Development of diagnostic reference frames for seizures. Part 1: inter-participant agreement in the selection of symptoms.
Our aim is to develop reliable descriptions of various seizure types, which will be used as a basis for decision support. We use expert opinions in this process. In this contribution we evaluate the inter-participant agreement in the selection of frequently occurring symptoms for the description of seizure types. We compared the actual agreement among participants with the agreement that would result from random symptom selection as well as with the maximal agreement attainable. For each seizure type we calculated the reliability coefficients of the responses. For all seizure types we found that the agreement in symptom selection among the participants is significantly higher than expected by chance, but not reaching the maximum agreement attainable. The reliability coefficients varied between 0.56 and 0.74 for the various seizure types. Although the participants do not reach the maximum agreement attainable in the selection of symptoms, the majority agreement on characteristic frequently occurring symptoms for the different seizure types does approach the maximum agreement attainable. Therefore, we conclude that expert opinions can be used for building descriptions of seizure types. However, to derive a reliable set of symptoms for the construction of the diagnostic reference frames (DRFs) more participants are needed.


Recurrent keratitis due to Acremonium potronii.
In a 15-year-old boy a culture-proved keratitis after a corneal perforation healed without antifungal agents after corneal suturing and application of tissue glue. Eight months later a posterior corneal abscess developed. Diagnostic and therapeutic penetrating keratoplasty was performed when the lesion failed to respond to pimaricin. Cultures were positive for Acremonium potronii, the same fungus isolated from the original corneal laceration eight months previously. To our acknowledge, this is the first case report of a central corneal ulcer or abscess due to this specific organism.


[Evaluation of the activity of the bladder detrusor muscle and analysis of bladder function in subjects with diabetes mellitus under insulin treatment].
The present report concerns investigations of detrusor muscle adrenergic innervations in patients affected by bladder neuropathy secondary to diabetes without obstructive disturbances. Detrusor contractile activity evoked by NE is markedly reduced which can probably be attributed to receptor deficit. Urodynamic evaluation demonstrated a prevalence of sensory peripheral neuropathy than a motor conduction abnormality. In vitro study demonstrated that motor conduction abnormality of detrusor contractile activity is present early without bladder disturbances. Therefore early urodynamic measurements are necessary to evaluate bladder dysfunction and neuropathy in diabetic patients.


Man is fashioned, not born: the contributions of George J. Heuer to surgical education.
George Heuer undertook his medical education and residency training in surgery at Johns Hopkins. He then joined the surgical faculty under Halsted. He became Chair of Surgery at the University of Cincinnati in 1922, where he developed the second formal surgical training program modeled on Halsted's principles. Subsequently, he became Chair of Surgery at Cornell where he founded another surgical residency. His training programs stressed broad and thorough experience, and he championed increasing resident responsibility and independence. The demonstrated efficacy of his surgical residencies assisted greatly in the formation of subsequent resident training programs across this country.


Start codon targeted (SCoT) polymorphism in toxic and non-toxic accessions of Jatropha curcas L. and development of a codominant SCAR marker.
Thirty six start codon targeted (SCoT) primers were used for characterization of 48 accessions of Jatropha curcas from different countries and include material with genetic variation for levels of phorbol esters, yield, seed oil content, test weight and plant type. SCoT analysis revealed high polymorphism and 74% of the primers generated polymorphic profiles. The SCoT6 primer discriminated edible and toxic accessions in a single reaction while the SCoT26 and 27 primers produced amplicons specific to toxic and non-toxic accessions, respectively. The polymorphic SCoT markers obtained with these three primers were converted to sequence characterized amplicon regions (SCARs) which resulted in codominant SCARs with SCoT6 primer and dominant SCARs with SCoT 26 and 27 primers. The codominant nature of SCoT6 primer and the resultant SCAR6 primer were validated on intraspecific hybrids derived from a cross between non-toxic and toxic accessions. The accession JP38 from Madagascar was found to be distinct and showed accession specific bands with 9 different SCoT primers. Sequence analysis of polymorphic amplicons obtained with SCoT6 primer showed a 65 bp deletion in accessions with low/zero phorbol esters. Diversity analysis separated the toxic and non-toxic accessions into two groups and the accessions JP29 and JP48 from Mexico formed a third cluster.


Impact of VEGF and VEGF receptor 1 (FLT1) expression on the prognosis of stage III esophageal cancer patients after radiochemotherapy.
High expression of vascular endothelial growth factor (VEGF) is negatively associated with clinical outcome. The prognostic value of VEGF receptor 1 (FLT1) is unclear. This retrospective study investigated the impact of tumor expression of VEGF and FLT1 on outcome in 68 stage III esophageal cancer patients. The impact of tumor VEGF and FLT expression (< or =10% vs. > 10%) and five additional potential prognostic factors on overaLL survival (OS) and Locoregional control (LC) was retrospectively evaluated. These factors included T-stage (T3 vs. T4), N-stage (NO vs. N1), treatment (radiochemotherapy plus resection vs. radiochemotherapy alone), erythropoietin (ERYPO 10000, Janssen-Cilag, Neuss, Germany) administration during radiotherapy, and majority of hemoglobin levels during radiotherapy (<12 vs. > or =12 g/dl). Subgroup analyses were performed for patients receiving resection (R0 vs. R1/2 resection). The factors found to be significant on univariate analyses (Kaplan-Meier method, log-rank test) were included in multivariate analyses performed with the Cox proportional hazard model. On univariate analysis, improved OS was associated with T3 stage (p = 0.011), surgery (p = 0.019), and hemoglobin > or =12 g/dl (p < 0.001). Improved LC was associated with T3 stage (p = 0.025), hemoglobin > or =12 g/dl (p < 0.001), and VEGF negativity (p = 0.045). On multivariate analyses, only hemoglobin maintained significance. In patients having surgery, RO resection was significantly better than R1/2 resection for OS (p < 0.001) and LC (p < 0.001). Preradiotherapy tumor VEGF expression appears negatively correlated with outcomes, whereas FLT1 expression appears to have no significant impact on OS and LC.


Monomeric pituitary growth hormone and prolactin variants in man characterized by immunoperoxidase electrophoresis.
Immunoperoxidase electrophoresis, combining SDS--ME--PAGE and the 'double bridge' immunoperoxidase staining was applied to crude human pituitary homogenates. With anti-hGH and anti-hPL sera, 4 hGH-related monomers were characterized: a Mr 22 000 peptide corresponding to hGH; a Mr 20 000 peptide corresponding to the known hGH variant and two unknown hGH variants (Mr 65 000 and Mr 75 000). With anti-ovine, rat and human PRL sera, 4 PRL-related monomers were immunostained: one comigrated with purified hPRL (Mr 25 000), and 3 were unknown (Mr 29 000; Mr 45 000; Mr 16 000).


Prevalence of HCV infection and associated factors among illicit drug users in Breves, State of Pará, northern Brazil.
Illicit drug users (DUs) are vulnerable to hepatitis C virus (HCV) infection. The shared use of illicit drugs is the main method of HCV transmission. A cross-sectional study was conducted in Breves, in northern Brazil. We surveyed 187 DUs to determine the prevalence of and factors associated with HCV infection. The prevalence of anti-HCV antibodies was 36.9%, and the prevalence of hepatitis C virus-ribonucleic acid (HCV-RNA) was 31%. Hepatitis C virus infection was associated with tattoos, intravenous drug use, shared use of equipment for drug use, drug use for longer than 3 years, and daily drug use. Strategies for preventing and controlling HCV transmission should be implemented among DUs.


Intradomiciliary and peridomiciliary captures of sand flies (Diptera: Psychodidae) in the leishmaniasis endemic area of Chapare province, tropic of Cochabamba, Bolivia.
In South America, cutaneous leishmaniasis is the most frequent clinical form of leishmaniasis. Bolivia is one of the countries with higher incidence, with 33 cases per 100,000 individuals, and the disease is endemic in 70% of the territory. In the last decade, the number of cases has increased, the age range has expanded, affecting children under 5 years old, and a similar frequency between men and women is found. An entomological study with CDC light traps was conducted in three localities (Chipiriri, Santa Elena and Pedro Domingo Murillo) of the municipality of Villa Tunari, one of the main towns in the Chapare province (Department of Cochabamba, Bolivia). A total of 16 specimens belonging to 6 species of the genus Lutzomyia were captured: Lu. aragaoi, Lu. andersoni, Lu. antunesi, Lu. shawi, Lu. yuilli yuilli and Lu. auraensis. Our results showed the presence of two incriminated vectors of leishmaniasis in an urbanized area and in the intradomicile. More entomological studies are required in the Chapare province to confirm the role of vector sand flies, the intradomiciliary transmission of the disease and the presence of autochthonous cases of cutaneous leishmaniasis.


Comparison of the two cerebral hemispheres in inhibitory processes operative during movement preparation.
Neuroimaging and neuropsychological studies suggest that in right-handed individuals, the left hemisphere plays a dominant role in praxis, relative to the right hemisphere. However hemispheric asymmetries assessed with transcranial magnetic stimulation (TMS) has not shown consistent differences in corticospinal (CS) excitability of the two hemispheres during movements. In the current study, we systematically explored hemispheric asymmetries in inhibitory processes that are manifest during movement preparation and initiation. Single-pulse TMS was applied over the left or right primary motor cortex (M1LEFT and M1RIGHT, respectively) to elicit motor-evoked potentials (MEPs) in the contralateral hand while participants performed a two-choice reaction time task requiring a cued movement of the left or right index finger. In Experiments 1 and 2, TMS probes were obtained during a delay period following the presentation of the preparatory cue that provided partial or full information about the required response. MEPs were suppressed relative to baseline regardless of whether they were elicited in a cued or uncued hand. Importantly, the magnitude of these inhibitory changes in CS excitability was similar when TMS was applied over M1LEFT or M1RIGHT, irrespective of the amount of information carried by the preparatory cue. In Experiment 3, there was no preparatory cue and TMS was applied at various time points after the imperative signal. When CS excitability was probed in the cued effector, MEPs were initially inhibited and then rose across the reaction time interval. This function was similar for M1LEFT and M1RIGHT TMS. When CS excitability was probed in the uncued effector, MEPs remained inhibited throughout the RT interval. However, MEPs in right FDI became more inhibited during selection and initiation of a left hand movement, whereas MEPs in left FDI remained relatively invariant across RT interval for the right hand. In addition to these task-specific effects, there was a global difference in CS excitability across experiments between the two hemispheres. When the intensity of stimulation was set to 115% of the resting threshold, MEPs were larger when the TMS probe was applied over the M1LEFT than over M1RIGHT. In summary, while the latter result suggests that M1LEFT is more excitable than M1RIGHT, the recruitment of preparatory inhibitory mechanisms is similar within the two cerebral hemispheres.


