Simple outpatient postoperative analgesia using an orbital catheter after enucleation.
To evaluate an indwelling orbital catheter, placed at enucleation, for repeatable delivery of local anesthetic on an outpatient basis. A retrospective, noncomparative, case series medical record review was performed of patients undergoing enucleation and receiving an indwelling orbital pain-control catheter at surgery by us from January 1, 1998, through December 31, 2001. Medical records were reviewed for hospitalization status postoperatively. Medical records of those patients treated on an outpatient basis were reviewed for patient and family comments about ease of use of the pain-control catheter and the degree of pain control and for any complications associated with catheter use. The main outcome measures included documented patient and family comments and physician medical record notes about catheter use and complications. Of the 85 patients, 67 were treated on an outpatient basis. The other 18 patients required a postoperative hospital admission for unassociated medical problems. Of the 67 patients, 58 (87%) reported using the catheter at home at least once. Of these 58 patients, 10 reported mild discomfort with catheter use, but in no case did the patient discontinue catheter use because of discomfort. All patients using the catheter reported pain relief lasting from 1(1/2) to 4 hours. No postoperative complications associated with catheter placement were observed. The orbital pain-control catheter allows a caregiver to easily and repeatedly deliver local anesthetic to the operative site following enucleation, resulting in effective postoperative analgesia while the patient recovers at home.


Short-term outcomes and costs analysis of robotic-assisted versus laparoscopic cholecystectomy-a retrospective single-center analysis.
Robotic-assisted surgery is an alternative technique for patients undergoing minimal invasive cholecystectomy (CHE). The aim of this study is to compare the outcomes and costs of laparoscopic versus robotic CHE, previously described as the major disadvantage of the robotic system, in a single Austrian tertiary center. A retrospective single-center analysis was carried out of all patients who underwent an elective minimally invasive cholecystectomy between January 2010 and August 2020 at our tertiary referral institution. Patients were divided into two groups: robotic-assisted CHE (RC) and laparoscopic CHE (LC) and compared according to demographic data, short-term postoperative outcomes and costs. In the study period, 2088 elective minimal invasive cholecystectomies were performed. Of these, 220 patients met the inclusion criteria and were analyzed. One hundred ten (50%) patients underwent LC, and 110 patients RC. There was no significant difference in the mean operation time between both groups (RC: 60.2 min vs LC: 62.0 min; p = 0.58). Postoperative length of stay was the same in both groups (RC: 2.65 days vs LC: 2.65 days, p = 1). Overall hospital costs were slightly higher in the robotic group with a total of €2088 for RC versus €1726 for LC. Robotic-assisted cholecystectomy is a safe and feasible alternative to laparoscopic cholecystectomy. Since there are no significant clinical and cost differences between the two procedures, RC is a justified operation for training the whole operation team in handling the system as a first step procedure. Prospective randomized trials are necessary to confirm these conclusions.


Hepatic steatosis as measured by the computed attenuation parameter predicts fibrosis in long-term methotrexate use.
To determine predictors of hepatic steatosis by the computed attenuation parameter (CAP) and fibrosis via transient elastography (TE) in persons on methotrexate (MTX) therapy with rheumatologic and dermatologic diseases. A single-centred retrospective cohort study was performed. Patients on >6 months of MTX for a rheumatologic or dermatologic disease who had undergone TE from January 2015 to September 2019 were included. Multivariate analysis was performed to determine predictors of steatosis and fibrosis. A total of 172 patients on methotrexate were included. Psoriasis was the most frequent diagnosis (n = 55), followed by rheumatoid arthritis (n = 45) and psoriatic arthritis (n = 34). Steatosis (CAP ≥245 dB/m) was present in 69.8% of patients. Multivariate regression analysis revealed that diabetes mellitus (OR 10.47, 95% CI 1.42-75.35), hypertension (OR 5.15, 95% CI 1.75-15.38), and BMI ≥30 kg/m2 (OR 16.47, 95% CI 5.56-45.56) were predictors of steatosis (CAP ≥245 dB/m). Predictors of moderate to severe fibrosis (Metavir ≥F2 = TE ≥8.0 kPa) by multivariate regression analysis included moderate to severe steatosis (CAP ≥270 dB/m) (OR 8.36, 95% CI 1.88-37.14), diabetes mellitus (OR 2.85, 95% CI 1.09-7.48), hypertension (OR 5.4, 95% CI 2.23-13.00), dyslipidemia (OR 3.71, 95% CI 1.50-9.18), and moderate alcohol use (OR 3.06, 95% CI 1.2-7.49). In patients on MTX for rheumatologic and dermatologic diseases, hepatic steatosis as measured by CAP was common and moderate to severe steatosis predicted moderate to severe fibrosis.


In-house validation of a multiplex real-time PCR method for simultaneous detection of Salmonella spp., Escherichia coli O157 and Listeria monocytogenes.
A wide variety of qPCR methods currently exist for Salmonella spp., Escherichia coli O157 and Listeria monocytogenes detection. These methods target several genes and use different detection chemistries, either in simplex or in multiplex formats. However, the majority of these methods have not been carefully validated, and the number of validated methods that use multiplex qPCR is even lower. The aim of the present study was to develop and validate a multiplex qPCR method from previously validated simplex qPCR primers and probes. A modified broth medium was selected and primary and secondary enrichment times were further optimized. Efficiency of the newly combined qPCR system was comprised between 91% and 108%, for simplex and multiplex analyses. A total of 152 food and environmental, natural and spiked samples, were analyzed for the evaluation of the method obtaining values above 91% that were reached for all the quality parameters analyzed. A very low limit of detection (5 cfu/25 g after enrichment) for simultaneous identification of these 3 pathogens was obtained.


Phosphodiesterase 7B/microRNA-200c relationship regulates triple-negative breast cancer cell growth.
Members of microRNA-200 (miRNA-200) family have a regulatory role in epithelial to mesenchymal transition (EMT) by suppressing Zeb1 and Zeb2 expression. Consistent with its role in suppressing EMT, Hsa-miR-200c-3p (miR-200c), a member of miR-200 family is poorly expressed in mesenchymal-like triple-negative breast cancer (TNBC) cells and ectopic miR-200c expression suppresses cell migration. In this study, we demonstrated that miR-200c potently inhibited TNBC cell growth and tumor development in a mechanism distinct from its ability to downregulate Zeb1 and Zeb2 expression, because silencing them only marginally affected TNBC cell growth. We identified phosphodiesterase 7B (PDE7B) as a bona fide miR-200c target. Importantly, miR-200c-led inhibition in cell growth and tumor development was prevented by forcing PDE7B transgene expression, while knockdown of PDE7B effectively inhibited cell growth. These results suggest that miR-200c inhibits cell growth by targeting PDE7B mRNA. To elucidate mechanism underlying miR-200c/PDE7B regulation of TNBC cell growth, we showed that cAMP concentration was lower in TNBC cells compared with estrogen receptor-positive (ER + ) cells, and that both miR-200c and PDE7B siRNAs were able to increase cAMP concentration in TNBC cells. High level of cellular cAMP has been shown to induce cell cycle arrest and apoptosis in TNBC cells. Our observation that ectopic expression of miR-200c triggered apoptosis indicates that it does so by elevating level of cellular cAMP. Analysis of breast tumor gene expression datasets revealed an inverse association between miR-200c and PDE7B expression. Especially, both low miR-200c and high PDE7B expression were correlated with poor survival of breast cancer patients. Our study supports a critical role of miR-200c/PDE7B relationship in TNBC tumorigenesis.


Meniscus-climbing insects.
Water-walking insects and spiders rely on surface tension for static weight support and use a variety of means to propel themselves along the surface. To pass from the water surface to land, they must contend with the slippery slopes of the menisci that border the water's edge. The ability to climb menisci is a skill exploited by water-walking insects as they seek land in order to lay eggs or avoid predators; moreover, it was a necessary adaptation for their ancestors as they evolved from terrestrials to live exclusively on the water surface. Many millimetre-scale water-walking insects are unable to climb menisci using their traditional means of propulsion. Through a combined experimental and theoretical study, here we investigate the meniscus-climbing technique that such insects use. By assuming a fixed body posture, they deform the water surface in order to generate capillary forces: they thus propel themselves laterally without moving their appendages. We develop a theoretical model for this novel mode of propulsion and use it to rationalize the climbers' characteristic body postures and predict climbing trajectories consistent with those reported here and elsewhere.


Lychnophora ericoides Mart. (Brazilian arnica) ethanol extract accelerates the skin wound healing process: Evidence for its mechanism of action.
Lychnophora ericoides Mart, also known as the Brazilian arnica or fake arnica, belongs to the Asteraceae family. Leaves and roots are used in alcoholic and hydroalcoholic preparations for the treatment of wounds, inflammation, and pain. The present study aimed to investigate the effects of L. ericoides ethanolic extract (EELE) on cutaneous wound healing and the mechanisms of action involved. A total of 72 C57BL/6 mice were randomly divided into four groups of six animals each. An excisional wound was made in the dorsal region of each mouse. The test groups were topically treated with the vehicle, a positive control commercial reference drug, EELE ointment (5%), and EELE ointment (10%). The treatments were applied over 14 days. The wound area was measured every two days to verify the wound closure kinetics. On days 3, 7, and 14 the wound tissue samples were processed for Hematoxylin and Eosin, Masson-Trichrome, and Toluidine blue staining. The expression of renin-angiotensin system (RAS) components, the vascular growth factor-A (VEGF-A), the basic fibroblast growth factor (FGF-2), and type I collagen genes were evaluated. Phytochemical analyses were performed using HPLC-DAD and HPLC-MS/MS. The EELE (10%) significantly reduced the wound area compared to the treatments used for the other groups. Histological analysis demonstrated that wounds treated with L. ericoides for 14 days developed improved anatomical skin features, healed with hair follicles and sebaceous glands, increased collagen production and angiogenesis, and decreased the number of mast cells at the injury site. Real-time PCR data demonstrated that groups treated with EELE (10%) showed increased Type I collagen, VEGF-A, FGF-2, and AT1R and decreased ACE II and receptor MAS. The healing action of L. ericoides may be related to the presence of phenolic compounds, such as phenolic acids, chlorogenic acid derivatives, and C-glycoside flavonoids. Topical treatment with EELE increases important factors for wound healing: FGF, VEGF, collagen formation, and the expression of the proliferative axis of the renin-angiotensin system. For the first time, the present study shows the healing action of L. ericoides at the molecular level in an animal model. This process can be used as an alternative therapy for wound healing and the development of herbal therapy.


