Living in violence: Neighborhood domestic violence and small for gestational age births.
To determine the association between neighborhood domestic violence and small-for-gestational-age (SGA) birth and to examine if there is a differential impact of neighborhood domestic violence on SGA births by race in a high crime community. This analysis includes all birth records issued in New Orleans, Louisiana from 2011 to 2012 geocoded by census tract (N=177 census tracts, N=8322 women). Hierarchical modeling and ecologic spatial analysis were used to examine the area-effect of neighborhood domestic violence on SGA births, independent of individual-level predictors and accounting for the propensity to live in high domestic violence neighborhoods. Tests for spatial autocorrelation reveled area-level clustering and overlap of SGA and domestic violent rates. Pregnant women living in high domestic violence areas were more likely to give birth to an SGA infant compared to women in low-domestic violence areas (OR=1.04, 95%CI: 1.01, 1.08), net of the effects of individual-level factors and propensity scores. Neighborhood-level attributes including rates of domestic violence may increase women's risk for SGA birth, highlighting a policy-relevant and potentially amenable exposure.


Influence of arbuscular mycorrhizae on photosynthesis and water status of maize plants under salt stress.
The influence of arbuscular mycorrhizal (AM) fungus Glomus mosseae on characteristics of the growth, water status, chlorophyll concentration, gas exchange, and chlorophyll fluorescence of maize plants under salt stress was studied in the greenhouse. Maize plants were grown in sand and soil mixture with five NaCl levels (0, 0.5, 1.0, 1.5, and 2.0 g/kg dry substrate) for 55 days, following 15 days of non-saline pretreatment. Under salt stress, mycorrhizal maize plants had higher dry weight of shoot and root, higher relative chlorophyll content, better water status (decreased water saturation deficit, increased water use efficiency, and relative water content), higher gas exchange capacity (increased photosynthetic rate, stomatal conductance and transpiration rate, and decreased intercellular CO(2) concentration), higher non-photochemistry efficiency [increased non-photochemical quenching values (NPQ)], and higher photochemistry efficiency [increased the maximum quantum yield in the dark-adapted state (Fv/Fm), the maximum quantum yield in the light-adapted sate (Fv'/Fm'), the actual quantum yield in the light-adapted steady state (phiPSII) and the photochemical quenching values (qP)], compared with non-mycorrhizal maize plants. In addition, AM symbiosis could trigger the regulation of the energy biturcation between photochemical and non-photochemical events reflected in the deexcitation rate constants (kN, kN', kP, and kP'). All the results show that G. mosseae alleviates the deleterious effect of salt stress on plant growth, through improving plant water status, chlorophyll concentration, and photosynthetic capacity, while the influence of AM symbiosis on photosynthetic capacity of maize plants can be indirectly affected by soil salinity and mycorrhizae-mediated enhancement of water status, but not by the mycorrhizae-mediated enhancement of chlorophyll concentration and plant biomass.


Hypersensitive pneumonitis: a case report.
Hypersensitivity pneumonitis, also known as extrinsic allergic alveolitis, constitutes a spectrum of granulomatous, interstitial, bronchiolar, and alveolar-filling lung diseases resulting from repeated inhalation and sensitization to a wide variety of organic aerosols and low-molecular-weight chemical antigens. We report a case of a 57 year-old-female with hypersensitive pneumonitis due to pigeon droppings. Early diagnosis during the acute phase of hypersensitive pneumonitis is important due to the irreversible damages caused by this chronic disease.


Relaxation is impaired in the diaphragm muscle of the cardiomyopathic Syrian hamster.
Relaxation was examined in diaphragm muscle strips of cardiomyopathic Syrian hamsters and control hamsters. Isotonic lengthening velocity and isometric tension decay were analyzed over the load continuum in response to twitch. For each load level (P), we measured the maximum extent of shortening (deltaL), the peak lengthening velocity (VL), and the peak rate of tension decline (-dP/dtmax). The kinetics of sarcomere length (SL) were simultaneously measured by laser diffraction. In an attempt to account for the influence of shortening and/or load on relaxation, we calculated the slopes of the VL - deltaL and -dP/dtmax - P relationships. In both groups, there was a direct relationship between (1) VL and deltaL and (2) -dP/dtmax and P. In myopathic hamsters, we observed a decrease in the slope of the VL - deltaL relationship (p < 0.05), a decrease in VL at any common value of both muscle and sarcomere extent of shortening, and an increase in the duration of overall lengthening. Isometric tension decay was significantly prolonged in myopathic muscle strips, while the -dP/dtmax - P relationship was not significantly different than in controls. At low-to-medium loads, SLs at the onset of tension decline were greater in myopathy. These data indicate that relaxation of the diaphragm was both slowed and prolonged in myopathic Syrian hamsters.


5-fluorouracil-carboplatin continuous infusion as salvage chemotherapy in advanced cancer.
5-fluorouracil given by continuous infusion allows higher dose delivery, causes less myelosuppression and may interfere with repair of DNA damage caused by carboplatin. With this rationale, we conducted a phase II study to test the activity and toxicity of 5-fluorouracil and carboplatin given in continuous infusion to patients with advanced cancer and pretreated with at least two chemotherapy regimens. Forty patients with advanced tumors (21 colon, 4 stomach, 3 breast, 3 bladder, 3 ovary, and 6 at other sites) were entered in the trial. 5-fluorouracil (200 mg/m2) and carboplatin (20 mg/m2) were administered by continuous infusion from days 1 to 20, every 4 weeks. All patients were assessable for response and toxicity. A total of 138 courses of chemotherapy were administered, with a mean of 3.5 per patient (range, 2-9). Toxicity, assessed using WHO criteria, was as follows: nausea and vomiting grade 2-3 in 34% of patients, alopecia grade 2-3 in 96%, and neutropenia grade 3-4 in 26%. One patient (2.5%) had a complete response to therapy and 7 (17.5%) had a partial response (response rate 20%; 95% Cl, 9.06-35.68%). Disease stability and progression occurred in 12 (30%) and 20 (50%) patients, respectively. Median time to progression was 5.6 months (range, 2.8-45.9+), with a median survival time of 7.7 months (range, 1.5-45.9+). Outpatient treatment with a combination of 5-fluorouracil and carboplatin in continuous infusion was active as salvage treatment for advanced tumors and may give prolonged palliation of symptoms with manageable toxicity.


Molecular constants of aluminum monohalides: caveats for computations of simple inorganic molecules.
Quantum chemical calculations have become an everyday tool in chemistry. There are commercial program packages and downloadable basis sets for most needs. However, many chemists rarely go beyond the routine use of these programs, rarely, if ever, checking the original references for basis sets. In this letter, we point out some of the pitfalls of such an approach. Structural parameters of the aluminum-monohalides, AlF, AlCl, AlBr, and AlI, have been calculated using the Gaussian 03 program package and different basis set combinations.


The Magnuson-Stack procedure for treatment of recurrent glenohumeral dislocations.
The Magnuson-Stack procedure was developed in 1943 as a treatment for recurrent anterior dislocation of the glenohumeral joint. Since that time, very little literature has been published on this procedure. The purpose of our study is to evaluate its efficacy in preventing further dislocations and, also, introduce the Cybex Isokinetic Dynamometer as a quantitative tool in scientifically evaluating total shoulder function. At the Bryn Mawr (Pennsylvania) Hospital from 1971 to 1978, 43 patients underwent a Magnuson-Stack procedure. Twenty-nine returned detailed questionnaires; 26 of these patients returned for clinical and roentgenographic examination by one of the authors, and 18 had their shoulder motion and power quantitatively compared to their contralateral normal arms with the Cybex Isokinetic Dynamometer. Eighty-five percent of shoulders did not dislocate postoperatively; 90% considered their results satisfactory. By gross physical examination, no shoulder atrophy was noted. Strength seemed to equal the uninjured shoulder. Range of motion showed a 10 degrees loss of external rotation as measured with a hand-held goniometer. However, by testing range of motion with the Cybex system, a 25 degrees lack of external rotation was noted. Force values measured at 60 degrees of arc/sec and 180 degrees of arc/sec showed an 18 and 10% deficit, respectively, in external rotation. The authors believe that the Magnuson-Stack procedure has a place in the treatment of recurrent anterior dislocations of the shoulder. Also, the Cybex II isolated joint testing system provides an accurate reproducible method of comparing the postoperative results of all patients treated for dislocation of the shoulder.(ABSTRACT TRUNCATED AT 250 WORDS)


Knowledge about breastfeeding in mothers of infants with gastroesophageal reflux.
Infants with gastroesophageal reflux disease (GERD) who are breastfed have significantly shorter clinical episodes of the condition than artificially fed infants. The purpose of this study was to identify the knowledge about the benefits of breastfeeding in mothers of babies 0-12 months of age with gastroesophageal reflux. A non-probabilistic sample was taken among patients from various private radiological centers. Sixty mothers completed a self-administered questionnaire, with a median age of 26 years and an educational level of 14 years. Seventy one percent breastfed their last baby, but only 18.6% practiced exclusive breastfeeding. The pediatrician suggested formula to 53.3% of the mothers, and 64% of the mothers were told to combine breast milk with vegetables as treatment for the GERD. Inadequate knowledge about the benefits of breastfeeding was exhibited by 27% of the mothers. Mothers of infants with GERD need education on the importance of breastfeeding. Further research is necessary on the factors which impact the duration of breastfeeding in this population.


Arthroscopic Repair of Anterosuperior Massive Rotator Cuff Tears: Does Repair Integrity Affect Outcomes?
The purpose of this study was to investigate clinical outcomes and structural integrity after arthroscopic repair of anterosuperior massive rotator cuff tears (RCTs) and to compare clinical outcomes between healed and retear groups. The authors hypothesized that although both groups would exhibit improved clinical outcomes compared with their preoperative status, the healed group would have better clinical outcomes than the retear group, and in the retear group, the subscapularis retear subgroup would have inferior outcomes compared with the intact subscapularis repair subgroup. Case-control study; Level of evidence, 3. This study included 73 of 90 eligible patients who underwent arthroscopic repair of an anterosuperior massive RCT. Functional outcomes after 2-year follow-up were assessed using the visual analog scale (VAS) pain score, subjective shoulder value (SSV), American Shoulder and Elbow Surgeons (ASES) score, University of California, Los Angeles (UCLA) shoulder score, and active range of motion. Patients were assigned to the healed group (group H, n = 34) or retear group (group R, n = 39) based on magnetic resonance arthrography results at 6 months postoperatively. Group R was composed of subgroup R1 (subscapularis retear) and subgroup R2 (intact subscapularis repair). Retearing occurred in 53% of patients. At 2-year follow-up, group H exhibited better outcomes for all functional scores versus group R, respectively ( P < .001): VAS pain score (1.0 vs 2.1), SSV (90.2 vs 77.4), ASES score (90.8 vs 76.6), and UCLA shoulder score (31.0 vs 24.9). Within both groups, all scores improved significantly compared with preoperative values ( P < .001). At follow-up, group H had significantly better forward flexion ( P = .018) and internal rotation ( P = .002) than group R; within both groups, active range of motion improved in all planes compared with the preoperative condition ( P < .001). Subgroup R1 exhibited inferior outcomes versus subgroup R2, respectively: VAS pain score (2.6 vs 1.5; P = .012), ASES score (70.9 vs 83.6; P = .013), SSV (70.9 vs 85.4; P = .005), and UCLA shoulder score (22.0 vs 28.5; P = .001). After arthroscopic repair of anterosuperior massive RCTs, 53% of patients exhibited retearing. The healed group had better functional outcomes than the retear group. The subscapularis retear subgroup exhibited significantly inferior outcomes compared with the intact subscapularis repair subgroup.