Knowledge Translation in Glomerulonephritis: Successes in Translational Research From the Bench to Bedside.
Glomerulonephritis refers to a rare group of diseases characterized by glomerular inflammation, which collectively are a common cause of kidney failure. Until recently, there was a lack of high-quality clinical trials to inform the care of patients with glomerulonephritides. We identified examples of successful translational research spanning from basic science to clinical applications, and highlight gaps in implementation science. The focus of our review was derived from discussions between health care professionals, researchers, and patient partners. We also performed literature searches pertaining to the treatment of glomerulonephritis in PubMed and Google Scholar. Examples of successful knowledge translation were generated through review of new evidence in the past 5 years and by iterative discussions by the authors. We then conducted a narrative review of several themes related to knowledge translation in glomerulonephritis. This was complemented by an interview with a patient partner to provide an example of a patient's perspective living with glomerulonephritis. We summarized selected recent advances in glomerulonephritis and its knowledge translation in the following domains: (1) identification of auto-antibodies in membranous nephropathy and minimal change disease; (2) clinical trials of novel targeted therapies for IgA nephropathy and lupus nephritis, which have led to approval of new treatments; (3) developments in research networks and clinical trials in glomerulonephritis; (4) recognition of the importance in developing standardized patient reported outcome measures in clinical trials; and (5) barriers in knowledge translation including access to medication. A systematic search of the literature and formal assessment of quality of evidence were beyond the scope of this review.


The analgesic efficacy of preoperative high dose (40 mg x kg(-1)) oral acetaminophen after bilateral myringotomy and tube insertion in children.
The purpose of this study was to measure the plasma levels and analgesic effectiveness of a dose of 40 mg x kg(-1) of preoperative oral acetaminophen. Thirty children aged 55 (17-72) months undergoing bilateral myringotomy and tube insertion (BMT) received acetaminophen 40 mg x kg(-1) p.o. preoperatively. Plasma levels were measured, at 29 (10-51) min and at 60 min in the postanaesthesia care unit (PACU). Children's Hospital of Eastern Ontario Pain Scale (CHEOPS), for all subjects and the Poker Chip Tool (PCT) a self-report scale for subjects aged > 4 years, were used. After discharge, 24-h analgesic efficacy was evaluated using an observer Visual Analogue Scale (VAS) score and further acetaminophen use was recorded. Plasma concentrations were 259 (60-391) micromol x l(-1) and 250 (135-450) micromol x l(-1), respectively. All 60 min plasma concentrations were > or = 70 micromol x l(-1) (ED50 for adenotonsillectomy) and less than 800 micromol x l(-1) (associated with toxicity). Twenty-six subjects (87%) had adequate analgesia (CHEOPS < or = 8). The PCT was only understood in the PACU by 13 of the 21 children > 4 years (62%). The median worst 24-h observer VAS was 0.5 (0-5.5) (27 subjects). No further analgesic was required after discharge in 16/28 (57%). A higher plasma level was associated with fewer doses of acetaminophen after discharge (r = -0.36, P=0.05). No relationship was evident between age, the 60 min plasma acetaminophen level and the CHEOPS carried out at the same time. Acetaminophen 40 mg x g(-1) p.o. results in 60 min plasma levels of 250 (135-450) micromol x l(-1). The in-hospital analgesic efficacy was 87% (CHEOPS < 9, no further analgesics) and the 24-h efficacy was 57% (need for further acetaminophen).


Fish-oil fat emulsion supplementation reduces the risk of retinopathy in very low birth weight infants: a prospective, randomized study.
Preliminary studies suggest that fish-oil lipid emulsion given parenterally to very preterm infants reduces the severity of retinopathy (ROP) and cholestasis. Infants weighing <1250 g at birth were randomly allocated to 2 groups: an experimental group of 60 infants that received an intravenous (IV) soybean, olive oil, and fish oil emulsion, and a control group of 70 infants that was given a parenteral soybean and olive oil emulsion. Plasma and erythrocyte concentrations of docosahexaenoic acid (DHA) were determined using a high-performance liquid chromatography-mass spectrometry analysis. Nine infants in the fish oil group required laser therapy for ROP compared with 22 infants in the standard intralipid group (risk ratio [RR], 0.48; 95% confidence interval [CI], 0.24-0.96). Three infants in the fish oil group developed cholestasis compared with 20 infants in the standard intralipid group (RR, 0.18; 95% CI, 0.055-0.56). The mean plasma DHA concentrations in treated infants were 2.9-fold higher in the fish oil group than in control infants on the 7th and 14th days of life. The mean DHA content in erythrocytes of treated infants was 4.5-fold and 2.7-fold higher compared with controls at 7 and 14 days of age. Premature infants receiving an IV fat emulsion containing fish oil had less ROP requiring laser treatment and less cholestasis than those receiving a standard lipid emulsion. These infants also had higher plasma and erythrocyte DHA levels at 7 and 14 days, suggesting potential long-term neurodevelopmental benefits.


Revisiting the epidemiology of pertussis in Canada, 1924-2015: a literature review, evidence synthesis, and modeling study.
Disease surveillance is central to the public health understanding of pertussis epidemiology. In Canada, public reporting practices have significantly changed over time, creating challenges in accurately characterizing pertussis epidemiology. Debate has emerged over whether pertussis resurged after the introduction of adsorbed pertussis vaccines (1981-1985), and if the incidence fell to its pre-1985 after the introduction of acellular pertussis vaccines (1997-1998). Here, we aim to assemble a unified picture of pertussis disease incidence in Canada. Using publicly available pertussis surveillance reports, we collected, analyzed and presented Canadian pertussis data for the period (1924-2015), encompassing the pre-vaccine era, introduction of vaccine, changes to vaccine technology, and the introduction of booster doses. Information on age began to be reported since 1952, but age reporting practices (full, partial or no ages) have evolved over time, and varied across provinces/territories. For those cases reported without age each year, we impute an age distribution by assuming it follows that of the age-reported cases. Below the age of 20 years, the adjusted age-specific incidence from 1969 to 1988 is substantially higher than existing estimates. In children < 1 year, the incidence in some years was comparable to that during the 1988-1999 resurgence. The results presented here suggest that the surge in the average yearly incidence of pertussis that began in 1988 was weaker than previously inferred, and in contrary to the past findings, below age 5, the average yearly incidence of pertussis from 1999 to 2015 (when the incidence dropped again) has been lower than it was from 1969 to 1988.


Revisiting Dosing Regimen Using Pharmacokinetic/Pharmacodynamic Mathematical Modeling: Densification and Intensification of Combination Cancer Therapy.
Controlling effects of drugs administered in combination is particularly challenging with a densified regimen because of life-threatening hematological toxicities. We have developed a mathematical model to optimize drug dosing regimens and to redesign the dose intensification-dose escalation process, using densified cycles of combined anticancer drugs. A generic mathematical model was developed to describe the main components of the real process, including pharmacokinetics, safety and efficacy pharmacodynamics, and non-hematological toxicity risk. This model allowed for computing the distribution of the total drug amount of each drug in combination, for each escalation dose level, in order to minimize the average tumor mass for each cycle. This was achieved while complying with absolute neutrophil count clinical constraints and without exceeding a fixed risk of non-hematological dose-limiting toxicity. The innovative part of this work was the development of densifying and intensifying designs in a unified procedure. This model enabled us to determine the appropriate regimen in a pilot phase I/II study in metastatic breast patients for a 2-week-cycle treatment of docetaxel plus epirubicin doublet, and to propose a new dose-ranging process. In addition to the present application, this method can be further used to achieve optimization of any combination therapy, thus improving the efficacy versus toxicity balance of such a regimen.


Proteomic characterization of larval and adult developmental stages in Echinococcus granulosus reveals novel insight into host-parasite interactions.
Cystic hydatid disease is an important zoonosis caused by Echinococcus granulosus infection. The expression profiles of its parasitic life stages and host-Echinococcus interactions remain to be elucidated. Here, we identified 157 adult and 1588 protoscolex proteins (1610 in all), including 1290 novel identifications. Paramyosins and an antigen B (AgB) were the dominant adult proteins. Dog proteins (30) identified in adults indicated diminished local inflammation caused by adult infection. The protoscolex expresses proteins that have been reported to be antigens in other parasites, such as 6-phosphofructokinase and calcineurin B. Pathway analyses suggested that E. granulosus uses both aerobic and anaerobic carbohydrate metabolisms to generate ATP. E. granulosus expresses proteins involved in synthesis and metabolism of lipids or steroids. At least 339 of 390 sheep proteins identified in protoscolex were novel identifications not seen in previous analyses. IgGs and lambda light chains were the most abundant antibody species. Sheep proteins were enriched for detoxification pathways, implying that host detoxification effects play a central role during host-parasite interactions. Our study provides valuable data on E. granulosus expression characteristics, allowing novel insights into the molecular mechanisms involved in host-parasite interactions. In this study, the Echinococcus granulosus adult worm proteome was analyzed for the first time. The protein identification of E. granulosus protoscoleces was extended dramatically. We also identified the most abundant host proteins co-purified with Echinococcus. The results provide useful information pertaining to the molecular mechanisms behind host-Echinococcus interaction and Echinococcus biology. This data also increases the potential for identifying vaccine candidates and new therapeutic targets, and may aid in the development of protein probes for selective and sensitive diagnosis of echinococcosis infection. In addition, the data collected here represents a valuable proteomic resource for subsequent genome annotation.


Knockdown of ABCB7 inhibits esophageal cancer progression by inhibiting the TGF-β/Smad signaling.
Esophageal cancer accounts for the seventh in human cancers, and the sixth in the global cancer death. ATP-binding cassette, sub-family B (MDR/TAP), member 7 (ABCB7) maintains intracellular iron homeostasis and involved in the regulation of tumor progression. However, the role and mechanism of ABCB7 in esophageal cancer remained unclear. Here, we investigated its role and regulatory mechanism by knocking down ABCB7 in Eca109 and KYSE30 cells. ABCB7 was significantly upregulated in esophageal cancer tissues, and was strongly associated with metastasis and poor prognosis of patients. ABCB7 knockdown inhibits the proliferation, migration and invasion of esophageal cancer cells. Importantly, ABCB7 knockdown induces apoptosis and non-apoptotic cell death in flow cytometry analysis. Higher intracellular total iron concentration was observed in ABCB7 knockdown Eca109 and KYSE30 cells. We further analyzed ABCB7 expression related genes in esophageal cancer tissues. COX7B were positively correlated with the expression of ABCB7 in 440 esophageal cancer tissues. COX7B rescued the inhibition of cell proliferation and elevated total iron concentration induced by ABCB7 knockdown. In addition, Western blot results showed that ABCB7 knockdown reversed the epithelial-mesenchymal transition (EMT) process and inhibited the TGF-β signaling pathway in Eca109 and KYSE30 cells. In conclusion, ABCB7 knockdown inhibits the TGF-β signaling pathway, inhibits the survival of esophageal cancer cells by inducing cell death, and reverses the EMT process. Targeting ABCB7 or COX7B could be a novel strategy for the treatment of esophageal cancer.