Incidence and in-hospital outcomes of Clostridium difficile infection among type 2 diabetes patients in Spain.
To examine incidence and in-hospital outcomes of Clostridium difficile infection (CDI) among patients with type 2 diabetes (T2DM); compare clinical variables among T2DM patients with matched non-T2DM patients hospitalised with CDI and identify factors associated with in-hospital mortality (IHM) among T2DM patients. We performed a retrospective study using the Spanish National Hospital Discharge Database, 2001-2015. We included patients that had CDI as primary or secondary diagnosis in their discharge report. For each T2DM patient, we selected a gender, age, readmission status and year-matched non-diabetic patient. We identified 44 695 patients with CDI (21.19% with T2DM). We matched 3040 and 5987 couples with a primary and secondary diagnosis of CDI, respectively. Incidence of CDI was higher in T2DM patients (IRR per hospital admission 1.12; 95% CI 1.09-1.14, IRR per population 1.26; 95% CI 1.22-1.29). IHM decreased over time in T2DM and non-T2DM patients (from 15.36% and 13.35%, in 2001-2003 to 10.36% and 11.73% in 2013-2015), despite a concomitant increase in CDI diagnoses overtime. Among those with CDI as secondary diagnosis IHM was higher in nondiabetic 16.17% than in T2DM patients 13.19% (P < 0.001). In T2DM patients higher mortality rates were associated with older age, comorbidities, severe CDI, and readmission. Primary diagnosis of CDI was associated with lower IHM (OR 0.71; 95% CI 0.60-0.84) than secondary diagnosis. Incidence of CDI was higher in T2DM patients. IHM decreased over time, regardless of the existence or not of T2DM. IHM was significantly lower in T2DM patients with CDI as primary diagnosis than non diabetic patients.


Gene expression of luteinizing hormone receptor in carp somatotrophs differentially regulated by local action of gonadotropin and dopamine D1 receptor activation.
In grass carp, luteinizing hormone (LH) can act locally within the pituitary to regulate growth hormone expression. To test if LH receptor (LHR) expression in the carp pituitary can also serve as a target of modulation for LH actions, grass carp LHR was cloned and characterized by functional expression. In carp pituitary cells, LHR mRNA (lhr) level could be reduced by LH or human chorionic gonadotropin (hCG) but up-regulated by dopamine treatment. Dopamine-induced lhr expression occurred mainly in carp somatotrophs via the cAMP/PKA pathway coupled to pituitary D1 receptors. This stimulatory effect could be blocked by LHR activation by hCG, presumably through phosphodiesterase III activation. These findings provide evidence that lhr expression in the carp pituitary is under the differential control of LH and dopamine via modification of cAMP-dependent signaling mechanisms, which may play a role in regulating somatotroph responsiveness to the paracrine action of LH in carp species.


Severe neonatal respiratory distress syndrome treated with the isolated phospholipid fraction of natural surfactant.
Ten newborn infants (795-1680 g) with severe respiratory distress syndrome (RDS) were treated with the isolated phospholipid fraction of bovine or porcine surfactant, which was administered via the airways (dose 200 mg/kg), at a median age of 10.5 h. Before receiving surfactant, all the infants were on artificial ventilation (FiO2 0.6-1.0). Within 2 h after surfactant replacement, the arterial-to-alveolar PO2 ratio increased from 0.1 to 0.35. There was a concomitant improvement in lung aeration on the chest roentgenograms and a significant reduction in the right-to-left shunt. Four patients died of cerebral hemorrhage; two of them also had a patent ductus arteriosus. One surviving infant developed bronchopulmonary dysplasia, and another succumbed 8 months later to the sudden infant death syndrome. No antibodies against surfactant were detected in the sera of the survivors. Since our results show a significant improvement in lung function after replacement therapy, the efficacy of this new surfactant preparation should be further tested in randomized clinical trials.


Alternatives to animal testing: information resources via the Internet and World Wide Web.
Many countries, including the United States, Canada, European Union member states, and others, require that a comprehensive search for possible alternatives be completed before beginning some or all research involving animals. Completing comprehensive alternatives searches and keeping current with information associated with alternatives to animal testing is a challenge that will be made easier as people throughout the world gain access to the Internet and World Wide Web. Numerous Internet and World Wide Web resources are available to provide guidance and other information on in vitro and other alternatives to animal testing. A comprehensive Web site is Alternatives to Animal Testing on the Web (Altweb), which serves as an online clearinghouse for resources, information, and news about alternatives to animal testing. Examples of other important Web sites include the joint one for the (US) Interagency Coordinating Committee on the Validation of Alternative Methods (ICCVAM) and the National Toxicology Program (NTP) Interagency Center for the Evaluation of Alternative Toxicological Methods (NICEATM) and the Norwegian Reference Centre for Laboratory Animal Science and Alternatives (The NORINA database). Internet mailing lists and online access to bulletin boards, discussion areas, newsletters, and journals are other ways to access and share information to stay current with alternatives to animal testing.


Isohormonal therapy of endocrine autoimmunity.
For most autoimmune disorders, the site (if any) of chronic immunization required for perpetuation of autoimmunity is unknown. However, one possible site is the target organ itself. If this were the case, feedback regulation of target cell activity might influence autoimmunity. Here, Nanette Schloot and George Eisenbarth review several recent studies suggesting that therapies that inhibit hormonal secretion of target endocrine organs, and/or modulate immunity by therapy with the isohormone, are associated with disease suppression.


Flexibility of beta-sheets: principal component analysis of database protein structures.
Protein folds are built primarily from the packing together of two types of structures: alpha-helices and beta-sheets. Neither structure is rigid, and the flexibility of helices and sheets is often important in determining the final fold (e.g., coiled coils and beta-barrels). Recent work has quantified the flexibility of alpha-helices using a principal component analysis (PCA) of database helical structures (J. Mol. Bio. 2003, 327, pp. 229-237). Here, we extend the analysis to beta-sheet flexibility using PCA on a database of beta-sheet structures. For sheets of varying dimension and geometry, we find two dominant modes of flexibility: twist and bend. The distributions of amplitudes for these modes are found to be Gaussian and independent, suggesting that the PCA twist and bend modes can be identified as the soft elastic normal modes of sheets. We consider the scaling of mode eigenvalues with sheet size and find that parallel beta-sheets are more rigid than antiparallel sheets over the entire range studied. Finally, we discuss the application of our PCA results to modeling and design of beta-sheet proteins.


Novel compounds that synergize with aminoglycoside G418 or eRF3 degraders for translational readthrough of nonsense mutant TP53 and PTEN.
The TP53 and PTEN tumour suppressor genes are inactivated by nonsense mutations in a significant fraction of human tumours. TP53 nonsense mutatant tumours account for approximately one million new cancer cases per year worldwide. We have screened chemical libraries with the aim of identifying compounds that induce translational readthrough and expression of full-length p53 protein in cells with nonsense mutation in this gene. Here we describe two novel compounds with readthrough activity, either alone or in combination with other known readthrough-promoting substances. Both compounds induced levels of full-length p53 in cells carrying R213X nonsense mutant TP53. Compound C47 showed synergy with the aminoglycoside antibiotic and known readthrough inducer G418, whereas compound C61 synergized with eukaryotic release factor 3 (eRF3) degraders CC-885 and CC-90009. C47 alone showed potent induction of full-length PTEN protein in cells with different PTEN nonsense mutations. These results may facilitate further development of novel targeted cancer therapy by pharmacological induction of translational readthrough.


Parental perspectives on a behavioral health music intervention for adolescent/young adult resilience during cancer treatment: report from the children's oncology group.
This article describes parental perspectives on the helpfulness and meaningfulness of a behavioral health music therapy intervention targeted to adolescents/young adults (AYA) with cancer undergoing stem cell transplantation. We demonstrate how qualitative methods may be used to understand critical aspects of an intervention and mechanisms by which the intervention impacts the target AYA outcomes of resilience and quality of life. A qualitative descriptive design was used to obtain parents' perspectives. A maximum-variation purposive sampling technique was used to sample 16 parents whose AYA had been randomized to the intervention group. A semistructured open-ended interview was conducted between 100 and 160 days after the AYA's transplant. Results were grouped into three categories: (1) helpfulness and meaningfulness of the intervention to AYA adjustment to the transplantation experience; (2) helpfulness and meaningfulness of the intervention for parents; and (3) AYA ability to participate in the intervention during the acute phase of transplant. Parents observed and interacted with their AYA who participated in a targeted behavioral intervention. Thus, parents were able to describe mechanisms through which the intervention was helpful and meaningful for the AYA and indirect personal benefits for themselves. The results suggest the importance of the targeted outcomes identified in the Resilience in Illness Model and mechanisms of action in the Contextual Support Model of Music Therapy, and identify approaches for future study.


Disappearance of human chorionic gonadotropin following removal of the fetus and placenta left in situ in a case of advanced abdominal pregnancy.
In a case of abdominal pregnancy, human chorionic gonadotropin (hCG) was determined twice during the first trimester and serially after removal of the fetus and placenta left in situ. From the 5th to the 7th week of gestation, the hCG values increased, from 5980 to 10000 U/l. After operation the hCG level decreased to 197 U/l after 51 days and hCG was not detectable 72 days postoperatively.


The Effects of Chronic Stress on Brain Myelination in Humans and in Various Rodent Models.
The myelination of axons, which is performed in brain tissues by specialized glial cells (oligodendrocytes) is crucial for correct formation of the complicated neural circuitry necessary for normal cognition, sensation, and motor function. Myelin-related anomalies are seen in many neurodegenerative diseases and in psychiatric disorders, including major depressive disorder and post-traumatic stress disorder. Chronic stress involving chronic stress early in life is believed to be a major etiological factor of neuropsychiatric disorders. Although molecular and cellular mechanisms underlying stress-induced psychopathologies are actively investigated, there is still little data about the role that is played in the development of these pathologies by myelin and oligodendrocyte impairments caused by chronic stress. In this article, after brief review of published data on myelin abnormalities in stress-related psychiatric disorders, we focus on recent cellular and molecular discoveries in various rodent models including models of chronic unpredictable stress, social isolation stress, chronic social defeat stress, and chronic immobilization stress. We also attempt to compile and analyze currently scarce data on myelin-related impairments resulting from early postnatal stress.


