Separated dental laminae are present in the upper jaw of Mesoamerican lungless salamanders (Amphibia, Plethodontidae).
Plethodontid salamander species from Northern America exhibit a single, unseparated dental lamina in the upper jaw, which consistently provides teeth for the unpaired premaxillary and the two maxillary bones. During the distinct mating season, adult males of these species bear long, monocuspid, unbladed teeth in the entire upper jaw, which are used during courtship. However, plethodontid salamander species from Southern Central America studied so far show either three separated dental laminae or a single dental lamina with three distinguishable tooth-producing parts connected by non-producing parts. These species reproduce aseasonally and sexually mature males permanently bear long, monocuspid, unbladed teeth on the premaxillary only. As the formation of these long, monocuspid teeth depends on the presence of androgen-receptors in the tooth-forming tissues, the morphological separation of the dental lamina in plethodontid salamanders from Southern Central America is very likely to be a prerequisite for a region-specific expression of androgen-receptors in the tooth-forming tissues controlling the differentiated shape formation of teeth in these species. Seven species of plethodontid salamanders from Costa Rica and Panama were examined and, in all, a tendency to exhibit three separate dental lamina in the upper jaw was found, although the morphological separation is definitive only in Bolitoglossa colonnea, B. lignicolor, B. pesrubra, B. schizodactyla and B. striatula. B. dofleini and B. marmorea show a continuous dental lamina with non-producing parts at the transitional sites between the parts associated with the premaxillary and the maxillary bones.


Transfer of effects from environmentally enriched and impoverished female rats to future offspring.
The effects of environmental enrichment on both brain and behaviour have been the subject of systematic investigation for more than two decades. However, scant attention has been paid to the possible effects on offspring of environmental enrichment of the parental generation. Experiments are described which demonstrate that manipulation of the environments of female rats even prior to pregnancy can significantly modify the behaviour of future offspring. The importance of the investigation of the mechanisms mediating this inter generation transfer is discussed in the context of recent interest in clinical applications of environmental enrichment research.


A bovine rotavirus serotype 1: serologic characterization of the virus and nucleotide sequence determination of the structural glycoprotein VP7 gene.
Bovine rotavirus T449 was isolated from feces of a calf with diarrhea. Serological characterization by serotype-specific monoclonal antibodies showed that the T449 virus belonged to serotype 1. This is the first report of a bovine rotavirus that does not belong to serotype 6, 8, or 10. The serotype 1 designation was confirmed by using an immunoperoxidase focus neutralization assay. The gene encoding the major neutralization antigen (VP7) was cloned and its nucleotide sequence was determined. The sequence obtained was 1062 bp in length and contained an open reading frame corresponding to 326 amino acid residues. Comparative analysis of the deduced amino acid sequence with the corresponding sequence of the human serotype 1 rotavirus strain, Wa, revealed a 90% identity. When compared to the predicted amino acid sequence of VP7 protein of the other serotypes an overall divergence of 20 to 25% was detected. These data show that the serological typing agrees with the result of the genetic analysis.


Blocking of Dendrodendritic Inhibition Unleashes Widely Spread Lateral Propagation of Odor-evoked Activity in the Mouse Olfactory Bulb.
The olfactory circuitry in mice involves a well-characterized, vertical receptor type-specific organization, but the localized inhibitory effect from granule cells on action potentials that propagate laterally in secondary dendrites of mitral cell remains open to debate. To understand the functional dynamics of the lateral (horizontal) circuits, we analyzed odor-induced signaling using transgenic mice expressing a genetically encoded Ca2+ indicator specifically in mitral/tufted and some juxtaglomerular cells. Optical imaging of the dorsal olfactory bulb (dOB) revealed specific patterns of glomerular activation in response to odor presentation or direct electric stimulation of the olfactory nerve (ON). Application of a mixture of ionotropic and metabotropic glutamate receptor antagonists onto the exposed dOB completely abolished the responses to direct stimulation of the ON as well as discrete odor-evoked glomerular responses patterns, while a spatially more widespread response component increased and expanded into previously nonresponsive regions. To test whether the widespread odor response component represented signal propagation along mitral cell secondary dendrites, an NMDA receptor antagonist alone was applied to the dOB and was found to also increase and expand odor-evoked response patterns. Finally, with dOB excitatory synaptic transmission completely blocked, application of 1 mM muscimol (a GABAA receptor agonist) to a circumscribed volume in the deep external plexiform layer (EPL) induced an odor non-responsive area. These results indicate that odor stimulation can activate olfactory reciprocal synapses and control lateral interactions among olfactory glomerular modules along a wide range of mitral cell secondary dendrites by modulating the inhibitory effect from granule cells.


Downregulation of the taurine transporter TauT during hypo-osmotic stress in NIH3T3 mouse fibroblasts.
The present work was initiated to investigate regulation of the taurine transporter TauT by reactive oxygen species (ROS) and the tonicity-responsive enhancer binding protein (TonEBP) in NIH3T3 mouse fibroblasts during acute and long-term (4 h) exposure to low-sodium/hypo-osmotic stress. Taurine influx is reduced following reduction in osmolarity, keeping the extracellular Na(+) concentration constant. TonEBP activity is unaltered, whereas TauT transcription as well as TauT activity are significantly reduced under hypo-osmotic conditions. In contrast, TonEBP activity and TauT transcription are significantly increased following hyperosmotic exposure. Swelling-induced ROS production in NIH3T3 fibroblasts is generated by NOX4 and by increasing total ROS, by either exogenous application of H(2)O(2) or overexpressing NOX4, we demonstrate that TonEBP activity and taurine influx are regulated negatively by ROS under hypo-osmotic, low-sodium conditions, whereas the TauT mRNA level is unaffected. Acute exposure to ROS reduces taurine uptake as a result of modulated TauT transport kinetics. Thus, swelling-induced ROS production could account for the reduced taurine uptake under low-sodium/hypo-osmotic conditions by direct modulation of TauT.


R-CHOEP14 in younger high-risk patients with large B cell lymphoma: an effective front-line regimen with cardiac toxicity: a real-life, single-center experience.
Currently, there is no consensus regarding optimal front-line treatment for younger high-risk patients with large B cell lymphoma. American recommendations list only R-CHOP as standard, while European also include R-ACVBP and R-CHOEP14. We have been routinely using the latter regimen at our institution since 2011 and performed this retrospective real-life single-center study to analyze outcomes. Between September 2011 and April 2019, 66 newly diagnosed patients aged 18 to 60 years with B-large cell lymphoma and high-risk age-adjusted International Prognostic Index score were scheduled to receive 6 or 8 cycles of bi-weekly chemoimmunotherapy with cyclophosphamide, doxorubicin, vincristine, etoposide, steroids, and rituximab (R-CHOEP14). After a median follow-up of 4.7 years, the estimated 3-year progression-free survival was 87% (95% CI 80-96%) and 3-year overall survival 90% (95% CI 83-98%). Grade ≥ 3 hematological side effects occurred in 83% and infectious in 41% of patients; one patient died of toxicity. Grade ≥ 2 cardiac toxicity occurred in 21% of patients, more frequently than previously reported. The cumulative 5-year risk of congestive heart failure with all-cause mortality as the competing risk was 17%. R-CHOEP14 is a very effective and manageable regimen for younger high-risk patients with B-large cell lymphoma, but the risk of cardiotoxicity warrants further investigations.


Routine amniotic fluid alpha-fetoprotein measurement in 34,000 pregnancies.
Of 34,000 initial amniotic fluid samples, 0.7% had an alpha-fetoprotein level greater than or equal to +3 SD above the mean. The risk of an open neural tube defect or other serious fetal abnormality was 60% when alpha-fetoprotein levels measured greater than or equal to +3 and 86% for levels greater than or equal to +5 SD. In this series there were 72 open neural tube defects, and all were identified. The true false positive rate was 0.9 per 10,000 cases screened.


Public spending on health care: how are different criteria related? A second opinion.
A natural response to difficult questions is to increase the number of objectives one pursues in the hope that each of them separately will be easy to satisfy. This note critically evaluates this strategy as employed in a recent paper in this journal [Musgrove, Health Policy 1999;47:207-223], especially its evaluation of the role of cost-effectiveness in priority setting in the health sector. It is suggested that cost-effectiveness measures provide information of limited use, and that the tools of applied welfare economics are sufficient to guide the policy choices addressed in the paper. Students of health economics and health policy makers would do well to be exposed to these tools.


Local coordination between intracortical bone remodeling and vascular development in human juvenile bone.
Although failure to establish a vascular network has been associated with many skeletal disorders, little is known about what drives development of vasculature in the intracortical bone compartments. Here, we show that intracortical bone resorption events are coordinated with development of the vasculature. We investigated the prevalence of vascular structures at different remodeling stages as well as their 3D organization using proximal femoral cortical bone from 5 girls and 6 boys (aged 6-15 years). A 2D analysis revealed that non-quiescent intracortical pores contained more vascular structures than quiescent pores (p < 0.0001). Type 2 pores, i.e., remodeling of existing pores, had a higher density of vascular structures than type 1 pores, i.e., de novo created pores (p < 0.05). Furthermore, pores at the eroded-formative remodeling stage, had more vascular structures than pores at any other remodeling stage (p < 0.05). A 3D reconstruction of an intracortical remodeling event showed that osteoclasts in the advancing tip of the cutting cone as well as preosteoclasts in the lumen expressed vascular endothelial growth factor-A (VEGFA), while VEGFA-receptors 1 and 2 mainly were expressed in endothelial cells in the adjacent vasculature. Consequently, we propose that the progression of the vascular network in intracortical remodeling events is driven by osteoclasts expressing VEGFA. Moreover, the vasculature is continuously reconfigured according to the demands of the remodeling events at the surrounding bone surfaces.


Reversible inhibition and mechanism-based irreversible inactivation of monoamine oxidases by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP).
It has been suggested (Chiba et al., Biochem. Biophys. Res. Communs. (1984) 120, 574) that the neurotoxic effects of MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine), which causes Parkinsonian symptoms in humans and other primates, are due to compounds resulting from the oxidation of MPTP by monoamine oxidase B in the brain. We reported recently that both monoamine oxidase A and B oxidize MPTP to MPDP+, the 2,3-dihydropyridinium form and that the reaction is accompanied by time-dependent, irreversible inactivation of the enzymes. Of the two forms of monoamine oxidase, the B enzyme oxidizes MPTP more rapidly and is also more sensitive to inactivation. We now wish to report that MPTP, as well as its oxidation products, MPDP+ and MPP+, the 4-phenylpyridinium form, are also potent reversible, competitive inhibitors of both monoamine oxidase A and B, particularly the former, and that the order of inhibition for the A enzyme is MPDP+ greater than MPP+ greater than MPTP, while for the B enzyme MPTP greater than MPDP+ greater than MPP+. We further report on the spectral changes and isotope incorporation accompanying the irreversible inactivation.


