Fish consumption and prenatal methylmercury exposure: cognitive and behavioral outcomes in the main cohort at 17 years from the Seychelles child development study.
People worldwide depend upon daily fish consumption as a major source of protein and other nutrients. Fish are high in nutrients essential for normal brain development, but they also contain methylmercury (MeHg), a neurotoxicant. Our studies in a population consuming fish daily have indicated no consistent pattern of adverse associations between prenatal MeHg and children's development. For some endpoints we found performance improved with increasing prenatal exposure to MeHg. Follow up studies indicate this association is related to the beneficial nutrients present in fish. To determine if the absence of adverse outcomes and the presence of beneficial associations between prenatal MeHg and developmental outcomes previously reported persists into adolescence. This study was conducted on the Main Cohort of the Seychelles Child Development Study (SCDS). We examined the association between prenatal MeHg exposure and subjects' performance at 17 years of age on 27 endpoints. The test battery included the Wisconsin Card Sorting Test (WCST), the California Verbal Learning Test (CVLT), the Woodcock-Johnson (W-J-II) Achievement Test, subtests of the Cambridge Neuropsychological Test Automated Battery (CANTAB), and measures of problematic behaviors. Analyses for all endpoints were adjusted for postnatal MeHg, sex, socioeconomic status, maternal IQ, and child's age at testing and the child's IQ was added for problematic behavioral endpoints. Mean prenatal MeHg exposure was 6.9 ppm. There was no association between prenatal MeHg and 21 endpoints. Increasing prenatal MeHg was associated with better scores on four endpoints (higher W-J-II math calculation scores, reduced numbers of trials on the Intra-Extradimensional Shift Set of the CANTAB), fewer reports of substance use and incidents of and referrals for problematic behaviors in school. Increasing prenatal MeHg was adversely associated with one level of referrals to a school counselor. At age 17 years there was no consistent pattern of adverse associations present between prenatal MeHg exposure and detailed domain specific neurocognitive and behavioral testing. There continues to be evidence of improved performance on some endpoints as prenatal MeHg exposure increases in the range studied, a finding that appears to reflect the role of beneficial nutrients present in fish as demonstrated previously in younger subjects. These findings suggest that ocean fish consumption during pregnancy is important for the health and development of children and that the benefits are long lasting.


Simultaneous evaluation of gastric and duodenal ulcers-healing activities of anti-ulcer agents in rats.
We investigated the effects of cimetidine, omeprazole and atropine, antisecretory anti-ulcer agents, on the healing of gastric and duodenal ulcers simultaneously induced in the same rats. Furthermore, we examined the effect of histamine, an acid secretory agent, on the healing of both ulcers. When the effects of test drugs were assessed on the 15th day after local application of acetic acid, repeated oral administration of cimetidine (50 and 100 mg/kg twice daily) or omeprazole (25 and 50 mg/kg once daily) markedly accelerated the healing of both gastric and duodenal ulcers. Atropine (10 mg/kg twice daily, p.o.) showed a healing effect on duodenal ulcers only. The repeated subcutaneous administration of histamine (30 mg/kg 3 times daily) apparently delayed the healing of duodenal ulcers but not gastric ulcers. In conclusion, this experimental chronic ulcer model in rats is useful for directly comparing the effects of anti-ulcer drugs on the healing of gastric and duodenal ulcers. In addition, the increase in acid secretion appears to have a greater influence on the delay of ulcer healing in the duodenum than in the stomach.


Postoperative Pulmonary Complications after Transcatheter Aortic Valve Implantation under Monitored Anesthesia Care versus General Anesthesia: Retrospective Analysis at a Single Large Volume Center.
Few studies to date have assessed the postoperative pulmonary complications after transcatheter aortic valve implantation (TAVI) according to the anesthesia method. The present study aims to compare the effects of general anesthesia (GA) or monitored anesthesia care (MAC) on postoperative outcomes in patients undergoing TAVI. This retrospective cohort study included 578 patients who underwent TAVI through the trans-femoral approach between August 2011 and May 2019 at a single tertiary academic center. The primary outcome was postoperative pulmonary complications, which were defined as the occurrence of one or more pulmonary complications, such as respiratory failure, respiratory infection, and radiologic findings, within 7 days after TAVI. Secondary outcomes included postoperative delirium, all-cause 30-day mortality rate, 30-day readmission rate, reoperation rate, vascular complications, permanent pacemaker/implantable cardioverter-defibrillator insertion, length of stay in the ICU, hospital stay, and incidence of stroke. Of the 589 patients, 171 underwent TAVI under general anesthesia (GA), and 418 under monitored anesthesia care (MAC). The incidence of postoperative pulmonary complications was significantly higher in the GA than in the MAC group (17.0% vs. 5.3%, p < 0.001). Anesthetic method significantly affected the occurrence of postoperative pulmonary complications, but not of delirium. ICU stay was significantly shorter in the MAC group, as were operation time, the volume of fluid administered during surgery, heparin dose, transfusion, and inotrope requirements. TAVI under MAC can increase the efficiency of medical resources, reducing the lengths of ICU stay and the occurrence of postoperative pulmonary complications, compared with TAVI under GA.


Exploration of the Role of Serine Proteinase Inhibitor A3 in Alcohol Dependence Using Gene Expression Omnibus Database.
Background: Alcohol dependence is an overall health-related challenge; however, the specific mechanisms underlying alcohol dependence remain unclear. Serine proteinase inhibitor A3 (SERPINA3) plays crucial roles in multiple human diseases; however, its role in alcohol dependence clinical practice has not been confirmed. Methods: We screened Gene Expression Omnibus (GEO) expression profiles, and identified differentially expressed genes (DEGs). Protein-protein interaction (PPI) networks were generated using STRING and Cytoscape, and the key clustering module was identified using the MCODE plugin. SERPINA3-based target microRNA prediction was performed using online databases. Functional enrichment analysis was performed. Fifty-eight patients with alcohol dependence and 20 healthy controls were recruited. Clinical variables were collected and follow-up was conducted for 8 months for relapse. Results: SERPINA3 was identified as a DEG. ELANE and miR-137 were identified after PPI analysis. The enriched functions and pathways included acute inflammatory response, response to stress, immune response, and terpenoid backbone biosynthesis. SERPINA3 concentrations were significantly elevated in the alcohol dependence group than in healthy controls (P < 0.001). According to the median value of SERPINA3 expression level in alcohol dependence group, patients were divided into high SERPINA3 (≥2677.33 pg/ml, n = 29) and low SERPINA3 groups (<2677.33 pg/ml, n = 29). Binary logistic analysis indicated that IL-6 was statistically significant (P = 0.015) Kaplan-Meier survival analysis did not indicate any difference in event-free survival between patients with low and high SERPINA3 levels (P = 0.489) after 8 months of follow-up. Receiver characteristic curve analysis revealed that SERPINA3 had an area under the curve of 0.921 (P < 0.0001), with a sensitivity and specificity of 93.1 and 80.0%, respectively. Cox regression analysis revealed that aspartate transaminase level was a negative predictor of relapse (β = 0.003; hazard ratio = 1.003; P = 0.03). Conclusions: SERPINA3 level was remarkably elevated in patients with alcohol dependence than healthy controls, indicating that SERPINA3 is correlated with alcohol dependence. However, SERPINA3 may not be a potential predictive marker of relapse with patients in alcohol dependence.


Role of nonresonant sum-frequency generation in the investigation of model liquid chromatography systems.
In vibrationally resonant sum-frequency generation (VR-SFG) spectra, the resonant signal contains information about the molecular structure of the interface, whereas the nonresonant signal is commonly treated as a background and has been assumed to be negligible on transparent substrates. The work presented here on model chromatographic stationary phases contradicts this assumption. Model stationary phases, consisting of functionalized fused-silica windows, were investigated with VR-SFG spectroscopy, both with and without experimental suppression of the nonresonant response. When samples are moved from CD(3)OD to D(2)O, the VR-SFG spectrum was found to change over time when the nonresonant signal was present but not when the nonresonant signal was suppressed. No effect was seen when the solvent was changed and pressurized to 900 psi. These results suggest that the response to the new solvent manifests primarily in the nonresonant response, not the resonant response. Any structural changes caused by the new solvent environment appear to be minor. The nonresonant signal is significant and must be properly isolated from the resonant signal to ensure a correct interpretation of the spectral data. Curve-fitting procedures alone are not sufficient to guarantee a proper interpretation of the experimental results.