Reactive oxygen species and PI3K/Akt signaling in cancer.
Reactive oxygen species (ROS) are chemically reactive molecules containing oxygen and associates with multiple cellular functions such as cell proliferation, differentiation, and apoptosis. In the present study, we showed that Insulin-like growth factor-1(IGF-1) modulates SKOV-3 ovarian cancer cell by regulation of generation of ROS. Akt mediates cellular signaling pathways in association with mammalian target of rapamycin complex (mTOR) and Rac small G protein. Insulin-like growth factor-1 (IGF-1)-induced generation of ROS was completely abolished by phosphatidylinositol 3-kinase (PI3K) (LY294002, 10?µM) or Akt inhibitors (SH-5, 50?µM), whereas inhibition of extracellular-regulated kinase by an ERK inhibitor (PD98059, 10?µM) or inhibition of mammalian target of rapamycin complex 1 (mTORC1) by an mTORC1 inhibitor (Rapamycin, 100?nM) did not affect IGF-1-induced generation of ROS. Inactivation of mTORC2 by silencing Rapamycin-insensitive companion of mTOR (Rictor), abolished IGF-1-induced SKOV-3 cell migration as well as activation of Akt. However, inactivation of mTORC1 by silencing of Raptor had no effect. Silencing of Akt1 but not Akt2 attenuated IGF-1-induced generation of ROS. Expression of PIP3-dependent Rac exchanger1 (P-Rex1), a Rac guanosine exchange factor and a component of the mTOR complex. Silencing of P-Rex1 abolished IGF-1-induced generation of ROS. Finally, inhibition of NADPH oxidase system completely blunted IGF-1-induced generation of ROS, whereas inhibition of xanthine oxiase,cyclooxygenase, and mitochondrial respiratory chain complex was not effective. Given these results, we suggest that IGF-1 induces ROS generation through the PI3K/Akt/ mTOR2/NADPH oxidase signaling axis.


A Potential Long-Acting LDL-Cholesterol-Lowering PCSK9 Monoclonal Antibody: Randomized, Placebo-Controlled Phase 1 Studies.
The aim of the studies was to evaluate the safety, tolerability, and efficacy of tafolecimab, a novel proprotein convertase subtilisin/kexin type 9 (PCSK9) monoclonal antibody, in Chinese healthy volunteers and patients with hypercholesterolemia. Fifty-eight healthy volunteers (phase 1a) were randomized to receive a single dose of 25, 75, 150, 300, 450, or 600 mg tafolecimab subcutaneously, 75 or 450 mg intravenously, or placebo. Sixty patients with hypercholesterolemia (phase 1b) were randomized to receive 75 or 140 mg tafolecimab every 2 weeks, 300 or 420 mg every 4 weeks, or 450 or 600 mg every 6 weeks subcutaneously or placebo for 12 weeks. Tafolecimab was well tolerated. Adverse events in both studies were either mild or moderate. In the phase 1a study, a single dose of tafolecimab reduced low-density lipoprotein-cholesterol (LDL-C) levels up to 72% in healthy volunteers. In the phase 1b study, tafolecimab reduced LDL-C levels up to 71.6% and by more than 50% consistently to week 12 for all tafolecimab dose regimens. Tafolecimab is a safe PCSK9 monoclonal antibody with significant and potential long-acting LDL-C-lowering effect. (Single Ascending Dose Study of PCSK-9 Inhibitor [IBI306] in Healthy Subjects; NCT03366688) (Multiple Ascending Dose Study of PCSK-9 Inhibitor [IBI306] in Chinese Patients With Hypercholesterolemia; NCT03815812).


Bone marrow dose in chest radiography: the posteroanterior vs. anteroposterior projection.
The dose to active bone marrow resulting from anteroposterior (AP) and posteroanterior (PA) chest examinations was estimated using an Alderson Rando phantom and extruded lithium fluoride dosimeters. The AP projections resulted in a mean marrow dose range of 1.9-2.6 mrad (0.019-0.026 mGy) as compared to doses for PA projections of 3.4-3.8 mrad (0.034-0.038 mGy) for optimally diagnostic exposure taken at 70, 90, and 120 kVp.


Adrenergic beta 2-selective blocker in isoprenaline-enhanced essential tremor.
A beta 2-selective adrenergic-receptor-blocking drug, ICI 118.551, 150 mg/day, prevented almost as effectively as the nonselective antagonist propranolol, 240 mg/day, the isoprenaline enhancement of essential tremor amplitude.


Do standard burn mortality formulae work on a population of severely burned children and adults?
Accurate prediction of mortality following burns is useful as an audit tool, and for providing treatment plan and resource allocation criteria. Common burn formulae (Ryan Score, Abbreviated Burn Severity Index (ABSI), classic and revised Baux) have not been compared with the standard Acute Physiology and Chronic Health Evaluation II (APACHEII) or re-validated in a severely (≥20% total burn surface area) burned population. Furthermore, the revised Baux (R-Baux) has been externally validated thoroughly only once and the pediatric Baux (P-Baux) has yet to be. Using 522 severely burned patients, we show that burn formulae (ABSI, Baux, revised Baux) outperform APACHEII among adults (AUROC increase p<0.001 adults; p>0.5 children). The Ryan Score performs well especially among the most at-risk populations (estimated mortality [90% CI] original versus current study: 33% [26-41%] versus 30.18% [24.25-36.86%] for Ryan Score 2; 87% [78-93%] versus 66.48% [51.31-78.87%] for Ryan Score 3). The R-Baux shows accurate discrimination (AUROC 0.908 [0.869-0.947]) and is well-calibrated. However, the ABSI and P-Baux, although showing high measures of discrimination (AUROC 0.826 [0.737-0.916] and 0.848 [0.758-0.938]) in children), exceedingly overestimates mortality, indicating poor calibration. We highlight challenges in designing and employing scores that are applicable to a wide range of populations.


In search of the next Holy Grail of polyoxide chemistry: explicitly correlated ab initio full quartic force fields for HOOH, HOOOH, HOOOOH, and their isotopologues.
Explicitly correlated ab initio methods have been used to compute full quartic force fields for the three chain minima for HOOOOH, which are found to lie within 1 kcal mol(-1). The CCSD(T)-F12 method with the cc-pVTZ-F12 basis set was used to compute equilibrium structures, anharmonic vibrational frequencies, and rotational constants for HOOH, HOOOH, and three chain isomers of HOOOOH, with the two former force fields being used as benchmarks for the latter three. The full quartic force fields were computed in such a way as to yield fundamental frequencies for all isotopologues at once. The present research confirms the recent experimental identification of HOOOH and provides reliable force fields in support of future experimental work on the enigmatic bonding paradigms involved in the HOOOOH chain.


Post mortem degradation of nucleosides in the brain: comparison of human and rat brains for estimation of in vivo concentration of nucleosides.
There is an increasing attention paid for nucleoside metabolism and changes of nucleoside concentrations in human brain because of its pathological and physiological relevance. In order to determine the post mortem degradation of nucleosides and nucleoside metabolites, the concentrations of four nucleosides and three nucleobases were measured in rat and neurosurgical human cerebral cortical samples with 30s to 24h post mortem delay. Adenosine degradation coefficient (a multiplying factor for calculating concentrations of investigated substances for the living state) was 0.886 for human brain at 2 h post mortem time, while it was 1.976 for rats. Hypoxanthine, an adenosine degradation product had coefficients 0.564 for human brain and 0.812 for the rat brain. We provide data and degradation coefficients for the concentrations of adenosine, guanosine, inosine, uridine, uracil, hypoxanthine and xanthine with 2, 4, 6 and 24 h post mortem delay. We also report a method how to validate human neurosurgical brain samples in terms of sample preparation and statistical analysis.


Parasitic fauna of domestic cavies in the western highlands of Cameroon (Central Africa).
Domestic cavies (Cavia porcellus) are increasingly reared in rural areas of Cameroon for meat and income generation. Unfortunately, health constraints due to various pathogens including parasites stand as one of the major obstacles to the development of cavy industry in the country. The main objective of this study was to investigate the species of gastrointestinal parasites in cavy husbandry in the western highlands of Cameroon and to detect external parasites in those animals affected with dermatological disorders. Pooled fecal samples were collected from 62 privately-own farms, as well as individual fecal samples from 21 animals at the Teaching and Research Farm of the University of Dschang, and examined for parasite eggs and oocysts/cysts. Ectoparasites were also collected from cavies and identified. The overall infection rate with both helminthes and arthropods was 40.3 %. Ectoparasites were found in 19 out of 62 farms (30.6 %) while 12.9 % of farms were infected with helminthes. Eggs of Graphidium strigosum (8.1 %), Trichostrongylus sp. (3.2 %) and Paraspidodera uncinata (3.2 %) were found at farm level. Oocysts of Eimeria caviae and eggs of Paraspidodera uncinata were found in 14.3 and 9.5 % of examined animals respectively. Concerning ectoparasites, Cordylobia anthropophaga and Pulex sp. were observed in 25.8 % and 6.6 % of farms respectively. The parasites are apparently composed of host-specific species in the original habitat (South America) and species acquired later from other mammals. These parasites are either deleterious to cavy health or zoonotic. Preventive measures should be put in practice to avoid their presence on farms due to their harmful effect on cavy rearing.


Usefulness of an animal behavioral model in studying the duration of action of LSD and the onset and duration of tolerance to LSD in the cat.
LSD elicits a number of emergent behaviors in the cat, including limb flicking, abortive grooming, investigatory and hallucinatory-like behaviors, which we have proposed as an animal behavior model for studying the actions of LSD and related hallucinogens. These emergent behaviors were used in the present study to investigate the duration of action of LSD, as well as the onset and duration of tolerance. A dose of 10 microgram/kg of LSD produced significant behavioral changes for up to 4h, while a dose or 50 microgram/kg produced changes lasting for at least 8 h. Tolerance to a test dose of 50 microgram/kg of LSD is virtually complete one day after a single 50 microgram/kg dose, and lasts for approximately 5 days. Tolerance to a test dose of 50 microgram/kh of LSD one day after a single dose of 10 microgram/kg is quite marked, and lasts for approximately 3 days. A significant tolerance to a test dose of 50 microgram/kg of LSD occurs within 2 h after a single injection of 10 microgram/kg. The limb flick was found to be the most sensitive index in all tests: it showed the longest time-course, as well as the most rapid and longest-lasting tolerance. These studies demonstrate that the LSD-induced behavioral syndrome in the cat parallels important parameters of the action of LSD in humans, and thus enhances the usefulness of the model.


"A recipe for elder abuse:" From sin to risk in anti-euthanasia activism.
Anti-euthanasia activists currently make their arguments against physician-assisted dying in terms of vulnerability and risk. Tensions in this strategy emerge because many are drawn to activism out of religious beliefs. This article will explain how they have reframed their argument that physician-assisted dying is a "recipe for elder abuse." This strategy attempts to manufacture uncertainty among vulnerable groups by strategically deploying doubt against medical institutions and governments, while generating distrust among family members. This article will argue that underlying this strategic deployment of risk are beliefs that posit assisted death as polluting to society.


Ants distinguish neighbors from strangers.
Ants are known to distinguish their own nests and nestmates from all others, using colony-specific odors. Here I show that harvester ants (Pogonomyrmex barbatus) can further distinguish between two kinds of non-nestmates of the same species: neighbors and strangers. Interactions between colonies were thought to depend on the numbers of alien ants that each colony encounters on its territory. The results described here show that such interactions also depend on information about colony identity. Encounters on foraging trails with ants from neighboring colonies, deter foraging more than encounters with ants from distant ones. The history of interactions between particular pairs of colonies may have important effects on intraspecific competition for food.