Unmet Clinical Needs for Transcatheter Pulmonary Valves.
A common feature of congenital heart disease is the presence of right ventricular outflow tract (RVOT) obstruction that can range from mild to severe and can lead to atresia of the pulmonary valve, in extreme conditions. RVOT abnormalities can frequently be corrected surgically or via interventional means. However, most of these patients will ultimately develop pulmonary valve insufficiency and eventual right ventricular dilation, which will require a pulmonary valve replacement at some point in their life to mitigate the detrimental effects of pulmonary valve regurgitation (PVR) on the right ventricle (RV). The evolution from the studies done by Philip Bonhoeffer to implant a pulmonary valve via transcatheter means, have provided a bedrock for transcatheter pulmonary valve replacement (TPVR). Yet, several areas of unmet need for a demographic of patients still exist. Here, we discuss the clinical unmet needs in children under 20 Kg and expand the use of hybrid and other TPVR approaches along with the current indications and contraindications for pulmonary valve replacement. The constraints and limitations from commercially available pulmonary valves will be discussed from a clinical standpoint. Finally, we explore the use of hybrid and periventricular delivery of transcatheter pulmonary valves in younger patients.


Association between type of drinking water and upper gastrointestinal cancer incidence in the Linxian General Population.
This study aimed to explore the association between drinking water source and risk of upper gastrointestinal (UGI) cancer, including esophageal cancer (EC) and gastric cancer (GC), in the Linxian General Population Nutrition Intervention Trial (NIT) cohort. In this study, we used data from the Linxian NIT cohort, which included 29,584 healthy adults aged 40 to 69 years. Subjects were enrolled in April 1986 and followed up until March 2016. Tap water drinking status and demographic characteristics were collected at baseline. Subjects who drank tap water were treated as the exposed group. Hazard ratios (HRs) and 95% confidence intervals (95% CIs) were estimated using the Cox proportional hazard model. A total of 5,463 cases of UGI cancer were identified during the 30-year follow-up period. After adjusting for multiple factors, the incidence rate of UGI cancer in participants who drank tap water was significantly lower compared with individuals in the control (HR = 0.91, 95% CI: 0.86-0.97). A similar association was observed between tap water drinking and EC incidence (HR = 0.89, 95% CI: 0.82-0.97). The association between drinking tap water and risk of UGI cancer and EC incidence did not vary across the subgroup by age and gender (All Pinteraction > 0.05). For EC incidence, an interaction effect was observed for riboflavin/niacin supplements and drinking water source (Pinteraction = 0.03). No association was observed between drinking water source and GC incidence. In this prospective cohort study in Linxian, participants who drank tap water had a lower risk of EC incidence. As a source of drinking water, use of tap water may reduce the risk of EC by avoiding exposure to nitrate/nitrite. Measures should be taken to improve the quality of drinking water in high-incidence areas of EC. The trial is registered with ClinicalTrials.gov (NCT00342654, 21/06/2006), and the trial name is Nutrition Intervention Trials in Linxian Follow-up Study.


Gas chromatographic determination of gallopamil and norgallopamil in human plasma.
A highly sensitive gas chromatographic assay is described for the simultaneous determination of gallopamil, a calcium channel blocking agent, and its major metabolite, norgallopamil. A multi-step extraction procedure is employed followed by on-column capillary gas chromatographic analysis using nitrogen-selective detection. Acetylation of norgallopamil is performed to enable accurate quantification of the metabolite. Linearity was achieved over the range 1-50 ng/ml for both analytes. Assay specificity, precision and accuracy were investigated.


An intestinal volvulus caused by multiple magnet ingestion: an unexpected risk in children.
It has been reported that ingested magnets can cause intestinal fistula formation or perforation, leading to intestinal obstruction. However, there are no previous case reports that magnet ingestion additionally caused an intestinal volvulus. We report herein the case of a 1-year-old boy in whom the ingested magnets caused a volvulus of part of the small intestine leading to the resection of the necrotic portion. We think that if more than one magnet is found as a foreign body in the intestine, they should be removed immediately by laparotomy. Clinicians who care for children should be aware of this unexpected risk.


Serum testosterone differences between patients with schizophrenia and those with affective disorder.
Serum testosterone levels (ng/dl) were measured at 2-week intervals during the course of hospitalization in 35 male inpatients in the following four diagnostic groups: undifferentiated schizophrenia, paranoid schizophrenia, bipolar I disorder-manic, and major depressive disorder (endogenous type). The mean (+/- SE) testosterone levels during hospitalization were significantly higher (p less than 0.001) in the schizophrenic patients (510 +/- 38) than in the affective disorder patients (347 +/- 25). This difference persisted throughout hospitalization, being present in the first sample following admission (p less than 0.03) and the final sample before discharge (p less than 0.01). The above group differences were largely due to high testosterone levels in the paranoid schizophrenic subgroup (mean +/- SE level of 559 +/- 41). A longitudinal, as well as cross-sectional, view of the hormonal and clinical data suggests that the testosterone system is linked to both state and trait psychological factors, and this issue is discussed in the light of prior basic psychoendocrine research on this system. The potential application of these findings for new approaches to the development of biological criteria for psychiatric diagnosis is discussed.


Long-term follow-up of nonvascularized fibular autografts for distal radial reconstruction.
Three patients with giant cell tumors of the distal radius had en bloc excision of the distal radius and replacement with the ipsilateral fibula. Two of the patients were followed for 16 years and one for 14 1/2 years. Forearm rotation, as well as wrist motion, was limited in all three patients, yet they remained functional and pain free except during periods of prolonged or excessive use. All three patients were pleased with the results. Bone union occurred primarily in all three patients without a supplemental bone graft or microvascular anastomosis. This method has a definite place in the hand surgeon's armamentarium when compared with radial allografts and microvascular free fibular translocation.


Giant iatrogenic splenic pseudocyst.
Partial splenic arterial embolization was used to treat hypersplenism in a 10-year-old boy with portal hypertension secondary to congenital hepatic fibrosis. After embolization the spleen remained enlarged, but the boy's platelet count increased and his variceal bleeding ceased. One month later, he returned with vomiting and an abdominal mass. Computed tomography showed a large cyst of the spleen with a small rim of residual splenic tissue. Percutaneous drainage with ultrasound guidance yielded 2,800 mL of brown fluid. Wedge-shaped infarctions are described early after splenic embolization, and these areas eventually fibrose and contract. In this case, the embolization resulted in splenic necrosis and liquefaction with pseudocyst formation. This unusual complication was effectively treated without surgery.


Ruthenium(II) complexes as mitochondrial inhibitors of topoisomerase induced A549 cell apoptosis.
Two new ruthenium(II) complexes [Ru(dip)2(PPβC)]PF6 (Ru1, dip = 4,7-diphenyl-1,10-phenanthroline, PPβC = N-(1,10-phenanthrolin-5-yl)-1-phenyl-9H-pyrido[3,4-b]indole-3-carboxamide) and [Ru(phen)2(PPβC)]PF6 (Ru2, phen = 1, 10-phenanthroline) with β-carboline derivative PPβC as the primary ligand, were designed and synthesized. Ru1 and Ru2 displayed higher antiproliferative activity than cisplatin against the test cancer cells, with IC50 values ranging from 0.5 to 3.6 μM. Moreover, Ru1 and Ru2 preferentially accumulated in mitochondria and caused a series of changes in mitochondrial events, including the depolarization of mitochondrial membrane potential, the damage of mitochondrial DNA, the depletion of cellular ATP, and the elevation of intracellular reactive oxygen species levels. Then, it induced caspase-3/7-mediated A549 cell apoptosis. More importantly, both complexes could act as topoisomerase I catalytic inhibitors to inhibit mitochondrial DNA synthesis. Accordingly, the developed Ru(II) complexes hold great potential to be developed as novel therapeutics for cancer treatment.


27-Hydroxycholesterol causes remodeling in endothelial cell membrane lipid composition comparable to remodeling in the failed vein grafts of CABG patients.
Our objective is to determine if vascular remodeling in CABG patients is related to oxysterols, therefore, we compared failed vein grafts from 18 patients, available after a second coronary artery bypass grafting (CABG), with human endothelial cells (ECs). The ECs were cultured in minimum essential medium (MEM) with or without 27-hydroxycholesterol (27OHC), one of the oxysterol products of oxidatively modified low density lipoproteins (ox-LDL), as an agent to alter molecular mechanisms in vascular cells. Significant changes in phospholipid composition, in fatty acid profile and in calcium concentration were found in the failed vein compared to the native saphenous vein from the same (CABG) patient. The failed vein contained significantly less phosphatidylethanolamine, more sphingomyelin, less arachidonic acid, more linoleic acid and more calcium than the native saphenous vein. Comparable changes in phospholipid composition, in fatty acid profile and increased calcium influx were reproduced in ECs cultured in medium containing 27OHC indicating that an oxysterol is an agent that can alter the lipid composition of vascular cell membranes. Our study indicates that a lipid agent, as well as protein agents that have previously been linked to the process of vascular remodeling, may be fundamental to many vascular diseases.


Membrane separation of solids from corn processing streams.
Corn processing streams are characterized by high water content. Removal of water and recovery of solids are major economic and logistical challenges. New technologies are needed to modify processing streams and to reduce variability and improve quality of coproducts. The objective was to determine the effectiveness of microfiltration and ultrafiltration systems in altering water, solids (protein) and ash contents of corn processing streams. Corn was either steeped with SO(2) (STW) or soaked (SKW) in water; STW contained more solids than SKW. Ultrafiltration of STW and SKW had little effect on water removal or solids recovery. Corn was processed by a conventional wet milling process and a wet milling process that used enzymes to eliminate use of SO(2) steeping. Protein streams from the conventional process (CG) and the enzymatic process (EG) were processed by microfiltration. Permeate streams from EG and CG had higher total solids and ash concentrations than retentate streams; much of the ash was recovered in permeate (67% and 83%, respectively). For CG, proteins were largely recovered in retentate, whereas for EG, proteins were recovered in permeate. SDS-PAGE data indicated a decrease in size of proteins in the EG process stream. Permeate streams from microfiltration were subject to ultrafiltration; there was little effect on solids and nutrient separations.