Autoimmune polyglandular syndrome type 1 with reversible dilated cardiomyopathy: complete recovery after correction of hypocalcemia and hypocortisolemia.
Autoimmune polyglandular syndrome type 1 (APS1) - characterized by the triad of mucocutaneous candidiasis, hypoparathyroidism, and primary adrenal insufficiency - is an uncommon entity. In this case report we describe the case of a young girl who presented with classic features of APS1 and dilated cardiomyopathy, which were missed during her presentation to the children's hospital. Her condition improved only when appropriate replacement therapy in the form of calcium, calcitriol and hydrocortisone was instituted. Hypocalcemia and hypocortisol state are curable causes of myocardial dysfunction and subsequent congestive cardiac failure, and should always be considered in the differential diagnosis of resistant congestive cardiac failure, especially in children. To the best of our knowledge, cardiomyopathy in the setting of APS1 has never been described previously and can remain unrecognized for a long time and present with life threatening complications.


Severe hemolysis due to a donor anti-D antibody after heart-lung transplantation. Association with lung and blood chimerism.
Hemolysis due to donor-derived red cell antibodies is a potential complication after minor ABO-mismatched solid organ transplantation. It has also been described in Rh-positive recipients receiving organs from previously isoimmunized Rh-negative donors. We report on a group O, Rh(D)-positive patient who received a heart-lung transplant from a group O, Rh(D)-negative donor presenting an anti-D antibody. Severe hemolytic anemia developed in the early postoperative period and lasted for 3 mo. Anti-D antibodies that were of donor origin were found in bronchoalveolar lavage fluid and serum. In addition, using the polymerase chain reaction for human leukocyte antigen class II genotyping, we were able to demonstrate the presence of a mixed population of donor and recipient cells in the lungs and the peripheral blood of the recipient. The chimeric state in the blood persisted until at least the fifty-seventh postoperative day. This first case report of hemolysis due to Rh(D) antibody after heart-lung transplantation emphasizes the need for routine red cell antibody screening of donors and for close monitoring of signs of red cell destruction in the recipient in cases of pretransplant donor isoimmunization.


Identification of Mycoplasma hyopneumoniae in formalin-fixed porcine lung, using an indirect immunoperoxidase method.
An indirect immunoperoxidase staining technique was evaluated for detection of Mycoplasma hyopneumoniae in formalin-fixed, paraffin-embedded porcine lung. Lungs from swine with induced (n = 4) or naturally occurring M hyopneumoniae infection (n = 31) were examined grossly, by light and immunofluorescent microscopy, and by an indirect immunoperoxidase test, using antibody raised in swine against M hyopneumoniae as the primary antibody. Organisms stained by the indirect immunoperoxidase method were identified in tissue sections as pleomorphic brown-staining structures corresponding to those observed with immunofluorescence. Mycoplasma hyosynoviae, M hyorhinis, and Acholeplasma laidlawii did not stain with the indirect immunoperoxidase method, using antibody raised against M hyopneumoniae.


Established practice in the treatment of patients with acute promyleocytic leukemia and the introduction of arsenic trioxide as a novel therapy.
First-line therapy for patients with newly diagnosed acute promyelocytic leukemia (APL) has been established in a series of randomized clinical trials. Remission induction and consolidation are based on the differentiation agent, all-trans retinoic acid (ATRA), and anthracycline-based chemotherapy. Maintenance therapy is also based on ATRA and may involve additional chemotherapy. Established protocols are associated with a high rate of complete responses (CRs) (87% to 97%), and long-term follow-up has indicated a 4-year disease-free survival of greater than 60%. Therapy for patients who relapse or are refractory to ATRA-based regimens is not standardized and there is a need for new approaches. Arsenic trioxide (ATO) has recently been licensed for use in patients with relapsed/refractory APL. Controlled clinical trials have indicated that ATO is associated with a CR rate of 87% in this population. This agent has a manageable toxicity profile and presents a welcome option for patients with relapsed disease for whom other, more debilitating therapies are unsuitable. Several prognostic factors have been defined in patients with APL, and it is possible that novel treatments such as ATO should be differentially applied to specific prognostic groups.


Use of visual, acoustic, and olfactory information during embedded invertebrate foraging in brown capuchins (Cebus apella).
Experiments were conducted to investigate which sensory cues are used by brown capuchins (Cebus apella) in embedded invertebrate foraging. The importance of visual, olfactory, and acoustic cues in such foraging was determined by presenting subjects with a stimulus log modified to block out given sensory cues. Experiment 1 was designed to investigate whether subjects could locate an invertebrate embedded in wood when only visual, acoustic, or olfactory information was available. Experiments 2 and 3 were designed to investigate extractive foraging behavior when two sensory cues were provided. It was hypothesized that the combination of visual and acoustic information would be necessary for subjects to successfully locate embedded invertebrates. Results indicated that subjects' performance was most successful when both visual and acoustic information was available.


Comparing the Marginal Adaptation of Cold Ceramic and Mineral Trioxide Aggregate by Means of Scanning Electron Microscope: An In vitro Study.
Long-term success of endodontic surgeries is often influenced by the type of root-end filling material (RFM). The aim of present study was to compare the marginal adaptation of two different RFM, cold ceramic (CC) and mineral trioxide aggregate (MTA), using scanning electron microscope (SEM). About 20 extracted human single-rooted teeth were collected and stored into sodium hypochlorite 5.25%. The teeth were decronated from the cemento-enamel junction to prepare 16 mm roots. The working length was measured, and 1/3 coronal of the canal was prepared by Gates-Glidden drills. Apical flaring was followed by K file size # 40-70 based on step back technique. After filling of the canals, 3 mm above the apex was cut at 90° to the long axis. Furthermore, 3 mm of the filling was removed from the apical part using the ultrasonic device. All of the prepared specimens were divided into two groups and were retro filled by MTA and CC. The roots were cut horizontally from 1 mm above the apical part, and dentin-filling material interface was observed by SEM. Finally, the collected data were analyzed by Mann-Whitney test and using SPSS software version 18 at a significant level of 0.05. The mean interfacial adaptation was higher in CC group. However, no significant differences were observed by statistical test (P = 0.35). Both CC and MTA had similar marginal adaptation as RFM however in vivo studies are recommended for better determination.


[Dynamics of ultrastructural changes in guinea pig cardiomyocytes in experimental diphtheria intoxication].
Electron microscopy of the left and right ventricles from guinea pigs was made 24, 72, and 120 hours after they were administered diphtheria toxin, 0.3 DLM/kg. The important pathogenetic mechanism responsible for dysfunction of the "diphtheritic heart" was found to be left and right ventricular cardiomyocytic lesion discordance developing in the mid-process, by causing serious intracardiac hemodynamic disorders. The lysosomal system influencing the ultrastructure of the two ventricles may exist in the heart. In diphtheritic intoxication, cardiomyocytic lysosomes exert mainly a damaging effect on their ultrastructure.


[Treatment-related pain, definitions and help with detection].
Treatment-related pain can be provoked, iatrogenic or induced. Some of its causes are known. They guide observation and clinical examination as well as the choice of assessment strategies and steps to prevent treatment-related pain.


Establishment of evaluation method for siRNA delivery using stable cell line carrying the luciferase reporter gene.
We determined the influence of siRNA (short interfering RNA) for expression of plasmid DNA (pDNA), when mismatched siRNA and pDNA encoding beta-galactosidase (beta-gal) were transfected into HeLa cells by the cotransfection method in which they were simultaneously added to the cells. Cationic liposomes (Lipofectamine2000) were used as a gene transfection reagent. The knockdown effect on beta-gal was observed even when mismatched siRNA was used, and the effect depended on the amount of added mismatched siRNA. But, there was not a distinct difference of introduction of pDNA into cells between using mismatched siRNA and without using it. We considered that the cotransfection method should be avoided when we confirm RNAi efficiency. The reliable evaluation method for siRNA delivery in vitro was thus established by using NFAT reporter HeLa stable cell line or CHO (pMAM-luc) cell line that had DNA encoding luciferase. The following experimental conditions for each cell line were optimized: cell numbers seeded, total incubation times, concentrations of added inducers, and incubation times after addition of inducers. Transfection performance was compared for six commercially available reagents by this method. No commercially available transfection reagent, however, could reduce luciferase activity by less than one tenth without causing cellular cytotoxicity. Development of novel reagents providing higher transfection effects without cytotoxicity is needed.


Emerging technologies in autoantibody testing for rheumatic diseases.
Testing for the presence of antinuclear antibodies (ANAs) is a key step in the diagnosis of systemic lupus erythematosus (SLE) and other systemic autoimmune rheumatic diseases (SARD). The standard slide-based indirect immunofluorescence (IIF) test is widely used, but is limited by a relative lack of specificity for SLE and not all SARD-ANAs are detected. Alternative immunoassays that might offer enhanced diagnostic and prognostic information have evolved, and some of these have entered clinical practice. This review summarizes the current state of ANA testing and multiplex techniques for detecting other autoantibodies, the possibility of point-of-care testing, and approaches for applications in early disease stages.