Isolated fetal pyelectasis and chromosomal abnormalities.
The primary objective of this study was to determine if isolated pyelectasis is a risk factor for trisomy 21. Twelve thousand, six hundred and seventy-two unselected singleton fetuses were examined by prenatal ultrasound during the second trimester at a single institution. The sensitivity, specificity, positive predictive value, negative predictive value, and likelihood ratio of pyelectasis (either isolated or in association with other soft markers/structural anomalies) to detect trisomy 21 were calculated. Pyelectasis (anteroposterior pelvic diameter >/=4 mm) was detected in 2.9% (366/12,672) of the fetuses. Among these, 83.3% (305/366) were isolated, and 16.7% (61/366) were associated with other markers/structural anomalies. The prevalence of trisomy 21 was 0.087% (11/12,672) and, among these fetuses, 2 (18.1%) had pyelectasis, 1 isolated, and 1 associated with other markers/structural anomalies. The presence of isolated pyelectasis had 9.09% sensitivity, 97.6% specificity, 0.33% positive predictive value, and 99.9% negative predictive value to detect fetuses with trisomy 21. The likelihood ratio of trisomy 21 in this group of fetuses was 3.79 (95% CI 0.582-24.616). Among fetuses with pyelectasis and other associated markers/structural anomalies, the sensitivity, specificity, positive predictive value, negative predictive value, and likelihood ratio for trisomy 21 were 9.09%, 99.5%, 1.64%, 99.9%, and 19.2 (95% CI 2.91-126.44). In the absence of other findings, isolated pyelectasis is not a justification for the performance of an amniocentesis.


Nephrectomy and inferior vena cava thrombectomy for renal cell carcinoma among patients with impaired renal function: defining predictors of outcomes.
Management of renal cell carcinoma (RCC) with inferior vena cava thrombus (IVCT) is associated with high morbidity. Chronic kidney disease (CKD) is a known risk factor for perioperative complications in many surgical procedures. The objective of this study was to review the association between preoperative CKD (eGFR < 60 mL/min) and post-operative outcomes in patients with RCC and IVCT undergoing radical nephrectomy (RN) and tumour thrombectomy (TT). A retrospective review of patients with RCC and IVCT treated with RN and TT was carried out. Complications were recorded according to the Clavien-Dindo classification. Multivariable models were fitted using logistic regression analyses for high-grade complications and salvage therapies and linear-regression for intraoperative blood loss (IBL). One hundred and one patients with RCC and IVCT, treated with RN and TT, were identified. Forty per cent of patients had preoperative CKD. Median IBL was higher in CKD arm (2.5 versus 1.6 L, P = 0.04). In a multivariate linear regression analysis, CKD (beta 1.34, P = 0.01) remained an independent predictor of IBL. High-grade complications were more frequent in the CKD group (34% versus 16%, P = 0.09) and in logistic regression analysis, CKD was an independent predictor of high-grade complications (OR 3.33, 95% CI 1.01-10.9). Furthermore, CKD patients were less likely to be considered for salvage therapies (62% versus 38%, P = 0.02). In patients treated with RN and TT, CKD is an independent predictor of perioperative morbidity. This clinical variable should be considered when selecting patients and subsequent efforts should be made to optimize other competing risk factors in order to reduce the incidence of perioperative adverse events in this patient population.


Epidemiology of gastrointestinal nematodes of sheep and goats in Haryana, India.
Epidemiological studies on some gastrointestinal nematodes of sheep and goats in Karnal, Ambala and Rohtak districts of Haryana (India) revealed that Haemonchus contortus and Trichostrongylus spp. were responsible for parasitic gastroenteritis in these hosts. The adult parasites persisted in the host throughout the year and there was no indication of hypobiosis. The maintenance of the parasite population depended on a continuous cycle of infection between the host and the pasture. The agroclimatic conditions of the districts revealed that, in general, favourable weather conditions for the development and survival of the free-living stages of the parasites existed all year round.


Pharmacokinetics of mexiletine in the elderly.
The effect of advancing age on the kinetics of the antiarrhythmic agent mexiletine was studied by comparing various kinetic parameters calculated after administration of a single oral dose of mexiletine hydrochloride to seven elderly and eight young healthy volunteers. The rate of absorption of the drug from the gastrointestinal tract was significantly slower in the elderly (1.37 +/- 0.51 hr-1) than in the young group (2.25 +/- 0.79 hr-1). The mean values for elimination half-life and oral clearance were 12.3 +/- 3.7 hr and 10.3 +/- 5.4 mL/min/kg respectively in the young group and 14.4 +/- 4.5 hr and 8.5 +/- 2.9 mL/min/kg respectively in the elderly group. Neither of these parameters was significantly different between the two groups. The amount of mexiletine eliminated in urine up to 48 hours postdose was identical in both groups and represented less than 5% of the administered dose. It is concluded that the age-related modifications in the kinetics of mexiletine are not clinically important during chronic administration of the drug.


Fluoroquinolone-resistant extraintestinal Escherichia coli clinical isolates representing the O15:K52:H1 clonal group from humans and dogs in Australia.
Antimicrobial-resistant extraintestinal pathogenic Escherichia coli (ExPEC) impact both human and veterinary medicine. One ExPEC clonal group that has become increasingly multidrug-resistant is serotype O15:K52:H1. Accordingly, we sought O15:K52:H1 strains among fluoroquinolone-resistant (FQ(r)) E. coli clinical isolates from humans (n=582) and dogs (n=120) in Australia. The phylogenetic group D isolates (267/702; 38%) were screened for O15:K52:H1-specific single-nucleotide polymorphisms (SNPs) in fumC and the O15 rfb variant. The 34 so-identified O15:K52:H1 isolates (33 human, 1 canine) underwent antimicrobial susceptibility profiling, virulence genotyping, and macrorestriction profiling. Although susceptibility profiles varied, the 34 isolates were closely related by pulsed-field gel electrophoresis and exhibited typical O15:K52:H1-associated virulence profiles (complete pap operon, F16 papA allele, papG allele II, iha, fimH, sat, fyuA, iutA, kpsMII, ompT). The canine isolate closely resembled human isolates. Thus, O15:K52:H1 strains contribute to the FQ(r) ExPEC population in Australia and may potentially be transferred between humans and dogs.


Trends in social inequalities in obesity: Belgium, 1997 to 2004.
Studies examining the time trend in social inequalities in obesity have yielded diverse results. The aim of this study is to investigate whether social inequalities in obesity have increased overtime in Belgium. We used data from three national cross-sectional health interview surveys (1997 n=7953, 2001 n=8887, and 2004 n=9709) to estimate age-standardized obesity prevalence and a series of summary measures reflecting health inequalities in men and women aged 18 years and older. For males, a clear socioeconomic gradient was observed between obesity and education. This gradient witnessed a large increase between the years 1997 and 2004. For instance, the relative index of inequality increased from 1.92 (95% CI: 1.16-3.18) to 3.71 (95% CI: 2.49-5.54). Social inequalities in female obesity indicate a different pattern. Our results revealed a very steep socioeconomic gradient for female obesity, but overtime, no significant change was observed. The relative index of inequality for female obesity was 4.04 (95% CI: 2.47-6.63) in 1997 and 4.03 (95% CI: 2.75-5.90) in 2004. Using three comparable nation-wide population-based surveys, our study has shown that in Belgium from 1997 to 2004, the socioeconomic gradient in obesity has increased for males and persisted for females.


Natural killer cell activity in peripheral blood of highly trained and untrained persons.
Natural killer (NK) cell activity and concentration of CD16+ cells (NK cells) and CD20+ cells (monocytes) in peripheral blood were measured in highly trained racing cyclists and in age- and sex-matched untrained controls. Median NK cell activity was 38.1% (range 20.0%-57.1%) in trained vs 30.3% (range 19.7%-43.1%) in untrained (P = 0.008). Median %CD16+ cells was 17% (range 7%-33%) in trained vs 11% (3%-29%) in untrained (P = 0.007). Indomethacin in vitro enhanced the NK cell activity in both groups. There was, however, no significant difference between the NK cell activity in trained and untrained after exposure to indomethacin in vitro. Indomethacin-enhanced NK cell activity was 45.9% (range 24.4%-67.5%) in trained and 40.0% (range 23.9%-68.5%) in untrained (P = 0.138). Mean %CD14+ cells was 8.3% (range 2%-15%) in trained vs 3.8% (2%-8%) in untrained (P less than 0.0001). The increased NK cell function thus demonstrated in highly trained persons might result in better resistance against infectious disease.


Occurrence, biochemistry and possible biotechnological application of the 3-hydroxypropionate cycle.
The 3-hydroxypropionate cycle, a pathway for autotrophic carbon dioxide fixation, is reviewed with special emphasis on the biochemistry of CO2 fixing enzymes in Acidianus brierleyi, a thermophilic and acidophilic archeon. In the 3-hydroxypropionate cycle, two enzymes, acetyl-CoA carboxylase and propionyl-CoA carboxylase, catalyze CO2 fixation. It has been shown in A. brierleyi, and subsequently in Metallosphaera sedula, that acetyl-CoA carboxylase is promiscuous, acting equally well on acetyl-CoA and propionyl-CoA. The subunit structure of the acyl-CoA carboxylase was shown to be alpha4beta4gamma4. Gene cloning revealed that the genes encoding the three subunits are adjacent to each other. accC encodes the beta-subunit (59 kDa subunit, biotin carboxylase subunit), accB encodes the gamma-subunit (20 kDa subunit, biotin carboxyl carrier protein), and pccB encodes the alpha-subunit (62 kDa subunit, carboxyltransferase subunit). Sequence analyses showed that accC and accB are co-transcribed and that pccB is transcribed separately. Potential biotechnological applications for the 3-hydroxypropionate cycle are also presented.


The role of essential trace elements in embryonic and fetal development in livestock.
This review addresses the concept that essential trace minerals play a vital role in many enzymatic and metabolic pathways that are critical for conceptus development during pregnancy in livestock species. The conceptus relies entirely on the maternal system for a sufficient supply of trace minerals and other nutrients needed for normal development. If this supply is inadequate, growth and/or health of the conceptus can be affected adversely, and many of these effects carry over into the neonatal period. Information, accumulated in our laboratory and presented herein, indicates that zinc, copper and manganese are among the trace minerals that have the greatest impact on reproduction. For example, levels of zinc, copper and manganese were several fold greater in the conceptus than in other reproductive tissues, indicating that the conceptus preferentially accumulates these minerals, an action that may be important for conceptus development, growth and survival. Moreover, some recent results indicate that increasing the biological availability of zinc, copper and manganese, by attachment to short peptide chains (i.e., proteinated trace minerals) can enhance reproductive performance of swine. Mineral concentrations in conceptuses from female pigs consuming proteinated trace minerals were greater than those from females that consumed only inorganic mineral salts. Elucidating the mechanisms whereby conceptus development and survival are enhanced by essential trace minerals may lead to development of specific feeding programs to increase the number and health of offspring at parturition, thereby allowing for further improvements in production efficiency in animal agriculture.