A two-sorted logic for structurally modeling systems.
Structural modeling of complex biological systems relies on formalisms inherited from physics. These formalisms scale poorly when dealing with interactions with many variables and agents working in systems that cohere at multiple layers. We propose a two sorted logic that supplements existing formalisms to mitigate these problems. The purpose of this second logic is to track how multiple contexts relate to each other, as well as to the dependent structures they inform: a situating of situations. In this way, we aim to capture the multi-layered and multi-system dynamics that have been elusive in modeling emergent systems. An apoptosis example is explored in the context of mental concepts.


A three-dimensional printed porous implant combined with bone grafting following curettage of a subchondral giant cell tumour of the proximal tibia: a case report.
Subchondral bone is commonly affected in cases of giant cell tumour (GCT) of the proximal tibia. Numerous studies have stated that retaining a sufficient subchondral bone layer could decrease the possibilities of postoperative degenerative changes and mechanical failure of the knee joint. However, the most commonly used methods of cement packing only or cement packing combined bone grafting have some limitations regarding the protection of subchondral bone after surgery. Our paper describes our attempt to reconstruct a tumorous defect associated with the subchondral area in the proximal tibia with a three-dimensional (3D)-printed porous implant combined with bone grafting and our evaluation of the short-term outcomes. A 42-year-old man with a Campanacci grade II GCT visited our institution for initial assessment. Radiographs showed a tumour located at the epiphyseal part of the proximal tibia, and had invaded the subchondral area. Considering that the residual subchondral bone had to be protected, we used an autograft to ensure a high integration rate between the graft and host subchondral bone. We also used three-dimensional (3D) printing technology to design and fabricate a personalized porous implant to mechanically support the graft and subchondral area and help avoid degenerative changes and mechanical failure. At the last follow-up at 29 months postoperatively, the patient had satisfactory limb function and no further damage was seen to the subchondral area and articular surface. The 3D-printed porous implant combined bone grafting may be a feasible option in the reconstruction of defects that are close to the subchondral area following extensive intracurettage of GCTs. Moreover, it can result in good postoperative function and low complication rates. However, consistent follow-up is required to clarify its long-term outcomes.


A new species of Leishmania parasite from the Venezuelan Andes region.
A new form of Leishmania is described from the Venezuelan Andes region. L. garnhami n.sp. is proposed for this parasite with amastigote stages showing a peculiar and unique organelle seen with light and electron microscope. It produces cutaneous lesions in people living at a height of between 800 and 1,8000 m. in urban and rural areas; the disease is associated with Lutzomyia townsendi, the main anthropophilic sandfly in the region. The parasite is easily inoculable into hamsters and grows slowly in vitro in blood-agar media with glucose, but more prolifically without glucose.


Ovariectomy attenuates aggression by female rats cohabiting with sexually active sterile males.
Female rats were individually housed with a single castrated male with a testosterone implant that maintained sexual and aggressive behavior. At weekly intervals, the resident male was removed and an unfamiliar female intruder was introduced into the colony. Attacks, bites, on-top, and piloerection of the resident female toward the intruder were scored. Females whose level of aggression toward the intruder was substantial and stable were either ovariectomized or sham-ovariectomized. Aggression tests resumed 1 week postoperatively and continued for an additional 3 weeks. The results confirm that female cohabiting with a sterile male become aggressive. They also demonstrate that ovariectomy greatly attenuates but does not entirely abolish aggression toward an unfamiliar female intruder. The results appear to contribute to a growing body of evidence suggesting that the biological substrate and behavioral form of aggression by females housed with males (including that following parturition) is a hormone-dependent aggression which parallels testosterone-dependent social aggression of males housed with females.


Accurately solving the electronic Schrodinger equation of atoms and molecules using explicitly correlated (r12-) multireference configuration interaction. VII. The hydrogen fluoride molecule.
We compute the potential-energy curve of the hydrogen fluoride molecule (HF) using a novel variant of the explicitly correlated multireference averaged coupled-pair functional method with a carefully selected basis set and reference space. After correcting for scalar relativistic effects and spin-orbit coupling, the potential is used to compute the dissociation energy, the equilibrium bond distance, the harmonic frequency, the anharmonicity, and the vibrational levels up to the dissociation limit. The errors in the equilibrium geometry constants compare favorably with the most elaborate (single reference) calculations of the literature. Starting at the region of RA/angstroms approximately 2,...,3, where the covalent HF bond begins to break and where single-reference methods become impractical, our potential begins to slightly underestimate the atomic interaction, which is reflected in an estimated error in the well depth of -0.2 kcal/mol.


Theoretical analysis for best defocus measurement plane for robust phase retrieval.
We study the phase retrieval (PR) technique using through-focus intensity measurements and explain the dependence of PR on the defocus distance. An optimal measurement plane in the out-of-focus region is identified where the intensity distribution on the optical axis drops to the first minimum after focus. Experimental results confirm the theoretical predictions and are in good agreement with an independent phase measurement.


Profile of Diphtheria Cases Hospitalized at Tertiary Referral Hospital in Indonesia: 10 Years' Experience.
This is a report about children diphtheria cases' profile in Cipto Mangunkusumo Hospital, Jakarta from 2006 to 2017. Occurrence was the highest in ≥5-years-old age group (67.7%) with male predominance (58.8%). Thirty five point three percent cases had no immunization history and 38.2% cases had incomplete booster history. Pseudomembrane occurred in all cases, mostly found in pharynx (67.6%) and tonsil (61.8%).


Impacts of microwave pretreatments on the semi-continuous anaerobic digestion of dairy waste activated sludge.
Microwave (MW) irradiation is one of the new and possible methods used for pretreating the sludge. Following its use in different fields, this MW irradiation method has proved to be more appropriate in the field of environmental research. In this paper, we focused on the effects of MW irradiation at different intensities on solubilization, biodegradation and anaerobic digestion of sludge from the dairy sludge. The changes in the soluble fractions of the organic matter, the biogas yield, the methane content in the biogas were used as control parameters for evaluating the efficiency of the MW pretreatment. Additionally, the energetic efficiency was also examined. In terms of an energetic aspect, the most economical pretreatment of sludge was at 70% intensity for 12 min irradiation time. At this, COD solubilization, SS reduction and biogas production were found to be 18.6%, 14% and 35% higher than the control, respectively. Not only the increase in biogas production was investigated, excluding protein and carbohydrate hydrolysis was also performed successfully by this microwave pretreatment even at low irradiation energy input. Also, experiments were carried out in semi continuous anaerobic digesters, with 3.5L working volume. Combining microwave pretreatment with anaerobic digestion led to 67%, 64% and 57% of SS reduction, VS reduction and biogas production higher than the control, respectively.


The dissociability of lexical retrieval and morphosyntactic processes for nouns and verbs: A functional and anatomoclinical study.
Nouns and verbs can dissociate following brain damage, at both lexical retrieval and morphosyntactic processing levels. In order to document the range and the neural underpinnings of behavioral dissociations, twelve aphasics with disproportionate difficulty naming objects or actions were asked to apply phonologically identical morphosyntactic transformations to nouns and verbs. Two subjects with poor object naming and 2/10 with poor action naming made no morphosyntactic errors at all. Six of 10 subjects with poor action naming showed disproportionate or no morphosyntactic difficulties for verbs. Morphological errors on nouns and verbs correlated at the group level, but in individual cases a selective impairment of verb morphology was observed. Poor object and action naming with spared morphosyntax were associated with non-overlapping lesions (inferior occipitotemporal and fronto-temporal, respectively). Poor verb morphosyntax was observed with frontal-temporal lesions affecting white matter tracts deep to the insula, possibly disrupting the interaction of nodes in a fronto-temporal network.


Esophageal adenocarcinoma 20 years after esophageal atresia repair.
We report a case of esophageal adenocarcinoma 20 years after esophageal atresia repair. From one case report it is premature to recommend cancer surveillance for all esophageal atresia patients. However, the first survivors are now reaching an age when esophageal cancer related to chronic esophagitis may become more prevalent.


Mammographic parenchymal pattern and breast cancer risk profile of Papua New Guinean women - A baseline study of the screening population.
The aim of this research is to evidence for the first time the breast density of Papua New Guinean (PNG) women as described by mammographic parenchymal patterns (MPPs) and profile breast cancer risk; to examine the relationship of age and MPPs. A retrospective analysis of 1161 screening mammograms of women who had undergone imaging at the Pacific International Hospital (PIH) was undertaken. Mammograms were classified into one of five Tabár MPPs; age was recorded in years. Descriptive analysis of the data for pattern distribution and a chi-square test, to test for relationships between age and pattern type were undertaken. The majority (51.42%) of women had Pattern I breasts; Pattern II (30.58%), Pattern III (4.31%), Pattern IV (7.24%), and Pattern V (6.46%). The mean age was 38.8 with a range of 30-80 years; there were no obvious differences in mean age across the categories of patterns. A chi-square test reported no evidence of a relationship between age and pattern type (p-value = 0.504). Pattern V differed from other patterns, with proportionally more women aged over 50 and less aged in their 40s. This study sets a baseline for future studies of the MPPs of PNG women, and demonstrated that in this snapshot of PNG women, there is no unique distribution of MPPs and no increased risk of breast cancer based on breast density profile. This result does not help to explain the high incidence of breast cancer in PNG. A more comprehensive study of the PNG screening population is required to validate this study.


Raman Spectroscopic Analysis of Highly-Concentrated Antibodies under the Acid-Treated Conditions.
Antibody drugs are usually formulated as highly-concentrated solutions, which would easily generate aggregates, resulting in loss of efficacy. Although low pH increases the colloidal dispersion of antibodies, acid denaturation can be an issue. Therefore, knowing the physical properties at low pH under high concentration conditions is important. Raman spectroscopy was used to investigate pH-induced conformational changes of antibodies at 50 mg/ml. Experiments in pH 3 to 7 were performed for human serum IgG and recombinant rituximab. We detected the evident changes at pH 3 in Tyr and Trp bands, which are the sensitive markers of intermolecular interactions. Thermal transition analysis over the pH range demonstrated that the thermal transition temperature (Tm) was highest at pH 3. Acid-treated and neutralized one showed higher Tm than that of pH 7, indicating that their extent of intermolecular interactions correlated with the Tm values. Onset temperature was clearly different between concentrated and diluted samples. Colloidal analyses confirmed the findings of the Raman analysis. Our studies demonstrated the positive correlation between Raman analysis and colloidal information, validating as a method for evaluating antibody conformation associated with aggregation propensities.