Intron Derived Size Polymorphism in the Mitochondrial Genomes of Closely Related Chrysoporthe Species.
In this study, the complete mitochondrial (mt) genomes of Chrysoporthe austroafricana (190,834 bp), C. cubensis (89,084 bp) and C. deuterocubensis (124,412 bp) were determined. Additionally, the mitochondrial genome of another member of the Cryphonectriaceae, namely Cryphonectria parasitica (158,902 bp), was retrieved and annotated for comparative purposes. These genomes showed high levels of synteny, especially in regions including genes involved in oxidative phosphorylation and electron transfer, unique open reading frames (uORFs), ribosomal RNAs (rRNAs) and transfer RNAs (tRNAs), as well as intron positions. Comparative analyses revealed signatures of duplication events, intron number and length variation, and varying intronic ORFs which highlighted the genetic diversity of mt genomes among the Cryphonectriaceae. These mt genomes showed remarkable size polymorphism. The size polymorphism in the mt genomes of these closely related Chrysoporthe species was attributed to the varying number and length of introns, coding sequences and to a lesser extent, intergenic sequences. Compared to publicly available fungal mt genomes, the C. austroafricana mt genome is the second largest in the Ascomycetes thus far.


What Malaysian women believe about Viagra: a qualitative inquiry.
This paper highlights women's perceptions of sildenafil citrate (Viagra, Pfizer). It is based on a qualitative study on perceptions of erectile dysfunction in the Malaysian multicultural society. Six focus groups were conducted, consisting of 69 women, aged between 40 and 70 years, recruited from the general public and who had given informed consent. The findings revealed that the women were aware of erectile dysfunction and Viagra. Due to their concern about the negative aspects of Viagra, the Chinese and Malay traditional methods of treatment were commonly mentioned. The women from three ethnic groups viewed the possibility of their husband starting to take Viagra with lots of suspicion, mistrust and fear. They would prefer their husband discussing with them the issue of resorting to taking Viagra. The Chinese and Indian women perceived that if a man takes Viagra, it will boost his ego and he will feel more manly. Indian women felt that a man taking Viagra is proof of his love for his wife. The Malay women felt that a man would be ashamed and have a low self-esteem if he were to resort to taking Viagra. Although Viagra is meant for the male, understanding of women's perception of it is beneficial for a couple's sexual relationship.


Cytotoxic lignans from the stem bark of Magnolia officinalis.
Three new lignans, 4'-methoxymagndialdehyde ( 1), 4'-methoxymagnaldehyde B ( 2), and 4'-methoxymagnaldehyde E ( 3), were isolated from hexane- and EtOAc-soluble fractions of the stem bark of Magnolia officinalis, together with eight known compounds ( 4- 11). The structures of compounds 1- 3 were determined on the basis of spectroscopic and physicochemical data analysis. Compounds 1- 11 were tested in vitro for their cytotoxic activity against the K562, HeLa, and A549 cancer cell lines. Among the compounds tested, compound 1 showed the most potent cytotoxic activity against these cancer cell lines, with IC50 values of 3.9, 1.5, and 3.7 microg/mL, respectively.


["Puerperal psychoses". An overview].
Since antiquity, puerperal mental disorders have always been the field of polemics concerning the different possible etiopathogenic hypothesis. XIXth century has been particularly marked by nosographic descriptions and subsequent hormonal speculations. Psychoanalytic approach has been prominent for thirty years but a trend to a come back of biological hypothesis is now noticeable. This overview represent an effort to synthetize clinical, epidemiological and current biological aspects of puerperal psychosis with a special mention to dopamine-oriented researches. The last part reports the main therapeutical available techniques.


Epidemiology of seasonal falciparum malaria in an urban area of Senegal.
A 15-month longitudinal survey was carried out to examine entomological and parasitological aspects of human malaria transmission in Pikine, a city located in the Sudan savanna zone on the Cap Vert peninsula in the west of Senegal. The anopheline population was sampled twice weekly indoors by night human bait capture. During the same period, thick and thin blood films were collected from 296 children at 2-month intervals. Anopheles arabiensis was the only species responsible for transmission of Plasmodium falciparum. The parasite rate showed a positive correlation with both the entomological inoculation rate and the vectorial capacity. In Pikine, malaria is epidemic and probably unstable, and the population enjoys a variable degree of immunity.


Vagus nerve stimulation: mechanisms and factors involved in memory enhancement.
Vagus nerve stimulation (VNS) has been recognized as a useful neuromodulation tool to target the central nervous system by electrical stimulation of peripheral nerves. Activation of the nucleus of the solitary tract (NTS) in the brainstem by vagal afferent nerve fibers allows for modulation of various higher order brain regions, including limbic and cerebral cortex structures. Along with neurological and psychiatric indications, clinical and preclinical studies suggest that VNS can improve memory. While the underlying mechanisms to improve memory with VNS involve brain areas, such as the prefrontal cortex and processes including alertness and arousal, here we focus on VNS-induced memory improvements related to the hippocampus, the main area implicated in memory acquisition. In addition, we detail research demonstrating that a targeted approach to VNS can modify memory outcomes and delve into the molecular mechanisms associated with these changes. These findings indicate that a greater understanding of VNS mechanisms while also considering stimulation parameters, administration site, timing in relation to training, and sex-specific factors, may allow for optimal VNS application to enhance memory.


Fermentative succinate production: an emerging technology to replace the traditional petrochemical processes.
Succinate is a valuable platform chemical for multiple applications. Confronted with the exhaustion of fossil energy resources, fermentative succinate production from renewable biomass to replace the traditional petrochemical process is receiving an increasing amount of attention. During the past few years, the succinate-producing process using microbial fermentation has been made commercially available by the joint efforts of researchers in different fields. In this review, recent attempts and experiences devoted to reduce the production cost of biobased succinate are summarized, including strain improvement, fermentation engineering, and downstream processing. The key limitations and challenges faced in current microbial production systems are also proposed.


Normative and Clinical Self-Perceptions of Sexuality and Their Links to Psychopathology among Adolescents.
Compulsive sexual behavior (CSB) has been linked to psychopathology among adults. Only preliminary research has been conducted on adolescents. In our study, we examined whether CSB is linked to psychopathology among adolescents or whether it is a part of normal sexual development. We also, examined potential risk and resiliency factors that might influence this link. The study population included 311 high school students (184 males and 127 females) aged 16-18 years who completed self-report measures regarding CSB, psychopathology, temperament, and attachment orientations. Adolescents with clinical CSB had more severe psychopathologies than nonclinical ones (with moderate and low levels of CSB) and were unable to utilize resilience factors (i.e., low negative affectivity, high effortful control, and/or attachment security). Low and moderate levels of CSB seem to be part of the normal development of sexuality among adolescents. Clinical CSB seems to be a deviation from this normal development.


Peptide-metal complexes: obtention and role in increasing bioavailability and decreasing the pro-oxidant effect of minerals.
Bioactive peptides derived from food protein sources have been widely studied in the last years, and scientific researchers have been proving their role in human health, beyond their nutritional value. Several bioactivities have been attributed to these peptides, such as immunomodulatory, antimicrobial, antioxidant, antihypertensive, and opioid. Among them, metal-binding capacity has gained prominence. Mineral chelating peptides have shown potential to be applied in food products so as to decrease mineral deficiencies since peptide-metal complexes could enhance their bioavailability. Furthermore, many studies have been investigating their potential to decrease the Fe pro-oxidant effect by forming a stable structure with the metal and avoiding its interaction with other food constituents. These complexes can be formed during gastrointestinal digestion or can be synthesized prior to intake, with the aim to protect the mineral through the gastrointestinal tract. This review addresses: (i) the amino acid residues for metal-binding peptides and their main protein sources, (ii) peptide-metal complexation prior to or during gastrointestinal digestion, (iii) the function of metal (especially Fe, Ca, and Zn)-binding peptides on the metal bioavailability and (iv) their reactivity and possible pro-oxidant and side effects.


Clonal Dissemination of Candida auris Clinical Isolates in Northern Italy, 2021.
Candida auris is a concerning pathogen in health care due to its ability to spread in medical settings. In this study, we characterized the genome of three C. auris clinical isolates collected in the Emilia-Romagna region of Northeastern Italy from January 2020 to May 2021. Whole-genome sequencing was performed using Illumina iSeq 100 and Oxford Nanopore MinION systems. Genomes were assembled with Flye. Phylogenetic analysis was carried out with RaxML. The ERG11, TAC1b, and FKS1 genes were examined for known substitutions associated with resistance to azoles and caspofungin using Diamond. All three C. auris isolates belonged to clade I (South Asian lineage) and showed high minimum inhibitory concentrations for fluconazole. Two of the three isolates were closely related to the first Italian index case of C. auris occurred in the 2019 and carried similar mutations associated to azole resistance. The third isolate showed a greater phylogenetic distance from these strains and had a different genetic determinant not previously seen in Italy. Our data suggest that two C. auris clinical isolates may have been epidemiologically related to the first outbreak previously observed in Italy, while the remaining isolate may have originated from a different source. Further research is needed to understand C. auris transmission and resistance and to control its spread.


Copyright in the digital classroom.
Copyright law was developed to protect the rights of authors. Many educators are aware of copyright law, but they may not be aware of how it applies to them or of the law's scope in regards to computer technology. As the computer is used increasingly to disseminate information, teaching professionals also must have knowledge of the applications of the law to this developing technology. This article reviews the laws defining copyright and fair use. It examines case law regarding copyright, computers, and the Internet. Recommendations for using computers to disseminate class materials to students are discussed.


Left paraduodenal hernia: an autopsy case.
We present a case of a left paraduodenal hernia diagnosed at autopsy. A left paraduodenal hernia is an internal hernia of congenital origin due to the abnormal rotation of the midgut during embryonic development. Internal hernias are a rare cause of intestinal obstruction, with the paraduodenal being the most frequent. The clinical course can be asymptomatic, cause chronic or intermittent abdominal pain, or present with acute abdomen. The clinical entity is a diagnostic challenge, which is illustrated in the present case where there patient died during hospital admission. The case also emphasizes the difficulty in diagnosing the disease by plain abdominal radiography.


Yttrium-90 microsphere radioembolization in unresectable intrahepatic cholangiocarcinoma.
Intrahepatic cholangiocarcinoma is increasing in frequency worldwide, but radical surgical treatment is practicable in 30-40% of cases. The median survival without therapy is about 8 months, increased to 12 months in combination with systemic chemotherapy. Therefore, locoregional therapies, such as, radiofrequency ablation or transarterial chemoembolization have been employed. Radioembolization with yttrium-90 microspheres (90Y-TARE) is a novel intrarterial treatment which could be included in the armamentarium of treatment options, having shown higher median survival (up to 22 months) and low complication rates. Evidence-based algorithms for staging and allocation to treatment should be defined in the future, after robust results obtained through randomized controlled trials, thus establishing the exact role and timing of 90Y-TARE in the treatment protocol of unresectable intrahepatic cholangiocarcinoma.


