic trees suggests that oil-producing trichomes may have played a key role in the diversification of the genus, a hypothesis that requires future testing.


Effect of tetraethylammonium chloride on action potential in cardiac Purkinje fibers.
Intracellular loading with 20 mM tetraethylammonium chloride (TEA) diffusing through the cut end of the preparations prolonged action potential duration (APD) in dog Purkinje fibers without changing maximum diastolic potential, overshoot, and dV/dtmax. The APD was prolonged at all rates of stimulation, but, contrary to the normal rules, APD increased more after longer than after shorter interstimulus intervals. TEA increased the number of beats required to achieve the new steady-state APD after an abrupt change in the rate of stimulation. The effect of varying extracellular potassium concentration on maximal diastolic potential suggested that intracellular loading with TEA had no effect on the time-independent "background" outward current (IK1). If we ascribe all observed TEA effects to the reduction of time dependent slow outward current Ix1, we can propose a hypothesis concerning the role of Ix1 in the regulation of APD at slow heart rates.


Parathyroid hormone and trabectedin have differing effects on macrophages and stress fracture repair.
Stress fractures occur as a result of repeated mechanical stress on bone and are commonly found in the load-bearing lower extremities. Macrophages are key players in the immune system and play an important role in bone remodeling and fracture healing. However, the role of macrophages in stress fractures has not been adequately addressed. We hypothesize that macrophage infiltration into a stress fracture callus site promotes bone healing. To test this, a unilateral stress fracture induction model was employed in which the murine ulna of four-month-old, C57BL/6 J male mice was repeatedly loaded with a pre-determined force until the bone was displaced a distance below the threshold for complete fracture. Mice were treated daily with parathyroid hormone (PTH, 50 μg/kg/day) starting two days before injury and continued until 24 h before euthanasia either four or six days after injury, or treated with trabectedin (0.15 mg/kg) on the day of stress fracture and euthanized three or seven days after injury. These treatments were used due to their established effects on macrophages. While macrophages have been implicated in the anabolic effects of PTH, trabectedin, an FDA approved chemotherapeutic, compromises macrophage function and reduces bone mass. At three- and four-days post injury, callus macrophage numbers were analyzed histologically. There was a significant increase in macrophages with PTH treatment compared to vehicle in the callus site. By one week of healing, treatments differentially affected the bony callus as analyzed by microcomputed tomography. PTH enhanced callus bone volume. Conversely, callus bone volume was decreased with trabectedin treatment. Interestingly, concurrent treatment with PTH and trabectedin rescued the reduction observed in the callus with trabectedin treatment alone. This study reports on the key involvement of macrophages during stress fracture healing. Given these observed outcomes on macrophage physiology and bone healing, these findings may be important for patients actively receiving either of these FDA-approved therapeutics.


Preputial reconstruction and tubularized incised plate urethroplasty in proximal hypospadias with ventral penile curvature.
Objective of this study was to assess the feasibility and results of preputial reconstruction and tubularized incised plate urethroplasty (TIP) in patients of proximal hypospadias with ventral penile curvature. Twenty-seven patients of proximal hypospadias who underwent preputioplasty with TIP were evaluated retrospectively. Ventral curvature was corrected by mobilization of the urethral plate with the corpus spongiosum and the proximal urethra; dorsal plication was added according to the severity of curvature. Feasibility of preputial reconstruction was assessed by applying 3 stay sutures-the first to fix the skin at the corona, the second at the junction of the inner and outer preputial skin for pulling up the skin over the glans, and the third stay on penile skin at the level of the corona for retracting the skin. Preputial reconstruction consisted of a standard 3 layered re-approximation of the margins of the dorsal hood. Age of the patients varied from 10 months to 21 years with an average of 6 years and 4 months. Ventral curvature (mild 10, moderate 13, and severe 4 cases) was corrected by the mobilization of the urethral plate and spongiosum in 14 patients, 11 cases had mobilization of the proximal urethra in addition and 2 patients required single stitch dorsal plication with the above-mentioned steps. Two patients developed urethral fistula and 1 had preputial dehiscence. Preputioplasty with TIP is feasible in proximal hypospadias with curvature without increasing the complication rate. Postoperative phimosis can be prevented by on-table testing of the adequacy of preputial skin by 3 stay sutures.


Aurora Kinase Inhibitors: Current Status and Outlook.
The Aurora kinase family comprises of cell cycle-regulated serine/threonine kinases important for mitosis. Their activity and protein expression are cell cycle regulated, peaking during mitosis to orchestrate important mitotic processes including centrosome maturation, chromosome alignment, chromosome segregation, and cytokinesis. In humans, the Aurora kinase family consists of three members; Aurora-A, Aurora-B, and Aurora-C, which each share a conserved C-terminal catalytic domain but differ in their sub-cellular localization, substrate specificity, and function during mitosis. In addition, Aurora-A and Aurora-B have been found to be overexpressed in a wide variety of human tumors. These observations led to a number of programs among academic and pharmaceutical organizations to discovering small molecule Aurora kinase inhibitors as anti-cancer drugs. This review will summarize the known Aurora kinase inhibitors currently in the clinic, and discuss the current and future directions.