Visual detection of hexokinase activity and inhibition with positively charged gold nanoparticles as colorimetric probes.
Positively charged gold nanoparticles can effectively differentiate ATP and ADP, thus providing a simple and visual approach to colorimetric detection of hexokinase activity and inhibition.


3-[(1-Bromo-naphthalen-2-yl)meth-oxy]-5,5-di-methyl-cyclo-hex-2-enone.
In the title compound, C19H19BrO2, the cyclo-hexenone ring adopts an envelope conformation with the C atom bearing the methyl substituents as the flap. In the crystal, weak π-π stacking is observed between parallel aromatic rings of adjacent mol-ecules, the centroid-centroid distance being 3.694 (6) Å. The entire bromonaphthylmethyl unit is disordered over two orientations, with a site-occupancy ratio of 0.5214 (19):0.4786 (19).


Left atrial compression and the mechanism of exercise impairment in patients with a large hiatal hernia.
The purpose of this study was to determine the association between cardiac compression and exercise impairment in patients with a large hiatal hernia (HH). Dyspnea and exercise impairment are common symptoms of a large HH with unknown pathophysiology. Studies evaluating the contribution of cardiac compression to the pathogenesis of these symptoms have not been performed. We collected clinical data from a consecutive series of 30 patients prospectively evaluated with resting and stress echocardiography, cardiac computed tomography, and respiratory function testing before and after laparoscopic HH repair. Left atrial (LA), inferior pulmonary vein, and coronary sinus compression was analyzed in relation to exercise capacity (metabolic equivalents [METs] achieved on Bruce treadmill protocol). Exertional dyspnea was present in 25 of 30 patients (83%) despite normal mean baseline respiratory function. Moderate to severe LA compression was qualitatively present in 23 of 30 patients (77%) on computed tomography. Right and left inferior pulmonary vein and coronary sinus compression was present in 11 of 30 (37%), 12 of 30 (40%), and 26 of 30 (87%) patients, respectively. Post-operatively, New York Heart Association functional class and exercise capacity improved significantly (number of patients in New York Heart Association functional classes I, II, III, and IV: 6, 11, 11, and 2 vs. 26, 4, 0, and 0, respectively, p < 0.001; METs [percentage predicted]: 75 ± 24% vs. 112 ± 23%, p < 0.001) and resolution of cardiac compression was observed. Absolute change in LA diameter on the echocardiogram was the only independent cardiorespiratory predictor of exercise capacity improvement post-operatively (p = 0.006). We demonstrate, for the first time, marked exercise impairment and cardiac compression in patients with a large HH and normal respiratory function. After HH repair, exercise capacity improves significantly and correlates with resolution of LA compression.


Clinical and medicolegal aspects of conscious awareness during anesthesia.
In summary, regarding the legal aspects of awareness during anesthesia, the questions for the court to answer are: Was the patient aware? If probably yes, did the anesthesia technique cause or materially contribute to the awareness? Alternatively, if res ipsa loquitur applies, can the anesthesiologist show that the technique was not negligent, if necessary by showing that it would have been acceptable to at least a responsible minority of practitioners? It will be clear from the foregoing that good recordkeeping cannot be overemphasized. Apart from the fact that a precise and clear record tends to convince the court that they are dealing with a careful practitioner, the most important factor is that the more you have recorded about the anesthesia course, the more you will be able to tell the court about it. Finally, if you are unfortunate enough to lose and the patient is awarded damages, how much will the patient get? In the United Kingdom recently, $20,000 was awarded to patients for awareness in orthopedic and obstetric cases--perhaps a modest amount by U.S. standards. If the patient develops posttraumatic stress disorder, a much larger award is likely, especially if the patient is unable to work as a result of it; loss of earnings always increases an award, and it could easily reach $750,000 for a big earner. Insurance or other indemnity should cover this, of course, but it pays to remember one's likely exposure to risk in the event of failing to pay one's premium.


Contingency Management: Using Incentives to Improve Outcomes for Adolescent Substance Use Disorders.
Multiple interventions for treating adolescents with substance use disorders have demonstrated efficacy, but most teens do not show an enduring positive response to these treatments. Contingency management (CM)-based strategies provide a promising alternative, and clinical research focused on the development and testing of innovative CM models continues to grow. This article provides information on the principles that underlie CM interventions, key metrics that define their development and implementation, a brief review of studies that have tested these approaches, and some clinical CM tools. As with other interventions to help youth with substance use problems, there is much to learn about CM approaches.


Long-term stability of LeFort III distraction osteogenesis with a rigid external distraction device in a patient with Crouzon syndrome.
A 6-year-old boy, diagnosed with Crouzon syndrome, had moderate exorbitism, a concave profile, an anterior crossbite of -4.0 mm, and a skeletal Class III jaw-base relationship caused by midfacial hypoplasia. At age 8 years 9 months, a LeFort III osteotomy was performed, and distraction osteogenesis was immediately started with the rigid external distractor system. The midface was advanced approximately 10.0 mm for 6 days, including overcorrection. After the distraction, a reverse headgear was used for 6 years to prevent relapse and to accelerate expected growth. At age 16 years 5 months, after extraction of the maxillary first premolars and mandibular third molars, 0.022-in preadjusted edgewise brackets were placed to treat the edge-to-edge incisor relationship and minor crowding. After 13 months of treatment, the facial profile was significantly improved, and an acceptable occlusion was achieved. During the 9-year observation period after the distraction, acceptable facial growth occurred, and no relapse of the maxillary advancement was observed. However, syndrome-specific growth and methodologically induced relapse should be considered when planning a LeFort III distraction in children for the treatment of Crouzon syndrome.


Recurrent refractive error after myopic laser-assisted in situ keratomileusis - What could be the reason?
Recurrence of myopia after myopic LASIK reduces the outcome of the procedure. Important causes include post-LASIK ectasia, regression of myopia, accommodative strain, and lens or axial length changes. Herein, we present a case of myopia recurring after LASIK and try to arrive at the possible diagnosis among these, as the treatment differs for each. The detailed evaluation showed that our patient had regression of myopia after LASIK. Of the multiple causes for recurrence of refractive error after myopic laser vision correction, it is important to identify the relevant reason as the treatment and prognosis for each of these is different.


Rhodoflexus caldus gen. nov., sp. nov., a new member of the phylum Bacteroidota isolated from a hot spring sediment.
A thermophilic bacterium, designated strain SYSU G04325T, was isolated from a hot spring sediment in Yunnan, China. Polyphasic taxonomic analyses and whole-genome sequencing were used to determine the taxonomic position of the strain. Phylogenetic analysis using 16S rRNA gene sequences indicated that strain SYSU G04325T shows high sequence similarity to Thermoflexibacter ruber NBRC 16677T (86.2%). The strain can be differentiated from other species of the family Thermoflexibacteraceae by its distinct phenotypic and genotypic characteristics. Cells of the strain SYSU G04325T were observed to be aerobic, Gram-stain negative and filamentous. Growth was found to occur optimally at 45 ºC and pH 7.0. In addition, the respiratory quinone was identified as menaquinone-7, while the major fatty acids (> 10%) were identified as iso-C15:0, iso-C17:0 and Summed Feature 9 (iso-C17:1ω9c). The polar lipids detected included phosphatidylethanolamine, three unidentified phospholipids, one unidentified glycolipid, five unidentified aminolipids and four unidentified polar lipids. The G + C content of the genomic DNA was determined to be 47.6% based on the draft genome sequence. On the basis of phenotypic, genotypic and phylogenetic data, strain SYSU G04325T is concluded to represent a novel species of a novel genus in the family Thermoflexibacteraceae, for which the name Rhodoflexus caldus gen. nov., sp. nov. is proposed. The type strain of Rhodoflexus caldus is SYSU G04325T (= MCCC 1K06127T = KCTC 82848T).


Integrated ESI-MS/MS and APCI-MS/MS based metabolomics reveal the effects of canning and storage on peach fruits.
The characterization of peach metabolites and carotenoids during canning and storage remains unclear. The present study identified 658 metabolites and 40 carotenoids in peach fruits throughout the canning and storage using ESI-MS/MS and APCI-MS/MS based metabolome approach. A total of 282 differentially accumulated metabolites were found, mainly including 78 phenolic acids, 74 lipids, 61 flavonoids. Five esterified carotenoids (rubixanthin palmitate, β-cryptoxanthin oleate, β-cryptoxanthin laurate, β-cryptoxanthin palmitate, and β-cryptoxanthin myristate) were the main peach carotenoids, with a proportion of approximately 90%, while free carotenoids accounted for 4.22-5.95% during the entire processing period. Moreover, the total carotenoid loss rates for canning and storage were 56.67% and 46.55%, respectively. Compared to the loss of free carotenoids, esterified carotenoids were more stable during storage, while canning led to a greater loss of esterified carotenoids. The results provided new insights into the maintenance of health-related phytochemicals from canning processes.


Interrelationship of serum 25-hydroxyvitamin D3 and 1,25-dihydroxyvitamin D in juvenile renal osteodystrophy after therapy with 25-hydroxyvitamin D3.
The interrelationship of circulating 25(OH)D3 and 1,25(OH)2D in children with uremic renalosteodystrophy has been examined in 19 patients treated for 1 to 4 yr with 25(OH)D3. There was a direct correlation between 25(OH)D3 and 1,25(OH)2D levels when the GFR was less than or equal to 25 but not greater than 25 ml/min/1.73m2 (r = 0.47, P = less than .01). This correlation was unchanged when 1,25(OH)2D was factored by serum phosphorus or serum creatinine but became nonsignificant when 1,25(OH)2D was factored by serum bicarbonate. Overall, parathyroid hormone (PTH) did not change the correlation. However, when the data were subdivided by levels of glomerular filtration rate (GFR) and PTH, the correlation between 25(OH)D3 and 1,25(OH)2D was significant only when GFR was less than or equal to 25 and the PTH was markedly elevated (P = less than .01), suggesting that a substantial elevation of PTH may be necessary to stimulate 1,25(OH)2D production in these patients. Individual 1,25(OH)2D levels measured over time (1-4 yr) fluctuated regardless of GFR. Despite high serum 25(OH)D3 levels after 25(OH)D3 therapy, there was no consistent increase in the 1,25(OH)2D levels, and many posttreatment levels were lower than pretreatment levels. The kinetics of 1,25(OH)2D metabolism failed to reveal a progressive increase in the serum levels between 2 and 24 hours after a pharmacologic dose of 25(OH)D3.