One new species and a new record of the genus Chordodes (Nematomorpha: Gordiida) from North-East India.
Fifteen species of freshwater Nematomorpha have been described from India, five of which belong to the genus Chordodes. This paper describes one new species of horsehair worms (Nematomorpha): Chordodes lasuboni and a new record, C. moutoni from North-East India, which raises the total number of described species from India to 17. Chordodes lasuboni is characterized by a novel cuticular pattern in the head region and by the presence of slender, hooked thorn areoles on the body cuticle. Compared to the large size and ecological diversity of India, the nematomorph fauna is regarded as under-sampled and several new species are to be expected.


Noise-induced barren plateaus in variational quantum algorithms.
Variational Quantum Algorithms (VQAs) may be a path to quantum advantage on Noisy Intermediate-Scale Quantum (NISQ) computers. A natural question is whether noise on NISQ devices places fundamental limitations on VQA performance. We rigorously prove a serious limitation for noisy VQAs, in that the noise causes the training landscape to have a barren plateau (i.e., vanishing gradient). Specifically, for the local Pauli noise considered, we prove that the gradient vanishes exponentially in the number of qubits n if the depth of the ansatz grows linearly with n. These noise-induced barren plateaus (NIBPs) are conceptually different from noise-free barren plateaus, which are linked to random parameter initialization. Our result is formulated for a generic ansatz that includes as special cases the Quantum Alternating Operator Ansatz and the Unitary Coupled Cluster Ansatz, among others. For the former, our numerical heuristics demonstrate the NIBP phenomenon for a realistic hardware noise model.


Multiple Roles of Isocyanides in Palladium-Catalyzed Imidoylative Couplings: A Mechanistic Study.
Kinetic, spectroscopic and computational studies examining a palladium-catalyzed imidoylative coupling highlight the dual role of isocyanides as both substrates and ligands for this class of transformations. The synthesis of secondary amides from aryl halides and water is presented as a case study. The kinetics of the oxidative addition of ArI with RNC-ligated Pd0 species have been studied and the resulting imidoyl complex [(ArC=NR)Pd(CNR)2 I] (Ar=4-F-C6 H4 , R=tBu) has been isolated and characterized by X-ray diffraction. The unprecedented ability of this RNC-ligated imidoyl-Pd complex to undergo reductive elimination at room temperature to give the amide in the presence of water and an F- /HF buffer is demonstrated. Its behavior in solution has also been characterized, revealing an unexpected strong tendency to give cationic complexes, and notably [(ArC=NR)Pd(CNR)3 ]+ with excess isocyanide and [(ArC=NR)Pd(PP^ )(CNR)]+ with bidentate phosphines (PP^ ). These species may be responsible for catalyst deactivation and side-reactions. Ab initio calculations performed at the DFT level allowed us to rationalize the multiple roles of RNC in the different steps of the catalytic cycle.


Characterizing and Modeling Breathing Dynamics: Flow Rate, Rhythm, Period, and Frequency.
The characterization of breathing dynamics provides researchers and clinicians the ability to differentiate respiratory compensation, impairment, disease progression, ventilator assistance, and the onset of respiratory failure. However, within many sub-fields of respiratory physiology, we still have challenges identifying changes within the breathing dynamics and critical respiratory states. We discuss one fundamental modeling of breathing and how modeling imprecise assumptions decades ago regarding breathing are still propagating into our quantitative analysis today, limiting our characterization and modeling of breathing. The assumption that breathing is a continuous sinusoidal wave that can consist of a single frequency which is composed of a stationary time-invariant process has limited our expanded discussion of breathing dynamics, modeling, functional testings, and metrics. Therefore, we address major misnomers regarding breathing dynamics, specifically rate, rhythm, frequency, and period. We demonstrate how these misnomers impact the characterization and modeling through the force equations that are linked to the Work of Breathing (WoB) and our interpretation of breathing dynamics through the fundamental models and create possible erroneous evaluations of work of breathing. This discussion and simplified non-periodic WoB models ultimately sets the foundation for improved quantitative approaches needed to further our understanding of breathing dynamics, compensation, and adaptation.


Influence of relative trophic position and carbon source on selenium bioaccumulation in turtles from a coal fly-ash spill site.
Selenium (Se) is a bioaccumulative constituent of coal fly-ash that can disrupt reproduction of oviparous wildlife. In food webs, the greatest enrichment of Se occurs at the lowest trophic levels, making it readily bioavailable to higher consumers. However, subsequent enrichment at higher trophic levels is less pronounced, leading to mixed tendencies for Se to biomagnify. We used stable isotopes ((1)(5)N and (13)C) in claws to infer relative trophic positions and relative carbon sources, respectively, of seven turtle species near the site of a recently-remediated coal fly-ash spill. We then tested whether Se concentrations differed with relative trophic position or relative carbon source. We did not observe a strong relationship between δ(15)N and Se concentration. Instead, selenium concentrations decreased with increasing δ(13)C among species. Therefore, in an assemblage of closely-related aquatic vertebrates, relative carbon source was a better predictor of Se bioaccumulation than was relative trophic position.


Carcinoma in a transplanted kidney detected with MAG3 scintigraphy.
We report on two cases of infiltrative renal tumor developing in two kidney transplant recipients from a single cadaveric donor source. Interestingly, while this is only the second case of a de novo renal allograft tumor, both were morphologically infiltrative. The fact that both tumors were infiltrative may be secondary to immunosuppression therapy. While computed tomography (CT) evaluation of suspected renal pathology provides excellent anatomical detail, renal transplant recipients are initially evaluated using ultrasound and renal scintigraphy to avoid contrast reagents which could further impair renal function, as well as to reduce the image procedure cost and the patient radiation dose. Unfortunately, infiltrative tumors may be isoechoic on ultrasound, providing a confusing or conflicting report when compared to scintigraphic findings. This case report is significant radiographically because the original neoplasm was initially detected using technetium-99m-labeled mercaptoacetyltriglycine (99mTc-MAG3) scintigraphy and was not appreciated by sonographic studies, even retrospectively. This case demonstrates the usefulness of 99mTc-MAG3 scintigraphy to follow-up evaluations of renal transplants by providing detailed anatomical information as well as functional analysis of the kidney.


Unusual presentation of GLUT-1 positive infantile haemangioma.
Infantile haemangiomas are usually not present at birth. This is a case of a female infant with an atypical congenital vascular tumour present at birth which ulcerated in the first few days of life, involuted over several months and showed histopathological features in keeping with either an involuting GLUT-1 positive infantile haemangioma or a reticular haemangioma of infancy. The initial clinical presentation was atypical for an infantile haemangiomas and for a congenital haemangioma, however the histopathology and immunohistochemistry assisted with confirmation of the diagnosis. Vacuum-assisted closure (VAC) therapy aided in the complete healing of the ulcerated infantile haemangioma which was not achievable with conventional dressings.


Synthesis and characterization of novel homoleptic N,N-dialkylcarbamato complexes of antimony: precursors for the deposition of antimony oxides.
A series of tris(N,N-dialkylcarbamato)antimony(III) complexes, Sb(O(2)CNR(2))(3) (R = Me, Et, Pr(i)()), have been synthesized and are the first members of this class of compound to have been crystallographically characterized. Sb(O(2)CNMe(2))(3) (1) exists as a weakly bound dimer, whereas its diethyl and diisopropyl analogues (2, 3) are monomeric. In addition, tetrakis(N,N-diethylcarbamato)tin(IV) (4) has been prepared for comparison and shown by single-crystal X-ray analysis to exhibit the relatively rare SnO(8) coordination. Crystallographic data: for 1, a = 8.7520(5) A, b = 14.2970(8) A, c = 11.8150(7) A, beta = 108.029(2) degrees, monoclinic, P2(1)/c, Z = 4; for 2, a = b = 14.4690(2) A, c = 16.6740(2) A, trigonal, Rthremacr;, Z = 6; for 3, a = 11.9881(2) A, b = 11.6521(3) A, c = 19.8780(6) A, beta = 90.401(1) degrees, monoclinic, P2(1)/n, Z = 4; for 4, a = 13.9654(2) A, b = 12.0817(2) A, c = 16.6752(2) A, beta = 108.1960(7) degrees, monoclinic, C2/c, Z = 4. Sb(O(2)CNMe(2))(3) has been used as a single-source precursor in the low-pressure chemical vapor deposition of the senarmonite form of Sb(2)O(3).