Clastogenicity of triazinoindole derivatives in relation with the physicochemical properties of the substituents.
The clastogenicity of four compounds of the series 3-(4'-substituted-benzylidenamino)5H-1,2,3-triazin [5,4-b]indol-4-one, which showed an important activity as inhibitors of platelet aggregation, has been evaluated. The compounds studied differed in the physicochemical properties of the substituent occupying the 4' position of the benzilidenamino group. The 4' substituents were: -H, -NO2, -OCH3 and -C6H5. They were tested on V-79 cells, both with and without metabolic activation, and structural chromosome aberrations were scored. Compounds with -H, -NO2 and -OCH3 radicals were active both with and without metabolic activation. Compound with -C6H5 radical was clastogenic only at the highest dose tested and with metabolic activation. It appears that the compound with the biggest and most hydrophobic substituent is the least clastogenic of the series. These results are in agreement with some previous ones obtained in bacteria and show a good correlation between the results of the Ames test and the structural chromosome aberrations test.


Expression of circadian core clock genes in fibroblasts of human gingiva and periodontal ligament is modulated by L-Mimosine and hypoxia in monolayer and spheroid cultures.
The circadian clock is involved in a plethora of physiological processes including bone formation and tooth development. While expression of circadian core clock genes was observed in various tissues, their role in the periodontium is unclear. We hypothesized that periodontal cells express circadian core clock genes and that their levels are modulated by hypoxia mimetic agents and hypoxia. Fibroblasts of human gingiva (GF) and periodontal ligament (PDLF) in monolayer and spheroid cultures were treated with the hypoxia mimetic agent L-Mimosine (L-MIM) or hypoxia. Reverse transcription and quantitative PCR were performed to assess the impact on mRNA levels of the circadian core clock genes Clock, Bmal1, Cry1, Cry2, Per1, Per2, and Per3. GF and PDLF expressed Clock, Bmal1, Cry1, Cry2, Per1, Per2, and Per3 in monolayer and spheroid cultures. In monolayer cultures, L-MIM significantly reduced Clock, Cry2, and Per3 mRNA expression in GF and Clock, Cry1, Cry2, Per1, and Per3 in PDLF. Hypoxia significantly reduced Clock, Cry2, and Per3 in GF and Cry1, Cry2, and Per3 in PDLF. In spheroid cultures, L-MIM significantly decreased Clock, Cry1, Cry2, and Per3 in GF and PDLF. Hypoxia significantly decreased Cry2 and Per3 in GF and Clock and Per3 in PDLF. GF and PDLF express circadian core clock genes. The hypoxia mimetic agent L-MIM and hypoxic conditions can decrease the expression of Clock, Cry1-2 and Per1 and Per3. The specific response depends on cell type and culture model. Future studies will show how this effect contributes to periodontal health and disease.


Safety and efficacy of rituximab in adult immune thrombocytopenia: results from a prospective registry including 248 patients.
We conducted a prospective multicenter registry of 248 adult patients with immune thrombocytopenia (ITP) treated with rituximab to assess safety. We also assessed response and predictive factors of sustained response. In total, 173 patients received 4 infusions of 375 mg/m(2) and 72 received 2 fixed 1-g infusions 2 weeks apart. The choice of the rituximab regimen was based on the physician's preference and not patient characteristics. Overall, 38 patients showed minor intolerance to rituximab infusions; infusions had to be stopped for only 3 patients. Seven showed infection (n = 11 cases), with an incidence of 2.3 infections/100 patient-years. Three patients died of infection 12 to 14 months after rituximab infusions, but the role of rituximab was questionable. In total, 152 patients (61%) showed an overall initial response (platelet count ≥30 × 10(9)/L and ≥2 baseline value). At a median follow-up of 24 months, 96 patients (39%) showed a lasting response. On multivariate analysis, the probability of sustained response at 1 year was significantly associated with ITP duration <1 year (P = .02) and previous transient complete response to corticosteroids (P = .05). The pattern of response was similar with the 2 rituximab regimens. With its benefit/risk ratio, rituximab used off-label may remain a valid option for treating persistent or chronic ITP in adults. This trial was registered at www.clinicaltrials.gov as #NC1101295.


Effectiveness and durability of Interceptor® long-lasting insecticidal nets in a malaria endemic area of central India.
In the present study, Interceptor®, long-lasting polyester net, 75 denier and bursting strength of minimum 250 kPa coated with alpha-cypermethrin @ 200 mg/m² was evaluated for its efficacy in reducing the mosquito density, blood feeding inhibition and malaria incidence in a tribal dominated malaria endemic area in Chhattisgarh state, central India. Its durability, washing practices and usage pattern by the community was also assessed up to a period of three years. The study was carried out in two phases. In the first phase (September 2006 to August 2007), 16 malaria endemic villages in district Kanker were randomized into three groups, viz. Interceptor net (LN), untreated polyester net (100 denier) and without net. Malaria cases were detected by undertaking fortnightly surveillance by home visits and treated as per the national drug policy. Mosquito collections were made by hand catch and pyrethrum space spray methods from human dwellings once every month. Slide positivity rate (SPR) and malaria incidence per 1000 population (PI) were compared between the three study arms to assess the impact of use of Interceptor nets. Simultaneously, wash resistance studies were carried out in the laboratory by doing cone bioassays on Interceptor LNs washed up to 20 times. Activities undertaken in second Phase (April 2008 to October 2009) after an interval of about 18 months post-net distribution included questionnaire based surveys at every six months, i.e. 18, 24, 30 and 36 months to observe durability, usage pattern of LNs and washing practices by the community. After 36 months of field use, 30 nets were retrieved and sampled destructively for chemical analysis. Interceptor nets were found effective in reducing the density, parity rate and blood feeding success rate of main malaria vector Anopheles culicifacies as compared to that in untreated net and no net villages. SPR in LN villages was 3.7% as compared to 6.5% in untreated and 11% in no net villages. PI in LN villages was 16.4 in comparison to 24.8 and 44.2 in untreated polyester net and no net villages respectively. In surveys carried out after three years of initial distribution, 78.7% (737/936) nets were still in possession with the households, of which 68% were used every night. An. culicifacies mortality was >80% in cone bioassays done on LNs washed up to 20 times in laboratory. Mean alpha-cypermethrin content was 43.5 ± 31.7 mg/m² on Interceptor LNs withdrawn after three years of household use against the baseline specification of 200 mg/m². A gradual increase in the proportion of holed nets was observed with the increased period of usage. Interceptor nets were highly effective in reducing vector densities as well as malaria incidence in the study villages. Availability of 78% nets with the households in usable condition clearly indicated durability of Interceptor LNs up to three years in the rural setting of India. The nets were found to contain an effective concentration of alpha-cypermethrin against malaria vector after three years of household use.


[Neurotransmitter changes in the rat brain under combined intoxication induced by alcohol and morphine].
We investigated the levels of biogenic monoamines and their metabolites in the rat hypothalamus, midbrain and cerebellum in acute complex intoxication with morphine and alcohol. The distinctive features of neurotransmitter disorders in various parts of the rat brain under a single exposure to ethanol and morphine, as well as the differences between acute morphine-alcohol and alcohol-morphine intoxication were established. Complex intoxication with alcohol and morphine resulted in signs of dopamine consumption only in the hypothalamus, regardless of the order of alcohol and morphine administration. Under conditions of alcohol-morphine intoxication an increase in the level of metabolites of the serotonergic system was noted in the investigated parts of the brain. In the midbrain and cerebellum the manifestation of combined action of ethanol and morphine is mainly determined by the effect of the last of the administered substances. There are features of changes in the indices of the dopaminergic and serotonergic systems in these experimental conditions, confirmed by the processes of dopamine catabolism and a decrease in the norepinephrine and serotonin concentration in the hypothalamus, which are not observed under individual action of ethanol and morphine.


Is One Style of Early Behavioral Treatment for Autism 'Scientifically Proven?'
Within the field of autism spectrum disorder, the attribute "scientifically proven' it moil commonly urn in reference to the results of early behavioral treatment, and in particular, one style of early behavioral treatment. In this brief article, such claims are evaluated. Concerns raised by other researchers about the methodology of the original Lovaas (1987) study are briefly summarized. A particular concern that has been raised repeatedly u the loch of random assignment of participants to treatment versus control group. A more recent study (Smith, Groen, & Wynn, ZOOO), which included the necessary random assignment of participants to treatment versus control group and assessed multiple outcome measures, is reviewed. The results of the Smith et al. (ZOOO) study with random assignment appear to be less dramatic than the results from the original Lovaas (1987) study.


A large retinoblastoma detected in a fetus at 21 weeks of gestation.
The facial tumour described here is the first reported case of a large retinoblastoma detected early in pregnancy and adds another item to the differential diagnosis of facial tumours visualized by prenatal ultrasound examination. Ultrasound examination of the fetal eyes can be offered in cases of retinoblastomas where prenatal DNA diagnosis is otherwise impossible.


Tissue Motion Annular Displacement Predicts Mortality/Transplant After the Bidirectional Glenn.
Quantifying right ventricular function in patients with a systemic right ventricle (RV) is difficult but important for prognosis. Tissue motion annular displacement tracks displacement of the tricuspid annulus toward the apex. We evaluated this measure alongside fractional area change (FAC) on patients with single, RV prior to the bidirectional Glenn procedure. We tested both measures for correlation with outcomes. Retrospective measurement of tissue motion annular displacement and FAC was performed on echocardiographic clips obtained prior to the bidirectional Glenn. A chart review included postoperative outcomes and midterm mortality/transplant. Bivariate correlations and Cox proportional hazards models were used for analyses. Fifty-one patients with dominant RV underwent the bidirectional Glenn procedure and all had image quality that allowed analysis. The age ranged from 3 to 11 months (median 4 months). Neither tissue motion annular displacement nor FAC correlated with short-term postoperative outcomes. Tissue motion annular displacement was independently predictive of mortality/transplant ( P = .03) in the Cox hazard model. The mean for survivors was 12.4% and for nonsurvivors/transplants was 10.0%. Tissue motion annular displacement intra-observer variability was 2.8% (1.2%-3.5%). Interobserver mean variability was 6.1% (3.3%-8.1%). Fractional area change was not predictive of mortality/transplant. Tissue motion annular displacement is an independent predictor of midterm mortality/transplant after the bidirectional Glenn procedure in patients with single, RV, in this study. It may outperform FAC in this regard and has good reproducibility. Tissue motion annular displacement may be a useful measure in identifying high-risk children in this population.