Functional subsets of circulating follicular helper T cells in patients with atherosclerosis.
Frequencies of circulating T follicular helper (cTfh) functional subsets vary in autoimmune diseases. We evaluated the frequencies and clinical relevance of functional subsets of cTfhs in patients with different degrees of stenosis. Blood samples were collected from high (≥50%) (n = 12) and low (<50%) stenosis (n = 12) groups and healthy controls (n = 6). Three subsets of cTfh cells including cTfh1 (CXCR3+ CCR6- ), cTfh2 (CXCR3- CCX6- ), and cTfh17 (CXCR3- CCR6+ ) were detected by flow cytometry. The frequency of cTfh1 cells was higher in control (p = .0006) and low-stenosis groups (p = .005) compared to high-stenosis group. The percentages of cTfh2 and cTfh17 cells were increased in high-stenosis compared to low-stenosis (p = .002 and p = .007) and control groups (p = .0004 and p = .0005), respectively. The frequency of cTfh1 cells negatively correlated with cholesterol (p = .040; r = -.44), C-reactive protein (CRP) (p = .015; r = -.68), erythrocyte sedimentation rate (ESR) (p = .002; r = -.79), neutrophil/lymphocyte ratio (NLR) (p = .028; r = -.67), and cTfh17 (p = .017; r = -.7244) in the high-stenosis group. The percentages of cTfh2 and cTfh17 cells positively correlated with cholesterol (p = .025; r = .77 and p = .033; r = .71), CRP (p = .030; r = .61 and p = .020; r = .73), ESR (p = .027; r = .69 and p = .029; r = .70), NLR (p = .004; r = .76 and p = .005; r = .74), and with each other (p = .022; r = .7382), respectively, in the high-stenosis group. The increased frequencies of cTfh2 and cTfh17 subsets and their correlation with laboratory parameters in patients with atherosclerosis may suggest their role in promoting the inflammatory response and atherosclerosis progression.


Molar mass characterization of sodium carboxymethyl cellulose by SEC-MALLS.
Two series of sodium carboxymethyl celluloses (NaCMCs) derived from microcrystalline cellulose (Avicel samples) and cotton linters (BWL samples) with average degrees of substitution (DS) ranging from DS=0.45 to DS=1.55 were characterized by size exclusion chromatography with multi-angle laser light scattering detection (SEC-MALLS) in 100 mmol/L aqueous ammonium acetate (NH4OAc) as vaporizable eluent system. The application of vaporizable NH4OAc allows future use of the eluent system in two-dimensional separations employing evaporative light scattering detection (ELSD). The losses of samples during filtration and during the chromatographic experiment were determined. The scaling exponent as of the relation [Formula: see text] was approx. 0.61, showing that NaCMCs exhibit an expanded coil conformation in solution. No systematic dependencies of as on DS were observed. The dependences of molar mass on SEC-elution volume for samples of different DS can be well described by a common calibration curve, which is of advantage, as it allows the determination of molar masses of unknown samples by using the same calibration curve, irrespective of the DS of the NaCMC sample. Since no commercial NaCMC standards are available, correction factors were determined allowing converting a pullulan based calibration curve into a NaCMC calibration using the broad calibration approach. The weight average molar masses derived using the so established calibration curve closely agree with the ones determined by light scattering, proving the accuracy of the correction factors determined.


Mapping Studies of Alcohol Use Among People Living with HIV/AIDS During 1990-2019 (GAPRESEARCH).
Alcohol drinking has long been reported to be common in people living with HIV/AIDS, having biological and behavioral impacts on the transmission, progression, and prevention of HIV/AIDS. A total of 7059 eligible articles and reviews published in English from 1990 to 2019 were extracted from the WOS. Results show an increase in publication volume, while citations peak for papers published in 2006. Content analysis reveals a wide-ranging coverage of topics, with the most popular being effects of alcohol consumption on ART adherence and outcomes, alcohol-related sexual behaviors, TB co-infection, and psycho-socio-cultural considerations in examining and designing measures targeting alcohol use and interventions to reduce alcohol dependence in PLWHA. This calls for more active engagement of governments in research and in designing and implementing interventions, as well as collaborations and knowledge transfer from high-income countries to developing counterparts, to effectively address alcohol use-related issues in PLWHA, moving toward the HIV/AIDS eradication target.


[Current status of monoclonal antibodies to human melanoma and its application].
Monoclonal antibodies to human melanoma associated antigens were reviewed from the viewpoint of a target structure recognized by them. In addition, phase I evaluation of a monoclonal antibody 225.28S in man and fundamental studies of the antibody-cytotoxic agent conjugates in melanoma-bearing nude mice were described.


p53 gene mutations in rectal cancer associated with schistosomiasis japonica in Chinese patients.
Mutations in p53 tumor suppressor gene were examined in 44 Chinese patients with rectal cancer, including 22 cases with advanced schistosomiasis japonica and 22 cases without schistosomiasis. In schistosomal rectal cancer (SRC), 13 mutations were found in 10 cases, which included 11 base-pair substitutions and two deletions. Of 11 base substitutions, nine were transitions and two were transversions and seven of them were located at CpG dinucleotides. In non-schistosomal rectal cancer (NSRC), 13 mutations were found in nine cases, all of which were base-pair substitutions. Of 13 substitutions, 10 were transitions and three were transversions and three of them were located at CpG dinucleotides. The proportion of base-pair substitutions at CpG dinucleotides was higher in SRC patients than in NSRC patients, although this was not statistically significant (P = 0.054). Point mutation was frequent at codon 248 in SRC. A higher frequency of arginine missense mutations was observed in SRC than in NSRC. These observations suggest that the mutations in SRC are the result of genotoxic agents produced endogenously through the course of schistosomiasis japonica.


Cor triatriatum: a multimodality imaging approach.
A 60-year-old man presented with congestive heart failure and was diagnosed with cor triatriatum after echocardiography. The various imaging modalities used for the definitive diagnosis of this condition are reviewed.


Fe-N complex biochar as a superior partner of sodium sulfide for methyl orange decolorization by combination of adsorption and reduction.
To enhance the decolorization of methyl orange (MO), Fe-N complex biochar (Fe-N-BC) was developed as an accelerator in the sodium sulfide (Na2S) reduction system. The decolorization effect and mechanism of MO in the Fe-N-BC/Na2S composite system were studied. Surface pore analysis, Raman spectroscopy, FT-IR, XPS, and electrochemical analysis were used to characterize Fe-N-BC and unmodified biochar (BC). These results demonstrated that Fe-N-BC had better adsorption performance (specific surface area 463.46 m2 g-1) and electron transfer capacity than BC. By adding Fe-N-BC to the Na2S reduction system for MO, it was found that the decolorization of MO was greatly improved (increased by 93%). Besides, the effects of critical factors such as the initial concentration of Na2S, the dosage of Fe-N-BC, pH value, and temperature on the decolorization rate of MO were evaluated. Through the analysis of the action mechanism, the cooperation mode of Fe-N-BC and Na2S was to form an infinite cycle of adsorption-reduction-regeneration, so as to realize the rapid decolorization of MO. On the one hand, Fe-N-BC could adsorb MO and Na2S on its surface to increase the contact opportunity; on the other hand, it could act as a redox mediator to accelerate the electron transfer of the reduction reaction. In addition, the degradation of MO by Na2S was also an in-situ regeneration of Fe-N-BC. These findings may provide a feasible method to decolorize azo dyes quickly by cooperating with chemical reducing agents from a new perspective.


Large scale spatial and temporal variation in recruitment to fish populations on coral reefs.
Visual census was used to sample young of the year of fish species recruited to each of two habitats on seven lagoonal platform reefs of the Capricorn-Bunker Group, Great Barrier Reef. The reefs sampled span an area 70 km in extent. In 1983, 62 species from 13 families were detected as recruits on reef slope sites. The total number of cruits, and the number of each of 6 of 16 species tested, differed significantly among reefs, despite the fact that differences among sites within reefs did not exist, and that sampled slopes were chosen to be hydrographically, and physiographically as similar as possible. Lagoonal patch reefs were sampled in two years. In 1982, 76 species of 11 families occurred as recruits. In 1983, 86 species of 12 families were recorded. All of 22 species common enough to test showed some significant variation in abundance among reefs, years, or both. For 9 species, significant year x reef interactions occurred, demonstrating that relative recruitment success among reefs varied between years. Reasons for the substantial levels of variability are discussed, and implications for the organisation of reef fish communities are considered.


The ectodermal control of mesodermal patterns of differentiation in the developing chick wing.
The influence of limb ectoderm on the dorso-ventral muscle and skeletal patterns in the chick wing was studied by recombining stage 14-21 limb mesoderm with the same stage ectoderm in dorso-ventrally reversed orientation. Recombinants grafted to the flank of host embryos were allowed to develop for 10 days. Fully developed wings obtained from stage 15-21 donor embryos have at their distal half d-v polarity conforming to the reversed ectoderm and proximally polarity conforming with the mesoderm. The ectodermal effect is generally observed as a bidorsal feather pattern at the autopod and an almost complete d-v reversal of muscle and skeletal patterns. In experimental wings from donor embryos younger than stage 15, the dorso-ventral pattern conforms with the polarity of the limb mesoderm. The results suggest that control of dorso-ventral polarity resides in the mesoderm until the onset of limb development at stage 15. At this stage, the ectoderm acquires dorso-ventral information which it can impose on the mesoderm.


Contribution of intracellular calcium stores to an increase in cytosolic calcium concentration induced by Mannheimia haemolytica leukotoxin.
The contribution of intracellular calcium stores to Mannheimia haemolytica leukotoxin (LKT)-induced increase in cytosolic calcium concentration was studied by pharmacologically inhibiting transport of calcium across the plasma and endoplasmic reticulum membranes of bovine neutrophils exposed to LKT. Active intracellular storage of calcium by sarcoplasmic/endoplasmic reticulum calcium ATPase, influx of extracellular calcium across the plasma membrane, and release of stored calcium via inositol triphosphate receptors and ryanodine-sensitive calcium channels were inhibited using thapsigargin, lanthanum chloride, xestospongin C, and magnesium chloride, respectively. Pre-incubation with thapsigargin attenuated the increase in cytosolic calcium concentration produced by LKT, thus confirming the involvement of intracellular calcium stores. Inhibitory effects of lanthanum chloride, xestospongin C, and magnesium chloride indicated that the increase in cytosolic calcium concentration induced by LKT resulted from both influx of calcium across the plasma membrane and release of calcium from intracellular stores.