[Results of a study of live mumps vaccine from strain L-3 produced by the Moscow research institute for viral preparations. Characteristics of the vaccine].
For some years the Moscow Research Institute of Virus Preparations carried out studies concerned with the elaboration of conditions for production and control of mumps vaccine from the Leningrad-3 (L-3) strain under experimental production conditions. Twenty nine batches of the vaccine were prepared, tested and studied in extensive field trials. The paper presents the optimal conditions for the preparation of the live mumps vaccine from the L-3 strain in Japanese quail embryo cell cultures. In monkey experiments the L-3 strain was shown to have no neurovirulence. The system of biological control for the mumps vaccine permits to release the preparation meeting the current requirements for safety of live tissue culture parenteral vaccines. The data on the stability of the mumps vaccine from the L-3 strain are presented.


Expression of CD200 on epithelial cells of the murine hair follicle: a role in tissue-specific immune tolerance?
CD200 (OX-2) is a transmembrane glycoprotein that transmits an immunoregulatory signal through the CD200 receptor (CD200R) to attenuate inflammatory reactions and promote immune tolerance. CD200 expression in the skin has not been described previously. We now report that freshly isolated cells of the murine epidermis contain a subpopulation of major histocompatibility complex (MHC) class II-negative, CD3-negative keratinocytes that are CD200-positive. CD200 expression was accentuated in keratinocytes comprising the outer root sheath of the murine hair follicle (HF). When syngeneic skin grafts were exchanged between gender-matched wild-type (WT) and CD200-deficient C57BL/6 mice, significant perifollicular and intrafollicular inflammation was observed, eventually leading to the destruction of virtually all HF (alopecia) without significant loss of the CD200-negative grafts. Minimal and transient inflammation was observed in WT grafts, which persisted long term with hair. There was a 2-fold increase in graft-infiltrating T cells in CD200-deficient skin at 14 d. Alopecia and skin lesions were induced in CD200-deficient hosts by adoptive transfer of splenocytes from WT mice previously grafted with CD200-negative skin, but not from mice grafted with WT skin. Collectively, these results suggest that the expression of CD200 in follicular epithelium attenuates inflammatory reactions and may play a role in maintaining immune tolerance to HF-associated autoantigens.


Directed integration of the physical and genetic linkage maps of swine chromosome 7 reveals that the SLA spans the centromere.
The first integrated physical and genetic linkage map encompassing the entire swine chromosome 7 (SSC7) reveals that the porcine MHC (SLA) spans the centromere. A SLA class II antigen gene lies on the q arm, whereas class I and III genes lie on the p arm, suggesting that the presence of a centromere within the SLA does not preclude a functional complex. The SLA appears smaller than other mammalian MHC, as the genetic distance across two class I, three class II, and three class III SLA gene markers is only 1.1 cM. There are significant variations in recombination rates as a function of position along the chromosome, and the SLA lies in the region with the lowest rate. Furthermore, the directed integration approach used in this study was more efficient than previous efforts that emphasized the screening of large insert libraries for random microsatellites.


Apoptosis induced by hematoporphyrin monomethyl ether combined with He-Ne laser irradiation in vitro on canine breast cancer cells.
Hematoporphyrin monomethyl ether (HMME) is a novel and promising porphyrin-related photosensitizer for photodynamic therapy (PDT). The aim of this study was to investigate HMME-induced apoptosis in CHMm cells, a canine breast cancer cell line. CHMm cells were treated with HMME and a He-Ne laser at a wavelength of 632.8 nm. Cell viability was determined using the trypan blue exclusion assay. Apoptosis was analyzed using Hoechst 33258, AO/EB, Annexin V/PI staining and single-cell gel electrophoresis (comet assay). Apoptotic morphology was further confirmed by Giemsa staining and transmission electron microscopy. Rates of apoptosis increased following PDT-HMME treatment in a time-dependent manner. Taken together, these results demonstrated that apoptosis plays a major role in PDT-HMME-induced reduction in the viability of CHMm cells.


Catalytic asymmetric synthesis of phthioceranic acid, a heptamethyl-branched acid from Mycobacterium tuberculosis.
The first total synthesis of phthioceranic acid (1) has been achieved by an iterative catalytic asymmetric 1,4-addition protocol. This method provides a robust and high-yielding route for the preparation of 1,3-oligomethyl (deoxypropionate) arrays. After the desired number of methyl groups has been introduced, these arrays can be further functionalized at both ends to polymethyl-substituted lipids such as phthioceranic acid, a heptamethyl-branched fatty acid from the virulence factor Sulfolipid-I (2), found in Mycobacterium tuberculosis.