Endoscopic placement of multiple artificial chordae with robotic assistance and nitinol clip fixation.
A totally endoscopic method of placing multiple premeasured artificial chordae with the assistance of the da Vinci surgical system (Intuitive Surgical Inc, Sunnyvale, Calif) and V60 U-clip devices (Medtronic Inc, Minneapolis, Minn) was evaluated. Totally endoscopic placement of multiple artificial chordae with robotic assistance and nitinol clips was performed in 30 patients. After subvalvular exposure with a robotically controlled Atrial Retractor (Intuitive Surgical Inc), artificial chordae constructed of 4-0 polytetrafluoroethylene (Gore-Tex; WL Gore & Associates Inc, Flagstaff, Ariz) were secured to the prolapsing leaflet edge with V60 U-clips. Transesophageal echocardiography to assess successful repair was performed. Repairs of the anterior leaflet, the posterior leaflet, and combinations of both were performed. Crossclamp and cardiopulmonary bypass times were in the range of 78.63 +/- 17.03 minutes and 118.17 +/- 22.55 minutes, respectively. Transesophageal echocardiography showed grade 0 to less than grade 1 mitral regurgitation postoperatively. All patients had an uneventful recovery phase and were discharged within 5 days. Endoscopic placement of premeasured artificial neochordae is greatly facilitated by applying robotic assistance and using nitinol clips for chordae fixation. The endoscopic robotic technique provides excellent functional and clinical outcomes.


3D digital image correlation evaluation of arthrodesis implants.
Hallux valgus is a pathological condition that is typically treated via the Lapidus procedure. The purpose of this study was to understand the biomechanical characteristics of bone, implant devices and the bone-implant interface. In-situ digital image correlation was performed on polyurethane foam, a known bone substitute in a modified three-point bend test frame. We introduced this modified rig as an enhanced methodology for characterizing bone and implant device mechanical performance. This new methodology was validated using aluminum rod specimens, in three and four-point bend setups followed by new configurations to reveal implications of load configurations on joint displacement and implant performance. Bone substitute specimens were constructed with nitinol staples or locking plate to minimize gapping at the 1st tarsometatarsal during testing. Bone-implant interface characterization was enabled by digital image correlation, identifying maximum strain concentrations of 1.5% along the interfaces. Interfacial characteristics were analyzed in context with gap displacement allowed by the implant over cyclical loading. The locking plate implant and nitinol staples gapped an average of 2.2 mm and 3.2 mm respectively under 50 Newtons. Removing all load, the locking plate implant and nitinol staples averaged ~0.8 mm and ~0.3 mm of residual gapping respectively. Our results demonstrate that locking plates provide more initial stability and resistance against gapping under load but are unable to recover compression throughout repetitive loading as seen with the nitinol staple technology. This could lead to a paradigm shift in materials used for early weight bearing protocols post-operation.


Clinicians' experiences in signposting an online mental health resource to expectant mothers: a qualitative study.
Poor maternal mental well-being and a lack of secure parent-infant attachment, have been identified as important factors associated with adverse mental health outcomes later in a child's life. Interventions designed to care for maternal mental well-being during pregnancy and early parenthood, are therefore likely to support healthy child development. Mentalization is a skill parents can practice, improving the emotional bond to the child, offering insights into their own and the child's mental states and potentially improving parental mental well-being. Most pregnant women in Denmark schedule antenatal consultations in general practice, potentially offering a solid platform to promote web-based interventions aiming to enhance mentalization skills. Signposting towards online resources has several advantages including high accessibility, ease of distribution and cost-effectiveness. We aimed to explore the attitudes and experiences of clinicians in general practice in signposting women towards a web-intervention to increase parental mentalization skills. The intervention was offered to pregnant women at their primary preventive antenatal consultation in Danish general practice around week eight of pregnancy, and was designed to be incorporated into the following antenatal- and pediatric consultations until the child's second birthday. Semi-structured interviews about clinicians' experiences with signposting the intervention were conducted with 11 general practitioners (GP), three practice midwives (MW) and one practice nurse (NR). Clinicians wanted to enhance the focus on mental well-being in pregnancy and early childhood during preventive consultations. The main barriers to signposting the web-program were decreasing motivation over time, lack of financial viability and time limitations. Utilizing a psychoeducational web-intervention was generally accepted by clinicians, but ideally not carried out solely in general practice. Signposting web-programs to improve parental mentalization skills can be welcomed by clinicians in general practice but need to be more tailored to suit the everyday workflow of the clinics. Addressing parental mentalization remains largely unchartered territory for pregnant women and clinicians alike, therefore training clinicians on the subject and its presentation should be offered. The study is part of a larger project that has been approved by the Research Ethics Committee at the University of Copenhagen, Nov. 2019 (reference number 504-0111/19-5000).


Angiotensin-receptor blockers: benefits beyond lowering blood pressure.
A number of controlled clinical trials provide evidence that angiotensin-receptor blockers improve the prognosis in a variety of conditions that place patients at high cardiovascular risk. The effect is more than one would expect from the effect of these agents on blood pressure alone. The results of some of these trials have expanded the indications for these drugs.


Novel CLDN14 mutations in Pakistani families with autosomal recessive non-syndromic hearing loss.
Mutations in the CLDN14 gene are known to cause autosomal recessive (AR) non-sydromic hearing loss (NSHL) at the DFNB29 locus on chromosome 21q22.13. As part of an ongoing study to localize and identify NSHL genes, the ARNSHL segregating in four Pakistani consanguineous families were mapped to the 21q22.13 region with either established or suggestive linkage. Given the known involvement of CLDN14 gene in NSHL, DNA samples from hearing-impaired members from the four families were sequenced to potentially identify causal variants within this gene. Three novel CLDN14 mutations, c.167G>A (p.Trp56*), c.242G>A (p.Arg81His), and c.694G>A (p.Gly232Arg), segregate with hearing loss (HL) in three of the families. The previously reported CLDN14 mutation c.254T>A (p.Val85Asp) was observed in the fourth family. None of the mutations were detected in 400 Pakistani control chromosomes and all were deemed damaging based on bioinformatics analyses. The non-sense mutation c.167G>A (p.Trp56*) is the first stop codon mutation in CLDN14 gene to be identified to cause NSHL. The c.242G>A (p.Arg81His) and c.694G>A (p.Gly232Arg) mutations were identified within the first extracellular loop and the carboxyl-tail of claudin-14, respectively, which highlights the importance of the extracellular domains and phosphorylation of cytoplasmic tail residues to claudin function within the inner ear. The HL due to novel CLDN14 mutations is prelingual, severe-to-profound with greater loss in the high frequencies.


Glasgow prognostic score is a predictive index for postoperative infectious complications after total proctocolectomy in ulcerative colitis patients.
Glasgow prognostic score is a systemic inflammatory-based score. The aim of this study was to determine whether the Glasgow prognostic score was a useful predictor of short-term outcomes in patients who undergo total proctocolectomy for ulcerative colitis. eighty ulcerative colitis patients who underwent a total proctocolectomy with ileal pouch-anal anastomosis or permanent end ileostomy from June 2014 to March 2020 were retrospectively analyzed. Patients were divided into a lower Glasgow prognostic score group and a higher Glasgow prognostic score group. postoperative infectious complication occurred more frequently in the higher Glasgow prognostic score group (8.3 % vs 29.5 %, p = 0.018). According to the univariate and multivariate analysis, only a higher Glasgow prognostic score was associated with an increased risk of postoperative infectious complication (OR: 5.478, 95 % CI: 1.236-24.279). Glasgow prognostic score is a simple and useful indicator of postoperative infectious complications.


Epidermal growth factor (hEGF) has no effect on murine intestine epithelial damage and regeneration after melphalan.
The effect of epidermal growth factor (hEGF) on intestinal epithelial damage by melphalan was explored in CBA mice. Human EGF was administered in doses of 100 micrograms kg-1 or 1000 micrograms kg-1 using a variety of schedules. Mucosal damage was assessed 4, 8 and 13 days later, by [14C]-xylose uptake and by microcolony survival of jejunum, ileum and colon. The only regimen to show enhanced jejunal crypt survival was administration of hEGF, 100 micrograms kg-1, i.p., 8 hourly, beginning 24 h before melphalan treatment. Oral administration of hEGF had no effect on melphalan induced damage nor on subsequent recovery of intestinal mucosa. Activity of hEGF in mice was confirmed by demonstration of precocious eyelid opening in newborn mice. No consistent protective or restorative effect of hEGF on melphalan-induced intestinal epithelial damage could be demonstrated with the doses and schedules used.


House mouse abundance and Ross River virus notifications in Victoria, Australia.
The number of emerging and re-emerging infectious diseases is increasing. As such, understanding the fundamental ecology of infectious disease is critical. Short-lived highly fecund amplification hosts are implicated to influence disease prevalence, but few empirical examples exist. We examined the relationship between mouse (Mus musculus) abundance and Ross River virus (RRV) incidence in northwest Victoria, Australia. We determined a biologically plausible distribution overlap of M. musculus, humans, and vector mosquitoes in our study region. We compared M. musculus abundance with human RRV notifications seasonally between 1997 and 2000. Trends in M. musculus and RRV were similar during summer, autumn, and summer plus autumn, but unrelated during winter, spring, and winter plus spring, coinciding with the seasonal abundance and relative absence of the vector, Culex annulirostris. Our results demonstrate a plausible association between M. musculus and RRV incidence, suggesting that short-lived highly fecund amplification hosts may profoundly influence disease transmission. Our results are supported by theoretical studies and empirical evidence from other systems. Further research is warranted to establish a causal relationship between amplification hosts and RRV, and in other infectious disease systems. Implications for the management of infectious disease may exist.