The influence of link protein stabilization on the viscometric properties of proteoglycan aggregate solutions.
The dynamic, steady-shear and transient shear flow properties of precisely prepared link-stable (s0 136, 66% aggregate) and link-free (s0 93, 59% aggregate) proteoglycan aggregate solutions at concentrations ranging from 10 to 50 mg/ml were determined using a cone-on-plate viscometer in a mechanical spectrometer. All proteoglycan solutions tested possessed: (1) linear viscoelastic properties - as measured by the dynamic complex modulus under small amplitude steady oscillatory conditions (1 less than or equal to omega less than or equal to 100 rad/s) - and (2) nonlinear shear-rate dependent apparent viscosities and primary normal stress difference under steady shearing conditions (0.25 less than or equal to gamma less than or equal to 250 s-1). Our transient flow data show that all proteoglycan aggregate solutions exhibited transient stress overshoot effects in shear stress and normal stress. From these steady and transient flow data, we conclude that link protein stabilized aggregates have significant effects on their dynamic and steady-shear properties as well as transient flow properties. The transient stress overshoot data provide a measure of the energy per unit volume of fluid required to overcome the proteoglycan networks in solution from a resting state. Thus we found that link-stable aggregates form much stronger networks than link-free aggregates. This is corroborated by the fact that link-stable aggregates form more elastic (lower than delta) and stiffer (higher [G*]) networks than link-free aggregates. The complete spectrum of viscometric flow data is entirely compatible with the proposed role of link protein in adding structural stability to the proteoglycan-hyaluronate bond. In cartilage, the enhanced strength of the networks formed by link-stable aggregates may play an important role in determining the material properties of the tissue and thereby contribute to the functional capacity of cartilage in diarthrodial joints.


Involvement of the neuronal phosphotyrosine signal adaptor N-Shc in kainic acid-induced epileptiform activity.
BDNF-TrkB signaling is implicated in experimental seizures and epilepsy. However, the downstream signaling involved in the epileptiform activity caused by TrkB receptor activation is still unknown. The aim of the present study was to determine whether TrkB-mediated N-Shc signal transduction was involved in kainic acid (KA)-induced epileptiform activity. We investigated KA-induced behavioral seizures, epileptiform activities and neuronal cell loss in hippocampus between N-Shc deficient and control mice. There was a significant reduction in seizure severity and the frequency of epileptiform discharges in N-Shc deficient mice, as compared with wild-type and C57BL/6 mice. KA-induced neuronal cell loss in the CA3 of hippocampus was also inhibited in N-Shc deficient mice. This study demonstrates that the activation of N-Shc signaling pathway contributes to an acute KA-induced epileptiform activity and neuronal cell loss in the hippocampus. We propose that the N-Shc-mediated signaling pathway could provide a potential target for the novel therapeutic approaches of epilepsy.


MTOR Variation Related to Heat Resistance of Chinese Cattle.
With the inexorable rise of global temperature, heat stress deserves more and more attention in livestock agriculture. Previous studies have shown that the mechanistic target of rapamycin (MTOR) (NC_037343.1:c.2062G>C) gene contributes to the repair of DNA damage repair and is associated with the adaptation of camels in dry and hot environments. However, it is unknown whether this mutation is related to the heat tolerance of Chinese cattle. In this study, PCR and sequencing were used to type the mutation locus in 1030 individuals of 37 cattle breeds. The analysis results showed that the frequency of G allele of the locus gradually diminished from the northern group to the southern group of native Chinese cattle, whereas the frequency of the C allele showed an opposite pattern, displaying a significant geographical difference across native Chinese cattle breeds. Additionally, an analysis of the locus in Chinese indigenous cattle revealed that this SNP was significantly associated with mean annual temperature (T), relative humidity (RH) and temperature humidity index (THI) (p < 0.01), suggesting that cattle with C allele was distributed in regions with higher T, RH and THI. In conclusion, this study proved that the mutation of MTOR gene in Chinese cattle could be associated with the heat tolerance.


Further evidence for segregated output channels from superior colliculus in rat: ipsilateral tecto-pontine and tecto-cuneiform projections have different cells of origin.
Two of the targets of the ipsilateral descending pathway from the superior colliculus are the cuneiform area (immediately ventral to the inferior colliculus), and the dorsolateral basilar pons. The cells of origin of the projections to these targets in rat were studied with a retrograde double-labelling technique, using the fluorescent tracers True blue and Diamidino yellow. Although many tectal cells were single-labelled by injections into basilar pons or the cuneiform area, less than 5% were double-labelled. The two projections thus appear to arise mainly from separate populations of cells within the superior colliculus.


Clinical outcomes following bowel resection versus reduction of intussusception.
Intussusception is most commonly managed with air-contrast reduction. However, when this fails, emergent operation with resection or manual reduction is indicated. It is not known if there are advantages to resection compared with manual reduction. A retrospective review of all patients receiving operative care for intussusception from February 2000 to December 2011. Patients undergoing intestinal resection were compared with those treated with manual reduction alone. Of 111 patients, 49 underwent resection and 62 underwent manual reduction. Mean (±SD) time to oral intake favored manual reduction (2.1 ± 1.2 versus 2.6 ± 1.2 d, respectively, P=0.05). Manual reduction was associated with a greater need for repeat imaging (47% versus 18%, P=0.002) and the only recurrences were with manual reduction (8% versus 0%, P=0.1). Mean duration of stay was no different (P=0.36), nor was the need for reoperation (P=0.9). Patients undergoing manual reduction have an increased number of radiographic imaging procedures. The surgeon should have a low threshold for resection for intussusceptions requiring operative management.


[Sponsored research, authorship and accountability; declarations by authors of their independence regarding publications].
The editorial board of the Nederlands Tijdschrift voor Geneeskunde (Dutch Journal of Medicine) has decided to disclose at the end of each article conflicts of interest (financial and otherwise), the sponsor of the research or its publication, and whether the authors were independent in their investigations, analysis and reporting of the data.


Gamahonolides A, B, and Gamahorin, Novel Antifungal Compounds from Stromata of Epichloe typhina on Phleum pratense.
Four novel antifungal compounds, gamahonolides A and B, gamahorin, and 5-hydroxyl-4-phenyl-2(5H)-furanone, were isolated from stromata of Epichloe typhina on Phleum pratense. Their structures were determined by spectroscopic methods. The absolute configuration of gamahonolide A was determined by its ORD spectrum and (1)H-NMR shift difference between the diastereomeric pair of its O-methylmandelates. The stereochemistry of gamahorin was determined by NOE difference spectra and its CD spectrum.


Peritoneal dialysis-associated tuberculous peritonitis in an intravenous drug user with acquired immunodeficiency syndrome.
A rare case of tuberculous peritonitis in a continuous ambulatory peritoneal dialysis (CAPD) patient who has multiple risk factors for extrapulmonary disease due to Mycobacterium tuberculosis is presented. This patient' acute course was atypical with a predominance of neutrophils and low levels of protein in the peritoneal fluid. Obtaining the diagnosis of tuberculous peritonitis by acid-fast smear was also unusual, probably facilitated by centrifugation of large amounts of fluid. The patient was successfully treated without catheter removal. Tuberculosis should be considered in patients with culture-negative CAPD peritonitis.


How valid are proxy assessment of mental health and sleep comorbidities of patients with epilepsy using standardized questionnaires?
The study aimed to determine the level of agreement between patients with epilepsy and their proxies when assessing psychiatric comorbidities, sleep disorders, and medication adherence using standardized questionnaires. This agreement study is an ancillary analysis of the PRERIES study, a matched case-control study exploring SUDEP risk factors. Controls aged 15 years and older, with active epilepsy or in remission for less than 5 years were recruited between 01/01/2011 and 03/31/2019. An interview was carried out by a trained psychologist on both the patient and a proxy-respondent. During these independent interviews, the following comorbidities were explored: psychiatric comorbidities using the MINI, the STAI- Y2 and NDDI-E scales, sleep disorders with the SDQ-SA and Epworth scales and medication adherence. Level of agreement between patient and their proxy was estimated using Gwet's AC1&2. Among the 107 patient-proxy dyads recruited, proxy respondents were mainly family members (65.4%) or spouses (30.8%). Exploration of present major depression showed excellent agreement at 0.81 [0.65;0.97], as well as exploration of dysthymia at 0.96 [0.61;1]. Suicidal risk evaluation had a lesser agreement at 0.77 [0.60;0.94]. Agreement on anxiety was moderate 0.5 [0.38;0.62]. For sleep disorder, SDQ-SA presented a better agreement than the Epworth questionnaire with respectively 0.73 [0.51;0.95] and 0.45 [0.26;0.63]. For medication adherence, the overall agreement rate was excellent (0.90 [0.78;1]). Exploration of potential risk factors through families can give valuable and relatively robust information, especially if the respondent lives with the patient, and should be retrieved, when possible, in usual clinical setting.


[Skull injuries caused by blow with glass bottles].
Six cases of blows with glass bottles on the skull are reported. The glass bottles varied in size, weight, shape and filling level. In all cases the bottles broke, but there were no fractures of the skull or injuries of the brain or meninges. As consequences of the blows with the glass bottles bruises, lacerations and incised wounds were seen. The only cause contributing or leading to death was a fatal bleeding from lacerations of the scalp.


Determination of the mineral fraction and rheological properties of microwave modified starch from Canna edulis.
The goal of this study was to evaluate the effect of the physical modification by microwave irradiation on the mineral fraction and rheological properties of starch isolated from Canna edulis rhizomes. Phosphorus, sodium, potassium, magnesium, iron, calcium and zinc were evaluated using atomic absorption spectrophotometry. Rheological properties were determined using both the Brabender amylograph and Brookfield viscosimeter. Except for the calcium concentration, mineral contents decreased significantly (p < 0.05) after microwave treatment. The amylographic profile was also modified, showing increased pasting temperature range and breakdown index, whereas the viscosity peak, viscosity at holding (95 degrees C) and cooling periods (50 degrees C), setback and consistency decreased as compared to the native starch counterpart. Although viscosity decreased in the microwaved sample, presumably due to starch changes at molecular level, it retained the general pseudo plastic behavior of native starch. It is concluded that canna starch may be modified by microwave irradiation in order to change its functional properties. This information should be considered when using microwave irradiation for food processing. Furthermore, the altered functional attributes of canna modified starch could be advantageous in new product development.