Assessing the burden of dengue among household members in Alaminos, Laguna, the Philippines: a prospective cohort study.
The incidence of dengue is increasing rapidly and is a challenging health issue in the Philippines. Epidemiological data are largely based on a passive-surveillance reporting system, which leads to substantial under-reporting of cases. To estimate dengue infection and disease incidence prospectively at the community level in an endemic area of the Philippines using an active surveillance strategy. We implemented active surveillance in the highly endemic community of Alaminos, Laguna. The study consisted of a 1-year follow-up with 2 visits scheduled at the start and end of the study, as well as regular active surveillance in between and unscheduled visits for suspected cases. Blood samples were collected and analyzed to detect dengue during the first scheduled visit and all unscheduled visits, and clinical examination was performed at all visits (registered at clinicaltrials.gov NCT02766088). We enrolled 500 participants, aged from 6 months to 50 years; 76.2% were found positive for immunoglobulin G (95% confidence interval [CI], 71.9-80.0), with 92.0% among those aged 9-17 years. Active (weekly) surveillance identified 4 virologically confirmed cases of dengue (incidence proportion 0.8; 95% CI 0.3-2.1); all in participants aged ≤14 years. Routine surveillance programs such as sentinel sites are needed to characterize the entire clinical spectrum of symptomatic dengue, disease incidence, and transmission in the community.


Longitudinal trajectories of childhood and adolescent attention deficit hyperactivity disorder diagnoses in three cohorts.
Attention deficit/hyperactivity disorder (ADHD) is usually conceptualized as a childhood-onset neurodevelopmental disorder, in which symptoms either decrease steadily into adulthood or remain stable. A recent study challenged this view, reporting that for most with ADHD, diagnostic status fluctuates with age. We ask if such a 'fluctuating' ADHD symptom trajectory subgroup is present in other population-based and clinic-based cohorts, centered on childhood and adolescence. Cohorts were the population-based Adolescent Brain Cognitive Development (ABCD: N = 9735), Neurobehavioral Clinical Research (NCR: N = 258), and the Nathan Kline Institute-Rockland (NKI-Rockland: N = 149). All participants had three or more assessments spanning different age windows. Participants were categorized into developmental diagnostic subgroups: fluctuant ADHD (defined by two or more switches between meeting and not meeting ADHD criteria), remitting ADHD, persisting ADHD, emerging ADHD and never affected. Data were collected between 2011 and 2022. Analyses were performed between May 2022 and April 2023. A subgroup with fluctuant child and adolescent ADHD diagnoses was found in all cohorts (29.3% of participants with ADHD in ABCD, 26.6% in NCR and 17% in NKI-Rockland). While the proportion of those with fluctuant ADHD increased with the number of assessments, it never constituted the dominant subgroup. We provide further evidence in three cohorts for the existence of a fluctuant ADHD diagnostic subgroup during childhood and adolescence, albeit in a minority of cases. Such fluctuant child and adolescent ADHD diagnoses may suggest a natural history more akin to relapsing-remitting mood disorders and/or a marked sensitivity to environmental shifts that occur across development. Intramural programs of the NHGRI and NIMH.


DSM-IV and the South Oaks Gambling Screen: diagnosing and assessing pathological gambling in Turkey.
The main purpose of this study was to investigate the effectiveness of the DSM-IV diagnostic criteria and the South Oaks Gambling Screen (SOGS) in identifying Turkish pathological gamblers. Fifty-nine subjects participated in the study. The subjects were diagnosed as either pathological gamblers or not (comparison group) through the use of the DSM-IV criteria and were given the Turkish version of the SOGS. Four of the ten DSM-IV criteria were found to be problematic in the diagnosis of Turkish pathological gamblers. The data concerning reliability and validity of the Turkish version of the SOGS suggested that the SOGS can be used as a reliable and valid instrument in identifying Turkish pathological gamblers. Most (16 out of 20) of the items of the SOGS appear to work well in discriminating pathological gamblers from the subjects in the comparison group. In the case of the two DSM-IV criteria and the four SOGS items that failed to discriminate, cultural factors seemed to be responsible for the failure.


Peptide Receptor Radionuclide Therapy in the Treatment of Neuroendocrine Tumors.
Peptide receptor radionuclide therapy (PRRT) is a promising new treatment modality for inoperable or metastasized gastroenteropancreatic neuroendocrine tumors patients. Most studies report objective response rates in 15% to 35% of patients. Progression-free (PFS) and overall survival (OS) compare favorably with that for somatostatin analogues, chemotherapy, or newer, "targeted" therapies. Prospective, randomized data regarding the potential PFS and OS benefit of PRRT compared with standard therapies is anticipated.


Metabolism of sulphobromophthalein II. Species differences between rats, guinea-pigs and rabbits.
Interesting species differences in the metabolism of sulphobromophthalein sodium have been observed between rats, guinea-pigs and rabbits. The species difference was measured in terms of sulphobromophthalein monoglutathione conjugate (mGSH) positional isomer formation. After an intravenous injection of sulphobromophthalein to rats, 92% of sulphobromophthalein-mGSH excreted into bile was the alpha-isomer. In contrast, in guinea-pigs the three isomers alpha, beta and delta were excreted in equivalent amounts. In rabbits, the majority of sulphobromophthalein-mGSH was excreted as the beta-isomer. The formation ratio of glutathione (GSH) conjugates in-vitro using cytosolic glutathione S-transferases (GSTs) prepared from livers generally accounted for the biliary excretion ratio of alpha-, beta- and delta-monomercaptide isomers in-vivo. GSTs from the livers of rat, guinea-pig, and rabbit were purified and characterized. Although their main GSTs produced different isomers, their 20 amino acid residues showed that they belonged to the same class mu of GSTs. The results suggested differences of the three-dimensional structure of GSTs that formed sulphobromophthalein-mGSH isomers between the three animal species.


Congenital cytomegalovirus reference material: a content analysis of coverage and accuracy.
Congenital cytomegalovirus (CMV) is the leading cause of birth defects and developmental delays in the United States. However, only 13-22% of women in the United States have heard of CMV. This research assessed (1) the quantity and accuracy of CMV information included on pregnancy-related websites and reference books, and (2) whether CMV information was included less often than information about other birth defects or infections. A content analysis of 37 pregnancy reference books and seven websites was conducted. The data collection instrument represented categories describing CMV, transmission, and prevention. CMV subject matter experts at the Centers for Disease Control and Prevention reviewed the instrument. Each book and website was coded independently by two different coders. Twenty-one reference books and seven websites included CMV content. CMV was less likely to be included as a topic than other infections or birth defects. There were fewer sentences about CMV than toxoplasmosis, Down syndrome, or HIV. Book length was associated with increased likelihood of including CMV. How to prevent CMV transmission was discussed only half the time. Though limited, nearly all the CMV information was accurate. Pregnancy-related reference books and websites contain limited CMV information. Books are less likely to include CMV as compared to other infections and birth defects. Most of the CMV information is accurate. There is inadequate coverage given to prevention of CMV transmission, which may contribute to CMV remaining a continued leading cause of birth defects in the United States.


Partial purification and characterization of a novel murine factor that augments the expression of class I MHC antigens on tumor cells.
A soluble factor which augments the expression of major histocompatibility complex class I (MHC I) antigens on a number of murine tumor cell lines, has been isolated from the culture supernatants of mixed lymphocyte reaction of spleen cells derived from C57B1/6, Balb/c and Swiss mice. The factor, termed MHC-augmenting factor (MHC-AF) has been partially purified by Sephadex G-100 column chromatography and reverse phase HPLC. MHC-AF activity is associated with an 18 kDa molecule. MHC-AF activity was resistant to pH 2.0 treatment and partially purified MHC-AF preparations did not have any activity in L929 cell/vesicular stomatitis virus (VSV) interferon bioassay system. Antibodies to IFN-gamma did not block the activity of MHC-AF. These results indicate that a MHC-AF distinct from IFN-gamma, is produced by mouse spleen cells undergoing a mixed lymphocyte reaction.


Acetylcholine compartments in skeletal muscle.
I studied acetylcholine compartments in skeletal muscle with the aim to find their anatomical origin, and, in addition, their correlation with functional compartments, i.e. the pools in which synthesis, storage and release take place.


Epithelial modulation of the relaxant activity of atriopeptides in rat and guinea-pig tracheal smooth muscle.
Three peptide components of atrial natriuretic factor (ANF) caused relaxation of carbachol-contracted guinea-pig isolated tracheal smooth muscle. These were the 1-28, 5-28 and 5-27 peptide sequences (ANF(1-28), ANF-(5-28) and ANF-(5-27)). The peptides were 10-30 times more potent in epithelium-denuded than in epithelium-intact preparations. In the absence of airway epithelium, ANF-(1-28) was the most potent relaxant (mean pD2 = 7.40 +/- 0.08), with ANF-(5-27) and ANF-(5-28) 2-3 fold less potent. The neutral endopeptidase inhibitor phosphoramidon (1 microM) increased the potency of ANF-(5-27) in both epithelium-intact and epithelium-denuded guinea-pig tracheal rings. In contrast, removal of the epithelium from rat trachea, or pretreatment with phosphoramidon (1 microM) decreased relaxant responsiveness to ANF-(5-27). Thus, in rat trachea, epithelial endopeptidase may convert ANF-(5-27) to a more active relaxant peptide. Human bronchial preparations with or without epithelium, obtained from non-diseased lung samples and from a single sample of asthmatic lung, were virtually unresponsive to ANF-(5-27). Consistent with the spasmolytic effects of ANF in guinea-pig trachea, autoradiographic analysis revealed the presence of a sparse population of specific binding sites for [125I]ANF-(1-28) over both tracheal smooth muscle and epithelium. The present study shows that the relaxant effects of atriopeptins in rat and guinea-pig airway smooth muscle were modulated by the epithelium and the activity of neutral endopeptidase. However, marked species differences in airway smooth muscle responsiveness to ANF and in the modulatory role of the airway epithelium were evident.


Synthesis of nanocrystals by discharges in liquid nitrogen from Si-Sn sintered electrode.
The synthesis feasibility of silicon-tin nanocrystals by discharges in liquid nitrogen is studied using a Si-10 at % Sn sintered electrode. Time-resolved optical emission spectroscopy shows that silicon and tin melt almost simultaneously. The presence of both vapours does not lead to the synthesis of alloyed nanocrystals but to the synthesis of separate nanocrystals of silicon and tin with average sizes of 10 nm. These nanocrystals are transformed into amorphous silicon oxide (am-SiO2) and β-SnO2 by air oxidation, after evaporation of the liquid nitrogen. The synthesis of an am-Si0.95Sn0.05 phase around large silicon crystals (~500 nm) decorated by β-Sn spheroids is achieved if the current flowing through electrodes is high enough. When the sintered electrode is hit by powerful discharges, some grains are heated and tin diffuses in the large silicon crystals. Next, these grains are shelled and fall into the dielectric liquid.