Anopheles gambiae in Brazil: the background to a "silent spread," 1930-1932.
The article analyzes the arrival and identification of the African mosquito Anopheles gambiae in Brazil in 1930, and the initial reactions of scientists and public health authorities against the epidemics of malaria caused by this species. Although this mosquito was recognized as a dangerous vector of malaria, its presence in Brazil was neglected after initial emergency actions in the city of Natal in 1932; this encouraged it to spread silently, resulting in a major malaria epidemic in 1938. This article examines scientific and political issues which caused the fight against mosquitoes to be pushed into the background until 1937 in cooperative efforts between the Rockefeller Foundation's International Health Division and the Brazilian authorities.


Morgagni hernia: rare presentations in elderly patients.
Morgagni hernia, which is both infrequent and generally asymptomatic, is often diagnosed when complications occur. Herein we present two elderly patients with Morgagni hernia, which were complicated with bowel perforation and upper gastro-intestinal bleeding. The recognition and management of these cases are discussed.


Duration of Catarina virus infection in the southern plains woodrat (Neotoma micropus).
Four adult male, 6 sub-adult, and 7 newborn southern plains woodrats (Neotoma micropus) each were inoculated subcutaneously with 3.1 log(10) median cell culture infectious doses (CCID(50)) of Catarina virus strain AV A0400135 (virus family Arenaviridae). The inoculated animals and the mothers of the newborn animals all became infected and remained asymptomatic. The infections in the adult male woodrats and in the mother woodrats were transient, the infections in 2 (33.3%) of the sub-adult woodrats persisted through month 4 post-inoculation, and 6 (85.7%) of the newborn woodrats were viruric through month 5 post-inoculation. Collectively these findings indicate that the duration of infection in the southern plains woodrat is dependent upon age at exposure to Catarina virus. The results of this study also indicate that chronically infected woodrats persistently shed Catarina virus into the environment.


Apical membrane turnover is accelerated near cell-cell contacts in an embryonic epithelium.
During embryogenesis, the killifish Fundulus heteroclitus forms a monolayered tight epithelium called the enveloping layer (EVL). These epithelial cells have been shown to rearrange during epiboly, as they spread to cover the large yolk cell. Membrane remodeling by exocytosis and endocytosis is important in establishing and maintaining the apical-basolateral polarity of many epithelial cells and is a necessary component of epithelial rearrangements, as cells constantly break contacts and reform tight junctions. To study these phenomena in Fundulus heteroclitus embryos, we labeled the apical membranes of EVL cells with fluorescent lectins and lipids and followed membrane dynamics. Apical membrane components were found to be highly immobilized, allowing us to observe localized sites of apical membrane turnover in situ, over the period of several days. We found that apical membrane turnover in the EVL cells of post-epiboly killifish embryos is accelerated at cell-cell contacts, in a peripheral band of apical membrane which closely borders circumferential tight junctions. Moreover, this turnover rate is increased during epiboly, when the cells are actively rearranging. To investigate whether this increased membrane turnover may be related to the mechanical forces experienced by the rearranging EVL cells, post- epiboly embryos, whose EVL cells no longer rearrange, were subjected to mechanical deformation. In these manipulated embryos, apical membrane turnover was accelerated at cell-cell contacts in EVL cells which experienced externally applied mechanical tension. These results suggest that local mechanical tension may modulate regional apical membrane turnover within EVL cells during the process of epiboly.


Coverage of iron and folic acid supplementation in India: progress under the Anemia Mukt Bharat strategy 2017-20.
High prevalence of anaemia is a severe public health problem in India. In 2018, India launched the Anemia Mukt Bharat (AMB) strategy that focuses on six beneficiary groups for coverage, six institutional mechanisms for health system strengthening and six programmatic interventions to accelerate reductions in anaemia prevalence. This paper uses the Health Management Information System data (2017-18 to 2019-20) to examine gains in IFA coverage across Indian states. A coverage-based AMB index is computed to review performance across states. After the launch of AMB strategy, the Iron and Folic Acid (IFA) supplementation coverage between 2017-18 and 2019-20 has increased for all beneficiary groups [pregnant women from 78% to 90%; lactating mothers from 34% to 49%; school going adolescent girls (boys) from 23% to 40% (21% to 42%); out-of-school adolescent girls from 6% to 23%; children 5-9 years from 8% to 3% and children 6-59 months from 7% to 15%]. Coverage was relatively low for target groups being served through a multi-departmental convergence mechanism (health and other departments such as education department for schools or women and child development department for Anganwadi centres) than compared to those served by health department alone. However, no major gender disparities are noted in the coverage of IFA supplementation among school-going girls and boys. Bulk of the variations in coverage is attributable to state-specific differences. Training and sensitization workshops for state and district officials are found to be associated with increased coverage across beneficiary groups. The paper argues that despite following international best practices in the field, it is important to harness synergy in programme implementation across line departments to eliminate coverage inefficiencies.


[Hearing outcome of canal wall reconstruction tympanoplasties for the treatment of cholesteatoma].
While the hearing outcome of patients undergoing a tympanoplasty with canal reconstruction is generally thought to be inferior to that of patients undergoing a canal-up tympanoplasty, a direct comparison of these two procedures, performed by the same operator, has not been reported. Consequently, we compared the hearing outcomes of these two techniques and discussed the postoperative complications that could accompany the procedures. Hearing was evaluated in 52 ears with middle ear cholesteatoma. Using the postsurgical hearing result assessment criteria published by the Japanese Society of Otology in 2000, hearing was then evaluated again at least 6 months after surgery. When the data was analyzed according to the type of operation, the success rates (as determined using the above assessment criteria) were 78.6% for type I, 88.5% for modified type III, and 50.0% for modified type IV. The success rate for the modified type III operations was superior to that of the modified type IV operations, and the incidence of a postoperative air-bone gap in the type IV tympanoplasties was significantly larger than that in other groups. Procedures involving external auditory canal surgery can be particularly problematic for the treatment of cholesteatoma. In this series, the same author (KH) performed all the canal-up tympanoplasty procedures that took place during 1990-1996, and all other tympanoplasties, mainly canal reconstruction procedures, that took place during 1998-2001. The success rate was 68.4% (13/19) for the canal-up tympanoplasties, 100% (8/8) for the atticotomies and 76% (19/25) for the canal wall reconstructions. The postoperative success rate in the atticotomy group was significantly higher than the rates of the other groups. Among the canal reconstructive tympanoplasty procedures, a second exploratory surgery was performed in 15/24 cases, and residual cholesteatoma was observed in 3 cases. The major postoperative complications were epitympanic pocket formation (12/24) and taste disturbances, caused by chordal damage (2/24). These findings indicate that tympanoplasties with canal reconstruction improve the hearing outcome, compared with the outcome of canal-up tympanoplasties. However, epitympanic retraction pocket formation, resulting in recurrent cholesteatoma, is a possible complication of both surgical procedures, and new approaches or techniques should be sought to minimize such postoperative changes.


Total scalp replantation based on one artery and one vein.
A successful replantation of a totally avulsed scalp, including both eyebrows, with only one arterial and one venous anastomosis to the superficial temporal vessels is described. Apart from a small partial skin necrosis of the right eyebrow, the entire transplant survived. Subsequently, the patient required only minor additional skin grafting, correction of scars with a skin expander, and reconstruction of the eyebrow with hair micrografts. Replantation of the total scalp based on two or more vessels has previously been recommended and reported elsewhere. In the present case, complete survival of the scalp on only one artery and one vein was demonstrated, indicating that replantation should be considered even if available vessels for anastomosis are minimal.