Toluene metabolism during exposure to varying concentrations combined with exercise.
The urinary excretion of hippuric acid (HA) and ortho-cresol (O-cr) in man was measured in two studies of 7-h exposure to toluene in a climate chamber, either constant concentration of 100 ppm or varying concentrations containing peaks of 300 ppm but with a time-weighted average of 100 ppm. In Study A, four males were exposed to clean air and to constant and varying concentrations of toluene in combination with rest and with 100 W exercise in 140 min. Exercise increased end exposure excretion rate of HA and O-cr by 47 and 114%, respectively. After exposure, all excess HA was excreted within 4 h, while O-cr was eliminated with a half life of about 3 h. Alveolar air concentration of toluene varied between 21 and 31 ppm during constant exposure and between 13 and 57 ppm during varying exposure, but no difference in mean alveolar toluene concentration or in metabolite excretion was seen between the exposure schedules. In Study B, 32 males and 39 females aged between 31 and 50 years were exposed once to either clean air, constant or varying concentrations of toluene. Background excretion rate of HA was 0.97 +/- 0.75 mg/min (1.25 +/- 1.05 g/g creatinine) and rose to 3.74 +/- 1.40 mg/min (3.90 +/- 1.85 g/g cr) during the last 3 h of exposure to 100 ppm toluene. The corresponding figures for O-cr were 0.05 +/- 0.05 micrograms/min (0.08 +/- 0.14 mg/g cr), and 2.04 +/- 0.84 micrograms/min (2.05 +/- 1.18 mg/g cr). The individual creatinine excretion rate was considerably influenced by sex, body weight and smoking habits, thus influencing the metabolite concentration standardised in relation to creatinine. It is concluded that both metabolites are estimates of toluene exposure. O-cr is more specific than HA, but the individual variation in excretion of both metabolites is large, and when implementing either of them as biological exposure indices, the influence of sex, body size, age as well as consumption of tobacco and alcohol has to be considered.


Functional Confirmation of DNA Repair Defect in Ataxia Telangiectasia (AT) Infants Identified by Newborn Screening for Severe Combined Immunodeficiency (NBS SCID).
The introduction of newborn screening for severe combined immunodeficiencies (NBS SCID) in 2010 was a significant public health milestone. Although SCID was the primary target, several other conditions associated with severe T-cell lymphopenia have subsequently been identified as secondary targets. The differential diagnosis in infants with an abnormal T-cell receptor excision circle result on NBS SCID who do not meet criteria for typical SCID is often broad, and often the evaluation of these conditions requires immunological and functional testing, in conjunction with genetic analysis, to obtain an accurate diagnosis and develop an appropriate management and treatment plan. We describe here 3 infants identified by NBS SCID, who required additional workup as they did not have a typical SCID phenotype and meet the relevant diagnostic criteria. Genetic testing identified pathogenic variants in ATM in all 3 patients, and the pathogenicity of the variants was confirmed by a functional flow cytometry assay. The patients underwent immunological and genetic workup to identify an underlying cause of their abnormal NBS SCID. Ataxia telangiectasia (AT) was suspected based on clinical and family history, and immunological analyses. The diagnosis was confirmed in all patients with a rapid functional flow cytometric assay and genetic testing. A rapid functional flow cytometry assay was used as a diagnostic and confirmatory tool, in conjunction with genetic testing, to make a diagnosis of AT. Experimental validation of the causal relationship between genotype and phenotype allowed for expeditious diagnosis, which facilitated early discussions with families regarding prognosis, treatment, and management. Even with increased rapidity and access to genetic results, functional testing is required for clinical diagnosis in infants identified by NBS SCID who do not fit into the classic categories or have novel genetic variants to confirm the diagnosis. Consideration should be given to the use of functional assays as an essential component of an integrated evaluation to characterize the genetics and mechanisms of inborn errors of immunity.


Influence of polymorphisms in the RANKL/RANK/OPG signaling pathway on volumetric bone mineral density and bone geometry at the forearm in men.
We sought to determine the influence of single-nucleotide polymorphisms (SNPs) in RANKL, RANK, and OPG on volumetric bone mineral density (vBMD) and bone geometry at the radius in men. Pairwise tag SNPs (r (2) ≥ 0.8) for RANKL (n = 8), RANK (n = 44), and OPG (n = 22) and five SNPs near RANKL and OPG strongly associated with areal BMD in genomewide association studies were previously genotyped in men aged 40-79 years in the European Male Ageing Study (EMAS). Here, these SNPs were analyzed in a subsample of men (n = 589) who had peripheral quantitative computed tomography (pQCT) performed at the distal (4%) and mid-shaft (50%) radius. Estimated parameters were total and trabecular vBMD (mg/mm(3)) and cross-sectional area (mm(2)) at the 4% site and cortical vBMD (mg/mm(3)); total, cortical, and medullary area (mm(2)); cortical thickness (mm); and stress strain index (SSI) (mm(3)) at the 50% site. We identified 12 OPG SNPs associated with vBMD and/or geometric parameters, including rs10505348 associated with total vBMD (β [95% CI] = 9.35 [2.12-16.58], P = 0.011), cortical vBMD (β [95% CI] = 5.62 [2.10-9.14], P = 0.002), cortical thickness (β [95% CI] = 0.08 [0.03-0.13], P = 0.002), and medullary area (β [95% CI] = -2.90 [-4.94 to -0.86], P = 0.005) and rs2073618 associated with cortical vBMD (β [95% CI] = -4.30 [-7.78 to -0.82], P = 0.015) and cortical thickness (β [95% CI] = -0.08 [-0.13 to -0.03], P = 0.001). Three RANK SNPs were associated with vBMD, including rs12956925 associated with trabecular vBMD (β [95% CI] = -7.58 [-14.01 to -1.15], P = 0.021). There were five RANK SNPs associated with geometric parameters, including rs8083511 associated with distal radius cross-sectional area (β [95% CI] = 8.90 [0.92-16.88], P = 0.029). No significant association was observed between RANKL SNPs and pQCT parameters. Our findings suggest that genetic variation in OPG and RANK influences radius vBMD and geometry in men.


Functional activity of the mouse flavin-containing monooxygenase forms 1, 3, and 5.
Three functional mouse flavin-containing monooxygenases (mFMOs) (i.e., mFMO1, mFMO3, and mFMO5) have been reported to be the major FMOs present in mouse liver. To examine the biochemical features of these enzymes, recombinant enzymes were expressed as maltose-binding protein fusion proteins (i.e., MBP-mFMO1, MBP-mFMO3, and MBP-mFMO5) in Escherichia coli and isolated and purified with affinity chromatography. The substrate specificity of these three mouse hepatic FMO enzymes were examined using a variety of substrates, including mercaptoimidazole, trimethylamine, S-methyl esonarimod, and an analog thereof, and a series of 10-(N,N-dimethylaminoalkyl)-2-(trifluoromethyl)phenothiazine analogs. The kinetic parameters of the three mouse FMOs for these substrates were compared in an attempt to explore substrate structure--function relationships specific for each mFMO. Utilizing a common phenothiazine substrate for all three enzymes, we compared the pH dependence for the recombinant enzymes under similar conditions. In addition, thermal stability for mFMO1, mFMO3, and mFMO5 enzymes was examined in the presence and absence of NADPH. The results revealed unique features for mFMO5, suggesting possible impact on the functional significance of this abundantly expressed FMO5 isoform in both human and mouse liver.


Putting to work organic sensing molecules in aqueous media: fluorene derivative-containing polymers as sensory materials for the colorimetric sensing of cyanide in water.
This paper describes a strategy followed to achieve a sensing phenomenon in aqueous media using water-insoluble organic molecules. A sensory polymeric material for the colorimetric sensing of cyanide in water has been developed based on the reactivity of this anion with a fluorene derivative.


Patient function in serial assessments throughout the post-ACL reconstruction progression.
To assess the changes in patient strength and function from 4- to 6-month assessments following ACLR, determine relationships between changes in strength to changes in subjective function, and identify factors that predict patients that fail to increase in strength. Prospective, Cohort Study. Controlled Laboratory. Forty-seven patients(27 female, 24.3 ± 11.1 years) completed a battery of performance assessments at approximately 4- and 6-months following primary ACLR (4.03 ±0 .49 and 6.46 ±0 .68 months). Subjective scores and isokinetic knee flexor and extensor strength were compared across visits. Patients were categorized per their ability to increase in strength beyond a previously defined threshold(0.22 Nm/kg). Binary logistic regression models were used to determine predictors of patients that failed to meet strength changes. Patients demonstrated improvements in patient-reported outcomes and strength measures between visits(P's < 0.05). Higher age (B = -0.073, P = .039), lower pre-injury activity levels (B = 0.61, P = .022), and higher limb symmetry indexes (B = -0.044, P = .05) at 4-months were predictors of patients that did not achieve improvements in quadriceps strength between assessments. From 4- to 6-months post-ACLR, increases in subjective function, strength and symmetry were observed. High quadriceps symmetry at interim assessments without consideration of the magnitude of strength values could overestimate recovery of quadriceps function.


Incorporation of intraportal ammonia-N into blood and tissue nitrogenous compounds in chickens fed low and high protein diets.
1. 15N-Percentage of the amide of glutamine in total blood non-protein-15N was 42 and 48% in chickens fed 5 and 20% protein diets, respectively, when 15N-ammonia was intraportally-infused for 6 hr. 2. The infused ammonia-15N also appeared in the amide of free glutamine in the liver and kidney in large amounts at both levels of protein intake. 3. The 15N incorporated into glutamine-amide in the blood, liver and kidney and non-protein-15N in plasma were greater in chickens fed the low protein diet than in those fed the high protein diet (P less than 0.05 except kidney of P less than 0.01). 4. About 60% of the amide-N of the glutamine which was increased during 6 hr infusion of ammonia was derived from infused ammonia-N and the remainder from endogenous nitrogen, irrespective of protein intake. 5. These results suggest that glutamine is the most important intermediate in detoxication of intraportal ammonia in chickens.