High Tibial Osteotomy for Varus Deformity of the Knee.
High tibial osteotomy is a powerful technique to treat symptomatic varus deformity of the knee and is successful when properly indicated and performed. Indications include varus deformity with medial compartment osteoarthritis, cartilage or meniscus pathology. Several techniques exist to correct symptomatic varus malalignment along with concomitant procedures to restore cartilage or meniscus injuries. Evidence supporting high tibial osteotomy for symptomatic medial compartment pathology exists, which provides a durable solution for joint preservation. This review will discuss the indications, techniques, and outcomes for high tibial osteotomies used in the treatment of symptomatic varus deformity of the knee.


Glutamine stimulates the S6K/4E-BP branch of insulin signalling pathway to mitigate human poly(Q) disorders in Drosophila disease models.
Since, the S6K/4E-BP sub-pathway can be stimulated by various amino acids; we extended our investigation to examine if oral feeding of amino acids delivers rescue against human poly(Q) toxicity in Drosophila. We utilised Drosophila models of two different poly(Q) disorders to test our hypothesis. Glutamine was fed to the test flies orally mixed in the food. Control and treated flies were then tested for different parameters, such as formation of poly(Q) aggregates and neurodegeneration, to evaluate glutamine's proficiency in mitigating poly(Q) neurotoxicity. Our study, for the first time, reports that glutamine feeding stimulates the growth promoting S6K/4E-BP branch of insulin signalling pathway and restricts pathogenesis of poly(Q) disorders in Drosophila disease models. We noted that glutamine treatment restricts the formation of neurotoxic poly(Q) aggregates and minimises neuronal deaths. Further, glutamine treatment re-establishes the chromatin architecture by improving the histone acetylation which is otherwise compromised in poly(Q) expressing neuronal cells. Since, the insulin signalling pathway as well as mechanism of action of glutamine are fairly conserved between human and Drosophila, our finding strongly suggests that glutamine holds immense potential to be developed as an intervention therapy against the incurable human poly(Q) disorders.


Alpha-fetoprotein levels in different strains of mice during development.
The levels of alpha-fetoprotein (AFP) were measured at birth and at 7 days of age in plasma from Q, C3H/He-mg/Crc, BALB/c/Crc, A/Crc, CBA/Ca/Crc and C57BL/Mcl mice, and in adult blood samples and amniotic fluid at 14 days' gestation from Q, C3H and BALB/c mice. The AFP levels in amniotic fluid and neonatal plasma were significantly higher in BALB/c mice than in the other strains tested, but by postnatal day 7, C57BL and C3H mice had the highest plasma levels. It seems therefore that the genetic mechanisms controlling the synthesis of AFP prenatally may be distinct from those concerned with its reduction after birth. At 6 weeks of age the level in C3H mice was somewhat higher than in BALB/c, and more than double that in Q mice. An attempt to increase AFP levels in response to galactosamine-induced liver damage was successful only in Q adult mice. When amniotic fluids and day 0 plasma from several strains of mice were tested by polyacrylamide gel electrophoresis, no differences in AFP mobility were detected. Preliminary studies were also carried out to see if the administration of sodium butyrate, claimed to delay the timing of the fetal to adult haemoglobin switch in some mammalian species, could also affect the rate of synthesis of AFP during fetal life.


Assessment of Hansenula polymorpha and Arxula adeninivorans-derived rDNA-targeting elements for the design of Arxula adeninivorans expression vectors.
Different targeting sequences derived from the Arxula adeninivorans and Hansenula polymorpha rDNA clusters were tested in A. adeninivorans integration/expression vectors. For element identification, the rDNA unit of A. adeninivorans (accession number ) was first isolated and characterized in addition to the known H. polymorpha unit. The rDNA is a cluster of some forty 7653-bp units without the 5S rDNA gene. The selected elements were integrated into a set of A. adeninivorans expression/integration vectors harbouring a TEF1 promoter - amyA ORF - PHO5 terminator sequence as reporter gene. No differences in mitotic stability, copy number and transformation frequency were observed. All transformants harboured a single copy integrated into the rDNA by a homologous recombination. In contrast, the choice of the rDNA targeting sequence was found to be of impact on productivity. Use of ETS-18S-5.8S fragments from both organisms resulted in a more than 50% increase in comparison to the use of other elements, independent of the orientation within the vector.


Vaginal Preservation in Shaft-Only Phalloplasty: Y-to-V Advancement Technique for Clitoral Hood Redundancy and Reduction Labiaplasty.
As volume and understanding of genital gender affirming surgery (gGAS) has grown, so has the spectrum of surgical techniques to better serve a wider range of transgender and non-binary individuals. Given the diverse spectrum of individuals seeking phalloplasty, we emphasize the importance of patient driven decision-making, beginning with the initial consultation. Phalloplasty surgery is not a one-size-fits-all surgery, but instead should be viewed from an individually-customized approach. This article discusses the technical details for vaginal preservation without scrotoplasty or clitoral tissue burial in a shaft-only phalloplasty (SOP). The technique involves degloving the clitoral shaft, with inset at the ventral base of the phallus, addressing the redundant clitoral hood, and accompanying reduction labiaplasty with a Y-to-V adjacent tissue transfer. The phallus may be neurotized with clitoral nerves from one side of the clitoris, and/or the ilioinguinal nerve. This technique obliterates the degloved clitoral hood and re-suspends the labia minora anteriorly, improving final aesthetics and striving to meet patient genital goals.


The WNT/Beta-catenin pathway in melanoma.
The Wnt/beta-catenin pathway is involved in various cellular activities--including determination, proliferation, migration and differentiation--in embryonic development and adult homeostasis. The deregulation or constitutive activation of the Wnt/beta-catenin pathway may lead to cancer formation. This review focuses on the role of the Wnt/beta-catenin canonical signaling pathway in the melanocyte lineage, and more specifically, in melanoma. Several components of the Wnt/beta-catenin pathway, such as APC, ICAT, LEF1 and beta-catenin are modified in melanoma tumors and cell lines, leading to activation of this signaling. A hallmark of the activation of this pathway is the presence of beta-catenin in the nucleus. Indeed, beta-catenin is found in about 30% of human melanoma nuclei, indicating a potentially specific role for this signaling pathway in this aggressive type of cancer. Beta-catenin can induce ubiquitous genes such as myc or cyclinD1, cell lineage-restricted genes such as Brn2 and melanocyte-specific genes such as Mitf-M and Dct. The Mitf-M and Brn-2 genes encode transcription factors. Mitf plays a critical role in melanocyte survival, proliferation and differentiation. Brn-2 is involved in melanoma proliferation. Determining how the Wnt/beta-catenin signaling pathway, alone or with other pathways, orchestrates the induction of target genes involved in a diverse range of activities represents a major challenge in research into melanoma formation and tumor progression.


High-Intensity Interval Training and Isocaloric Moderate-Intensity Continuous Training Result in Similar Improvements in Body Composition and Fitness in Obese Individuals.
This study aimed to determine the effects of 12 weeks of isocaloric programs of high-intensity intermittent training (HIIT) or moderate-intensity continuous training (MICT) or a short-duration HIIT (1/2HIIT) inducing only half the energy deficit on a cycle ergometer, on body weight and composition, cardiovascular fitness, resting metabolism rate (RMR), respiratory exchange ratio (RER), nonexercise physical activity (PA) levels and fasting and postprandial insulin response in sedentary obese individuals. Forty-six sedentary obese individuals (30 women), with a mean BMI of 33.3 ± 2.9 kg/m2 and a mean age of 34.4 ± 8.8 years were randomly assigned to one of the three training groups: HIIT (n = 16), MICT (n = 14) or 1/2HIIT (n = 16) and exercise was performed 3 times/week for 12 weeks. Overall, there was a significant reduction in body weight, waist (p < .001) and hip (p < .01) circumference,, trunk and leg fat mass (FM; p < .01) and an increase in trunk and leg fat free mass (FFM; p < .01) and cardiovascular fitness (VO2max in ml/kg/min; p < .001) with exercise. However, no significant differences were observed between groups. There was no significant change in RMR, RER, nonexercise PA levels, fasting insulin or insulin sensitivity with exercise or between groups. There was a tendency for a reduction in AUC insulin with exercise (p = .069), but no differences between groups. These results indicate that isocaloric training protocols of HIIT or MICT (or 1/2HIIT inducing only half the energy deficit) exert similar metabolic and cardiovascular improvements in sedentary obese individuals.


Presence of ferric hydroxide clusters in mutants of Haemophilus influenzae ferric ion-binding protein A.
The periplasmic iron binding protein plays an essential role in the iron uptake pathway of Gram-negative pathogenic bacteria from the Pasteurellaceae and Neisseriaceae families and is critical for survival of these pathogens within the host. In this study, we report the crystal structures of two mutant forms of ferric ion-binding protein A (FbpA) from Haemophilus influenzae with bound multinuclear oxo-metal clusters. Crystals of site-directed mutants in the metal or anion binding ligands contain protein in the open conformation, and two mutant FbpAs, H9A and N175L, contain different cluster arrangements in the iron-binding pocket. The iron clusters are anchored by binding to the two tyrosine ligands (Tyr195 and Tyr196) positioned at the vertex of the iron-binding pocket but are not coordinated by the other metal binding ligands. Our results suggest that the metal clusters may have formed in situ, suggesting that the mutant FbpAs may serve as a simple model for protein-mediated mineralization.


Location of preganglionic neurons is independent of birthdate but is correlated to reelin-producing cells in the spinal cord.
Many studies suggest that during neuronal development the birthdate of a neuron appears to have significant consequences for its ultimate location and identity. Our past study shows that sympathetic preganglionic neurons (SPN) in mice lacking the reelin gene settle in abnormal positions in the spinal cord. In the present study we determined that birthdate is not a factor contributing to the abnormal position of SPN in reeler. In both normal and reeler mice the period of neurogenesis of SPN was similar, and the final location of SPN in the spinal cord was independent of birthdate. Additionally, we have identified at least two types of ventral interneurons, V1 and V2, that are involved in the production of Reelin and the positioning of SPN in the spinal cord.