Engineering and commercialization of human-device interfaces, from bone to brain.
Cutting edge developments in engineering of tissues, implants and devices allow for guidance and control of specific physiological structure-function relationships. Yet the engineering of functionally appropriate human-device interfaces represents an intractable challenge in the field. This leading opinion review outlines a set of current approaches as well as hurdles to design of interfaces that modulate transfer of information, i.a. forces, electrical potentials, chemical gradients and haptotactic paths, between endogenous and engineered body parts or tissues. The compendium is designed to bridge across currently separated disciplines by highlighting specific commonalities between seemingly disparate systems, e.g. musculoskeletal and nervous systems. We focus on specific examples from our own laboratories, demonstrating that the seemingly disparate musculoskeletal and nervous systems share common paradigms which can be harnessed to inspire innovative interface design solutions. Functional barrier interfaces that control molecular and biophysical traffic between tissue compartments of joints are addressed in an example of the knee. Furthermore, we describe the engineering of gradients for interfaces between endogenous and engineered tissues as well as between electrodes that physically and electrochemically couple the nervous and musculoskeletal systems. Finally, to promote translation of newly developed technologies into products, protocols, and treatments that benefit the patients who need them most, regulatory and technical challenges and opportunities are addressed on hand from an example of an implant cum delivery device that can be used to heal soft and hard tissues, from brain to bone.


Detection of brief tones in noise by rats.
Two rats were trained to detect brief 8000-Hz tones centered in a one-third octave band of noise. The procedure was analogous to the yes-no method of human psychophysics in that one response was defined as correct and reinforced if the tone were present in the noise, and another response was correct and reinforced if the tone were absent. The percentage of correct responses was determined principally by the energy in the tone for the range of durations studied (75 to 600 msec): if the tone's duration were halved, for example, its power had to be doubled to keep the percentage of correct responses about the same. The ratio of the energy in the tone to the power per cycle of the noise needed to maintain 75% correct responses was about 36 db for one animal and 41 db for the other. Although the two responses were similar, and their consequences equal, biases in responding were sometimes observed.


Noncirrhotic hepatoma presenting with paraneoplastic neurologic manifestations: two cases.
Hepatocellular carcinoma usually occurs in patients with cirrhosis and is rarely associated with paraneoplastic neurologic disorders. We describe two young patients with hepatomas occurring in noncirrhotic livers, both of whom presented with neurologic symptoms. A 19-yr-old man who presented with coma and a 23-yr-old woman with a 3-month history of progressive hemiparesis, dysarthria, and altered affect were each found, at autopsy, to have hepatocellular carcinoma occurring in a noncirrhotic liver. Neuropathologic examinations revealed widespread multifocal necrotizing leukoencephalopathy in the man and occlusive noninflammatory cerebral vasculopathy with widespread cortical and subcortical infarcts in the woman. It is unlikely that the neuropathologic findings in these patients are explicable on the basis of antibody-mediated tissue injury.


Beauvericin and Enniatins: In Vitro Intestinal Effects.
Food and feed contamination by emerging mycotoxins beauvericin and enniatins is a worldwide health problem and a matter of great concern nowadays, and data on their toxicological behavior are still scarce. As ingestion is the major route of exposure to mycotoxins in food and feed, the gastrointestinal tract represents the first barrier encountered by these natural contaminants and the first structure that could be affected by their potential detrimental effects. In order to perform a complete and reliable toxicological evaluation, this fundamental site cannot be disregarded. Several in vitro intestinal models able to recreate the different traits of the intestinal environment have been applied to investigate the various aspects related to the intestinal toxicity of emerging mycotoxins. This review aims to depict an overall and comprehensive representation of the in vitro intestinal effects of beauvericin and enniatins in humans from a species-specific perspective. Moreover, information on the occurrence in food and feed and notions on the regulatory aspects will be provided.


Sphingosine Kinase 1 Cooperates with Autophagy to Maintain Endocytic Membrane Trafficking.
Sphingosine kinase 1 (Sphk1) associates with early endocytic membranes during endocytosis; however, the role of sphingosine or sphingosine-1-phosphate as the critical metabolite in endocytic trafficking has not been established. Here, we demonstrate that the recruitment of Sphk1 to sphingosine-enriched endocytic vesicles and the generation of sphingosine-1-phosphate facilitate membrane trafficking along the endosomal pathway. Exogenous sphingosine and sphingosine-based Sphk1 inhibitors induce the Sphk1-dependent fusion of endosomal membranes to accumulate enlarged late endosomes and amphisomes enriched in sphingolipids. Interestingly, Sphk1 also appears to facilitate endosomal fusion independent of its catalytic activity, given that catalytically inactive Sphk1G82D is recruited to endocytic membranes by sphingosine or sphingosine-based Sphk1 inhibitor and promotes membrane fusion. Furthermore, we reveal that the clearance of enlarged endosomes is dependent on the activity of ceramide synthase, lysosomal biogenesis, and the restoration of autophagic flux. Collectively, these studies uncover intersecting roles for Sphk1, sphingosine, and autophagic machinery in endocytic membrane trafficking.


Rotationplasty in the elderly.
Purpose. Rotationplasty has proven its efficacy in the treatment of malignant bone tumors of the lower extremity in predominantly young patients. To our knowledge this procedure has not been reported in patients over 60 years before. Materials and Methods. 3 patients over 60 years with an A1-rotationplasty because of a sarcoma were included in this study. Complications and functional results were recorded. In one patient an electromyography was done. Results. Despite electromyography showing good adaptation of the muscles to the altered function, the functional results of these three patients were limited. two out of three patients needed a cane for walking distances over 200 meters. No secondary amputation was necessary. Discussion. Our study demonstrates that rotationplasty is an alternative to an above-knee amputation in older patients but with poorer functional results in comparison to younger patients. However, limb-salvage surgery should be preferred whenever possible.


Electrochemical properties of graphene flakes as an air cathode material for Li-O2 batteries in an ether-based electrolyte.
We employed graphene flakes as an air-cathode material for Li-O2 batteries and investigated their electrochemical properties in the dimethyl ether electrolyte. Graphene flakes were prepared by microwave-assisted reduction of graphene oxide, and their electrochemical properties were compared with those of Ketjen Black and carbon nanotubes. The catalytic effect of the prepared graphene flake-air cathode was demonstrated using cyclic voltammetry and discharge-charge testing performed under a limited discharge capacity. The catalytic effect of graphene flakes was also supported by morphological and spectroscopic analysis of the discharge-charge products formed on the graphene surface. Scanning electron microscopy, X-ray diffraction, and Fourier-transform infrared spectroscopy revealed that Li2O2, Li2O, and Li2CO3 were the main discharge products on all carbon-air cathode surfaces. Raman spectroscopy revealed that LiRCO3 was additionally formed on Ketjen Black and carbon nanotubes during the first discharge; however, its formation was not observed on the graphene flakes. The catalytic effect of the graphene flakes and the absence of LiRCO3 in the discharge product could explain the higher Coulombic efficiency in the discharge-charge tests.


Effect of color on contrast sensitivity with two different accommodative stimuli.
We studied the influence of color and accommodation on the contrast sensitivity function (CSF). At the same time, we measured the effect of axial chromatic aberration (ACA) on the CSF. The CSF's of two observers were determined using red, green, blue, and white light, at 5- and 0.5-m viewing distances. At 5 m the CSF's were measured with natural vision and also with lenses which compensated the ACA. Results show that the effect of ACA on the CSF is to reduce the sensitivity to blue with respect to the red. The difference in sensitivity between these two colors is between 50 and 150% and varies with the frequency and the subject. When the ACA is compensated the influence of the color on the CSF is very small, in our experiment, and this result is discussed in relation to the compensating effects of chromatic adaptation of the color mechanisms. In near vision, the CSF's were measured with natural vision and also with the lenses required to give the same accommodative stimulus for all colors. We discuss the effect of accommodation on the CSF. For both far and near the results are compared with the CSF with white light.