Apoplastic gamma-glutamyl transferase activity encoded by GGT1 and GGT2 is important for vegetative and generative development.
Gamma-glutamyl transferase (GGT; EC 188.8.131.52) is the only enzyme capable of degrading glutathione (GSH) in extra-cytosolic spaces. In plant cells, the GGT1 and GGT2 isoforms are located in the apoplast, bound respectively to the cell wall and the plasma membrane. GGT1 is expressed throughout plants, mainly in the leaves and vascular system, while GGT2 is more specifically expressed in seeds and trichomes, and weakly in roots. Their role in plant physiology remains to be clarified, however. Obtaining the ggt1/ggt2 double mutant can offer more clues than the corresponding single mutants, and to prevent any compensatory expression between the two isoforms. In this work, ggt1/ggt2 RNAi (RNA interference) lines were generated and characterized in the tissues where both isoforms are expressed. The seed yield was lower in the ggt1/ggt2 RNAi plants due to the siliques being fewer in number and shorter in length, with no changes in thiols and sulfur compounds. Proline accumulation and delayed seed germination were seen in one line. There were also fewer trichomes (which contain high levels of GSH) in the RNAi lines than in the wild type, and the root elongation rate was slower. In conclusion, apoplastic GGT silencing induces a decrease in the number of organs with a high GSH demand (seeds and trichomes) as a result of resource reallocation to preserve integrity and composition.


Interdisciplinary knowledge translation: lessons learned from a mental health: fire service collaboration.
Collaborative approaches are being increasingly advocated for addressing a variety of health, mental health and social needs for children, youth and families. Factors important for effective knowledge translation of collaborative approaches of service delivery across disciplines, however, have not been rigorously examined. TAPP-C: The Arson Prevention Program for Children is an intervention program for child and adolescent firesetters provided collaboratively by fire service and mental health professionals. The present study examined the adopter, innovation, and dissemination characteristics associated with TAPP-C implementation, protocol adherence and extent of collaboration by 241 community-based fire service professionals from communities across Ontario. Results revealed that dissemination factors are particularly important for understanding program implementation, adherence and cross-discipline collaboration. Moreover, the findings of this study show significant benefits to both within discipline (intra-disciplinary) and across discipline (interdisciplinary) knowledge translation strategies.


Efficacy and safety of parenteral and local application of tramadol in mandibular third molar extraction: a qualitative systematic review of current evidence.
To assess the efficacy and safety of perioperative parenteral administration or submucosal infiltration of tramadol for perioperative pain control on the basis of pain intensity or analgesics consumption and perioperative outcomes in mandibular third molar surgery. An electronic database search was conducted up to 10 November 2022 to retrieve all randomized controlled trials (RCTs), assessing the analgesic efficacy of parenteral use of tramadol implemented as an adjunct to local anesthesia or intraoperative sedation/general anesthesia, in surgical extraction of mandibular third molars. Modified Jadad scale and Cochrane bias tool were used for the qualitative appraisal. Nineteen RCTs were selected for qualitative analysis. Nine studies involved intravenous, and 5 intramuscular administration of tramadol, while 5 evaluated submucosal infiltration with tramadol. Intravenous or intramuscular tramadol provided a weaker analgesic effect compared with non-steroidal anti-inflammatory drugs (NSAIDs), while intravenous tramadol induced an enhanced analgesic effect than oral tramadol. Parenteral administration of tramadol improved the quality of postoperative analgesia versus placebo. No notable adverse effects were recorded. Parenteral or submucosal infiltration of tramadol constitutes an effective and safe alternative analgesic approach in surgical extraction of mandibular third molars, yet the nociceptive effect of this analgesic modality could not supersede that of NSAIDs. PROSPERO No CRD42021227574.


Functional Respiratory Disorders in Children.
Functional respiratory disorders (FRDs) are those characterized by respiratory symptoms without anatomic or organic etiology. Clinicians caring for children encounter these disorders and should be familiar with diagnosis and treatment. FRDs encompass the habit cough syndrome and its variants, vocal cord dysfunction, hyperventilation disorders, functional dyspnea, and sighing syndrome. Failure to identify these disorders results in unnecessary testing and medication. This article reviews the clinical presentation, manifestation, and treatment of respiratory FRDs in children. How health care providers can successfully identify and treat these reversible conditions in the clinical setting is discussed.


Treatment Implications of Sleep-Related Problems in Pediatric Anxiety Disorders: A Narrative Review of the Literature.
Pediatric anxiety disorders and sleep-related problems (SRPs) are highly prevalent and are associated with serious health or psychopathological consequences. This narrative review aims to provide an overview of the current evidence of the associations between anxiety disorders and SRPs, to examine how this relationship may affect treatment, and to evaluate future directions for the field. Despite their strong bi-directional relationship, SRPs are often neglected in pediatric anxiety literature. There is little consensus on the conceptualization and related measurements of SRPs, which has led to methodological limitations and difficulties. Furthermore, available research suggests that anxiety treatment alone may be inadequate as clinically impairing SRPs were still present post-treatment, which may, in turn, diminish effects of therapy. Understanding the implications of the relationship between anxiety and SRPs on treatment outcomes may be helpful in recognizing opportunities for high impact and enduring interventions.


A high cholesterol diet ameliorates hippocampus-related cognitive and pathological deficits in ovariectomized mice.
Both sex hormone deficiency and hypercholesterolemia are related to cognitive decline or Alzheimer's disease. However, their interactive influence on the neurodegenerative progress is not clear. This study was designed to assess the effects of ovarian hormone depletion and high cholesterol diet alone or in combination on hippocampus-related cognitive and pathological deficits in adult female ICR mice. Depletion of ovarian hormones by ovariectomy for 9 weeks resulted in significant spatial learning and memory deficits as revealed by the water maze testing. Such cognitive alteration was accompanied with increases in neuron death and decreases in choline acetyltransferase activity and synaptopysin expression in the hippocampus. On the other hand, the high cholesterol diet (3% cholesterol plus normal chow) did not exacerbate, but slightly alleviated cognitive decline and significantly attenuated hippocampal pathological changes in ovariectomized mice. Moreover, ovariectomized mice fed high cholesterol had increased serum estrogen levels compared with those fed a normal chow. These results indicate that high cholesterol intake increases the sex hormone synthesis and in turn partially attenuates hippocampus-related cognitive and pathological deficits caused by ovariectomy.


Ia antigens in the normal rat nervous system and in lesions of experimental allergic encephalomyelitis.
The distribution of the class II major histocompatibility (Ia) antigens has been studied in the normal nervous system and in acute lesions of experimental allergic encephalomyelitis (EAE). EAE was induced in Lewis rats with guinea pig spinal cord in Freund's complete adjuvant. Frozen sections from cord, including the roots and ganglia, were stained for Ia antigens, and some sections were also stained for the hydrolytic enzyme acid phosphatase. In the normal CNS and PNS, there were a few vessel-associated cells or small leukocyte-like cells which expressed Ia antigens. No cells were found which expressed both Ia and acid phosphatase [the phenotype used to describe the activated macrophage group of antigen presenting cells (APCs)]. In EAE, Ia positive cells increased in number prior to the detection of clinical signs. Some of these Ia-positive cells were thought to be astrocytes rather than inflammatory cells. At the height of the disease process large numbers of cells in the EAE lesions were Ia-positive. Among these infiltrating cells were some large acid phosphatase-positive cells which also expressed Ia antigens. These double-positive cells appeared to be APCs in the form of activated macrophages, cells known to be involved in the demyelinating processes of EAE. Our results show that some vascular and vessel-associated cells in the normal nervous system express Ia antigens. We suggest that these and other Ia-positive cells in acute EAE lesions may have a role in antigen presentation.


Improving the Continuous Multiple Tube Reactor: an Innovative Bioreactor Configuration with Great Potential for Dark Fermentation Processes.
The continuous multiple tube reactor (CMTR) has been developed as a promising technology to maximize biohydrogen production (BHP) by dark fermentation (DF) by preventing excess biomass accumulation, leading to suboptimum values of specific organic loading rates (SOLR). However, previous experiences failed to achieve stable and continuous BHP in this reactor, as the low biomass retention capacity in the tube region limited controlling the SOLR. This study goes beyond the evaluation of the CMTR for DF by inserting grooves in the inner wall of the tubes to ensure better cell attachment. The CMTR was monitored in 4 assays at 25ºC using sucrose-based synthetic effluent. The hydraulic retention time (HRT) was fixed at 2 h, while the COD varied between 2-8 g L-1 to obtain organic loading rates in the 24 - 96 g COD L-1 d-1. Long-term (90 d) BHP was successfully attained in all conditions due to the improved biomass retention capacity. Optimal values for the SOLR (4.9 g COD g-1 VSS d-1) were observed when applying up to 48 g COD L-1 d-1, in which BHP was maximized. These patterns indicate a favorable balance between biomass retention and washout was naturally achieved. The CMTR looks promising for continuous BHP and is exempt from additional biomass discharge strategies.


A model of the regional uptake of gaseous pollutants in the lung. II. The sensitivity of ozone uptake in laboratory animal lungs to anatomical and ventilatory parameters.
An O3 dosimetry model is used to simulate the local absorption of O3 in the lower respiratory tract of rats and guinea pigs. The model takes into account lower respiratory tract anatomy, transport in the lumen and air spaces, and transport and chemical reactions in the mucous and surfactant layers and in the underlying tissue and capillaries. For each species two anatomical models were used to investigate their influence in predicting absorption. Results with all four anatomical models and various ventilatory parameters showed a qualitative similarity in the shape of the dose versus airway number curves but significant differences in predicted percentage total and percentage pulmonary uptake. The percentage uptake was also sensitive to breathing frequency and tidal volume. Rat lobe models were used to study absorption in lobes and show that O3 tissue dose in centriacinar regions decreases with increasing distance from the trachea. The effect on results of values used for functional residual capacity and of values used for the chemical rate constants for O3 reactions in mucous were explored. Results differed quantitatively but not qualitatively.


The basics of echocardiography.
Cardiac echocardiography is becoming an essential diagnostic tool for a variety of cardiac pathology. Acquiring the necessary knowledge will help non cardiac and the cardiac specialist to understand the echocardiography images and reports and in return will improve the care of the patients. The aim of these of publication is to address the basic knowledge of cardiac echocardiography and the recent advances of its applications.


Coronary stenting in the setting of spontaneous coronary artery dissection.
Spontaneous coronary artery dissection is a rare cause of myocardial ischaemia. Typically it affects young, apparently healthy females, and may result in significant myocardial loss or even death. Due to the rarity of the condition there are no clear guidelines for its management. We describe two cases of spontaneous coronary artery dissection and report successful coronary stenting of the affected artery in one patient. We believe that this interventional technique may be the treatment of choice in selected patients with this condition.


Epilepsia partialis continua in relapsing-remitting multiple sclerosis: A possible distinct relapse phenotype.
Epilepsia partialis continua (EPC) is a rare phenomenon in multiple sclerosis (MS). We describe a patient with relapsing-remitting MS and three episodes of EPC, with refractoriness to anti-seizure drugs but corticosteroid-responsiveness. No lesions likely attributable to her episodes of EPC were seen on 1.5 Tesla MRI, which we hypothesize was due to the small volume of presumed cortical/juxtacortical lesions involving the primary motor cortex. The association with relapsing-remitting disease, corticosteroid responsiveness, and dissemination of episodes of EPC in both space and time in our patient suggest that EPC may represent a distinct relapse phenotype in MS.