Comparison of multilocus sequence typing and multilocus typing microarray of Chlamydia trachomatis strains from Argentina and Chile.
This study compared conventional ompA genotyping of Chlamydia trachomatis with multilocus sequence typing (MLST) and multilocus typing (MLT) DNA microarray. DNA extracts of 104 C. trachomatis positive specimens were analyzed by ompA sequencing and MLST and of these 76 by MLT array. Obtained MLST sequence types (STs) were compared to sequences in the database http://mlstdb.uu.se. The resolution obtained for MLST (35 STs) was 2.1 higher than for ompA sequencing (17 variants) and 1.3 higher than MLT array (27 MLT groups). Among the 104 samples the predominant genotype E could be divided into 5 ompA variants and 23 STs of which 16 had not been reported in previous studies. The most common STs, ST3 and ST56, were identified as founders and are common in several countries on a global scale. The MLST and the MLT array provided similar strain discrimination capacity and showed considerably higher resolution than conventional ompA sequencing.


Long-term stabilization of crop residues and soil organic carbon affected by residue quality and initial soil pH.
Residues differing in quality and carbon (C) chemistry are presumed to contribute differently to soil pH change and long-term soil organic carbon (SOC) pools. This study examined the liming effect of different crop residues (canola, chickpea and wheat) down the soil profile (0-30cm) in two sandy soils differing in initial pH as well as the long-term stability of SOC at the amended layer (0-10cm) using mid-infrared (MIR) and solid-state 13C nuclear magnetic resonance (NMR) spectroscopy. A field column experiment was conducted for 48months. Chickpea- and canola-residue amendments increased soil pH at 0-10cm in the Podzol by up to 0.47 and 0.36units, and in the Cambisol by 0.31 and 0.18units, respectively, at 48months when compared with the non-residue-amended control. The decomposition of crop residues was greatly retarded in the Podzol with lower initial soil pH during the first 9months. The MIR-predicted particulate organic C (POC) acted as the major C sink for residue-derived C in the Podzol. In contrast, depletion of POC and recovery of residue C in MIR-predicted humic organic C (HOC) were detected in the Cambisol within 3months. Residue types showed little impact on total SOC and its chemical composition in the Cambisol at 48months, in contrast to the Podzol. The final HOC and resistant organic C (ROC) pools in the Podzol amended with canola and chickpea residues were about 25% lower than the control. This apparent priming effect might be related to the greater liming effect of these two residues in the Podzol.


Gingivo-periodontal manifestations in chronic benign neutropenia.
A case of chronic benign neutropenia in a 7-year-old Caucasian male is reported. The predominant clinical symptoms were persistent gingivitis and periodontitis. The clinical, hematological, oral radiographical, histological, and therapeutical features of this uncommon disease are discussed.


A hybrid clustering algorithm for multiple-source resolving in bioluminescence tomography.
Bioluminescence tomography is a preclinical imaging modality to locate and quantify internal bioluminescent sources from surface measurements, which experienced rapid growth in the last 10 years. However, multiple-source resolving remains a challenging issue in BLT. In this study, it is treated as an unsupervised pattern recognition problem based on the reconstruction result, and a novel hybrid clustering algorithm combining the advantages of affinity propagation (AP) and K-means is developed to identify multiple sources automatically. Moreover, we incorporate the clustering analysis into a general multiple-source reconstruction framework, which can provide stable reconstruction and accurate resolving result without providing the number of targets. Numerical simulations and in vivo experiments on 4T1-luc2 mouse model were conducted to assess the performance of the proposed method in multiple-source resolving. The encouraging results demonstrate significant effectiveness and potential of our method in preclinical BLT applications.


What you extract is what you see: Optimising the preparation of water and wastewater samples for in vitro bioassays.
The assessment of water quality is crucial for safeguarding drinking water resources and ecosystem integrity. To this end, sample preparation and extraction is critically important, especially when investigating emerging contaminants and the toxicity of water samples. As extraction methods are rarely optimised for bioassays but rather adopted from chemical analysis, this may result in a misrepresentation of the actual toxicity. In this study, surface water, groundwater, hospital and municipal wastewater were used to characterise the impacts of common sample preparation techniques (acidification, filtration and solid phase extraction (SPE)) on the outcomes of eleven in vitro bioassays. The latter covered endocrine activity (reporter gene assays for estrogen, androgen, aryl-hydrocarbon, retinoic acid, retinoid X, vitamin D, thyroid receptor), mutagenicity (Ames fluctuation test), genotoxicity (umu test) and cytotoxicity. Water samples extracted using different SPE sorbents (Oasis HLB, Supelco ENVI-Carb+, Telos C18/ENV) at acidic and neutral pH were compared for their performance in recovering biological effects. Acidification, commonly used for stabilisation, significantly altered the endocrine activity and toxicity of most (waste)water samples. Sample filtration did not affect the majority of endpoints but in certain cases affected the (anti-)estrogenic and dioxin-like activities. SPE extracts (10.4 × final concentration), including WWTP effluents, induced significant endocrine effects that were not detected in aqueous samples (0.63 × final concentration), such as estrogenic, (anti-)androgenic and dioxin-like activities. When ranking the SPE methods using multivariate Pareto optimisation an extraction with Telos C18/ENV at pH 7 was most effective in recovering toxicity. At the same time, these extracts were highly cytotoxic masking the endpoint under investigation. Compared to that, extraction at pH 2.5 enriched less cytotoxicity. In summary, our study demonstrates that sample preparation and extraction critically affect the outcome of bioassays when assessing the toxicity of water samples. Depending on the water matrix and the bioassay, these methods need to be optimised to accurately assess water quality.


Multiple micronutrient deficiencies: future research needs.
There has been a rising current of calls for a moratorium on international nutritional research in favor of an investment in intervention programs, per se. The topic of multiple-micronutrient supplementation reviewed at the International Workshop on Multi-Micronutrient Deficiency Control in the Life Cycle (May 30-June 1, 2001) has confirmed once again, however, the intimate interaction between program development and a supporting agenda of applied research. The areas of research required to produce successful intervention programs include biologic availability, safety and efficacy, communications and behavior, effectiveness, cost-effectiveness (efficiency), and food and pharmaceutical technology. Attention to safety and surveillance for unintended adverse effects has acquired new relevance as we analyze the multi-center International Research on Infant Supplementation (IRIS) I studies. All professionals involved in research projects in this area must assure both the quality and reliability of investigations and adhere to the highest principles of ethical conduct of research in human studies. The fundamental principles of research design and hypothesis development, quality assurance, reliability of measurements, and sound and unbiased interpretation of findings apply to all experimental science, and must be guaranteed for this mission. Agencies, academic institutions, and industry alike must work to create a system in which researchers can uphold these standards, and realize at the same time that the area of multi-micronutrient supplementation in developing countries can be a fertile area for training future researchers.


Survival and Inflammatory Response in Adipose-derived Mesenchymal Stem Cell-enriched Mouse Fat Grafts.
Adipose tissue-derived mesenchymal stem cells (ATMSCs) are currently used in grafting procedures in a number of clinical trials. The reconstructive role of such cells in fat graft enrichment is largely unclear. This study was undertaken to assess survival and inflammatory response in fat grafts enriched with ATMSCs in mice. ATMSC-enriched adipose tissue was grafted subcutaneously in a clinically relevant manner in mice, and survival and inflammatory response were determined by bioluminescence imaging of transgenic tissue constitutively expressing luciferase or driven by inflammation in wild-type animals. Only a minor fraction of ATMSCs transplanted subcutaneously were found to survive long term, yet fat grafts enriched with ATMSCs showed improved survival for a limited period, compared with no enrichment. NF-κB activity was transiently increased in ATMSC-enriched grafts, and the grafts responded adequately to a proinflammatory stimulus. In one animal, cells originating from the subcutaneous graft were found at a site of inflammation distant from the site of engraftment. ATMSCs display limited subcutaneous survival. Still, ATMSC enrichment may improve the outcome of adipose tissue grafting procedures by facilitating short-term graft survival and adequate inflammatory responses. Migration of cells from grafted adipose tissue requires further investigation.


Bladder cancer in crack testers applying azo dye-based sprays to metal bodies.
Bladder cancer may be produced by azo dyes due to the presence of carcinogenic aromatic amines. Nine cases of suspected occupational bladder cancer that were exposed to different crack test sprays in metal-related jobs were examined. A detailed occupational history was taken and, if possible, the N-acetyltransferase 2 (NAT2) status was determined. The first exposure to crack test sprays ranged from 1957 to 1986. Age at first exposure was between 14 and 33 yr. Age at first diagnosis of bladder cancer varied from 35 to 64 yr. Latency periods were between 17 and 45 yr. The maximal reported exposure period was 29 yr. Four of six genotyped cases were slow NAT2 acetylators. The handling of the crack test spray included spraying the red dye-containing matter on the metal body and washing off the spray with a rag. Thus, workers were exposed by dermal contact as well as by inhalation. The crack test spray, which makes the cracks visible after washing off the red testing spray compounds and applying an additional white spray, contained dyes such as solvent red 19 (Sudan red 7B, N-ethyl-1[[4-(phenylazo)phenyl]azo]-2-naphthylamine) or a mixture of p-phenylazoaniline-N-ethyl-2-naphthylamine and p-phenylazoaniline-N-ethyl-1-naphthylamine. The aromatic amine 2-naphthylamine is classified as human carcinogen by IARC and the national authorities and has been banned in many countries since the mid 1950s. Bladder cancer patients with metal-related jobs need to be explicitly asked about the use of crack test sprays.


Quantitative 3D Determination of Radiosensitization by Bismuth-Based Nanoparticles.
The nanoparticle-induced dose enhancement effect has been shown to improve the therapeutic efficacy of ionizing radiation in external beam radiotherapy. Whereas previous studies have focused on gold nanoparticles (AuNPs), no quantitative studies have been conducted to investigate the potential superiority of other high atomic number (Z) nanomaterials such as bismuth-based nanoparticles. The aims of this study were to experimentally validate and quantify the dose enhancement properties of commercially available bismuth-based nanoparticles (bismuth oxide (Bi2O3-NPs) and bismuth sulfide (Bi2S3-NPs)), and investigate their potential superiority over AuNPs in terms of radiation dose enhancement. Phantom cuvettes doped with and without nanoparticles where employed for measuring radiation dose enhancement produced from the interaction of radiation with metal nanoparticles. Novel 3D phantoms were employed to investigate the 3D spatial distribution of ionising radiation dose deposition. The phantoms were irradiated with kilovoltage and megavoltage X-ray beams and optical absorption changes were measured using a spectrophotometer and optical CT scanner. The radiation dose enhancement factors (DEFs) obtained for 50 nm diameter Bi2O3-NPs and AuNPs were 1.90 and 1.77, respectively, for 100 kV energy and a nanoparticle concentration of 0.5 mM. In addition, the DEFs of 5 nm diameter Bi2S3-NPs and AuNPs were determined to be 1.38 and 1.51, respectively, for 150 kV energy and a nanoparticle concentration of 0.25 mM. The results demonstrate that both bismuth-based nanoparticles can enhance the effects of radiation. For 6 MV energy the DEFs for all the investigated nanoparticles were lower (< 15%) than with kilovoltage energy.