Light-induced adenovirus gene transfer, an efficient and specific gene delivery technology for cancer gene therapy.
A main issue for further clinical progress of cancer gene therapy is to develop technologies for efficient and specific delivery of therapeutic genes to tumor cells. In this work, we describe a photochemical treatment that substantially improves gene delivery by adenovirus, one of the most efficient gene delivery vectors known. Transduction of two different cell lines was studied by microscopy, flow cytometry, and an enzymatic assay, employing a beta-galactosidase-encoding adenovirus. The photochemical treatment induced a >20-fold increase in gene transduction, compared with conventional adenovirus infection, both when measured as the percentage of cells transduced, and when measured as the total beta-galactosidase activity in the cell population. The effect was most pronounced at lower virus doses, where in some cases the same transduction efficiency could be achieved with a 20 times lower virus dose than with conventional infection. Photochemical treatments are already in clinical use for cancer therapy, and generally are very specific and have few side effects. The photochemical internalization technology described thus has a clear potential for improving both the efficiency and the specificity of gene delivery in cancer gene therapy, making it possible to achieve efficient site-specific in vivo gene delivery by adenoviral vectors.


Modulation by various locally applied anti-inflammatory and anti-allergic compounds of the immune and non-immune inflammation induced by picryl chloride in mice.
The authors studied the primary irritation and contact delayed hypersensitivity inflammation induced by picryl chloride in mice. The primary irritation reaction was induced by the application of various concentrations of the phlogogenic agent on an ear. Seven days after contact sensitization of the animals on their shaved abdomen, the immune inflammation was also induced on an ear by various doses of picryl chloride. Clear 24 hour-delayed hypersensitivity reactions were induced only by picryl chloride doses that induced a primary oedematous irritation 3 to 6 hours after application. After selection of the 3%-concentration of picryl chloride for challenge on ear, attempts were made to modulate these two types of reaction pharmacologically with various anti-allergic or anti-inflammatory compounds mixed with the inflammation-inducing agent. The inhibition of the non-immune reaction by mepyramine, methysergide, and the two anti-allergic compounds F 1865 and disodium cromoglycate demonstrated the participation of histamine and serotonin in this inflammation. Vasoactive amines seemed also to be involved in the immune reaction, but to a lesser extent. Hydrocortisone reduced the two types of inflammation by the same amount, while desonide had more effect on the delayed hypersensitivity reaction. In addition, both indomethacin and acetylsalicylic acid affected the two reactions equally, whereas phenylbutazone had a greater effect on the primary irritation inflammation.


Stability of permanent transvenous dual-chamber pacing electrodes during cardiopulmonary resuscitation.
For long-term dual-chamber permanent pacing, atrial and ventricular lead stability is essential. In our overall experience with such pacing systems, four patients suffered cardiac arrest at a time distant from their pacemaker implantation. Since all four patients received prolonged closed chest cardiopulmonary resuscitation, we analyzed these events to determine whether dual-chamber endocardial electrodes would remain stable in such traumatic conditions. Reliable atrial and ventricular lead position was confirmed at autopsy in the three patients whose resuscitation attempts were unsuccessful and, in the fourth patient, by continued normal lead position and pacing function post-resuscitation. The keys to this stability include the use of tined atrial and ventricular endocardial leads and specific maneuvers at the time of implantation to verify fixation. Long-term stability of presently available endocardial leads in dual-chamber pacing systems can thus be anticipated.


"No allogeneic blood transfusion" protocol for the surgical correction of craniosynostoses. I. Rationale.
Improved anesthesiological and surgical care has resulted in a progressively declining need for allogeneic blood transfusion. In infants with craniosynostosis, however, allogeneic blood transfusion is still performed as a routine procedure. In the present paper, the authors describe a protocol they have devised with the aim of limiting or even avoiding allogeneic blood transfusion even in very young patients, consequently avoiding the risks of infective or immunologic reactions associated with the procedure. The protocol is based on stimulation of the hematopoietic system with erythropoietin, selection of an appropriate age for operation when a favorable balance between fetal and adult-type hemoglobin is established (that is after 4-6 months), preoperative preparation of the autologous blood supply, and intraoperative blood salvage.


Evidence-Based Approaches to Successful Oral Feeding in Infants with Feeding Difficulties.
Infants in the neonatal intensive care unit (NICU) frequently have feeding difficulties with the root cause remaining elusive to identify. Evaluation of the provider/parent/infant feeding process may provide objective clues to sources of feeding difficulty. Specialized testing may be necessary to determine if the infant's swallowing skills are dysfunctional, immature, or maldeveloped, and to determine the risk of feeding failure or chronic tube feeding. Current evidence-based diagnostic and management approaches resulting in successful oral feeding in the NICU infant are discussed.


Cognitive constraints on vocal combinatoriality in a social bird.
A critical component of language is the ability to recombine sounds into larger structures. Although animals also reuse sound elements across call combinations to generate meaning, examples are generally limited to pairs of distinct elements, even when repertoires contain sufficient sounds to generate hundreds of combinations. This combinatoriality might be constrained by the perceptual-cognitive demands of disambiguating between complex sound sequences that share elements. We test this hypothesis by probing the capacity of chestnut-crowned babblers to process combinations of two versus three distinct acoustic elements. We found babblers responded quicker and for longer toward playbacks of recombined versus familiar bi-element sequences, but no evidence of differential responses toward playbacks of recombined versus familiar tri-element sequences, suggesting a cognitively prohibitive jump in processing demands. We propose that overcoming constraints in the ability to process increasingly complex combinatorial signals was necessary for the productive combinatoriality that is characteristic of language to emerge.


A hot topic at the environment-health nexus: investigating the impact of climate change on infectious diseases.
COVID-19 pandemic aside, climate change is the ultimate challenge of our time. However, to date, there has been insufficient political thrust to make that much-needed climate action a reality. Infectious diseases represent only one facet of the threats arising from climate change. Direct impacts from climate change include the more frequent occurrence and increased magnitude of extreme weather events, as well as changing temperatures and precipitation patterns. For climate-sensitive infectious diseases, these changes implicate a shift in geographical and temporal distribution, seasonality, and transmission intensity. Susceptibility to the deleterious effects of climate change is a net result of the interplay of not only environmental factors, but also human, societal, and economic factors, with social inequalities being a major determinant of vulnerability. The global South is already disproportionately affected by the climate crisis. The financial capacity to pursue adaptation options is also limited and unevenly distributed. Climate change-induced mortality and morbidity from both infectious and non-infectious diseases, among other adverse scenarios, are expected to rise globally in the future. The coming decade will be crucial for using all remaining opportunities to develop and implement adequate mitigation and adaptation strategies.


Postoperative infections in colonic surgery after enteral bacitracin-neomycin-clindamycin or parenteral mezlocillin-oxacillin prophylaxis.
In a prospective randomized, blind trial, three groups of patients undergoing elective colonic surgery were compared for frequency of surgical wound infection, intra-operative wound contamination and other postoperative infections. All patients allotted to the three groups received whole gut irrigation (101 balanced salt solution) by gastric tube on the evening before surgery and were treated as follows. Group A: no antibiotics; Group B: neomycin (1 g/l) + bacitracin (50,000 IU/l) + clindamycin (900 mg/l), contained in the last 31 of irrigation fluid; Group C: mezlocillin (4 g) + oxacillin (2 g) intravenously (iv) at induction of anaesthesia, followed by two identical doses at 8 and 16 h. The rate of postoperative wound infection was highest in A (38 per cent) and much lower in B (3.3 per cent, P less than 0.002) and C (6.9 per cent, P less than 0.004). The difference between B and C was statistically not significant. In A a correlation was established between the degree of wound contamination and the occurrence of wound infection. Intra-operative wound contamination was lowest in B (30 per cent), equal in A (58.1 per cent) and B (55.2 per cent). Other infections were least frequent in group C (four of 29 patients), but were not significantly different to groups B (six of 30) and A (nine of 31). It is concluded that antibiotics together with an effective mechanical preparation considerably reduce the rate of wound infection in colonic surgery.


Effectiveness of integrated body-mind-spirit group intervention on the well-being of Indian patients with depression: a pilot study.
Depression is a leading cause of disability worldwide. There is a need to develop effective strategies to treat depression and prevent recurrence. Treatments that combine pharmacological and psychotherapeutic approaches are preferred for treating severe forms of depression. The study assesses the effect of an integrated body-mind-spirit group intervention in patients with depression. This pilot study was a pretest-posttest design study. Thirty adult patients diagnosed with depression attending the psychiatric outpatient department at a district hospital were randomly assigned to either the intervention group or comparison group. Each group had 15 patients. The intervention group received both the intervention and routine hospital treatment and underwent four group integrated body-mind-spirit group intervention therapy sessions. These sessions were held once per week on either Saturday or Sunday, with each session lasting more than 3 hours. Comparison group participants received routine hospital treatment only. Outcome measures, including level of depression, well-being, and work and social adjustment, were measured using the Beck Depression Inventory-II, body-mind-spirit well-being scale, and work and social adjustment scale. Both groups were evaluated at baseline, 1 month, 2 months, and 3 months. Results showed that both groups had significant reductions in the level of depression, improvements in well-being, and work and social adjustment at 3-month follow-up compared with baseline. In addition, the intervention group showed significant mean differences in levels of depression, well-being, and work and social adjustment compared with the comparison group. The integrated body-mind-spirit group intervention model appears to reduce depressive symptoms and improve well-being in patients with depression.