Impact of haemodialysis hours on outcomes in older patients.
Previous studies report an association between longer haemodialysis treatment sessions and improved survival. Worldwide, there is a trend to increasing age among prevalent patients receiving haemodialysis. This analysis aimed to determine whether the mortality benefit of longer haemodialysis treatment sessions diminishes with increasing age. This was a retrospective cohort study of people who first commenced thrice-weekly haemodialysis aged ≥65 years, reported to the Australia and New Zealand Dialysis and Transplant (ANZDATA) Registry from 2005 to 2015, included from 90 days after dialysis start. The primary outcome was all-cause mortality. Cox regression analysis was performed with haemodialysis session duration the exposure of interest. Of 8224 people who commenced haemodialysis as their first treatment for kidney failure aged ≥65 years during this period, 4727 patients died. Longer dialysis hours per session was associated with a decreased risk of death in unadjusted analyses [hazard ratio, HR, for ≥5 h versus 4 to <4.5 h: 0.81 (0.75-0.88, p < .001)]. Patients having longer dialysis sessions were younger but had greater co-morbidity. In an adjusted model including age and other variables, the survival benefit of longer hours was only partially attenuated [HR for previous comparison: 0.75 (0.69-0.82, p < .001)], and no interaction between age and hours was demonstrated (p = .89). The apparent survival benefit associated with longer haemodialysis session length appears to be preserved in patients 65 years or older. In practice, the benefit of longer dialysis hours should be carefully weighed against other factors in this patient group.


Treadmill walking and overground walking of human subjects compared by recording sole-floor reaction force.
In order to clarify differences of treadmill from overground locomotion, experiments were carried out on 10 volunteers (five males and five females). Sole-floor reaction force was recorded from five anatomically discrete points with strain gauge transducers of 14 mm diameter attached firmly to the sole of bare-foot. At first the subject was asked to walk on the laboratory floor at his/her preferred velocity. After the average velocity was obtained, the subject was asked to walk on the treadmill at the same velocity of average overground walking. Stance period at treadmill walking shortened to 93.3% (P < 0.01) of the value at overground walking. Coefficient of variation of stance period was significantly smaller at the treadmill walking than at overground walking. Strain gauge-floor contact times were shorter in the treadmill walking; heel 81.2%, first metatarsal 93.5%, third metatarsal 93.6%, fifth metatarsal 90.6% and at great toe 93.2% of overground locomotion. Cadence during treadmill locomotion was significantly larger than overground walking (106.6%, P < 0.05). These results show that when subjects walk on the treadmill and on laboratory floor at the identical speed, stance period shortened by 6.7% while cadence increased by 6.6% on the treadmill.


Lipids, biomarkers, and subclinical atherosclerosis in treatment-naive HIV patients starting or not starting antiretroviral therapy: Comparison with a healthy control group in a 2-year prospective study.
To assess the effect of HIV infection and combined antiretroviral therapy (c-ART) on various proatherogenic biomarkers and lipids and to investigate their relationship with subclinical atherosclerosis in a cohort of treatment-naive HIV-infected patients. We performed a prospective, comparative, multicenter study of 2 groups of treatment-naive HIV-infected patients (group A, CD4>500 cells/μL, not starting c-ART; and group B, CD4<500 cells/μL, starting c-ART at baseline) and a healthy control group. Laboratory analyses and carotid ultrasound were performed at baseline and at months 12 and 24. The parameters measured were low-density lipoprotein (LDL) particle phenotype, lipoprotein-associated phospholipase A2 (Lp-PLA2), interleukin-6 (IL-6), high-sensitivity C-reactive protein (hs-CRP), sCD14, sCD163, monocyte chemoattractant protein-1(MCP-1), and asymmetric dimethylarginine (ADMA). A linear mixed model based on patient clusters was used to assess differences in biomarkers between the study groups and over time. The study population comprised 62 HIV-infected patients (group A, n = 31; group B, n = 31) and 22 controls. Age was 37 (30-43) years, and 81% were men. At baseline, the HIV-infected patients had a worse LDL particle phenotype and higher plasma concentration of sCD14, sCD163, hs-CRP, and LDL-Lp-PLA2 than the controls. At month 12, there was an increase in total cholesterol (p = 0.002), HDL-c (p = 0.003), and Apo A-I (p = 0.049) and a decrease in sCD14 (p = <0.001) and sCD163 (p<0.001), although only in group B. LDL particle size increased in group B at month 24 (p = 0.038). No changes were observed in group A or in the healthy controls. Common carotid intima-media thickness increased in HIV-infected patients at month 24 (Group A p = 0.053; group B p = 0.048). Plasma levels of sCD14, sCD163, and hs-CRP correlated with lipid values. In treatment-naive HIV-infected patients, initiation of c-ART was associated with an improvement in LDL particle phenotype and inflammatory/immune biomarkers, reaching values similar to those of the controls. HIV infection was associated with progression of carotid intima-media thickness.


Clinical exhibition of increased accommodative loads for binocular fusion in patients with basic intermittent exotropia.
To investigate the accommodative loads change needed to maintain binocular fusion in patients with intermittent exotropia (IXT). Seventeen consecutive patients with basic IXT and 15 normal controls were recruited. The WAM-5500 autorefractor (GrandSeiko, Fukuyama, Japan) was used to measure refractive error (D) under binocular and monocular viewing conditions at 6 m, 50 cm, 33 cm and 20 cm. The difference between binocular and monocular refractive error (D) at each distance defined the change in the accommodative load. The changes in accommodative load were compared between IXT patients and normal controls. We also investigated the change in accommodative loads according to the fixing preference in patients with IXT. In IXT patients, the mean angles of deviation were 20.2 ± 7.19 and 21.0 ± 8.02 prism diopters at 6 m and 33 cm, respectively. Under binocular viewing, the changes in accommodative loads of each eye in IXT patients were significantly higher at 50, 33 and 20 cm than those of normal controls (p < 0.05, all). The changes in accommodative loads of fixating and deviating eyes at 6 m were not significantly different between IXT patients and normal controls (p = 0.193, 0.155, respectively). The changes in accommodative loads of the fixating eye at each distance were not significantly different from those of the deviating eye in IXT patients (p > 0.05). The changes of accommodative loads at near fixation increased more in IXT patients than they did in normal controls while maintaining binocular fusion.


Persistent organic pollutants in human milk in women from urban and rural areas in northern China.
Human milk specimens from 55 women in Shijiazhuang urban and Tangshan rural areas in Hebei Province in northern China were collected and analyzed for persistent organic pollutants, such as p,p'-dichlorodiphenyldichloroethylene (p,p'-DDE), hexachlorobenzene (HCB), beta-hexachlorocyclohexane (beta-HCH), and dioxins. We administered a questionnaire to milk donors at collection time, asking about lifestyle factors that potentially influence organochlorine pesticide (OCP) levels in human milk. We found that the concentrations of p,p'-DDE and beta-HCH in human milk from the primiparous mothers in Shijiazhuang (3330 and 108.8 ng/g fat, respectively) were higher than in samples from mothers from Tangshan (1916 and 21.2 ng/g fat, respectively). In addition, we found the level of p,p'-DDE correlated positively with a dietary history of meat consumption or consumption of internal organs of pigs and sheep (r=0.38 and r=0.52, respectively), but not with intake frequencies of vegetables and fruits in primiparous mothers. The higher level for p,p'-DDE may be due to a greater intake of contaminated fatty foods in the industrialized areas. We also showed that the body burden of p,p'-DDE was higher in the urban group compared to the values in other regions in China after 1998. However, there was no difference in dioxin levels between the two regions. Comprehensive monitoring of persistent organic pollutants in human milk and food is needed in China.


Complications of Proximal Biceps Tenotomy and Tenodesis.
The long head of biceps tendon (LHBT) is a well-recognized cause of anterior shoulder pain. Tenotomy or tenodesis of the LHBT is an effective surgical solution for relieving pain arising from the LHBT. Cosmetic deformity of the arm, cramping or soreness in the biceps muscle, and strength deficits in elbow flexion and supination are the three most common adverse events associated with tenotomy of the LHBT. Complications associated with tenodesis of the LHBT include loss of fixation resulting in cosmetic deformity, residual groove pain, pain or soreness in the biceps muscle, infection, stiffness, hematoma, neurologic injury, vascular injury, proximal humerus fracture, and reflex sympathetic dystrophy.


Origin, dietary exposure, and toxicity of endocrine-disrupting food chemical contaminants: A comprehensive review.
Endocrine-disrupting chemicals (EDCs) are a growing public health concern worldwide. Consumption of foodstuffs is currently thought to be one of the principal exposure routes to EDCs. However, alternative ways of human exposure are through inhalation of chemicals and dermal contact. These compounds in food products such as canned food, bottled water, dairy products, fish, meat, egg, and vegetables are a ubiquitous concern to the general population. Therefore, understanding EDCs' properties, such as origin, exposure, toxicological impact, and legal aspects are vital to control their release to the environment and food. The present paper provides an overview of the EDCs and their possible disrupting impact on the endocrine system and other organs.


Humor creation during efforts to find humorous cognitive reappraisals of threatening situations.
This interdisciplinary study examined the structure of humor creation in the specific context of efforts to positively reappraise stressful situations for effective coping. In a sample of n = 101 participants, a performance test was used to assess the quantity (fluency, number of generated ideas that qualified as humor) and quality (rated funniness) of humor creation in cognitive reappraisal. Linguistic mechanisms were identified and quantified using cognitive-linguistic methods of corpus analysis, and their employment was correlated with humor production performance on the level of the individual. Almost all individuals were able to come up with reappraisal ideas that qualified as humorous. Depressive symptoms, a negative mood state, and high perceptions of threat did not compromise the participants' capability to create humor. Individuals who were more serious-minded as a trait produced ideas that were rated as less funny, but their basic ability to create humor was unaffected. Metonymy (a contiguity-based principle of meaning extension) emerged as by far the most prominent semantic mechanism in the creation of humorous re-interpretations. Furthermore, its use was related to good humor creation performance in terms of quantity and quality, which is in line with its assumed importance in the extension of meaning in general and the creation of humor in particular. Further effective linguistic mechanisms and conceptual phenomena were identified. The empirical data may be valuable for the development of interventions involving the creation of humorous ideas for cognitive reappraisal.