Acclimation and repair of DNA damage in recombinant bioluminescent Escherichia coli.
The aim of this study is to understand different adaptive responses in bacteria caused by three different mutagens, namely, an intercalating agent, an alkylating agent and a hydroxylating agent, and the repair systems according to the type of DNA damage, that is, DNA cross-linking and delayed DNA synthesis, alkylation and hydroxylation of DNA. A recombinant bioluminescent Escherichia coli, DPD2794 with the recA promoter fused to luxCDABE originating from Vibrio fischeri, was used in this study. The recombinant bioluminescent E. coli strain DPD2794, containing a recA promoter fused to luxCDABE from V. fischeri, was used to detect adaptive and repair responses to DNA damage caused by mitomycin C (MMC), and these responses were compared with those when the cells were induced with N-methyl-N-nitro-N-nitrosoguanidine (MNNG) and hydrogen peroxide (H2O2). The response ratio between the induced samples and that of the controls decreased suddenly when the induced culture was used in further inductions, indicating a possible adaptive response to DNA damage. DNA damage, or the proteins produced, because of MMC addition does not appear to be completely resolved until the seventh sub-culture after the initial induction, whereas simple damage, such as the base modification caused by MNNG and H2O2, appears to be repaired rapidly as evidenced by the quick recovery of sensitivity. These results suggest that it takes more time to completely repair DNA damage caused by MMC, as compared with a simple repair such as that required for the damage caused by MNNG and H2O2. Therefore, repair of the damage caused by these three mutagens is controlled by different regulons, even though they all induced the recA promoter. Using a bioluminescent E. coli harbouring a recA promoter-lux fusion, it was found that different adaptive responses and repair systems for DNA damage caused by several mutagens exists in E. coli.


[Studies on structure modification of (+)-praeruptorin A].
In order to look for new active compounds, the structure of (+)-praeruptorin A is modified. (+)-Praeruptorin A was isolated from the root of Peucedanum praeruptorum, basic hydrolysis of (+)-praeruptorin A and acyled reactions of hydrolysis product of (+)-praeruptorin A were carried out. Eighteen compounds were semi-synthesized from (+)-praeruptorin A. Fourteen compounds (5-18) among them are new compounds. Preliminary bioactivity assay indicated that the new compounds show calcium antagonist activity, but they are not as strong as (+)-praeruptorin A.


Contrahentes digitorum muscle.
Variations of the adductor pollicis muscle of the hand are seemingly rare. We describe an unusual finding of this muscle made during the routine dissection of a cadaveric hand as part of our medical school's gross anatomy course. We believe this case report represents persistence of a portion of the contrahentes digitorum in a human hand. As muscle variations may compress the median nerve while in the carpal tunnel, the clinician should be aware of such a variation.


Ecological conditions that determine when grazing stimulates grass production.
We report the results of a pot experiment that examined the effects of three ecologically important factors controlling plant growth rates in savanna grasslands: defoliation, soil nitrogen and soil water availability. The experiment was conducted in the Amboseli region in east Africa, and was designed to simulate natural conditions as far as possible, using local soils and a grass species that is heavily grazed by abundant large herbivores. Productivity by different plant components was reduced, stimulated or unchanged by defoliation, depending on specific watering and fertilization treatments. Total above-ground production was stimulated by defoliation and was maximized at moderate clipping intensities, but this was statistically significant only when plants were watered infrequently (every 8 days), and most important, periods between clipping events were extended (at least 24 days). Under these conditions, plant growth rates were limited by water availability at the time of clipping, and soil water conserved in clipped, compared to unclipped plants. Within a given fertilization treatment, whole-plant production was never stimulated by defoliation because root growth was unaffected or inhibited by clipping. However, when fertilization was coupled to defoliation, as they are in the field, whole-plant production by fertilized and moderately clipped plants exceeded production by infertilized, unclipped plants. Under this interpretation, maximum whole-plant production coincided with optimum conditions for herbivores (maximum nitrogen concentration in grass leaves) when watering was frequent, and plants were moderately defoliated. However, these conditions were not the same as those that maximized relative above-ground stimulation of growth (infrequent watering and clipping).The results indicate that above-ground grass production can be stimulated by grazing, and when that is likely to occur. However, the results emphasize that plant production responses to defoliation can vary widely, contigent upon a complex interaction of ecological factors.


A ratiometric fluorescent probe for aluminum ions based-on monomer/excimer conversion and its applications to real samples.
Excessive amount of aluminum is detrimental to growing plants or animals and people are likely to suffer from various diseases upon long-term exposure to aluminum ions. Therefore, sensitive and selective detection of trace amounts of Al(3+) in real samples is of great importance. Herein, a ratiometric fluorescent probe for detecting aluminum ions based on pyrene-1-butyric acid (Py-L-COOH) was developed, which function via monomer/excimer conversion. In the presence of Al(3+), the original monomer-state Py-L-COOH molecules coordinate with Al(3+) and form excimer, thus changing the emission wavelength from 350-400nm to 450-500nm and achieving the ratiometric detection for Al(3+). The probe responds to Al(3+) quickly and can be operable in aqueous media with a very low detection limit of 0.29µM. This system is capable of detecting Al(3+) in real samples and shows high selectivity. Furthermore, the probe exhibits low cytotoxicity and can be used in fluorescence imaging in Hela cell lines. The approach may provide an effective simple probe for aluminum ions determination with application to real samples, as well as offering insights for designing facile ratiometric fluorescent sensors.


Hungry for colours? Attentional bias for food crucially depends on perceptual information.
Attentional bias has been consistently investigated with both threatening and rewarding stimuli, such as food. Several studies demonstrated the presence of an attentional bias for high-calorie food cues compared to neutral (non-food) cues. Authors have interpreted this effect in the context of top-down processes (e.g. the food draws attention thanks to the experience we have with it). The aim of the present study is to test whether perceptual features (bottom-up processes) can modulate the attentional bias effect of food stimuli. Using a dot-probe task, we investigated the relevance of colours in the occurrence of the attentional bias. We compared two different categories of naturalistic food images (high-calorie versus low-calorie) both coloured (Exp. 1) and greyscale (Exp. 2). While we found the occurrence of the attentional bias with high-calorie food coloured images, we did not obtain any significant differences with greyscale images. In Experiments 3 and 4, we compared greyscale office items images, respectively, with greyscale high-calorie food images (Exp. 3) and greyscale low-calorie food images (Exp. 4). In both these last experiments, we did not find any attentional bias. Thus, taken together, our results show that colours convey crucial identity information that could orient our attention. We interpret these results as linked to the relevance of visual appearance in our experience of food.


Estimates of exclusive breastfeeding rates among mother-infant dyads in Quetzaltenango, Guatemala, vary according to interview method and time frame.
The World Health Organization (WHO) recommends exclusive breastfeeding, defined as receiving only breastmilk, through the first 6 months of life to optimize survival, health, and development. To assess exclusive and predominant breastfeeding rates, as defined by WHO, in a sample of Guatemalan infants using three dietary assessment methods. Mothers of 156 infants (78 boys and 78 girls) in the 6th month of life, attending a public health center in Quetzaltenango, an urban area located in the Highlands of Guatemala, were recruited. A single face-to-face interview was performed to assess infant dietary intake using three methods: previous day dietary recall (as suggested by WHO), current feeding practices, and recall of feeding practices since birth. Based on the previous day dietary recall method, exclusive breastfeeding was reported by 87 (56%) of the mothers. Exclusive breastfeeding rates were much lower when estimated by current feeding practices questions (20%) and even lower when based on recall of feeding practices since birth (9%). The sum of exclusive and predominant breastfeeding (full breastfeeding) rates was 58%, 49%, and 31% based on previous day dietary recall, current feeding practices, and recall of feeding practices since birth, respectively. The WHO method of dietary assessment, based solely on the previous day dietary recall, overestimates the exclusive breastfeeding rate compared with recall of feeding practices since birth. In our population sample, adherence to the WHO guidelines for feeding in the first semester of infancy was less than ideal and in need of strengthening.


Fine needle aspiration of the thyroid. Use in an average health care facility.
Fine needle aspiration of the thyroid is suggested as an initial diagnostic procedure in the evaluation of thyroid nodules. Some proponents of the procedure, however, believe that fine needle aspiration should be restricted to centers in which each operator obtains at least 500 biopsy specimens annually. Reviewed were 155 biopsy specimens obtained over three and one-half years, and the sensitivity of fine needle aspiration was determined to be 100 percent, the specificity to be 47.4 percent, and the accuracy to be 73 percent. A review of the literature revealed the sensitivity in larger series to range between 92 and 98 percent, specificity to range between 52 and 99.5 percent, and accuracy to range between 56.1 and 91.3 percent. The surgical yield of carcinoma was 64 percent in patients evaluated with fine needle aspiration, whereas the yield was 26 percent in those who underwent surgery without fine needle aspiration. These results appear to justify the use of fine needle aspiration in the evaluation of nodular thyroid disease at average-sized health care centers.


Both muscle mass and muscle strength are inversely associated with depressive symptoms in an elderly Chinese population.
Few population studies have examined the association between skeletal muscle and depressive symptoms. The aim of this study was to examine whether low muscle mass and muscle strength were associated with the depressive symptoms in elderly Chinese. A cross-sectional study was conducted with 1046 elderly in Tianjin, China. Depressive symptoms were examined using the 30-item Geriatric Depression Scale. A Geriatric Depression Scale score of ≥11 was used to indicate depressive symptoms. Skeletal muscle mass was indicated using a skeletal muscle mass index (SMI) that was measured by bioimpedance analysis and muscle strength was measured by dynamometer. In a multiple logistic regression analysis, subjects in the lowest quartile of SMI or muscle strength had a significantly higher risk for depressive symptoms compared with those in the fourth quartile. The odds ratios and 95% confidence interval for depressive symptoms risk in the lowest quartile of SMI compared with the highest after adjusting for potential confounding factors were 10.1 (2.25, 58.3) in men and 3.17 (1.07, 9.95) in women. The odds ratios (95% confidence interval) for depressive symptoms risk in the lowest quartile of muscle strength compared with the highest after adjusting for potential confounding factors were 2.55 (1.02, 6.67) in men and 4.18 (1.83, 10.2) in women. Both muscle mass and muscle strength are inversely associated with depressive symptoms in elderly Chinese. These findings may provide novel insights linking skeletal muscle and depressive symptoms. Copyright © 2016 John Wiley & Sons, Ltd.