Eucaloric Ketogenic Diet Reduces Hypoglycemia and Inflammation in Mice with Endotoxemia.
Dietary strategies to alter the immune response to acute inflammation have the potential to improve outcomes in critically ill patients. A eucaloric ketogenic diet (EKD), composed predominantly of fat with very small amounts of carbohydrate, can provide adequate caloric support while minimizing spikes in blood glucose and reducing oxidative stress. The purpose of this study was to evaluate the effects of an EKD on glycemic control and the inflammatory response after acute endotoxemia in mice. Mice received either an EKD or a carbohydrate-based control diet (CD) for 4 weeks. Animals subsequently underwent either a 2-h fast (postprandial) or an overnight fast (postabsorptive), and half of the animals in each diet group were randomized to receive either intraperitoneal lipopolysaccharide (1 mg/kg) or an equivalent volume of saline. Glycemic response, insulin resistance, inflammatory cytokine levels, and the expression of key inflammatory and metabolic genes were measured. After endotoxin challenge, hypoglycemia was more frequent in mice fed a CD than an EKD in the postprandial period. This was due in part to the preservation of hepatic glycogen stores despite endotoxin exposure and prolonged fasting in mice fed an EKD. Furthermore, mice fed the CD had higher levels of IL-6 and TNF-α in the postabsorptive period, with a fivefold higher expression of hepatic NFκB compared to mice fed the EKD in both fasting periods. These results suggest that the unique metabolic state induced by an EKD can alter the response to acute inflammation in mice.


Differential returns from globalization to women smallholder coffee and food producers in rural Uganda.
Globalization-related measures to liberalize trade and stimulate export production were applied in Uganda in the late 1980s, including in the coffee production sector, to revitalize agricultural production, increase incomes to farmers and improve rural food security. To explore the different effects of such measures on the health and dietary outcomes of female coffee and food small holder farmers in Uganda. We gathered evidence through a cross-sectional comparative interview survey of 190 female coffee producers and 191 female food producers in Ntungamo district. The study mostly employed quantitative methods of data collection, targeting the sampled households. We also utilized qualitative data; collected three months after the household survey data had been collected and their analysis had been accomplished. Using qualitative interviews based on an unstructured interview guide, extra qualitative information was collected from key informants at national, district and community levels. This was among other underlying principles to avoid relying on snapshot information earlier collected at household level in order to draw valid and compelling conclusions from the study. We used indicators of production, income, access to food and dietary patterns, women's health and health care. Of the two groups selected from the same area, female coffee producers represented a higher level of integration into liberalised export markets. Document review suggests that, although Uganda's economy grew in the period, the household economic and social gains after the liberalization measures may have been less than expected. In the survey carried out, both food and coffee producers were similarly poor, involved in small-scale production, and of a similar age and education level. Coffee producers had greater land and livestock ownership, greater access to inputs and higher levels of income and used a wider variety of markets than food producers, but they had to work longer hours to obtain these economic returns, and spent more cash on health care and food from commercial sources. Their health outcomes were similar to those of the food producers, but with poorer dietary outcomes and greater food stress. The small-scale women farmers who are producing food cannot rely on the economic infrastructure to give them support for meaningful levels of production. However, despite having higher incomes than their food producing counterparts, the evidence showed that women who are producing coffee in Uganda as an export commodity cannot rely on the income from their crops to guarantee their health and nutritional wellbeing, and that the income advantage gained in coffee-producing households has not translated into consistently better health or food security outcomes. Both groups have limited levels of autonomy and control to address these problems.


Are increased levels of systemic oxidative stress and inflammation associated with age-related cataract?
Oxidative stress and inflammation may be involved in the etiology of age-related cataract. This study is the first to investigate the association between urinary levels of 8-iso-prostaglandin F₂α (PGF₂α; as a biomarker for systemic oxidative stress in vivo) and 15-keto-dihydro-PGF₂α (as a biomarker for systemic inflammation in vivo) and risk of age-related cataract. We observed in a nested case-control study, including 258 women with incident cataract diagnosis and/or cataract extraction and 258 women without cataract, matched on age and date of urine sample collection that, women with higher levels of urinary 8-iso-PGF₂α as compared with lower levels had an increased risk of age-related cataract. There was no difference in 15-keto-dihydro-PGF₂α levels between cases and controls. Our observations lead to the hypothesis that higher systemic oxidative stress increases the risk of developing age-related cataract.


Impact of vigorous exercise on serum levels of L-carnitine in prisoners in Colombia.
Objective To assess the effect of a program of vigorous physical exercises on the serum concentration of free and total L-carnitine, in male inmates at a prison in Boyacá, Colombia. Methods Pre-post intervention population-based study. 44 male prisoners with overweight and/or obesity, from a jail in Boyacá, Colombia were randomly assigned into two groups: an intervention group and a control group. The intervention consisted in participating in a vigorous exercise program over twelve weeks. Anthropometric measures and levels of free and total L-carnitine were every four weeks. Results There were significant increases in serum levels of free and total L-carnitine in the intervention group compared to the control group. Concurrently, in this group there was a reduction in body mass index (BMI), while in the control group there were no changes. Conclusion In overweight and/or obese patients, the routine practice of vigorous exercise plus caloric restriction offers significant benefits in reducing body fat volumes through the mechanisms of energetic consumption of long chain fatty acids.