Skeletal site-dependent expression of the androgen receptor in human osteoblastic cell populations.
There are obvious sexual differences in adult skeletal morphology which for the most part are related to differences in size. Higher androgen serum levels in males exert potent osteoanabolic effects and therefore may contribute to this sexual dimorphism of the skeleton. The presence of androgen receptors (AR) in bone cells is a prerequisite for a direct osteoanabolic action of androgens. To investigate the possibility that, in addition to gender-related differences in androgen serum levels, there are also gender-related differences in the osteoblastic expression pattern of the androgen receptor, we examined AR mRNA expression, androgen binding sites, and mitogenic responses to the androgen dihydrotestosterone (DHT) in human osteoblastic cell (HOC) populations. HOCs were isolated from bone biopsy specimens derived from different skeletal sites of healthy adult males and females (2-69 years old). We found that male and female HOCs of all examined ages express similar AR mRNA levels and similar numbers of androgen binding sites. Using whole-cell-binding assays, we observed 3129-8417 androgen binding sites per femoral HOC with apparent KDs of 1.45-2.83 nM depending on the age of the investigated HOC population. Mandibular and cortical HOC of both sexes expressed higher AR mRNA levels, significantly more androgen binding sites per cell, and exhibited significantly greater mitogenic responses to DHT than iliac crest-derived and trabecular HOC of the same skeletal system and the same skeletal-site, respectively. In early adulthood, HOCs of both sexes appear to express somewhat higher AR mRNA levels and to possess more androgen binding sites than prepubertal and senescent HOC. Because sex hormone serum levels rise in puberty, we investigated the regulation of the AR mRNA expression by various steroids. We found that dexamethasone (dexa) and in some experiments also 17beta-estradiol (E2) and 1,25-dihydroxyvitamin D3 (D3) increased AR mRNA levels and androgen binding in HOC cultures. A pretreatment with dexa, E2, and D3 significantly increased the mitogenic response of HOCs to DHT. We conclude that (1) higher androgen serum levels in males together with a higher AR expression at certain skeletal sites may contribute to the development of sex-related differences in skeletal morphology, (2) glucocorticoids induce AR gene expression in HOC cultures, and (3) glucocorticoids, E2, and D3 enhance the mitogenic action of DHT.


Reversible transformation between chiral and achiral Dy6Mo4 clusters through a symmetric operation.
Three polynuclear lanthanide clusters: (NH4)2[Dy6Mo4O12(rac-L(3-))4(OOCCH3)8]·4CH3OH·6H2O (I), (Et3NH)2[Dy6Mo4O12(rac-L(3-))4(OOCCH3)8]·18H2O (II), and (Me4N)2[Dy6Mo4O12(rac-L(3-))4(OOCCH3)8]·CH3OH·14H2O (III) (H3L = (E)-2-((2,3-dihydroxypropylimino)methyl)-phenol) were synthesized. Single-crystal analysis reveals that cluster I crystallized in the centrosymmetric space group (P42/n), while clusters II and II crystallized in the chiral space group (P3121 or P3221), and cluster I can be transformed into clusters II and III, when Et3NH(+) and Me4N(+), respectively, are used to replace NH4(+). Investigation on the solid-state vibrational circular dichroism (VCD) spectra shows that the clusters II and III are homochiral crystallization. Powder X-ray diffraction study demonstrates that the transformation between chiral and achiral clusters is reversible.


Service use Decision-Making among Youth Accessing Integrated Youth Services: Applying the Unified Theory of Behavior.
With the development of 75% of mental health disorders before age 25, it is alarming that service use among youth is so low. Little theoretically driven research has explored the decision-making process youth make when accessing services. This study utilized a decision-making framework, the Unified Theory of Behavior (UTB), to understand service use among youth attending Foundry, a network of integrated youth services centres designed to support the health and wellbeing of youth. Forty-one participants were recruited from one Foundry centre in an urban community in Canada. Semi-structured interviews with participants aged 15 - 24 explored the relationship between UTB constructs and service use. Youth and parent advisory teams were engaged in the research process. Analysts used content analysis methodology to develop a taxonomy of the top categories for each construct. Categories with the most salient and rich content were reported for each construct. The impact of emotions on service use was most commonly discussed in relation to the framework. The UTB constructs 'self-efficacy' and 'knowledge' were found to be interrelated. Differences in UTB categories emerged by symptom severity. Findings pointed towards a dynamic nature of service use, whereby service use experiences, may lead youth to consider future decisions surrounding service use within Foundry. This study contributes to a new understanding of integrated youth services utilization. The results can help shape the development of interventions to increase service access and retention, in addition to informing the design of systems of care that are accessible to all.


Boronate affinity chromatography of gamma-glutamyltransferase in patients with hepatocellular carcinoma.
We analyzed the serum gamma-glutamyltransferase (gamma-GT) by boronate affinity chromatography to ascertain the presence or absence of any changes in the binding properties of gamma-GT toward boronate gels in patients with hepatocellular carcinoma and liver cirrhosis, and in normal controls. The mean gamma-GT activity ratio of the bound (peak 2) and nonbound (peak 1) fraction in patients with hepatocellular carcinoma was significantly higher than that in patients with liver cirrhosis or in normal controls. Thus, the gamma-GT, which has adjacent cis-hydroxyl groups in its carbohydrate moieties, was found to increase in the serum of patients with hepatocellular carcinoma. The positivity rate was examined in patients with hepatocellular carcinoma and liver cirrhosis, using a cut-off level for the peak 2:peak 1 ratio of 1.05 (mean + 2 SD of liver cirrhosis). Nineteen (42.2%) patients with hepatocellular carcinoma had a ratio of peak 2:peak 1 higher than 1.05. Nine of the 19 patients who had serum alpha-fetoprotein levels below 100 ng/ml had an elevated peak 2:peak 1 ratio. In total, 77.8% of the occurrence of hepatocellular carcinoma could be detected by a combination of these two markers. Three patients who had developed hepatocellular carcinoma during the course of cirrhosis but remained negative for alpha-fetoprotein throughout the course developed higher levels of peak 2:peak 1 ratio when hepatocellular carcinoma occurred. These results indicate that the two markers, the peak 2:peak 1 ratio of serum gamma-GT activity and serum alpha-fetoprotein level, may be considered to serve as complementary markers for the diagnosis of hepatocellular carcinoma.


Racial differences in breast carcinoma survival.
Survival after breast carcinoma diagnosis is significantly worse among African American women for reasons unknown. The purpose of this study was to update reports on the National Surveillance, Epidemiology, and End Results Program and to examine the effect of race on breast carcinoma survival. Subjects were 135,424 women diagnosed with primary breast carcinoma between 1988-1995. Patient age, tumor stage at the time of diagnosis, hormone receptor status, tumor histology, menopausal status, and survival were compared by race category. African American women diagnosed with breast carcinoma (n = 11,159) had a significantly increased risk of death from breast carcinoma and from all cancers compared with white women (n = 124,265), independent of the effects of other predictor variables. African American women were significantly younger at the time of diagnosis, with approximately 33% of the population age </= 50 years, compared with slightly <25% of the white women belonging to that younger age group. African American women were significantly more likely to present with advanced stages of breast carcinoma and, within each stage category, had significantly poorer survival compared with white women. African American women were significantly less likely to have tumors positive for estrogen or progesterone receptors, as well as histologically confirmed lobular and tubular carcinomas, whereas they were more likely to have inflammatory, medullary, and papillary histology compared with white women. The results of the current study show that race is an independent predictor of survival from breast carcinoma. These findings are consistent with other large, population-based studies of racial differences in breast carcinoma survival and have been comported by studies of racial differences in the molecular biology of breast carcinoma, thus providing support for the epidemiologic credibility of the independence of the association.


Cardiovascular Outcomes with Finerenone According to Glycemic Status at Baseline and Prior Treatment with Newer Antidiabetics among Patients with Type 2 Diabetes Mellitus.
Type 2 diabetes mellitus (T2DM) and cardiovascular disease are closely interconnected. We sought to determine the cardioprotective action of finerenone according to prior treatment with newer antidiabetics and glycemic status. We searched PubMed and Cochrane Library from inception to October 1, 2021 for randomized controlled trials (RCTs) assessing the effect of finerenone on major adverse cardiovascular outcomes in patients with T2DM. We set the primary endpoint as major adverse cardiovascular events (MACE), defined as the composite of death from cardiovascular causes, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for heart failure. We finally included two RCTs in our quantitative synthesis. Compared to placebo, finerenone induced a 23% risk reduction for the composite cardiovascular endpoint, regardless of prior glycemia. We also showed that finerenone provided significant cardiovascular benefit for obese patients with T2DM compared to placebo, although this benefit was diminished for subjects with a body mass index lower than 30 kg/m2. Finally, the combination of finerenone with sodium-glucose co-transporter-2 inhibitors or glucagon-like peptide-1 receptor agonists did not produce a significant risk reduction for MACE. We conclude that finerenone provides significant cardiovascular benefits for patients with T2DM, especially for those who are obese, while glycemic status or treatment with newer antidiabetics at baseline does not affect the observed cardioprotective action.