Subclinical and clinical atherosclerosis in non-alcoholic fatty liver disease is associated with the presence of hypertension.
Non-alcoholic fatty liver disease (NAFLD) is associated with increased cardiovascular (CV) risk. However, it is unclear whether NAFLD contributes independently to the development of CV disease. Our study aimed at assessing the differences in several indices of atherosclerosis, arterial stiffness and cardiac morphology among patients with isolated NAFLD, isolated hypertension (HT) or a combination of the two conditions. A total of 169 participants (mean age = 50.4 ± 10.2 yrs; males = 73.6%) were divided according to the presence of NAFLD and HT into three groups: only NAFLD (55 patients), only HT (49 patients), and NAFLD + HT (65 patients). Exclusion criteria were a BMI≥35 kg/m2 and a diagnosis of diabetes mellitus. Carotid ultrasonography was performed to measure markers of atherosclerosis and arterial stiffness. Cardiac remodeling was analyzed using echocardiography. The prevalence of subclinical and overt atherosclerosis was significantly higher in the NAFLD + HT patients as compared to the other two groups (atherosclerotic plaques: 43.1%, 10.9%, and 22.4% (p < 0.001) in NAFLD + HT, NAFLD, and HT groups, respectively). No differences were found among indices of arterial stiffening and cardiac remodeling across the three groups. In multivariate regression analysis, the coexistence of NAFLD and HT was an independent risk factor for overt atherosclerosis (OR = 4.88, CI 95% 1.14-20.93), while no association was found when either NAFLD or HT was considered alone. Overt atherosclerosis was significantly present only in NAFLD + HT patients, but not in patients with isolated NAFLD. This implies that the impact of NAFLD on vascular structure and function could depend on the coexistence of other major CV risk factors, such as HT.


Subcellular mechanisms of lead neurotoxicity.
The neurotoxic effects of inorganic lead (Pb) involve inhibition of calcium-dependent acetylcholine release and increases in calcium-dependent dopamine release. These apparently differential effects of Pb are associated with differing Pb-calcium (Ca) interactions: Pb blocks 45Ca binding to peripheral cholinergic ganglia and increases 45Ca binding to synaptosomes prepared from caudate nucleus (CN). Pb-induced increases in CN 45Ca binding did not result from nonspecific disruption of selective ion permeability of the membrane. Also, the Na-K ATPase-linked Ca extrusion system of synpatosomes was not affected by Pb. A Pb-sodium (Na) interaction was found such that elevation of intrasynaptosomal Na reversed effects of Pb on 45Ca binding. The intracellular localization of this effect appeared to be primarily at the mitochondrial level. Pb inhibited Na-induced release of 45Ca from preloaded mitochondria. This action may be translated into increased transmembrane flux of exogenous Ca, and thence into increased exocytotic events at the synapse. The apparently neurotransmitter-specific effects of Pb, cholinergic inhibition and dopaminergic augmentation, are hypothesized to result from different Pb-Ca interactions which are determined by the specific localization of Pb within nerve endings.


Strategy for chemically riveting catenated nitrogen chains.
Catenated nitrogen chains (CNCs) attract considerable attention because of their structural novelty, their high energy, and their potential as precursors for all-nitrogen materials. However, pure CNCs are unstable under ambient conditions, limiting their on-site or practical applications. Chemical riveting of a CNC involves the maintenance of the structure of a CNC and placing the CNC in a special chemical structure as a moiety of an entire molecule to stabilize it. Other structures, except from the CNC, are named rivets. In this study, the molecular geometry, bond order, natural bond orbital charge, and frontier orbital among the pure CNCs (Nx), Nx-, Nx+, and NxHy (x = 2-11) and CNCs riveted and implemented experimentally in several former studies are systematically analyzed and compared. The lone-pair repulsion between two neighboring N atoms is one of the primary factors for the low molecular stability of the pure CNCs and their derivatives. The riveted CNCs with rings are usually more stable than those with open chains. Moreover, the standard deviation of the bond orders or the bond lengths can be employed as an indicator for molecular stability, i.e., a lower standard deviation suggests higher molecular stability. Hence, electron-donating groups, groups with electronegativity within those of H and N atoms, as well as atoms or groups with empty orbitals are proposed to trap the lone pairs of CNCs as rivets to stabilize the CNCs. This strategy is expected to facilitate the creation of stable CNC-contained compounds with high structural novelty or high energy contents. Graphical abstractA strategy is proposed for chemically riveting instable CNCs to transform them into more stable ones.


Animal study on lung injury caused by simulant segmented shock waves.
To study the lung injury caused by segmented shock waves. A total of 60 rabbits and 20 rats were used in this study. The process of transmission of shock waves was divided into three phases, i.e., the recompression phase (RP), the decompression phase (DP) and the underpressure phase (UP). And the recompression wave (RW), the decompression wave (DW) a nd the underpressure wave (UW) simulated the three phases, respectively, generated by the equipment designed by us. The RW test, DW test and UW test were respectively applied to the animals. And lung injuries caused by segmented shock waves were discussed. Under the experimental conditions, the RW did not cause obvious lung injury, but the DW could cause different severities of lung injuries. The greater the decompression ranged and the shorter the decompression duration was adopted, the more severe the lung injury was observed. The UW, to some extent, could cause obvious lung injury. It suggests that lung injury under shock waves probably occurs during the DP primarily. It probably does not cause direct obvious lung injury during the RP, but significantly influences the capability of causing lung injury during the DP.


Troponin I concentrations of shed blood might influence monitoring of myocardial injury after coronary operations.
In a prospective study we evaluated the concentration of cardiac troponin I (cTnI) and creatine kinase activities (CK) in shed mediastinal blood in the early postoperative period after coronary artery bypass grafting (CABG). Forty seven patients who underwent first time elective CABG were studied. CTnI levels and CK activities in arterial blood and shed mediastinal blood were measured after admission to the intensive care unit (ICU) and 6 h after unclamping the aorta. Mediastinal shed blood samples were drawn from 23 patients (group A) before the filter of the cardiotomy reservoir and from 24 patients (group B) behind. Additionally, both markers were measured in blood samples collected from the cell-saver. There were no significant differences between both groups (A and B) with regard to perioperative parameters. Mean loss of mediastinal shed blood in all patients was 207 +/- 127 ml within the first 6 h after operation. There was a positive correlation between CK activities and cTnI concentrations in serum and mediastinal shed blood, but shed blood contained significantly higher concentrations of cTnI as well as CK activities than the circulating blood after admission to the ICU and 6 h after unclamping the aorta. At both time points the cTnI-concentrations and CK activities in shed blood in group B were lower than those in group A but much higher than in serum. The effects of the use of a blood filter diminishes with time. Mediastinal shed blood contains extremely high cTnI concentrations and CK activities. Retransfusion of higher quantities of shed blood might lead to false-positive diagnosis of perioperative myocardial infarction.


F-actin binding and bundling properties of fimbrin, a major cytoskeletal protein of microvillus core filaments.
Fimbrin, previously recognized as a major structural protein of the microfilament core bundles of intestinal epithelial cell microvilli, has been purified to homogeneity and characterized. It is a nearly globular monomeric protein of apparent molecular weight 68,000 and has a single calcium binding site (Kd = 9 microM), for which magnesium ions compete. Fimbrin binds to F-actin and this interaction is characterized in detail. Under our optimal binding of conditions, fimbrin induces tightly packed F-actin bundles, similar to the bundles induced by villin, another microvillus structural protein. The formation of mixed fimbrin-villin-actin bundles provides a further step toward the full in vitro reconstitution of microvillus core filaments from its purified individual components. The reconstituted fimbrin-villin-actin bundles do not display the side arms characteristic of isolated microvillus cores. These results are discussed in terms of our current understanding of the organization of the microvillus core filaments and indicate that this structure contains two bundling proteins, villin and fimbrin. The results complement previous studies and now provide a minimal biochemical characterization of all four major actin-associated structural proteins so far identified in core filaments. Three of these (villin, fimbrin, and calmodulin) are calcium-binding proteins, emphasizing the concept of calcium control over submembranous microfilament organization.


Consistent removal of hair cells in vestibular end organs by time-dependent transtympanic administration of gentamicin in guinea pigs.
Vestibular hair cell loss and its role in balance disorders are not yet completely understood due largely to the lack of precise hair cell damage protocols. Our damage protocol aims to selectively remove type I hair cells in a way that produces consistent and predictable lesions that can be used for reliable inter-animal and inter-group comparison in balance research. This objective is achieved by transtympanic injection of gentamicin on both the round window membrane and oval window over a fixed time period followed by thorough washing. We achieved nearly total and consistent loss of type I hair cells at 94 % for the crista ampullaris of the lateral semicircular canal (LSC) and 86 % for the utricular macula with negligible loss of type II hair cells at 4% for the crista ampullaris of the LSC and 6% for the utricular macula. While the vestibular function was compromised in the relevant study group, this group had a zero mortality rate with no significant suppression of body weight gain. Gentamicin is typically administered via intraperitoneal systemic injection or, more recently, transtympanic injection. The intraperitoneal method is simple, but mortality rate is high. The transtympanic injection method produces ototoxic damage but with inconsistent lesion size. This inconsistency prevents reliable comparisons among animals. This protocol employs a transtympanic injection method which selectively targets type I hair cells for removal in the vestibular epithelia in a time-dependent manner, uniformly damages vestibular function, and causes uniform hair cell loss.


Cervical entrapment of a polythene vaginal ring pessary--a clinical curiosity.
An extremely rare complication of cervical entrapment of a polythene ring pessary within an epithelial 'tunnel' of the cervix is reported. The pessary was removed by dividing a segment of it with bone cutting forceps.


DXYS267: DYS393 and its X chromosome counterpart.
The GATA repeat DYS393 was reported in 1987 among other Y-specific short tandem repeats. It has since been used for forensic and evolutionary studies. We decided to test its Y-specificity when we found that female DNA gave amplicons, in agreement with recent GDB-recorded experiences on radiation hybrids. Parent-child triplets revealed that heterozygous daughters always carried the same paternally derived amplicon which, however, was not amplified in their fathers' DNAs. The X-assignment was verified in larger families. A half-new primer set with a new reverse DYS393 primer, outside the old one, resulted in X amplicons in females as well as Y and X amplicons in males. This new primer set defines the new DXYS267 (GDB Data Curation). DNA-sequencing revealed four base pair differences between the Y- and the X-sequences. Two are within the reverse primer site sequence, thus probably causing preferential hybridization to the Y sequence when using the conventional primers. The two others are within the repeat array, giving the regular repeat GATA in the Y-sequence, and TATA and GACA, respectively, in the X-sequence. Allele frequency distribution in DYS393 was studied in 300 unrelated Norwegian males, allele distribution in the X-locus in 48 Norwegian women. Even if allele repeat numbers are overlapping between the loci, leading to identical fragment lengths, the allele distribution is different between DYS393 and the X-chromosome locus. The differences between the two homologous loci on the Y and X indicate a considerable lap of time since common ancestry. To avoid co-amplification of the X-locus in DYS393 typing, primer A was elongated to include one of the sequence differences between the two loci. This to a considerable extent improved the specificity of the DYS393 primers.