Monoaminergic compensation in the neuropeptide Y deficient mouse brain.
Neuropeptide Y (NPY) is an important central regulator of food consumption and energy expenditure via the hypothalamus. NPY containing neurons have a broad central distribution and are often colocalized with norepinephrine (NE). However, NPY deficient mice do not exhibit any substantial changes in food consumption, body weight or body composition when compared to wild type mice. Since NE and serotonin (5HT) are also important regulators of appetite and metabolism, we evaluated these systems in NPY deficient mice. Brain sections from NPY deficient and wild type mice were labeled with either (3)H-nisoxetine for the NE transporter (NET) or (3)H-citalopram for the 5HT transporter (SERT). Tyrosine hydroxylase expression was evaluated by radioimmunohistochemistry. Brain monoamines and metabolites were evaluated using HPLC. NPY deficient mice exhibited a substantial decrease in NET binding in most brain regions examined. NET binding was less than 50% of control binding in the cerebral cortex and subregions of the thalamus with the greatest decrease seen in the hypothalamus. In contrast, more modest and regionally variable changes were observed in the SERT binding with decreases in regions such as the accessory olfactory nucleus, glomerular layer of the olfactory bulb and the CA1 region of the hippocampus. Measurement of NE and 5HT content as well as the primary metabolites revealed increased NE turnover and decreased 5HT content in the hypothalamus. Therefore, developmental compensation by the NE and 5HT systems may contribute to the absence of a body weight phenotype in NPY deficient mice.


Properties of neuronal type acetylcholine receptors in voltage clamped mouse neuroblastoma cells.
The pharmacological and physiological characteristics of nicotinic acetylcholine receptor-mediated ion current in mouse neuroblastoma N1E-115 cells have been investigated by superfusion of voltage clamped cells with known concentrations of agonists and antagonists for short periods. The acetylcholine-induced inward current is blocked by d-tubocurarine and by kappa-bungarotoxin with IC50 values of 0.5 microM and 30 nM, respectively. The inward current is resistant to alpha-bungarotoxin up to a concentration of 0.5 microM. This allows classification of the acetylcholine receptors of N1E-115 cells as neuronal type nicotinic receptors. The amplitude of the inward current increases with increasing concentration of the agonists acetylcholine and carbamylcholine, resulting in concentration-effect curves with EC50 values of 53 and 240 microM and slope factors slightly below unity. Conversely, at the highest concentrations of the agonists the amplitude of the inward current is reduced and a transient increase of the current appears when the agonist is removed. The characteristics of this transient tail current indicate that the agonists cause rapid ion channel block by interacting with a low affinity site. In the continued presence of acetylcholine the peak inward current is reduced by desensitization. The IC50 value and the slope factor of the steady-state desensitization curve are 1.1 microM and 0.58, respectively. At a low concentration of acetylcholine both the onset of desensitization and the inward current decay are described by similar dual exponential kinetics, but the steady-state inward current is smaller than expected from the degree of desensitization. Neuronal nicotinic receptors in N1E-115 cells and end-plate nicotinic receptors have several characteristics in common. However, the present results indicate that these receptors are distinct, not only in their sensitivity to snake toxins, but also with respect to functional properties.


Positional changes in lumbar disc herniation during standing or lumbar extension: a cross-sectional weight-bearing MRI study.
To investigate biomechanical changes in lumbar disc herniations. Patients with lumbar disc herniation verified on a 1.5-3-T magnetic resonance imaging (MRI) scanner were imaged in a weight-bearing 0.25-T MRI scanner in (1) standing position, (2) conventional supine position with relative lumbar flexion, and (3) supine position with a forced lumbar extension by adding a lumbar pillow. The L2-S1 lordosis angle, the disc cross-sectional area, the disc cross-sectional diameter, and the spinal canal cross-sectional diameter were measured for each position. Disc degeneration and nerve root compression were graded, and the pain intensity was reported during each scan position. Forty-three herniated discs in 37 patients (36.7 ± 11.9 years) were analyzed in each position. The L2-S1 lumbar angle increased in the standing position (mean difference [MD]: 5.61°, 95% confidence interval [95% CI]: 3.44 to 7.78) and with the lumbar pillow in the supine position (MD: 14.63°, 95% CI: 11.71 to 17.57), both compared with the conventional supine position. The herniated disc cross-sectional area and diameter increased during standing compared with during conventional supine position. No changes were found in the spinal canal cross-sectional diameter between positions. Higher nerve root compression grades for paracentral herniations were found during standing compared with during conventional supine position. This was neither found with a lumbar pillow nor for central herniations in any position compared with conventional supine. Disc herniations displayed dynamic behavior with morphological changes in the standing position, leading to higher nerve root compression grades for paracentral herniated discs. • Lumbar herniated discs increased in size in the axial plane during standing. • Increased nerve root compression grades for paracentral herniated discs were found during standing. • Weight-bearing MRI may increase the diagnostic sensitivity of nerve root compression in lumbar disc herniations.


Zinc in human health and disease.
The importance of zinc in human health and disease has been reviewed by reporting data from the recent literature. The role of zinc in human nutrition, general health, skin diseases, acrodermatitis enteropathica, reproductive physiology and pathophysiology, pregnancy, non-insulin-dependent diabetes mellitus as well as atherosclerosis is discussed. The consequences of zinc deficiency and toxicity are also illustrated.


[Ion excretion by the rat kidney in depressed reabsorption in proximal tubule and ascending protion of the loop of Henle].
Simultaneous suppression of reabsorption in the proximal tubule with the aid of polyethylenglucole 400 (PEG) and in ascending part of Henle's loop with furosemide increased diuresis by 121 times and natri-uresis by 242 times on the average. The increase was based on changes in the tubule reabsorption and secretion. The changes of sodium and calcium excretion as well as excretion of potassium and magnesium were parallel. Excretion of sodium and calcium was lesser than the diuresis while that of magnesium and potassium exceeded it. Furosemide reduced the reabsorption of osmotically free water.


Biosensor for label-free DNA quantification based on functionalized LPGs.
A label-free fiber optic biosensor based on a long period grating (LPG) and a basic optical interrogation scheme using off the shelf components is used for the detection of in-situ DNA hybridization. A new methodology is proposed for the determination of the spectral position of the LPG mode resonance. The experimental limit of detection obtained for the DNA was 62±2nM and the limit of quantification was 209±7nM. The sample specificity was experimentally demonstrated using DNA targets with different base mismatches relatively to the probe and was found that the system has a single base mismatch selectivity.


Adnexal torsion with paraovarian cysts in pediatric and adolescent populations: A retrospective study.
Determination of the clinical characteristics associated with adnexal torsion involving paraovarian cysts in pediatric and adolescent populations. Retrospective review of all cases of paraovarian cysts operated on in our department between 2007 and 2019. Demographic characteristics, clinical and sonographic findings were reviewed. The cohort was composed of 39 pediatric and adolescent patients with an operative diagnosis of adnexal masses located in the paraovarian area. The patients were classified into two groups: 19 girls (48.7%) with a confirmed operative diagnosis of adnexal torsion and 20 girls (51.3%) without torsion. The preoperative diagnosis of adnexal torsion was correct in ≈70% of the cases. The mean BMI were similar in both groups. The preoperative sonographic detection rate of paraovarian cysts was also similar (11/19 [57.9%] vs. 14/20 [70.0%]; P = 0.514). The mean cyst diameter did not differ between groups, nor did the classification into cyst size groups (≤50 mm, 51-99 mm and ≥100 mm). Adnexal torsion is a common complication diagnosed in girls undergoing surgery for paraovarian cysts, and is not associated with sonographic appearance or cyst diameter. In order to prevent torsion, surgical removal of paraovarian cysts should thus be considered in young girls undergoing surgery for paraovarian cysts. Retrospective case series. IV.


Preparation of large size, few-layer black phosphorus nanosheets via phytic acid-assisted liquid exfoliation.
Ultrathin uniform BP nanosheets with lateral dimensions of up to several tens of micrometers were prepared via a small molecule-assisted liquid phase exfoliation method, which exhibited attractive electron accepting abilities from photosensitizers and was thus promising in diverse applications such as photocatalysis and photovoltaics.


[Study of pancreases β-cell function in first-degree relatives of type 2 diabetes patients].
To investig the pancreases β-cell function in no-diabetic first-degree relatives of type 2 diabetes mellitus( FDR) patients. Collect T2DM first-degree relatives, and divided them into three groups:no-diabetes group with normal sugar tolerance (NGT); no-diabetes with abnormal sugar tolerance (IGT); new-confirmed T2DM. apart from that three group patients, 30 normal people with no-related disease risks were also collected as normal control (NC). All four groups of patients were experienced with intravenous glucose tolerance test (IVGTT) and counting the first phase of pancreases function by statistic AIR35 and insulin sensitive index (ISI). New-confirmed T2DM patients with the significantly abnormal statistic results about AIR3.5 and ISI, while NGT patients had the abnormal results compared with normal control group but better than T2DM patients. Compared with normal group patients, NGT group appeared decrease of pancreases first phase secretes and insulin resistance but not aggravate enough to induce type 2 diabetes.


TAZ upregulates MIR-224 to inhibit oxidative stress response in multiple myeloma.
Oxidative stress within the bone marrow niche of multiple myeloma contributes to disease progression and drug resistance. Recent studies have associated the Hippo pathway with miRNA biogenesis and oxidative stress in solid tumors. Oxidative stress and miRNA pathway inter-relates in several cancers. Our group recently showed that TAZ functions as a tumor suppressor in MM. However, the role of TAZ in oxidative stress in MM is unknown. We sought to examine the role of TAZ in myeloma cells' response to BM oxidative stress. We postulated that TAZ might be associated with an oxidative stress phenotype and distinct miRNA signature in MM. Using human myeloma cell lines and clinical samples, we demonstrate that TAZ promotes myeloma cells' sensitivity to oxidative stress and anticancer-induced cytotoxicity by inducing miR-224 to repress the NRF2 antioxidant program in MM. We show that low expression of TAZ protein confers an oxidative stress-resistant phenotype in MM. Furthermore, we provide evidence that overexpression of miR-224 in myeloma cells expressing low amounts of TAZ protein inhibits cell growth and enhances sensitivity to anti-myeloma therapeutics. Our findings uncover a potential role for TAZ in oxidative stress response in MM via the miR-224-NRF2 molecular pathway. This provides the scientific ground to explore miR-224 as a potential molecular target to modify TAZ expression and enhance myeloma sensitivity to treatment.