Humoral immunodeficiency.
Humoral (or antibody) immunodeficiency syndromes may occur as apparent congenital or acquired abnormalities, with deficiencies in all or in only some classes of immunoglobulins. Most patients are recognized because of recurrent infections with high-grade extracellular encapsulated bacterial pathogens, but some with selective IgA deficiency or with transient hypogammaglobulinemia of infancy may have few or no infections. Although general population statistics are not available, most defects are thought to be rare; humoral immunodeficiency is more prevalent than cellular immunodeficiency, possibly due to early death from the latter defects. Disorders affecting B-cell function may be inherited as X-linked recessive or as autosomal traits. Although considerable information exists about such defects at a functional and cellular level, the primary biologic errors are as yet unknown for all of them. Apparent abnormalities of B-cell maturation and/or intrinsic B-cell malfunction are seen in a majority of these defects. The heterogeneity of B-cell morphology and function in large pedigrees of patients with X-linked agammaglobulinemia makes it unlikely that the defect is due to a distinct gene rearrangement abnormality at a specific stage of B-cell maturation. Early recognition of B-cell deficiency and institution of adequate immunoglobulin replacement therapy can prevent extensive damage to the lungs and other life-threatening problems from infection and allow a relatively normal childhood and adult life.


The hot plasma environment at jupiter: ulysses results.
Measurements of the hot plasma environment during the Ulysses flyby of Jupiter have revealed several new discoveries related to this large rotating astrophysical system. The Jovian magnetosphere was found by Ulysses to be very extended, with the day-side magnetopause located at approximately 105 Jupiter radii. The heavy ion (sulfur, oxygen, and sodium) population in the day-side magnetosphere increased sharply at approximately 86 Jupiter radii. This is somewhat more extended than the "inner" magnetosphere boundary region identified by the Voyager hot plasma measurements. In the day-side magnetosphere, the ion fluxes have the anisotropy direction expected for corotation with the planet, with the magnitude of the anisotropy increasing when the spacecraft becomes more immersed in the hot plasma sheet. The relative abundances of sulfur, oxygen, and sodium to helium decreased somewhat with decreasing radial distance from the planet on the day-side, which suggests that the abundances of the Jupiter-derived species are dependent on latitude. In the dusk-side, high-latitude region, intense fluxes of counter-streaming ions and electrons were discovered from the edge of the plasma sheet to the dusk-side magnetopause. These beams of electrons and ions were found to be very tightly aligned with the magnetic field and to be superimposed on a time- and space-variable isotropic hot plasma background. The currents carried by the measured hot plasma particles are typically approximately 1.6 x 10(-4) microamperes per square meter or approximately 8 x 10(5) amperes per squared Jupiter radius throughout the high-latitude magnetosphere volume. It is likely that the intense particle beams discovered at high Jovian latitudes produce auroras in the polar caps of the planet.


Dynamic large-scale chromosomal rearrangements fuel rapid adaptation in yeast populations.
Large-scale genome rearrangements have been observed in cells adapting to various selective conditions during laboratory evolution experiments. However, it remains unclear whether these types of mutations can be stably maintained in populations and how they impact the evolutionary trajectories. Here we show that chromosomal rearrangements contribute to extremely high copper tolerance in a set of natural yeast strains isolated from Evolution Canyon (EC), Israel. The chromosomal rearrangements in EC strains result in segmental duplications in chromosomes 7 and 8, which increase the copy number of genes involved in copper regulation, including the crucial transcriptional activator CUP2 and the metallothionein CUP1. The copy number of CUP2 is correlated with the level of copper tolerance, indicating that increasing dosages of a single transcriptional activator by chromosomal rearrangements has a profound effect on a regulatory pathway. By gene expression analysis and functional assays, we identified three previously unknown downstream targets of CUP2: PHO84, SCM4, and CIN2, all of which contributed to copper tolerance in EC strains. Finally, we conducted an evolution experiment to examine how cells maintained these changes in a fluctuating environment. Interestingly, the rearranged chromosomes were reverted back to the wild-type configuration at a high frequency and the recovered chromosome became fixed in less selective conditions. Our results suggest that transposon-mediated chromosomal rearrangements can be highly dynamic and can serve as a reversible mechanism during early stages of adaptive evolution.


Purposive Design of Stretchable Composite Electrodes for Strain-Negative, Strain-Neutral, and Strain-Positive Ionic Sensors.
Soft ionic sensors have emerged as a promising device form to accommodate various future electronic applications. One of the hurdles in ionic sensors is that the sensing signals by mechanical deformation and other stimuli are mixed up. Although the performance of the ionic sensors is highly dependent on the structure of electrodes, systematic investigation of purposive electrode design has been rarely explored. This study proposes a simple strategy for designing stretchable composite electrodes which make the ionic sensor strain-negative, strain-neutral, and strain-positive. This study reveals that such strain-responses can be obtained by adjusting the surface coverage of the electrically-effective conductive fillers. On the basis of the concept, deposition of a Au film on an elastomer composite and crack formation of the Au film are presented for the practical fabrication of a highly reproducible strain-neutral ionic sensor. A completely strain-independent temperature sensor is demonstrated by using the Au crack-based ionic sensor. In addition, this study demonstrates a two-terminal shear sensor capable of recognizing shear directions by combining the strain-positive and strain-negative electrodes.