Protection of human HepG2 cells against oxidative stress by cocoa phenolic extract.
Cocoa is a rich source of flavanols and procyanidin oligomers with antioxidative properties, providing protection against oxidation and nitration. The present study investigated the potential protective effect of a polyphenolic extract from cocoa on cell viability and antioxidant defenses of cultured human HepG2 cells submitted to oxidative stress induced by tert-butylhydroperoxide (t-BOOH). Pretreatment of cells with 0.05-50 microg/mL of cocoa polyphenolic extract (CPE) for 2 or 20 h completely prevented cell damage and enhanced activity of antioxidant enzymes induced by a treatment with t-BOOH. Moreover, lower levels of GSH caused by t-BOOH in HepG2 cells were partly recovered by a pretreatment with CPE. Increased reactive oxygen species (ROS) induced by t-BOOH was dose-dependently prevented when cells were pretreated for 2 or 20 h with CPE. These results show that treatment of HepG2 in culture with CPE (within the physiological range of concentrations) confers a significant protection against oxidation to the cells.


Simulation on electrical field distribution and fiber falls in melt electrospinning.
Electrospinning is now a typical way of direct and consecutive producing nanofibers. In order to comprehensively understand the change of fiber chains in falling process of electrospinning, the article import dissipative particle dynamics (DPD) mesoscale simulation method into electrospinning study. In current work, an electrical force formula is proposed after simulation of the distribution of electrostatic field in electrospinning using Finite Element Method. Then, various electrostatic force, temperature and viscosity in electrospinning system are qualitatively simulated by DPD simulation. Results showed that the falling velocity of fiber increased with the increase of electrostatic force. It was found that the lower the polymer viscosity, the quicker the fiber falls. And the diameter of fiber significantly increased with augment of viscosity. Both of above are agree with experimental results. We also found that the falling velocity of fiber is in contrast with length of polymer chains, which has not been found in experiments.


In vivo and in vitro toxicological evaluations of aqueous extract from Cecropia pachystachya leaves.
leaves are popularly used to treat asthma and diabetes. Despite the widespread consumption of this plant, there are few scientific studies regarding its toxicological potential. In order to conduct a thorough study concerning the potential adverse effects, the aim of this study was to assess acute and subacute toxicity tests of crude aqueous extract from C. pachystachya leaves (CAE-Cp) using in vivomodel, as well as in vitro cytotoxicity, genotoxicity and antioxidant activity. In addition, genotoxicity, and cytotoxicity of chlorogenic acid (CGA) and cytotoxicity of isoorientin (ISOO) were also evaluated. The antioxidant activity was verified by DPPH, cytotoxicity using sulforhodamine B (SRB) assay and genotoxicity by comet assay on V79 cells. The phytochemical analysis of CAE-Cp detected flavonoids and tannins, CGA and ISOO as the major compounds utilizing HPLC. The total flavonoid content (6.52 mg/g EQ) and antioxidant activity (EC50 = 62.15 µg/ml) of CAE-Cp were determined. In vitro evaluations with CAE-Cp showed genotoxic effects at 0.31 to 2.5 mg/ml and an expressive cytotoxicity on HT-29 (IC50 = 4.43 µg/ml) cells. CGA was genotoxic against V79 cells at 0.07 mg/ml and cytotoxic against to HT-29 (IC50 = 71.70 µg/ml), OVCAR-3 (IC50 = 80.07 µg/ml), MCF-7 (IC50 = 45.58 µg/ml) and, NCI-H460 (IC50 = 71.89 µg/ml) cancer cell lines. Wistar rats treated with a single dose (2,000 mg/kg) CAE-Cp decreased hemoglobin levels after 14 days, although no significant toxicity was observed in animals after 28 days. In view of the in vitro cytotoxicity and genotoxicity detected, further studies are necessary to establish the safe use of CAE-Cp.


[Hypergalactosemia in newborns as uncovered by the Austrian screening program in 12 years (author's transl)].
The Austrian Screening Program examined during 12 years 1,002.424 newborns and uncovered 23 cases of Galactosemia by Transferase deficiency, 6 by Kinase deficiency as well as 1 case of Phosphoglucomutase deficiency, 1 of porto-caval shunt and 1 congenital liver cirrhosis. Among the 23 Transferase deficiencies 18 took a fulminating course and 8 of these died. Since introduction of exchange transfusion as emergency treatment and acceleration of the screening procedure only 2 among 11 have died. Half of all Galactosemia cases, Transferase and Kinase, show already at the first examination (2. week) a cataract which however is reversible. In contrast to Kinase deficiency all cases of Transferase deficiency exhibit mental retardation if they grow older. Since treatment is early (9, 7 days), easy and the IQ already at 4 years 10 points below that of treated PKU's of same age a congenital brain damage has to be considered. Galactosemia by Transferase deficiency is in Western-Austria significantly more frequent than in Eastern-Austria. 17 boys compare with 6 girls. Among 6 cases of Galactosemia by Kinase deficiency 1 belonged to a Gippsy and 2 to Yugoslavian guest worker families. The 23 cases with Transferase deficiency had 45 siblings among whom 11 also were galactosemic. In 8 sibships the clinical course was of the same typ, but in 1 family one child showed the fulminating the other the subacute course.


Interactions of drought and shade effects on seedlings of four Quercus species: physiological and structural leaf responses.
Here, we investigated the physiological and structural leaf responses of seedlings of two evergreen and two deciduous Quercus species, grown in a glasshouse and subjected to contrasted conditions of light (low, medium and high irradiance) and water (continuous watering vs 2-months drought). The impact of drought on photosynthetic rate was strongest in high irradiance, while the impact of shade on photosynthetic rate was strongest with high water supply, contradicting the hypothesis of allocation trade-off. Multivariate causal models were evaluated using d-sep method. The model that best fitted the dataset proposed that the variation in specific leaf area affects photosynthetic rate and leaf nitrogen concentration, and this trait determines stomatal conductance, which also affects photosynthetic rate. Shade conditions seemed to ameliorate, or at least not aggravate, the drought impact on oak seedlings, therefore, the drought response on leaf performance depended on the light environment.


Lumenal Galectin-9-Lamp2 interaction regulates lysosome and autophagy to prevent pathogenesis in the intestine and pancreas.
Intracellular galectins are carbohydrate-binding proteins capable of sensing and repairing damaged lysosomes. As in the physiological conditions glycosylated moieties are mostly in the lysosomal lumen but not cytosol, it is unclear whether galectins reside in lysosomes, bind to glycosylated proteins, and regulate lysosome functions. Here, we show in gut epithelial cells, galectin-9 is enriched in lysosomes and predominantly binds to lysosome-associated membrane protein 2 (Lamp2) in a Asn(N)-glycan dependent manner. At the steady state, galectin-9 binding to glycosylated Asn175 of Lamp2 is essential for functionality of lysosomes and autophagy. Loss of N-glycan-binding capability of galectin-9 causes its complete depletion from lysosomes and defective autophagy, leading to increased endoplasmic reticulum (ER) stress preferentially in autophagy-active Paneth cells and acinar cells. Unresolved ER stress consequently causes cell degeneration or apoptosis that associates with colitis and pancreatic disorders in mice. Therefore, lysosomal galectins maintain homeostatic function of lysosomes to prevent organ pathogenesis.


Ratios between number of neuroglial cells and number and volume of nerve cells in the spinal ganglia of two species of reptiles and three species of mammals.
We studied the ratios between number of neuroglial (=satellite) cells and number and volume of neurons with which they are associated in the spinal ganglia of two species of reptiles (lizard and gecko) and three species of mammals (mouse, rat, and rabbit). In all five species, we found that the number of satellite cells associated with a nerve cell body increased with increasing volume of the latter. This result shows that there is a quantitative balance between neuroglia and nerve tissue in spinal ganglia. This balance seems to be maintained by a tight regulation of the number of satellite cells. We also found that the mean volume of nerve cell body corresponding to a satellite cell was lower for small neurons than for large ones. Since satellite cells metabolically support spinal ganglion neurons, the metabolic needs of small neurons are better satisfied than those of large ones. For a nerve cell body of a given size, the number of associated satellite cells did not differ between the lizard and gecko, nor between the mouse, rat, and rabbit. However, this number was significantly smaller in the reptiles than in the mammals. This result could be explained by the lower metabolic rate in the nervous system of poikilotherms than mammals, or could have a phylogenetic significance. These two interpretations are not mutually exclusive.