Effect of intraoral scanning on the passivity of fit of implant-supported fixed dental prostheses.
Passive fit between restorations and implants is considered a significant factor in preventing mechanical and biologic failures in implant dentistry. Since impression taking and master cast fabrication have been shown to cause substantial errors, it was the aim of this study to evaluate the effect of intraoral scanning on the passivity of fit of three-unit cement-retained implant-supported fixed dental prostheses (FDPs). Conventional and optical impressions (n = 10) of an in vitro situation with two implants in the mandibular left quadrant were made. Based on the scans, 10 FDP frameworks were CAD/CAM fabricated from zirconia ceramic; stereolithographic casts were also made. On both the stereolithographic casts and the casts obtained from the conventional impressions, 10 frameworks were waxed and cast in dental training alloy. Subsequently, all samples were cemented on the in vitro model, while the strains emerging were recorded for statistical analysis (MANOVA with Pillai trace; β = .05). The restorations fabricated on the stereolithographic casts showed significantly lower levels of strain than the conventionally fabricated ones (P = .013). No significant difference could be found between conventionally and CAD/CAM-fabricated frameworks (P = .080). Intraoral digitization of dental implants appears to be at least as precise as conventional impression taking and master cast fabrication using prefabricated transfer components and laboratory analogs.


Decreased T-Cell Programmed Death Receptor-1 Expression in Pregnancy-Associated Melanoma.
Pregnancy depends on tolerance of an immunologically foreign fetus through type 1 T-cell suppression. Worse melanoma outcomes have been described within 1 year of childbirth. We assessed immunopathologic factors that may account for the observed negative impact of pregnancy on outcome. Women of child-bearing age with ≥24 months follow-up were identified from our Institutional Melanoma Registry. Women with available primary tumor blocks were compared [history of childbirth within 1 year of diagnosis (CB1Y) (n = 18) vs. nonpregnant age-matched controls (n = 13)]. Immunohistochemical staining with quantification of immune infiltrates: CD68 tumor-associated macrophages, CD3 tumor-infiltrating T cells, and PD-1 activated/exhausted T cells; and hematolymphangiogenesis: CD31/D2-40 blood vessels and D2-40 lymphatics was performed by 2 blinded dermatopathologists. CB1Y tumors showed decreased CD3 tumor-infiltrating T cells (P < 0.05) with significantly reduced PD1 expression (P ≤ 0.05). The CD3:PD1 ratio was higher in CB1Y (P < 0.05). Other tested parameters did not significantly differ between the 2 groups. As PD1 expression is induced during type 1 T-cell activation, these data suggest that immune ignorance or suppression may predominate in CB1Y. Further studies are required to identify interventions that may promote tumor-associated T-cell inflammation in such patients.


Species richness and traits predict overyielding in stem growth in an early-successional tree diversity experiment.
Over the last two decades, empirical work has established that higher biodiversity can lead to greater primary productivity; however, the importance of different aspects of biodiversity in contributing to such relationships is rarely elucidated. We assessed the relative importance of species richness, phylogenetic diversity, functional diversity, and identity of neighbors for stem growth 3 yr after seedling establishment in a tree diversity experiment in eastern Minnesota. Generally, we found that community-weighted means of key functional traits (including mycorrhizal association, leaf nitrogen and calcium, and waterlogging tolerance) as well as species richness were strong, independent predictors of stem biomass growth. More phylogenetically diverse communities did not consistently produce more biomass than expected, and the trait values or diversity of individual functional traits better predicted biomass production than did a multidimensional functional diversity metric. Furthermore, functional traits and species richness best predicted growth at the whole-plot level (12 m2 ), whereas neighborhood composition best predicted growth at the focal tree level (0.25 m2 ). The observed effects of biodiversity on growth appear strongly driven by positive complementary effects rather than by species-specific selection effects, suggesting that synergistic species' interactions rather than the influence of a few important species may drive overyielding.


Evaluating comfort measures for commonly performed painful procedures in pediatric patients.
Management of pediatric pain from medical procedures is of great importance for improving both patient care and experience. In this study, we investigated methods of managing acute pain in infants and children by studying the correlation between the number of attempts to complete painful procedures, given different comfort measures. The study is a retrospective review of 74,276 procedures performed at two pediatric hospitals in an integrated academic children's health system between 2013 and 2016. We compared three comfort measures most frequently offered: positions of comfort (POC), distraction (DIST), and pharmacological (PHARM). These methods were compared in the setting of four procedures: peripheral intravenous (PIV) catheter insertion, gastrointestinal tube placement, incision procedures, and bladder catheterization. We used the number of attempts needed to complete a procedure as a measure of efficacy minimizing distressing experience in an acutely painful setting (single attempt vs repeat attempts). Among younger children, DIST appears superior to the other two methods; it performs significantly better for three of the four procedures (PIV catheterization, incision wound, and urinary catheterization) among infants aged <1 year and for PIV catheterization among toddlers aged 1-3 years. For older children, POC tends to perform slightly better than the other two methods, although it is significantly better only for PIV catheterization among adolescents aged 13-21 years and urinary catheterization among children aged 9-12 years. Results from this study may be used to determine appropriate comfort measures for painful procedures in pediatric setting.


Comparsion analysis of data mining models applied to clinical research in traditional Chinese medicine.
To help researchers selecting appropriate data mining models to provide better evidence for the clinical practice of Traditional Chinese Medicine (TCM) diagnosis and therapy. Clinical issues based on data mining models were comprehensively summarized from four significant elements of the clinical studies: symptoms, symptom patterns, herbs, and efficacy. Existing problems were further generalized to determine the relevant factors of the performance of data mining models, e.g. data type, samples, parameters, variable labels. Combining these relevant factors, the TCM clinical data features were compared with regards to statistical characters and informatics properties. Data models were compared simultaneously from the view of applied conditions and suitable scopes. The main application problems were the inconsistent data type and the small samples for the used data mining models, which caused the inappropriate results, even the mistake results. These features, i.e. advantages, disadvantages, satisfied data types, tasks of data mining, and the TCM issues, were summarized and compared. By aiming at the special features of different data mining models, the clinical doctors could select the suitable data mining models to resolve the TCM problem.


Alternative splicing: a promising target for pharmaceutical inhibition of pathological angiogenesis?
In eukaryotes, genes consist in coding sequences (exons) interspersed with non-coding ones (introns). The regulation of alternative inclusion/exclusion of exons, or part of exons, during the maturation of the pre-mRNA into mRNA (alternative splicing) allows a dramatic increase of the protein versus the gene repertoire. In a number of cases, alternative splicing decision generates proteins with distinct, sometimes opposite, functions from a given gene. Angiogenesis is the process of vascularisation in physiological conditions and a series of pathologies, including cancer where it favours tumour progression and dissemination of metastasis. In this issue, we discuss some key examples showing how alternative splicing may induce a switch from anti-angiogenic to pro-angiogenic functions and reciprocally. For some of these splicing events, the molecular mechanisms that trigger alternative splicing toward one or the other direction start to be elucidated. The emergence of strategies enabling to regulate alternative splicing opens new routes for anti-angiogenic therapies.


Self-assembly of condensable "bola-amphiphiles" in water/tetraethoxysilane mixtures for the elaboration of mesostructured hybrid materials.
The self-assembly of condensable amphiphile molecules in water is an attractive approach for the synthesis of mesostructured hybrid materials. In this article, we focus on aminoundecyltriethoxysilane (AUT), a condensable "bola-amphiphile", i.e., an amphiphilic molecule possessing two polar heads on both sides of an aliphatic chain. In the present case, one side is a condensable triethoxysilane, and the other side is an amino group. We report on the self-assembly of AUT in mixtures of water and tetraethoxysilane (TEOS). In situ small-angle X-ray scattering (SAXS) measurements allowed us to follow the evolution of the structure from the liquid state up to the solid material formed upon catalytic polycondensation. Depending on the medium composition, hexagonal or lamellar structures can be observed in the final material. These observations allowed us to propose a model for the self-assembly of AUT in water/TEOS mixtures that we were able to validate by simulations of the SAXS profiles. By taking advantage of the modularity of such a system, it proves possible to prepare in a simple way various structured hybrid materials possessing a high number of available organic functions without using sacrificial surfactant molecules.


Assessing interactions between mdm-2, p53, and bcl-2 as prognostic variables in muscle-invasive bladder cancer treated with neo-adjuvant chemotherapy followed by locoregional surgical treatment.
Tumor proliferation and apoptosis may be influenced by the mdm-2 gene product, which can block the antiproliferative effects of p53. bcl-2, one of a family of related genes that regulates the apoptotic pathway, exhibits a negative influence. Both individual and cooperative effects of these gene products may affect the biological behavior of primary bladder cancers and long-term outcome to standard therapy. This study retrospectively evaluated the association with survival of mdm-2, p53, and bcl-2 expression in 59 patients with muscle-invasive, node-negative transitional cell carcinoma (TCC) treated with neo-adjuvant chemotherapy followed by locoregional surgery. Each marker was defined as an altered phenotype if >or=20% malignant cells in the primary tumor exhibited staining; normal or minimal expression was defined as <20% cells exhibiting staining. Altered mdm-2, p53, and bcl-2 expression was observed in 37%, 54%, and 46% of patients, respectively. In single marker analysis, altered p53 expression correlated with long-term survival (P = 0.05) but mdm-2 (P = 0.42) or bcl-2 (P = 0.17) did not. In the multiple-marker analysis, a prognostic index simultaneously assessing mdm-2, p53, and bcl-2 correlated with survival (P = 0.01). The 5-year survival for patients in which all markers were normally expressed was 54% compared with 25% in those with all three markers aberrantly expressed. Patients with aberrant expression of either one or two markers had an intermediate 5-year survival (49%). There was no association of molecular markers either alone or in combination with pathologic downstaging after neo-adjuvant chemotherapy. The cooperative effects of phenotypes determined by mdm-2, p53, and bcl-2 expression may predict survival in patients with muscle-invasive TCC of the bladder.