[Effects of low intensity laser (632.8 nm) and ultraviolet radiation on spectral properties and functional activity of human ceruloplasmin].
Photoinduced changes of human ceruloplasmin (hCp) under laser and ultraviolet (UV) radiation have been studied. A complex character of hCp spectral modifications points to a different degree of the protein molecule folding. After the influence of UV radiation (240-390 nm) in a dose range 906-4530 J/m2 the decrease of oxidase hCp activity was registered. These changes are thought to be connected with modification of the conformation of hCp active centre or copper reduction that was confirmed by the decrease of optical density at 610 nm. An inactivation constant (kf = 3.8 x 10(-4) 1/s) and a photoinactivation quantum yield (1.4 x 10(-4)) were calculated. Kinetic dependencies of o-phenilen-diamine oxidation by intact and UV-modified glycoprotein do not correspond to Michaelis-Menten equation. UV radiation in a dose range 151-4530 J/m2 induced increasing of ceruloplasmin superoxiddismutase activity. The influence of He-Ne laser radiation (1.3 mW; lambda = 632.8 nm, exposure time from 1 up to 30 min) leads to the raise of the hCp functional activity; superoxiddismutase activity changes more significantly. Possible photophysical and photochemical processes in hCp molecule, leading to photomodification and changes of protein functional activity have been represented on the scheme.


TLR9 and RIG-I signaling in human endocervical epithelial cells modulates inflammatory responses of macrophages and dendritic cells in vitro.
The innate immune system has evolved to recognize invading pathogens through pattern recognition receptors (PRRs).Among PRRs, Toll like receptors (TLRs 3, 7/8,9) and RIG-I like receptors (RLRs) have been shown to recognize viral components. Mucosal immune responses to viral infections require coordinated actions from epithelial as well as immune cells. In this respect, endocervical epithelial cells (EEC's) play an important role in initiating innate immune responses via PRRs. It is unknown whether EEC's can alter immune responses of macrophages and dendritic cells (DC's) like its counterparts in intestinal and respiratory systems. In this study, we show that endocervical epithelial cells (End1/E6E7) express two key receptors, TLR9 and RIG-I involved in anti-viral immunity. Stimulation of End1/E6E7 cells lead to the activation of NF-κB and increased secretion of pro-inflammatory cytokines, IL-6 and IL-8. Polarized End1/E6E7 cells responded to apical stimulation with ligands of TLR9 and RIG-I, CpG-ODN and Poly(I:C)LL respectively, without compromising End1/E6E7 cell integrity. At steady state, spent medium from End1/E6E7 cells significantly reduced secretion of pro-inflammatory cytokines from LPS treated human primary monocyte derived macrophages (MDMs) and DC:T cell co-cultures. Spent medium from End1/E6E7 cells stimulated with ligands of TLR9/RIG-I restored secretion of pro-inflammatory cytokines as well as enhanced phagocytosis and chemotaxis of monocytic U937 cells. Spent medium from CpG-ODN and Poly(I:C)LL stimulated End1/E6E7 cells showed significant increased secretion of IL-12p70 from DC:T cell co-cultures. The anti-inflammatory effect of spent media of End1/E6E7 cell was observed to be TGF-β dependent. In summary, the results of our study indicate that EEC's play an indispensable role in modulating anti-viral immune responses at the female lower genital tract.


Triangular titanium implants for sacroiliac joint fusion.
Sacroiliac joint (SIJ) dysfunction is an underdiagnosed condition. Several published cohorts have reported favorable midterm outcomes after SIJ fusion using titanium implants placed across the SIJ. Herein, we report 12-month follow-up from SIJ fusion in a standard clinic setting. A carefully selected group of 160 consecutive patients with painful SIJ dysfunction were diagnosed at a single center and underwent unilateral or staged bilateral SIJ fusion using triangular titanium implants. Patients were routinely seen in clinic for follow-up every 3 months where they completed visual analog scale (0-10 range) pain ratings and Oswestry Disability Index (ODI). Follow-up CT scan was performed at 1 year. Mean patient age was 58 years, and 68% were women. 30% underwent staged bilateral SIJ fusion. By month 12, SIJ pain decreased from 8.0 to 2.5 (p < 0.0001) and disability (ODI) decreased from 45.3 to 16.4 (p < 0.0001). The proportion with clinically significant improvements in SIJ pain and ODI was high (> 95%). Perioperative adverse events were mild and decreased with increasing surgical experience with the procedure. Subgroup analysis showed slightly smaller improvements in those undergoing bilateral surgery and those with a spinal cord stimulator in place. CT scan at 1 year showed reabsorption along one or more implants in 16% of cases, but there were no breakages or implant removals. In standard clinical practice, SIJ fusion with triangular titanium implants produces significant improvement in pain and disability related to SIJ dysfunction. These slides can be retrieved under Electronic Supplementary Material.