The effect of Er,Cr:YSGG laser on periodontopathic bacteria elimination: an in vitro study.
In vitro bacterial elimination using the erbium, chromium: yttrium-scandium-gallium-garnet (Er,Cr:YSGG) laser against periodontopathic bacteria was investigated. Bacterial suspensions of Aggregatibacter actinomycetemcomitans and Porphyromonas gingivalis were spread on agar plates and the Er,Cr:YSGG laser was applied at 40 mJ pulse energy for durations of 30 s, 60 s, and 90 s. The agar plates were incubated, and growth inhibition zones were assessed. Optimal laser irradiation durations to achieve maximal bacterial elimination were evaluated using laser ablation on the bacterial colonies. The remaining viable bacteria were determined by the colony-forming unit (CFU) counting method. Growth inhibition zones were observed at all irradiation durations for both A. actinomycetemcomitans and P. gingivalis. Mean logarithmic values of CFU/ml after bacterial colony irradiation for 0 s (control), 12 s × 1 lap, 24 s × 1 lap, 48 s × 1 lap, and 24 s × 2 laps were 8.82 ± 0.35, 7.31 ± 0.94, 6.32 ± 0.61, 3.17 ± 2.90, and 0.00, respectively, for A. actinomycetemcomitans and 9.83 ± 0.50, 9.42 ± 0.11, 6.90 ± 1.60, 2.33 ± 3.19, and 0.00 for P. gingivalis. Significant differences were found between the control group and the two irradiated groups 48 s × 1 lap and 24 s × 2 laps (p < 0.05), and also between irradiated groups 12 s × 1 lap and 24 s × 2 laps (p < 0.05). An Er,Cr:YSGG laser with power setting 1.5 W and 30 Hz frequency showed potential for bacterial elimination against A. actinomycetemcomitans and P. gingivalis in vitro. Significant bacterial elimination (> 99.99%) was observed after 48 s of irradiation.


Neurally plausible mechanisms for learning selective and invariant representations.
Coding for visual stimuli in the ventral stream is known to be invariant to object identity preserving nuisance transformations. Indeed, much recent theoretical and experimental work suggests that the main challenge for the visual cortex is to build up such nuisance invariant representations. Recently, artificial convolutional networks have succeeded in both learning such invariant properties and, surprisingly, predicting cortical responses in macaque and mouse visual cortex with unprecedented accuracy. However, some of the key ingredients that enable such success-supervised learning and the backpropagation algorithm-are neurally implausible. This makes it difficult to relate advances in understanding convolutional networks to the brain. In contrast, many of the existing neurally plausible theories of invariant representations in the brain involve unsupervised learning, and have been strongly tied to specific plasticity rules. To close this gap, we study an instantiation of simple-complex cell model and show, for a broad class of unsupervised learning rules (including Hebbian learning), that we can learn object representations that are invariant to nuisance transformations belonging to a finite orthogonal group. These findings may have implications for developing neurally plausible theories and models of how the visual cortex or artificial neural networks build selectivity for discriminating objects and invariance to real-world nuisance transformations.


The radial tunnel syndrome.
Twenty patients with symptoms present for an average of 21.1 months and who in most cases had been treated by several conservative techniques for chronic tennis elbow were diagnosed as having radial tunnel syndrome, as originally described by Roles and Maudsley. Release of the tunnel was followed by eventual relief in 19 instances (95%).


Adolescents' Perceptions of Gender Aspects in a Virtual-Reality-Based Alcohol-Prevention Tool: A Focus Group Study.
Virtual reality (VR) is an innovative tool for alcohol prevention among adolescents. However, many aspects of virtual simulations for alcohol prevention remained unstudied, and research on opportunities for tailoring such tools to users' gender using avatar-based pathways is lacking. The present study, therefore, explores adolescents' perceptions of gender portrayal and gender tailoring using Virtual LimitLab-a VR simulation for building refusal skills for dealing with peer pressure to consume alcohol. Focus groups were conducted after individual simulation testing with 13 adolescents in four groups, whose statements and discussion underwent thematic analysis. Three main themes were identified: the relevance of gender, opinions on different tailoring options for gender, and opinions on flirt orientation. Divergent arguments for different tailoring options and representations of gender in the simulation were proposed. Some participants changed opinions during discussions. Sexual harassment was consensually deemed an important issue that is linked to both partying and alcohol and was concluded to require being addressed along with alcohol prevention. A consensus also formed around open flirting possibilities (regardless of gender), and awareness of non-binary peers was raised. Based on the observed sensitivity of the adolescents to gender diversity, it is necessary to include LGBTQIA+ adolescents when developing gender-sensitive simulations.


Assessment of prescribing potentially inappropriate medications listed in Beers criteria and its association with the unplanned hospitalization: a cross-sectional study in Lahore, Pakistan.
Due to physiological and pharmacological variations, geriatrics are at high risk of experiencing life-threatening outcomes related to the use of potentially inappropriate medications (PIMs). Thus, the present study aims to evaluate prescribing practices of PIMs among elderly patients who may lead to unplanned hospitalization and associated risk factors. A cross-sectional study was conducted in different hospitals of Lahore, Pakistan. The study population consisted of geriatric patients aged ≥65 years. Data were collected from the medical records of geriatric patients, who attended these selected hospitals between December 1, 2017, and February 28, 2018. Data were analyzed using SPSS (IBM SPSS Statistics for Windows, Version 21.0) and Microsoft Excel (MS Office 2010). The records of 385 geriatric patients were investigated. More than half (60.8%) of the patients were subjected to polypharmacy, which can be defined as the utilization of 5-9 drugs by the patient at the same time, whereas 36.4% were prescribed with one PIM and 56.4% were hospitalized due to PIMs. Majority of them were prescribed with PIMs including N02BA01 (aspirin, 32.4%), A02BC01 (omeprazole, 23.6%), A10AB02 (insulin, 17.4%), A02BC05 (esomeprazole, 8.5%), C08CA01 (amlodipine, 8.3%), and R06AA02 (diphenhydramine, 5.9%). Results of regression analysis revealed that patients exposed to polypharmacy (OR=2.556, 95% CI=1.579-4.135, P-value≤0.001) and excessive polypharmacy (OR=37.828, 95% CI=4.754-300.9, P-value≤0.001) were significantly associated with unplanned hospitalization, whereas factors such as age 75-84 years (OR=0.343, 95% CI=0.156-0.756, P-value=0.008) and polypharmacy (OR=2.480, 95% CI=1.219-5.048, P-value=0.012) were significantly correlated with PIMs. The utilization of PIMs listed in Beers criteria among geriatric population can cause unplanned hospitalization. As the patients receiving polypharmacy are at high risk of unplanned hospitalization, so caution must be exercised in prescribing PIMs for elderly people.


Embryology of bladder exstrophy.
A hypothesis in respect to the teratogenesis of bladder exstrophy and its variants is offered. The central feature of this hypothesis is the abnormal persistence of the caudal position of the insertion of the body stalk on the embryo. As a consequence of this, the normal advance and interposition of mesenchymal tissue to the midline becomes impossible. The cloaca cannot be translocated backwards into the body cavity, and the cranial end of the cloacal membrane remains in contact with the inferior aspect of the low-set body stalk. This, in contrast to the previously proposed abnormal rostral extension of the cloacal membrane, causes a wedge-effect resulting in the lateralization of the abdominal wall structures and also in the prevention of the midline fusion of the genital hillocks (labioscrotal or genital folds). A cloacal membrane normally is an unstable structure lacking mesoderm, and it retains these characteristics in the superficial and infraumbilical position to be described. It has a strong tendency to disintegrate. It may rupture at variable times and to a variable extent. The consequence of such an embryonic event is either a typical bladder exstrophy or one of the variants of the exstrophy malformation. Three different variants are presented that the proposed embryologic hypothesis can readily explain.


Diagnosis of breast cancer by X-ray diffraction of hair.
This article presents the results of analyses of hair fibers from women with breast cancer using synchrotron-derived X-ray diffraction. These diffraction patterns contained a new feature superimposed on the normal diffraction pattern of alpha-keratin. The feature appeared as a ring with a molecular spacing determined to be 4.76 +/- 0.07 nm. This feature was not present in the diffraction patterns of hair from women without breast cancer as assessed by other routine clinical diagnostic techniques. Furthermore, different hairs from the same subject analysed on two different synchrotron beamlines give remarkably consistent diffraction patterns. Previous studies by other investigators have suggested that analysis of X-ray diffraction patterns of hair can reveal the presence of breast cancer in clinical and preclinical trials. This finding, however, has not been independently confirmed. The methodologies of sample handling, sample exposure and image analysis are known to be vital. We discuss some of these issues and provide a detailed description of the methodology employed for the sample handling and image analysis and new methodologies developed from this work. We conclude that X-ray diffraction of hair has the potential to provide a non-invasive test for the presence of breast cancer.


Documentary series shows transformation in services.
MEDICATION REVIEW in care homes is the subject of the first in a series of mini documentaries developed by charity the Health Foundation and hosted on its website.


Reversible combined cognitive impairment and severe polyneuropathy resulting from primary hyperparathyroidism.
Central and peripheral nervous systems may be involved in primary hyperparathyroidism (PHP). The efficacy of parathyroidectomy in reversing neurological symptoms is still a matter of controversy. We describe the case of a 71-year-old white male with a 10-year history of PHP who developed progressive cognitive dysfunction and severe sensorimotor axonal polyneuropathy. Successful parathyroidectomy reversed with a different temporal course both the central and peripheral nervous system involvements.


Overlapping distributions of orexin/hypocretin- and dopamine-beta-hydroxylase immunoreactive fibers in rat brain regions mediating arousal, motivation, and stress.
A double-label immunohistochemical study was carried out to investigate overlap between dopamine-beta-hydroxylase (DbetaH) -immunopositive projections and the projections of hypothalamic neurons containing the arousal- and feeding-related peptide, orexin/hypocretin (HCRT), in rat brain. Numerous intermingled HCRT-immunopositive and DbetaH-immunopositive fibers were seen in a ventrally situated corridor extending from the hypothalamus to deep layers of the infralimbic cortex. Both fiber types avoided the nucleus accumbens core, caudate putamen, and the globus pallidus. In the diencephalon, overlap was observed in several hypothalamic areas, including the perifornical, dorsomedial, and paraventricular nuclei, as well as in the paraventricular thalamic nucleus. Intermingled HCRT-containing and DbetaH-containing fibers extended from the hypothalamus into areas within the medial and central amygdala, terminating at the medial border of the lateral subdivision of the central nucleus of the amygdala. Dense overlap between the two fiber types was also observed in the periaqueductal gray, particularly in the vicinity of the dorsal raphe, as well as (to a lesser extent) in the ventral tegmental area, the retrorubral field, and the pedunculopontine tegmental nucleus. Hypocretin-containing cell bodies, located in the perifornical and lateral hypothalamus, were embedded within a dense plexus of DbetaH-immunopositive fibers and boutons, with numerous cases of apparent contacts of DbetaH-containing boutons onto HCRT-immunopositive soma and dendrites. HCRT-containing fibers were observed amid the noradrenergic cells of the locus coeruleus, and in the vicinity of the A1, A2, and A5 cell groups. Hence, the projections of these two arousal-related systems, originating in distinctly different parts of the brain, jointly target several forebrain regions and brainstem monoaminergic nuclei involved in regulating core motivational processes.