The Neural Consequences of Age-Related Hearing Loss.
During hearing, acoustic signals travel up the ascending auditory pathway from the cochlea to auditory cortex; efferent connections provide descending feedback. In human listeners, although auditory and cognitive processing have sometimes been viewed as separate domains, a growing body of work suggests they are intimately coupled. Here, we review the effects of hearing loss on neural systems supporting spoken language comprehension, beginning with age-related physiological decline. We suggest that listeners recruit domain general executive systems to maintain successful communication when the auditory signal is degraded, but that this compensatory processing has behavioral consequences: even relatively mild levels of hearing loss can lead to cascading cognitive effects that impact perception, comprehension, and memory, leading to increased listening effort during speech comprehension.


Quantitative analyses of matrices, osteoblasts, and osteoclasts during bone remodeling using an in vitro system.
Bone remodeling plays a central role in the maintenance of bone homeostasis. Our group has established an in vitro system by which the cellular events during bone remodeling can be observed longitudinally. This study used this system to quantitatively analyze osteoblasts, osteoclasts, and matrices to elucidate their temporal changes and correlations. Osteoblasts from EGFP mice were cultured to form calcified nodules, followed by co-culture with bone marrow macrophages from Tnfrsf11aCre/+ x Ai14 mice for 3 weeks (resorption phase). Then cells were cultured with osteoblast differentiation medium for 3 weeks (formation phase). The same sites were observed weekly using 2-photon microscopy. Matrices were detected using second harmonic generation. Parameters related to matrices, osteoblasts, and osteoclasts were quantified and statistically analyzed. Resorption and replenishment of the matrix were observed at the same sites by 2 photon microscopy. Gross quantification revealed that matrix and osteoblast parameters decreased in the resorption phase and increased in the formation phase, while osteoclast parameters showed the opposite pattern. When one field of view was divided into 16 regions of interest (ROIs) and correlations between parameters were analyzed in each ROI, decreased and increased matrix volumes were moderately correlated. Parameters of matrices and osteoblasts, and those of matrices and osteoclasts exhibited moderate correlations, while those of osteoblasts and osteoclasts were only weakly correlated. Several correlations between cells and matrix during remodeling were demonstrated quantitatively. This system may be a powerful tool for the research of bone remodeling.


Combined immunodeficiency disease associated with absence of cell-surface HLA-A and -B antigens.
An infant with a family history suggestive of immunodeficiency presented with combined immunodeficiency. No HLA-A and -B antigens were present on lymphocyte and platelet surfaces, but they were found in the serum. HLA-D determinants were present on lymphocytes. In spite of a fetal thymus transplantation, the infant died of infections associated with the immunodeficiency. The thymus and lymphoid organs were present but hypoplastic and contained few lymphocytes at postmortem examination. The finding of an immodeficiency associated with an absence of cell-surface HLA-A and -B antigens may be regarded as the consequence of the lack of cellular histocompatibility antigens on immune development. Alternatively, other membrane components may have also been defective and partly responsible for the observed abnormalities.


Childhood cancer following neonatal oxygen supplementation.
To evaluate the relationship between neonatal oxygen supplementation (O2) and childhood cancer in the Collaborative Perinatal Project (CPP). The CPP consisted of 54,795 children born between 1959 and 1966 and followed to age 8 years. We used Cox proportional hazards modeling to examine the association between history of neonatal O2 and cancer (n = 48). The hazard ratio (HR) for any O2 was 1.77 (95% confidence interval [CI] = 0.94 to 3.35). The HR for continuous duration of O2 was near 1 and not significant. However, the HRs were 0.69 (95% CI = 0.17 to 2.88) and 2.87 (95% CI = 1.46 to 5.66) when comparing 0 to 2 and 3 or more minutes of O2, respectively, to no O2. The latter association was weaker (HR = 2.00; 95% CI = 0.88 to 4.54) and not significant ( P = .10) when analysis was restricted to cancers diagnosed after age 1 year (n = 41). These findings are consistent with an association between O 2 for 3 minutes or longer and cancer in childhood, and should serve as a basis for further study.


Immunohistochemical detection of Influenza virus infection in formalin-fixed tissues with anti-H5 monoclonal antibody recognizing FFWTILKP.
The worldwide outbreak of avian influenza among poultry species and humans is associated with the H5N1 subtype of avian influenza A virus (AIV). This highlighted the need to develop safe H5 AIV diagnostic methods. 7H10, an H5-specific monoclonal antibody (Mab), can be used for immunohistochemical (IHC) staining for formalin-fixed tissue. An assortment of H5N1 tissue specimens infected naturally in paraffin sections from Asia, between years 2002-2006, including one human specimen, were tested. 7H10 detected H5 infection in all of these tissue samples infected naturally. In addition, 24 different human H5N1 isolates from Indonesia, 5 avian H5 isolates and 3 non-H5 isolates from Asia were inoculated into BALB/C mice and chicken embryos. Among these influenza viruses, 7H10 detected 28 of the 29 H5 virus strains by immunohistochemical staining, while none of non-H5 strains used in this study could be detected by 7H10, confirming its specificity to H5. Further, the eight-residue-long linear epitope, "FFWTILKP", identified through epitope mapping, enables 7H10 to detect >98.3% of H5 subtype viruses reported worldwide before 2007. This study describes a specific H5 diagnostic system with minimal possibility of exposure to live virus based on immunochemical staining.


Three-dimensional registration of prostate images from histology and ultrasound.
A whole mount histology protocol for 3-D tissue reconstruction to compare the size and spatial location of tumors (and other components) identified in histology data with that from 3-D ultrasound (US) images is presented. Prostate specimens are imaged in 3-D using B-mode (US) and sonoelastography. The prostate surface is outlined in each B-mode image and a 3-D surface reconstruction is made. The specimen is then prepared for whole mount histology and the histology slides are digitally reconstructed to make a 3-D surface. These two surfaces are then aligned using a 3-D correlation algorithm, and the tumor boundary determined by the pathologist is compared with that using sonoelastography. 3-D images showing the overlapping histology and sonoelastography of prostate surface reconstructions for one prostate are presented to illustrate the technique; results for four prostates yielded an accuracy of 92% +/- 3%.


Optimization of culture conditions for stable expression of recombinant fc-fused human extracellular CD99 in HEK293T cells.
CD99 has been demonstrated to play a key role in several biological processes, including the regulation of T-cell activation, cell adhesion, and cell migration. We have also demonstrated that CD99 and its ligands regulate proinflammatory cytokines in NK cells, monocytes and activated T cells. These data suggest CD99 as a potential therapeutic target in cancer. However, the molecular mechanisms by which CD99 and CD99 counter receptors participate in such processes are unclear. High-quality CD99 recombinant proteins produced in large amounts are essential for biological studies and clinical research. In this study, we optimized the various culture conditions for increasing amounts of recombinant protein production with good biological activity. Intracellular immunofluorescence staining was performed to identify the highly expressing CD99HIgG cells. We further investigated the culture conditions for recombinant protein production. A double antibody sandwich enzyme-linked immunosorbent assay was employed to determine the level of secreted CD99HIgG proteins in the culture supernatant of various culture conditions. Later, affinity chromatography using protein G was used to purify CD99HIgG proteins from the culture supernatant of three proper culture conditions. According to our previous report, which utilized Western blotting, the purified CD99HIgG obtained from all tested culture conditions is composed of the CD99 extracellular part fused with the human IgG Fc part in dimer form. For biological activity, the obtained CD99HIgG proteins showed the ability to ligate with the CD99 counter receptor, resulting in the induction of cytokine production.


Comfort in the last 2 weeks of life: relationship to accessing palliative care services.
Specialised palliative care services (SPCS) aim to address the needs of patients and caregivers confronting life-limiting illnesses but only half of the potential cohort are referred. Randomised controlled trials of SPCS provision can no longer be ethically justified so there is a need to develop new methods to evaluate the net impact of SPCS for the whole community, not just for those who access SPCS. The aim of this study was to assess whether perceived comfort in the last 2 weeks of life was associated with accessing SPCS. This study utilised a whole-of-population random survey (n = 4,366) in South Australia. A total of 802 respondents had someone close to them die within the last 5 years due to a terminal illness, and they had the complete data. A subsequent question was asked whether SPCS had been accessed. Perceived comfort levels for those who had used SPCS were compared with those who did not by using stereotype logistic regression, weighted to a standardised population. Higher levels of comfort of the deceased having been assessed 'very comfortable' was associated with the use of SPCS (p = 0.04; odds ratio, 1.78; 95% confidence interval, 1.02-3.08). For people who accessed SPCS, 13.3% were reported as 'very comfortable' compared with 8.0% without SPCS. Almost one half of respondents (48.4%) reported that the deceased was considered 'uncomfortable' or 'very uncomfortable', irrespective of SPCS access. While this study provides further incremental evidence of benefit from access to SPCS, there is much that still needs to be done to improve care for the whole community at the end of life.


Mechanism of viral carcinogenesis by deoxyribonucleic acid mammalian viruses. IV. Related virus-specific ribonucleic acids in tumor cells induced by "highly" oncogenic adenovirus types 12, 18, and 31.
Formation of hybrids between viral deoxyribonucleic acid (DNA) and ribonucleic acid (RNA) was used to detect virus-specific RNA in the nuclei and polyribosomes of transformed and tumor cells induced by "highly" oncogenic human adenovirus (Ad) types 12, 18, and 31. The presence of virus-specific RNA in the cell nucleus, and the inhibitory effect of actinomycin D on its synthesis, suggest that adenovirus-specific RNA is transcribed from a DNA template in the nucleus. Ad 12, 18, and 31 virus-specific RNA did not hybridize significantly with the DNA of the "weakly" oncogenic adenovirus group (Ad 3, 7, 11, 14, 16, and 21) or with that of nononcogenic Ad 2 and 4. Labeled RNA from Ad 12, 18, and 31 tumor cells hybridized with heterologous Ad 12, 18, and 31 DNA 30 to 60% as efficiently as with homologous DNA. Thus, common viral genes are transcribed in tumor cells induced by Ad 12, 18, and 31.