Metabolic Syndrome Induced Bladder Cannabinoid Receptor Changes in the Fructose-Fed Rats.
To investigate the effect of metabolic syndrome on the bladder cannabinoid receptors 1 and 2 (CB1/CB2) expression and function in the fructose-fed rats (FR). Adult male Sprague-Dawley rats were divided into two groups: (i) Control rats fed with normal chow; and (ii) Rats fed with high-fructose diet (FR) for 9 weeks. The body weight, blood pressure, plasma sugar, insulin, triglyceride and cholesterol were measured. Bladder muscle strips were prepared in organ bath and pre-contracted with 1 µM/L acetylcholine (ACh) or 50 mM/L KCl. The relaxation responses to CB1/CB2 agonist Bay59-3047 (0.01-1 µM/L) were recorded. The effects of CB1 antagonist AM251, CB2 antagonist AM630, protein kinase A (PKA) inhibitor H-89 and ATP-sensitive potassium channel (KATP) inhibitor glibenclamide on the Bay59-3047-induced response were tested. Western blotting and real-time polymerase chain reaction (RT-PCR) analyses were performed for bladder CB1/CB2 receptors. Significant increases of body weight, blood pressure, plasma glucose, insulin, cholesterol and triglyceride levels were found in the FR. Bay59-3047 reduced ACh and KCl pre-contracted bladder strip tension in a dose-dependent fashion. The relaxation responses were significantly decreased in the FR. The Bay59-3047-induced relaxation was attenuated by AM251, glibenclamide and H-89. Western blotting and RT-PCR showed decreased expressions of FR bladder CB1 and CB2 receptor protein and mRNA. CB1/CB2 receptors mediate rat bladder relaxation through the PKA and KATP pathway. The CB1 receptor may play a more prominent role. The response is decreased in the FR bladder due to reduced expressions of the cannabinoid receptors.


Chemist, entomologist, Darwinian, and man of affairs: Raphael Meldola and the making of a scientific career.
Raphael Meldola FRS (1849-1915) was professor of chemistry at the City and Guilds Technical College in Finsbury. He was a colleague and close friend of Silvanus Phillips Thompson FRS (1851-1916), the college principal and professor of physics. This paper follows an earlier one on Thompson and the making of his career. It is intended to illustrate further the ways in which scientists of Meldola and Thompson's generation gained advancement within the scientific community. Meldola had interests beyond chemistry, including a serious interest in field entomology. In this he had several well-known mentors including Alfred Russel Wallace and Charles Darwin. The paper, which includes much new information derived from archival work, is presented as six thematic narratives related, among other things, to chemical and technical education, dye chemistry, the Royal Society solar eclipse expedition of 1875, natural history and Darwinism, field clubs, learned societies, and the honouring of scientists. Together these narratives illustrate a generalist/voluntarist career pattern that came to an end with the First World War.


Evaluation of the chimpanzee breeding program at the Southwest Foundation for Biomedical Research.
The history of the chimpanzee (Pan troglodytes) breeding colony of the Southwest Foundation for Biomedical Research was evaluated over a 24-year period to determine age at conception, breeder rearing history, maternal competence, and infant rearing history. The records of 107 breeders and 268 live births were reviewed. Of the breeders with known rearing histories, 40 were wild-born (12 male and 28 female), 16 were reared by their mothers for at least 1 month (8 male and 8 female), and 13 were removed from their mothers immediately after birth (2 males and 11 females). The age of successful mating for males ranged from 7 to 32 years and for females from 7 to 41 years, although the upper limit indicates the age of the population and not reproductive senescence. The mother's rearing history was related to her maternal competence, defined as caring for an infant for at least 1 month. Of the wild-born females, 82% (18/22) were competent mothers. For females that had been reared in captivity with their mothers for 1 to 12 months, 71% (5/7) were competent. For females that had been removed from their mothers immediately and reared in a nursery by humans, only 14% (1/7) were competent. The rearing strategies have changed during the period under consideration. The number of infants reared by their mothers increased in the 1980s, while the number of infants removed from their mothers immediately for experimental reasons decreased and dropped to zero in the 1990s. Information on the history of the breeding colony has been used to make management decisions and to determine the expectations of the Southwest Foundation chimpanzee breeding program.


Gene delivery to breast cancer by incorporated EpCAM targeted DARPins into AAV2.
The aim of this study is to evaluate an AAV vector that can selectively target breast cancer cells and to investigate its specificity and anti-tumor effects on breast cancer cells both in vitro and in vivo, offering a new therapeutic approach for the treatment of EpCAM-positive breast cancer. In this study, a modified AAV2 viral vector was used, in which EpCAM-specific DARPin EC1 was fused to the VP2 protein of AAV2, creating a viral vector that can target breast cancer cells. The targeting ability and anti-tumor effects of this viral vector were evaluated through in vitro and in vivo experiments. The experimental results showed that the AAV2MEC1 virus could specifically infect EpCAM-positive breast cancer cells and accurately deliver the suicide gene HSV-TK to tumor tissue in mice, significantly inhibiting tumor growth. Compared to the traditional AAV2 viral vector, the AAV2MEC1 virus exhibited reduced accumulation in liver tissue and had no impact on tumor growth. This study demonstrates that AAV2MEC1 is a gene delivery vector capable of targeting breast cancer cells and achieving selective targeting in mice. The findings offer a potential gene delivery system and strategies for gene therapy targeting EpCAM-positive breast cancer and other tumor types.