MicroRNA: Basic concepts and implications for regeneration and repair of neurodegenerative diseases.
MicroRNAs (miRNA) are small non-coding molecules that revolutionized our knowledge about the regulation of gene expression. Capable to target a large number of mRNA, miRNA are thought to regulate around 30% of the entire human genome. Therefore, these molecules are able to regulate several biological processes, including neuronal survival, differentiation and regeneration. Additionally, miRNA might act as valuable clinical agents in brain pathological conditions. Their specific expression patterns in the brain parenchyma and/or in circulating fluids have been highlighted as potential biomarkers, while the modulation of their activity may have therapeutic value for several neurodegenerative diseases. In this review, we describe miRNA biogenesis, signaling and regulation as well as the role of miR-9, miR-124, miR-132 and miR-137 in both adult neurogenesis and neurodegeneration, namely in Alzheimer's disease, Parkinson's disease, Huntington's disease and amyotrophic lateral sclerosis. The relationship between miRNA, neurodegeneration and neurogenesis will be highlighted. Moreover, the benefits, outcomes and limitations of therapies using miRNA technology for neurodegenerative disorders will also be discussed.


The effect of age on mitochondrial ultrastructure.
The ultrastructure of perfused livers and of mitochondrial fractions from 6-month-old and 30-month-old C57/BL mice were studied. In old mice the liver cell mitochondria were enlarged and rounded with a light 'foamy', vacuolated matrix, short cristae and a loss of dense granules. Quantitative studies showed a 60% increase in the mean size and an increased proportion of larger mitochondria in intact 30-month-old perfused livers. Endothelial and Kupffer cell mitochondria were smaller than those of the parenchymal cells. Mitochondria in pellets prepared from 6- and 30-month-old livers were rounded and condensed, although there were a few larger and 'foamy' mitochondria in the preparations from old mice. Up to 47% of large mitochondria in the old livers were lost during cell fractionation.


Association of connexin36 with zonula occludens-1 in HeLa cells, betaTC-3 cells, pancreas, and adrenal gland.
The PDZ domain-containing protein zonula occludens-1 (ZO-1), a well-established component of tight junctions, has recently been shown to interact with various connexin proteins that form gap junctions. We investigated the association of connexin36 (Cx36) with ZO-1 in various cultured cells and tissues. Punctate immunofluorescence labeling for Cx36 was detected in Cx36-transfected HeLa cells, betaTC-3 cells, pancreatic islets, and adrenal medulla. Immunofluorescence for ZO-1 was also punctate in cells and tissues, and was colocalized with Cx36 at points of cell-cell contact. Immunoprecipitation of either Cx36 or ZO-1 from cell lysates and tissue homogenates resulted in immunoblot detection of ZO-1 or Cx36, respectively, in immunoprecipitates. A 14-amino acid peptide corresponding to the carboxy-terminus of Cx36 showed binding capacity to the PDZ1 domain of ZO-1, which was eliminated after removal of the last 4 carboxy-terminus amino acids. Low micromolar concentrations of the 14-amino acid peptide produced up to 85% inhibition of Cx36 interaction with the PDZ1 domain of ZO-1. These results provide evidence for molecular interaction between Cx36 and ZO-1 in vitro, and in vivo, and suggest that the interference with Cx36/ZO-1 interaction by short carboxy-terminus peptides of Cx36 may be of value for functional studies of this interaction.


[A De-Noising Algorithm for Fluorescence Detection Signal of Mineral Oil in Water by SWT].
Fluorescence analysis is an important means of detecting mineral oil in water pollutants because of high sensitivity, selectivity, ease of design, etc. Noise generated from Photo detector will affect the sensitivity of fluorescence detection system, so the elimination of fluorescence signal noise has been a hot issue. For the fluorescence signal, due to the length increase of the branch set, it produces some boundary issues. The dbN wavelet family can flexibly balance the border issues, retain the useful signals and get. rid of noise, the de-noising effects of dbN families are compared, the db7 wavelet is chosen as the optimal wavelet. The noisy fluorescence signal is statically decomposed into 5 levels via db7 wavelet, and the thresholds are chosen adaptively based on the wavelet entropy theory. The pure fluorescence signal is obtained after the approximation coefficients and detail coefficients quantified by thresholds reconstructed. Compared with the DWT, the signal de-noised via SWT has the advantage of information integrity and time translation invariance.


TOR signalling is required for host lipid metabolic remodelling and survival following enteric infection in Drosophila.
When infected by enteric pathogenic bacteria, animals need to initiate local and whole-body defence strategies. Although most attention has focused on the role of innate immune anti-bacterial responses, less is known about how changes in host metabolism contribute to host defence. Using Drosophila as a model system, we identify induction of intestinal target-of-rapamycin (TOR) kinase signalling as a key adaptive metabolic response to enteric infection. We find that enteric infection induces both local and systemic induction of TOR independently of the Immune deficiency (IMD) innate immune pathway, and we see that TOR functions together with IMD signalling to promote infection survival. These protective effects of TOR signalling are associated with remodelling of host lipid metabolism. Thus, we see that TOR is required to limit excessive infection-mediated wasting of host lipid stores by promoting an increase in the levels of gut- and fat body-expressed lipid synthesis genes. Our data support a model in which induction of TOR represents a host tolerance response to counteract infection-mediated lipid wasting in order to promote survival. This article has an associated First Person interview with the first author of the paper.


A pressure-controlled rat ventilator with electronically preset respirations.
Major experimental surgery on laboratory animals requires adequate anesthesia and ventilation to keep the animal alive throughout the procedure. A ventilator is a machine that helps the anesthesized animal breathe through an endotracheal tube by pumping a volume of gas (oxygen, air, or other gaseous mixtures), comparable with the normal tidal volume, into the animal's lungs. There are two main categories of ventilators for small laboratory rodents: volume-controlled and pressure-controlled ones. The volume-controlled ventilator injects a preset volume into the animal's lungs, no matter the airways' resistance (with the peak inspiratory pressure allowed to vary), while the pressure ventilator controls the inspiratory pressure and allows the inspiratory volume to vary. Here we show a rat pressure ventilator with a simple expiratory valve that allows gas delivery through electronic expiration control and offers easy pressure monitoring and frequency change during ventilation.


Effects of 6-aminochrysene on liver microsomal enzyme activity.
1. No transformation of 6-aminochrysene took place during its incubation with rat liver microsomes under oxygen or anaerobic conditions. 2. 6-Aminochrysene inhibited the hydroxylation of aniline, O-demethylation of p-nitroanisole, and N-demethylation of aminopyrine by rat liver microsomes. 3. Pre-treatment of rats with 6-aminochrysene markedly decreased the N-demethylation in vitro but significantly increased the hydroxylation and the O-demethylation. Similar effects were observed also with microsomal preparations from livers perfused with 6-aminochrysene.


Flexible Composites for Piezocatalysis.
Despite piezoelectric materials have a long history of application, piezoelectric catalysis has continued to be a hot topic in recent years. Flexible piezoelectric materials have just emerged in recent years due to their versatility and designability. In this paper, we review the recent advances in flexible piezoelectric materials for catalysis, discuss the fundamentals of the catalytic properties of composite materials, and detail the typical structures of these materials. We pay special attention to the types of filler in flexible piezoelectric composites, their role and the interaction between the particles and the flexible substrate. Notable examples of flexible piezoelectric materials for organic pollutants degradation, enhanced piezo-photocatalysis and antibacterial applications are also presented. Finally, we present key issues and future prospects for the development of flexible piezoelectric catalysts.


Increasing melanoma incidence and survival trend shifts with improved melanoma-specific survival between 1990 and 2020 in Sweden.
Melanoma-specific survival (MSS) is heterogenous between stages and is highly dependent on the T stage for primary localized disease. New systemic therapies for metastatic cutaneous melanoma (CM) have been introduced since 2012 in Sweden. To analyse the incidence and MSS time trends between 1990 and 2020 in Sweden. Nationwide, population-based and prospectively collected clinico-pathological data on invasive CM from the Swedish Melanoma Registry (SweMR) were analysed for survival trends between 1990 and 2020 using Kaplan-Meier curves and Cox proportional hazard ratios (HRs). In total, 77 036 primary invasive CMs were diagnosed in 70 511 patients in Sweden between 1990 and 2020. The 5-year MSS [95% confidence interval (CI)] was 88.9% (88.3-89.4) for 1990-2000, 89.2% (88.7-89.6) for 2001-2010 and 93.0% (92.7-93.9) for 2011-2020. The odds ratios for being diagnosed with nodular melanoma (vs. superficial spreading melanoma) was significantly reduced by 20% (2001-2010) and by 46% (2011-2020) vs. the reference period 1990-2000. Overall, the MSS improved over both diagnostic periods (2001-2010 and 2011-2020) vs. the reference period 1990-2000 among men and women, respectively [HRmen: 2001-2010: 0.89 (95% CI 0.82-0.96) and 2011-2020: 0.62 (95% CI 0.56-0.67); HRwomen: 2001-2010: 0.82 (95% CI 0.74-0.91) and 2011-2020: 0.62 (95% CI 0.56-0.70)]. The risk of death from CM was significantly lower in all age groups for both men and women in the most recent diagnostic period (2011-2020 vs.1990-2000). The results emphasize the improved MSS among men and women in Sweden. The MSS improvements, specifically for the period 2011-2020, may be correlated to the introduction of new systemic therapies and are here shown for the first time in detail for Sweden.


Asian, American, and deaf: a framework for professionals.
The authors present a multicultural framework for thinking about, assessing, and working with Deaf people from Asian and Asian Deaf backgrounds. Emphasis is placed on cultural awareness and cultural competence for professionals and on building bridges across cultural networks.


A Review of the Estimation of Sensitivity and Specificity in the Context of Time-Dependent Outcomes.
Time is an essential element in the field of survival analysis. Time to an event is essential in adjudicating diagnostic utility and determining the effectiveness of treatment. However, time-to-event outcomes-in a sense-are complicated to deal with, since they involve both a binary component, which is the outcome itself (death or recurrence) and a continuous component, which is the time for the occurrence of the outcome. In such scenarios, simpler metrics such as sensitivity, specificity, positive predictive value, negative predictive value, and area under the curve are insufficient to establish the utility of a diagnostic marker. Given the above constraint, this review discusses established ways in which sensitivity and specificity can be determined and are therefore sufficient in establishing utility in the context of time-dependent outcomes. This review also discusses how studies investigating the sensitivity and specificity of a diagnostic marker in the context of time-dependent outcomes can be improved through the use of existing user-friendly statistical software. LEVEL OF EVIDENCE: 5 TECHNICAL EFFICACY: Stage 3.


Massive biventricular rhabdomyoma in a neonate.
Rhabdomyoma is a well characterised entity in a neonate. Herein, we report a massive biventricular rhabdomyoma in a neonate presenting with cyanosis and congestive heart failure which was confirmed on autopsy. The report is for documentation of an unusually large tumour.