CD8+ T-cells of CLL-bearing mice acquire a transcriptional program of T-cell activation and exhaustion.
Chronic lymphocytic leukemia (CLL) is associated with an accumulation of oligoclonal CD8+ effector T-cells, which control leukemia progression in mice, but gradually acquire a dysfunctional phenotype along with disease progression. Exhaustion of CD8+ T-cells is characterized by increased expression of inhibitory receptors like PD-1, decreased proliferation, and reduced effector function such as cytokine production, which reduces anti-tumor control. Despite the accumulation of exhausted PD-1+ CD8+ T-cells in secondary lymphoid organs of CLL patients, immune checkpoint blockade as a means to reinvigorate anti-tumor T-cell activity has not shown the expected efficacy. This highlights the need for a better understanding of T-cell exhaustion in CLL. Here, we uncover the transcriptional program of T-cell exhaustion in CLL by comparing naïve with dysfunctional effector CD8+ T-cells with high PD-1 expression from mice after adoptive transfer of Eµ-TCL1 leukemic cells. Our data provide clear evidence for activation-induced dysfunction of CD8+ T-cells in the CLL microenvironment and assess the heterogeneity in the expression of functionally relevant proteins in specific clusters of CD8+ T-cells at a single-cell level.


Identification of Key Success Factors for Private Science Parks Established from Brownfield Regeneration: A Case Study from China.
Private science parks (PSPs) are infrastructure elements of national high technology industrial development zones. Increasing private capital is being invested in this field to transform abandoned factories into science parks through brownfield regeneration, which not only effectively utilizes urban space, but also greatly strengthens the power of scientific and technological innovation. The evolution of these PSPs, however, is not satisfactory, and some operation and innovation-related problems often lead to their failures. Therefore, identifying key success factors is crucial for the sustainable growth of PSPs. This study employs Fuzzy Analytic hierarchy process (FAHP) and Fuzzy-DEMATEL (Decision Making Trial and Evaluation Laboratory) methods to construct an identification model for key success factors of PSPs established from brownfield regeneration. Associated influencing factors were collected through literature analysis, on-site interviews, and questionnaire, based on which key success factors were identified. The results of the study showed that five factors-resources sharing capacity of the park, park scale, financing and financial services, legal policy services and administrative capability, and construction level of facilities in the park-are the key success factors for such PSPs. The results also provide a theoretical basis for the development of PSPs established from brownfield regeneration, and support the formulation of PSP-related policies.


The transcription factor HLH-26 controls probiotic-mediated protection against intestinal infection through up-regulation of the Wnt/BAR-1 pathway.
Probiotics play a critical role in the control of host intestinal microbial balance, protecting the host from gastrointestinal pathogens, modulating the host immune response, and decreasing host susceptibility to infection. To understand the mechanism underlying the protective effect of probiotics against infections through immune regulation, we examined protection against Salmonella enterica infection following exposure to nonpathogenic Enterococcus faecium in the nematode Caenorhabditis elegans. We found that the transcription factor HLH-26, a REF-1 family member of basic helix-loop-helix transcription factors, was required in the intestine for E. faecium-mediated protection of C. elegans against a lethal S. enterica infection. In addition, we uncovered that defense response genes controlled by the canonical Wnt/BAR-1 pathway were activated upon exposure to E. faecium in an HLH-26-dependent manner. Our findings highlight a role for REF-1/HLH-26 in the control of the Wnt/BAR-1 pathway in probiotic-mediated protection against gut infection.


Properties of the cardiac pacemaker (if) current.
The cardiac pacemaker if current, once thought to be a pure K+ current, is shown to be carried by both Na and K. It is inward and activating during hyperpolarizations negative to -50/-60 mV in normal conditions. Its kinetics are delayed during both activation and deactivation.


Primary pancreatic lymphomas.
Primary pancreatic lymphomas are extremely rare. Clinically, primary pancreatic lymphomas usually present with symptoms of carcinoma of the pancreatic head. Patients with primary pancreatic lymphomas are between 35 and 75 years of age and with a strong male predominance. Common clinical manifestations include abdominal pain, jaundice, acute pancreatitis, small bowel obstruction, and diarrhea. An accurate cytopathologic diagnosis by fine-needle aspiration (FNA) is imperative because the primary treatment is non-surgical. Cytomorphologic features include hypercellularity with discohesive cells with round nuclei, often prominent nucleoli, mitoses, and karyorrhexis. Flow cytometry analysis demonstrates a monoclonal pattern of immunoglobulin light chain expression. FNA coupled with flow cytometry analysis appears to be highly accurate in the diagnosis of primary pancreatic lymphomas. Fluorescence in-situ hybridisation technique has been established its role in the diagnosis of lymphoid malignancies, including primary pancreatic lymphomas. LDH and beta-2 microglobulin are important diagnostic and prognostic tumor markers. The differential diagnoses of primary pancreatic lymphomas include secondary lymphoma, pancreatic endocrine neoplasm, and florid chronic pancreatitis. The role of surgery is limited to the rare occasions when initial FNA and flow cytometry analysis are non-diagnostic. Treatment usually consists of a combination of chemotherapy and radiation therapy, or stem cell transplantation. Primary pancreatic lymphomas has a much better prognosis than adenocarcinoma of the pancreas.


Failure of gonadotropin-releasing hormone (GnRH) pulses to increase luteinizing hormone beta messenger ribonucleic acid in GnRH-deficient female rats.
Gonadotropin subunit gene transcription and messenger RNA (mRNA) levels are differentially regulated by GnRH pulse frequency and amplitude in the male rat. The rapid changes of subunit mRNA levels and LH and FSH secretion during the estrous cycle, particularly the rapid rise in LH-beta subunit mRNA on proestrus afternoon, suggest that physiological changes in the pattern of GnRH action may also be important in female rats. However, in the absence of a GnRH-deficient female model the role of varying GnRH stimulation remains to be determined. We have characterized a GnRH-deficient model by administering the alpha-adrenergic antagonist phenoxybenzamine (PBZ) to ovariectomized (OVX) rats. Initial experiments showed that PBZ given 24 h earlier abolished the afternoon LH surge in OVX estradiol (E2) replaced rats whereas LH responses to exogenous GnRH were preserved. A PBZ regimen of 15 mg/kg ip at OVX followed by 10 mg/kg at 24 h and 5 mg/kg at 48 h prevented the increase in alpha, LH-beta, and FSH-beta mRNAs and LH and FSH secretion for 72 h post-OVX. LH and FSH responses to GnRH pulses were preserved suggesting that PBZ blocked the post-OVX increase in hypothalamic GnRH secretion. The suppressive effect of PBZ appeared to be specific to the hypothalamic-pituitary-ovarian axis as plasma PRL, TSH, and corticosterone were not decreased compared to controls. We have used this GnRH-deficient OVX female model to investigate the effects of exogenous GnRH pulses on subunit mRNA expression. GnRH pulses (5-250 ng/30 min for 12-24 h) were administered via an intraatrial catheter beginning 24 h after OVX and the first PBZ injection (OVX+PBZ+saline pulses to controls). Expression of alpha and FSH-beta mRNAs and LH and FSH secretion were increased by GnRH pulse doses of 5-25 ng to values similar to or greater than those in OVX controls though the higher doses of GnRH/pulse did not increase FSH-beta mRNA or plasma FSH. However, LH-beta mRNA levels were not increased by GnRH pulses. GnRH pulses were also given to rats replaced with proestrus concentrations of estradiol alone or in combination with progesterone (P). Again, no demonstrable increases in LH-beta mRNA expression were observed. alpha-mRNA concentrations were further increased in the presence of E2 alone, and P in combination with E2, produced an augmented response of FSH-beta subunit mRNA. These data suggest that ovarian steroid hormones act directly on the gonadotrope to augment alpha and FSH-beta mRNA responses to GnRH.(ABSTRACT TRUNCATED AT 400 WORDS)


Dynamics of the HD regulatory subdomain of PARP-1; substrate access and allostery in PARP activation and inhibition.
PARP-1 is a key early responder to DNA damage in eukaryotic cells. An allosteric mechanism links initial sensing of DNA single-strand breaks by PARP-1's F1 and F2 domains via a process of further domain assembly to activation of the catalytic domain (CAT); synthesis and attachment of poly(ADP-ribose) (PAR) chains to protein sidechains then signals for assembly of DNA repair components. A key component in transmission of the allosteric signal is the HD subdomain of CAT, which alone bridges between the assembled DNA-binding domains and the active site in the ART subdomain of CAT. Here we present a study of isolated CAT domain from human PARP-1, using NMR-based dynamics experiments to analyse WT apo-protein as well as a set of inhibitor complexes (with veliparib, olaparib, talazoparib and EB-47) and point mutants (L713F, L765A and L765F), together with new crystal structures of the free CAT domain and inhibitor complexes. Variations in both dynamics and structures amongst these species point to a model for full-length PARP-1 activation where first DNA binding and then substrate interaction successively destabilise the folded structure of the HD subdomain to the point where its steric blockade of the active site is released and PAR synthesis can proceed.