Can depression be diagnosed by response to mother's face? A personalized attachment-based paradigm for diagnostic fMRI.
Objective measurement of depression remains elusive. Depression has been associated with insecure attachment, and both have been associated with changes in brain reactivity in response to viewing standard emotional and neutral faces. In this study, we developed a method to calculate predicted scores for the Beck Depression Inventory II (BDI-II) using personalized stimuli: fMRI imaging of subjects viewing pictures of their own mothers. 28 female subjects ages 18-30 (14 healthy controls and 14 unipolar depressed diagnosed by MINI psychiatric interview) were scored on the Beck Depression Inventory II (BDI-II) and the Adult Attachment Interview (AAI) coherence of mind scale of global attachment security. Subjects viewed pictures of Mother (M), Friend (F) and Stranger (S), during functional magnetic resonance imaging (fMRI). Using a principal component regression method (PCR), a predicted Beck Depression Inventory II (BDI-II) score was obtained from activity patterns in the paracingulate gyrus (Brodmann area 32) and compared to clinical diagnosis and the measured BDI-II score. The same procedure was performed for AAI coherence of mind scores. Activity patterns in BA-32 identified depressed subjects. The categorical agreement between the derived BDI-II score (using the standard clinical cut-score of 14 on the BDI-II) and depression diagnosis by MINI psychiatric interview was 89%, with sensitivity 85.7% and specificity 92.8%. Predicted and measured BDI-II scores had a correlation of 0.55. Prediction of attachment security was not statistically significant. Brain activity in response to viewing one's mother may be diagnostic of depression. Functional magnetic resonance imaging using personalized paradigms has the potential to provide objective assessments, even when behavioral measures are not informative. Further, fMRI based diagnostic algorithms may enhance our understanding of the neural mechanisms of depression by identifying distinctive neural features of the illness.


Analyses of hepatocellular proliferation in a mouse model of alpha-1-antitrypsin deficiency.
alpha-1-Antitrypsin (alpha1-AT) deficiency is the most common cause of metabolic pediatric liver disease. Hepatocellular injury is caused by toxicity of the mutant alpha-1-antitrypsin Z (alpha1-ATZ) molecule retained within hepatocytes. In these studies, we used the PiZ transgenic mouse model of alpha1-AT deficiency to examine hepatocellular proliferation in response to chronic liver injury resulting from this metabolic disease. The results showed increased hepatocellular proliferation and caspase 9 activation in male PiZ mice compared with female PiZ and wild-type mice. Hepatic alpha1-AT mRNA and protein expression also were increased in male PiZ mice, suggesting that greater hepatocellular proliferation and caspase activation in males results from increased hepatotoxicity associated with greater intracellular alpha1-ATZ accumulation. Testosterone treatment of female PiZ mice increased alpha1-ATZ expression and hepatocellular proliferation to a level comparable with that in males. In PiZ mice, hepatocytes devoid of intracellular alpha1-AT globules had a proliferative advantage compared with globule-containing hepatocytes. However, this advantage is relative because both globule-containing and globule-devoid hepatocytes exhibited comparable proliferation after partial hepatectomy. In conclusion, these data indicate that intracellular retention of mutant alpha1-ATZ is associated with a regenerative stimulus leading to increased hepatocellular proliferation, that gender-specific signals influence the degree of alpha1-AT expression and associated hepatic injury, and that hepatocytes devoid of alpha1-ATZ have a proliferative advantage over cells that accumulate the mutant protein. This selective proliferation suggests that hepatocellular transplantation may be applicable for treatment of this and other slowly progressive metabolic liver diseases.


Intrinsic regenerative mechanisms of central nervous system neurons.
Injuries to the adult central nervous system (CNS), such as spinal cord injury and brain contusion, can cause permanent functional deficits if axonal connections are broken. Spontaneous functional recovery rarely occurs. It has been widely accepted that the extracellular environment of the CNS inhibits neuronal regeneration. However, it should be noted that another reason for injured neurons failing to regenerate is their weak intrinsic ability to do so. The regeneration of injured neurons is a process involving many intracellular phenomena, including cytoskeletal changes, gene and protein expression, and changes in the responsiveness to extracellular cues. The capacity of injured neurons to regenerate is modulated to some extent by changes in the expression of intracellular signaling molecules such as glycogen synthase kinase-3beta and cyclic adenosine 3',5'-monophosphate. Knowledge of these effects has guided the development of animal models for regenerative therapies of CNS injury. Enhancing the intrinsic regenerative machinery of injured axons in the adult CNS is a potentially powerful strategy for treating patients with a CNS injury.