KIR3DL3 Is an Inhibitory Receptor for HHLA2 that Mediates an Alternative Immunoinhibitory Pathway to PD1.
Blockade of the PD1 pathway is a broadly effective cancer therapy, but additional immune-inhibitory pathways contribute to tumor immune evasion. HERV-H LTR-associating 2 (HHLA2; also known as B7H5 and B7H7) is a member of the B7 family of immunoregulatory ligands that mediates costimulatory effects through its interaction with the CD28 family member transmembrane and immunoglobulin domain containing 2 (TMIGD2). However, HHLA2 has also been known to have inhibitory effects on T cells. Here, we report that we have identified killer cell immunoglobulin-like receptor, three immunoglobulin domains and long cytoplasmic tail 3 (KIR3DL3) as an inhibitory receptor for HHLA2 in T cells and natural killer (NK) cells and have generated HHLA2 and KIR3DL3 antibodies that block the immune-inhibitory activity of HHLA2, preserving the costimulatory signal. It is known that HHLA2 is frequently expressed in several tumor types, including clear cell renal cell carcinoma (ccRCC). We found that HHLA2 expression was nonoverlapping with PDL1 expression in ccRCC, suggesting that HHLA2 mediates a mechanism of tumor immune evasion that is independent from PDL1. Blockade of both the PD1 and KIR3DL3 pathways may be a more effective way to reverse tumor immune evasion.See related Spotlight on p. 128.


The combined role of the main olfactory and vomeronasal systems in social communication in mammals.
The main olfactory and the vomeronasal systems are the two systems by which most vertebrates detect chemosensory cues that mediate social behavior. Much research has focused on how one system or the other is critical for particular behaviors. This has lead to a vision of two distinct and complexly autonomous olfactory systems. A closer look at research over the past 30 years reveals a different picture however. These two seemingly distinct systems are much more integrated than previously thought. One novel set of chemosensory cues in particular (MHC Class I peptide ligands) can show us how both systems are capable of detecting the same chemosensory cues, through different mechanisms yet provide the same general information (genetic individuality). Future research will need to now focus on how two seemingly distinct chemosensory systems together detect pheromones and mediate social behaviors. Do these systems work independently, synergistically or competitively in communicating between individuals of the same species?


Unexpected elevated production of Aquifex aeolicus cytochrome c555 in Escherichia coli cells lacking disulfide oxidoreductases.
Mutant strains of Escherichia coli lacking DsbA, DsbB, or DsbD (proteins required for disulfide bond formation in the periplasm) did not produce mitochondrial or chloroplast cytochromes c, as previously observed for bacterial ones. Unexpectedly, however, cytochrome c(555) (AA c(555)) from a hyperthermophile, Aquifex aeolicus, was produced in the E. coli periplasm without Dsb proteins, three times more than with them. These results indicate that the Dsb proteins are not necessarily required for AA c(555) production in E. coli, possibly because of hyperthermophilic origin compared with the others.


Effect of dantrolene sodium on the spastic external urethral sphincter recorded by sphincterometry.
An improved method of sphincterometry is described, which is easy to perform in men and also may be used in women. It gives reproducible results in the individual patient. The maximum pressure was found by radiographic and reflexological examinations of the external urethral sphincter. When 0.5 mg./kg. body weight dantrolene sodium was injected intravenously the resistance of the external urethral sphincter was found to be reduced significantly, presumably reflecting a reduction of reflex activity.


Prognostic use of echocardiography 1 year after a myocardial infarction.
Left ventricular (LV) and right ventricular (RV) function are known predictors of morbidity and mortality after an acute myocardial infarction (MI). However, the prognostic use of a late evaluation of cardiac function after an MI remains unclear. We analyzed echocardiograms obtained 1 year after MI in patients with LV dysfunction at baseline (ejection fraction [EF] < or = 40%) from 291 patients enrolled in the SAVE echocardiographic substudy who did not develop heart failure (HF) or a recurrent MI during this first year. Left ventricular EF and RV fractional area change were assessed. After a median follow-up of 22 months after the 1-year echocardiogram, a low LVEF (< 30%) at 1 year was associated with an increased risk of death and/or HF (hazards ratio [HR] 2.7, 95% CI 1.3-5.3). Presence of RV dysfunction was also associated with an increased risk of death (HR 8.9, 95% CI 3.5-22.1), development of HF (HR 7.1, 95% CI 3.4-15.0), and the composite end point of death or HF (HR 7.6, 95% CI 4.1-14.2). In multivariate analyses, both low LVEF and RV dysfunction remained independently predictive of the composite end point of death or HF. Patients with biventricular dysfunction were at the greatest risk of death and/or HF (HR 19.4, 95% CI 8.2-46.0) in follow-up. In a stable population of survivors of MI, impaired LV and RV function at 1 year after MI are independently and additively predictive of increased risk of HF or death.


Effect of differentiating agents on nucleolar organizer region activity in human melanoma cells.
A human cell line established from a metastatic melanoma had both multiple numerical and structural chromosome aberrations including one to two copies of a submetacentric marker chromosome with an insertion of an active nucleolar organizer region (NOR). Treatment of this cell line with retinoic acid (RA) induced morphologic differentiation and reduced the cellular saturation density concomitant with a significant decrease in Ag-NOR activity. RA-treated cells grown in the absence of this differentiating agent, however, displayed a return to normal Ag-NOR activity, indicating the effect of this chemical on ribosomal genes is reversible.


Comparing the efficacy of xylitol-containing and conventional chewing gums in reducing salivary counts of Streptococcus mutans: An in vivo study.
Dental caries is among the most common chronic diseases in humans. Streptococcus mutans is generally responsible for most cases of dental caries. The present study sought to compare the effects of xylitol-containing and conventional chewing gums on salivary levels of S. mutans. This study adopted a crossover design. Two type of chewing gums (one containing 70% xylitol and approved by the Iranian Dental Association, and another containing sucrose) were purchased. The participants were 32 individuals aged 18-35 years whose oral hygiene was categorized as moderate or poor based on a caries risk assessment table. Salivary levels of S. mutans were measured at baseline, after the first and second phases of chewing gums, and after the washout period. The measurements were performed on blood agar and mitis salivarius-bacitracin agar (MSBA). Pairwise comparisons were then used to analyze the collected data. Salivary levels of S. mutans in both groups were significantly higher during the two stages of chewing gum than in the washout period or baseline. Moreover, comparisons between the two types of gums suggested that chewing xylitol-containing gums led to greater reductions in S. mutans counts. This effect was more apparent in subjects with poor oral hygiene than in those with moderate oral hygiene. Xylitol-containing chewing gums are more effective than conventional gums in reducing salivary levels of S. mutans in individuals with poor-moderate oral hygiene.


Ontogenetic shifts and spatial associations in organ positions for snakes.
Snakes possess an elongated body form and serial placement of organs which provides the opportunity to explore historic and adaptive mechanisms of organ position. We examined the influence of body size and sex on the position of, and spatial associations between, the heart, liver, small intestine, and right kidney for ten phylogenetically diverse species of snakes that vary in body shape and habitat. Snake snout-vent length explained much of the variation in the position of these four organs. For all ten species, the position of the heart and liver relative to snout-vent length decreased as a function of size. As body size increased from neonate to adult, these two organs shifted anteriorly an average of 4.7% and 5.7% of snout-vent length, respectively. Similarly, the small intestine and right kidney shifted anteriorly with an increase in snout-vent length for seven and five of the species, respectively. The absolute and relative positioning of these organs did not differ between male and female Burmese pythons (Python molurus). However, for diamondback water snakes (Nerodia rhombifer), the liver and small intestine were more anteriorly positioned in females as compared to males, whereas the right kidney was positioned more anteriorly for males. Correlations of residuals of organ position (deviation from predicted position) demonstrated significant spatial associations between organs for nine of the ten species. For seven species, individuals with hearts more anterior (or posterior) than predicted also tended to possess livers that were similarly anteriorly (or posteriorly) placed. Positive associations between liver and small intestine positions and between small intestine and right kidney positions were observed for six species, while spatial associations between the heart and small intestine, heart and right kidney, and liver and right kidney were observed in three or four species. This study demonstrates that size, sex, and spatial associations may have potential interacting effects when testing evolutionary scenarios for the position of snake organs.


Toxicity and Adverse Effects in Clozapine-Related Presentations to a Medical Toxicology Service in Western Sydney.
Clozapine is an anti-psychotic agent, reserved for treatment-resistant schizophrenia, with demonstrated efficacy in an otherwise therapeutically challenging patient population. We aimed to review the full spectrum casemix of clozapine presentations to our tertiary toxicology service. In this retrospective study, we reviewed consecutive clozapine related toxicity presentations to a tertiary medical toxicology inpatient and consultation service-including deliberate self-poisoning (DSP), adverse drug reaction (ADR), recreational use, and therapeutic misadventure over a 10-year period from 2011 to 2021. Data were extracted for demographics, ingested dose, exposure characteristics, and patient outcome. We identified 83 patients with clozapine-related presentations over the 10-year period. Twenty-two patients were excluded. Of the remaining 61 patients, 28 patients presented with DSP, 20 patients with accidental overdose, and 13 patients with an ADR; no patients presented with recreational use. It was noted that ADRs were largely idiosyncratic reactions and not always related to dose adjustments. In the context of therapeutic misadventure and DSP, we noted that a lower mean dose achieved a higher poison severity score (PSS) in clozapine-naive patients when compared to those patients on regular clozapine. The presentation of clozapine-related toxicity differs depending on the modality of ingestion, whether DSP, accidental, or as a result of ADR. Patients naive to clozapine therapy tend to experience higher PSS with lower doses ingested either in a deliberate self-poisoning or accidental ingestion context. This is likely due to tolerance to the sedative properties of clozapine. No patients manifested clinical toxicity greater than 8 hours after ingestion, with an observation period of 6 hours accurately identifying toxicity in most patients.


Holistic approach to community in crisis.
This report emphasizes the belief that whatever the type and scale of disaster, the period of transition from relief to recovery is the most critical. Following the severe earthquake that struck Kachchh, Gurjarat, India on 26 January 2001, emotions spanned grief over the lives lost; anxiety over property and other economic losses; profound feelings of isolation, helplessness, and guilt; and panic in the face of problematic communications from authorities. In an attempt to manage this vast array of psychosocial problems, a large cadre of volunteers was rapidly trained and supervised by experts to work as grass-roots counselors for the community.