Integrating a triplet-triplet annihilation up-conversion system to enhance dye-sensitized solar cell response to sub-bandgap light.
The poor response of dye-sensitized solar cells (DSCs) to red and infrared light is a significant impediment to the realization of higher photocurrents and hence higher efficiencies. Photon up-conversion by way of triplet-triplet annihilation (TTA-UC) is an attractive technique for using these otherwise wasted low energy photons to produce photocurrent, while not interfering with the photoanodic performance in a deleterious manner. Further to this, TTA-UC has a number of features, distinct from other reported photon up-conversion technologies, which renders it particularly suitable for coupling with DSC technology. In this work, a proven high performance TTA-UC system, comprising a palladium porphyrin sensitizer and rubrene emitter, is combined with a high performance DSC (utilizing the organic dye D149) in an integrated device. The device shows an enhanced response to sub-bandgap light over the absorption range of the TTA-UC sub-unit resulting in the highest figure of merit for up-conversion assisted DSC performance to date.


Analysis of pH variation of various calcium hydroxide compounds in vitro.
Among the reasons for the use of calcium hydroxide products, there is their alkalinity. Variations in the alkalinity of six commonly used calcium hydroxide compounds were studied in vitro at different time intervals. All these compounds rendered the saline solution strongly alkaline. Dycal, Life, Nucap and Reocap, had a weaker effect as compared with Contrasil and to Pulpdent paste. Such differences in the pH values were accompanied by differences in calcium loss, as revealed by scanning electron microscopy. Differences in the alkaline pH values and calcium losses among these calcium hydroxide compounds may account for their different clinical effectiveness in vivo.


[Assessment of atrial fibrillation ablation outcome: from symptoms to continuous monitoring with an implantable loop recorder].
Pulmonary vein isolation by catheter ablation (CA) is an effective and indicated treatment for patients with drug refractory symptomatic atrial fibrillation (AF). It is noteworthy that patients with symptomatic AF show also a high incidence of asymptomatic episodes of arrhythmia. The main clinical studies on CA of AF have considered symptomatic recurrences of AF as the primary endpoint, thus potentially overestimating the success rate. Patient monitoring by means of daily transtelephonic ECG or repeated 7-day Holter has demonstrated an incidence of asymptomatic episodes of AF as high as 50% of all arrhythmic recurrences after CA. Moreover, the percentage of asymptomatic episodes significantly increases after CA. Changes in arrhythmia pattern and autonomic nervous system together with placebo effects and post-interventional antiarrhythmic therapy could account for the increase in asymptomatic episodes of AF observed after CA. A watchful monitoring of AF recurrences is of extreme importance not only to assess the real overall efficacy of CA but also to tailor therapeutic strategies for the individual patient. The decision to withdraw anticoagulation and antiarrhythmic therapies should be based on the demonstrated absence of both symptomatic and asymptomatic recurrences. The use of an implantable loop recorder with a dedicated software for AF and atrial tachycardia detection could be a valuable alternative to current monitoring strategies after CA of AF. Patient acceptability of such a minimally invasive strategy for AF monitoring has still to be proven.


Direct Synthesis of N-formamides by Integrating Reductive Amination of Ketones and Aldehydes with CO2 Fixation in a Metal-Organic Framework.
Formamides are important feedstocks for the manufacture of many fine chemicals. State-of-the-art synthesis of formamides relies on the use of an excess amount of reagents, giving copious waste and thus poor atom-economy. Here, we report the first example of direct synthesis of N-formamides by coupling two challenging reactions, namely reductive amination of carbonyl compounds, particularly biomass-derived aldehydes and ketones, and fixation of CO2 in the presence of H2 over a metal-organic framework supported ruthenium catalyst, Ru/MFM-300(Cr). Highly selective production of N-formamides has been observed for a wide range of carbonyl compounds. Synchrotron X-ray powder diffraction reveals the presence of strong host-guest binding interactions via hydrogen bonding and parallel-displaced π⋅⋅⋅π interactions between the catalyst and adsorbed substrates facilitating the activation of substrates and promoting selectivity to formamides. The use of multifunctional porous catalysts to integrate CO2 utilisation in the synthesis of formamide products will have a significant impact in the sustainable synthesis of feedstock chemicals.


[Effects of radiation of decimeter range on the motor function of the gastrointestinal and biliary tracts].
Characteristics of the motor function of the upper gastrointestinal tract, small intestine and colon and biliary tract under radiation of dm range were obtained. The radiation source was a mobile phone brand Nokya. Motor function of the gastrointestinal and biliary tract was evaluated recording electromyogram (EMG) from silver electrodes imposed on the body surface in the projection point of the corresponding abdominal organs; frequency (in minutes) and amplitude (mV) and EMG spikes are measured. The maximums of dm radiation induced stimulatory effect on motor function recorded at the esophagus, stomach, jejunum and descending part of the colon.