Correlations between PNPLA3 Gene Polymorphisms and NAFLD in Type 2 Diabetic Patients.
Background and Objectives: Non-alcoholic fatty liver disease is a worldwide significant public health problem, particularly in patients with type 2 diabetes mellitus. Identifying possible risk factors for the disease is mandatory for a better understandingand management of this condition. Patatin-like phospholipase domain-containing protein 3 (PNPLA3) has been linked to the development and evolution of fatty liver but not to insulin resistance. The aim of this study isto evaluate the relationships between PNPLA3 and fatty liver, metabolic syndrome and subclinical atherosclerosis. Materials and Methods: The study group consisted of patients with type 2 diabetes mellitus without insulin treatment. The degree of liver fat loading was assessed by ultrasonography, and subclinical atherosclerosis was assessed using carotid intima-media thickness (CIMT). PNPLA3 rs738409 genotype determination was performed by high-resolution melting analysis that allowed three standard genotypes: CC, CG, and GG. Results: Among the 92 patients, more than 90% showed various degrees of hepatic steatosis, almost 62% presented values over the normal limit for the CIMT. The majority of the included subjects met the criteria for metabolic syndrome. Genotyping of PNPLA3 in 68 patients showed that the difference between subjects without steatosis and subjects with hepatic steatosis was due to the higher frequency of genotype GG. The CC genotype was the most common in the group we studied and was significantly more frequent in the group of subjects with severe steatosis; the GG genotype was significantly more frequent in subjects with moderate steatosis; the frequency of the CG genotype was not significantly different among the groups.When we divided the group of subjects into two groups: those with no or mild steatosis and those with moderate or severe steatosis it was shown that the frequency of the GG genotype was significantly higher in the group of subjects with moderate or severe steatosis. PNPLA3 genotypes were not associated with metabolic syndrome, subclinical atherosclerosis, or insulin resistance. Conclusions: Our results suggest that PNPLA3 does not independently influence cardiovascular risk in patients with type 2 diabetes mellitus. The hypothesis that PNPLA3 may have a cardioprotective effect requires future confirmation.


Transcranial direct current stimulation combined with peripheral stimulation in chronic pain: a systematic review and meta-analysis.
The combination of Transcranial Direct Current Stimulation (tDCS) with peripheral stimulation may optimize their effects and bring positive results in treatment of people with chronic pain. A systematic review with meta-analysis of randomized and non-randomized trials was performed to investigate the combination of tDCS with peripheral stimulation in adults with chronic pain. The primary outcome was pain intensity. Six studies were included in this review (sample of 228 participants), which investigated the combination of tDCS and transcutaneous electrical nerve stimulation, peripheral electrical stimulation, breathing-controlled electrical stimulation and intramuscular electrical stimulation. The conditions studied were knee osteoarthritis, spinal cord injury, chronic low back pain, and neurogenic pain of the arms. Pain intensity, measured by visual analog scale or numerical rating scale, was reduced in all included studies when at least one of the interventions was active, regardless they were combined or alone, with or without tDCS. However, meta-analysis showed superiority of tDCS used in combination with peripheral stimulation. This systematic review and meta-analysis suggests positive effects of tDCS combined with peripheral stimulation in chronic pain conditions. However, the evidence of the primary outcome was classified as low quality due to the limited number of studies.


Prognostic Impact of Atrial Fibrillation in Electrical Storm.
Data regarding the prognostic impact of atrial fibrillation (AF) in patients with electrical storm (ES) is rare. This study sought to assess the prognostic impact of AF in patients with ES on mortality, rehospitalization, major adverse cardiovascular events (MACE) and recurrence of ES (ES-R). All consecutive implantable cardioverter defibrillator (ICD) patients presenting with ES were included retrospectively from 2002 to 2016. Patients with AF were compared to non-AF patients. The primary prognostic endpoint was all-cause mortality. Secondary endpoints were in-hospital mortality, rehospitalization rates, MACE and ES-R. A total of 87 ES patients with ICD were included and followed up to 2.5 years; 43% suffered from AF. The presence of AF was associated with increased all-cause mortality (47 vs. 29%, log-rank p = 0.052; hazard ratio [HR] 1.969, 95% confidence interval [CI] 0.981-3.952, p = 0.057), which was no longer present after multivariable adjustment for age, diabetes and dilated cardiomyopathy. Furthermore, AF was associated with increased rates of overall rehospitalization (61 vs. 31%, log-rank p = 0.013; HR 2.381, 95% CI 1.247-4.547, p = 0.009), especially due to AF (14 vs. 0%, p = 0.001) and acute heart failure (AHF) (28 vs. 10%, p = 0.018; HR 3.754, 95% CI 1.277-11.038, p = 0.016). Notably, AF was not associated with differences in MACE (55 vs. 37%, log rank p = 0.339) and ES-R (28 vs. 25%, log rank p = 0.704). In ES patients, presence of AF was univariably associated with increased rates of all-cause mortality at 2.5 years. Furthermore, AF was multivariably associated with overall rehospitalization, especially due to AF and AHF.


Alcohol consumption, ART usage and high-risk sex among women infected with HIV.
We examine the role of alcohol consumption on sexual risk behavior among a cohort of 187 sexually active HIV-infected women (aged 18-61) in care at an urban ambulatory clinic in New Orleans, Louisiana, U.S. Sexual risk behavior among women on and off antiretroviral therapy (ART) and the relationship between alcohol use, ART, and behavior was also explored. One-fourth of respondents were classified as binge drinkers and the average number of drinking occasions per week ranged from none to 10-12. Approximately 60% were prescribed ART and self-reported adherence was 90%. One-third of the women reported no condom use at last vaginal sex, 62% reported inconsistent condom use for vaginal sex, and 7% had multiple male sex partners in the last month. Binge alcohol users and women on ART were significantly more likely to participate in each sexual risk outcome examined. Partner refusal of condom use was also significantly associated with binge drinking patterns. Results lend strength to the equivocal literature on the relationship between both alcohol and prescription of ART and sexual behavior. Enhanced detection of alcohol abuse, coupled with risk reduction counseling especially among women prescribed ART are important clinical practices in treating women with HIV.


Decane-1,10-diaminium dinitrate.
The crystal structure of the title compound, C(10)H(26)N(2) (2+)·2NO(3) (-), exhibits a back-to-back paired double-stacked packing arrangement culminating in an overall double zigzag pattern of the dications. Each pair of double-stacked dications is surrounded by a ring of ten nitrate anions. An intricate three-dimensional N---H...O and N---H...(O,O) hydrogen-bonding network exists in the crystal structure.


Male but not female Wistar rats show increased anxiety-like behaviour in response to bright light in the defensive withdrawal test.
The defensive withdrawal test (DWT) is used to model anxiety-like behaviour in rats. The aim of this study was to investigate whether an aversive stimulus, bright light, affects the behaviour in this test. Additionally, the effect of habituation to the apparatus was studied. Both male and female Wistar rats were used to study whether sex differences exist in the DWT, as reported for other tests of anxiety. On day 1 half of the rats were tested under low light and half under bright light. Two to seven days after trial one the same rats were repeatedly tested under the same light condition for five consecutive days. The male rats showed a higher degree of anxiety-like behaviour when tested under bright light than under low light. In contrast, the behaviour of the female rats was not affected by changes in illumination. Male rats also exhibited elevated anxiety-like behaviour compared to female rats under bright light, whereas under low light conditions no sex difference was seen. Males in low light habituated much faster than males tested under bright light, whereas in females there was little difference in habituation between low and bright light. In summary, we found that bright light is aversive for male but not female Wistar rats in the DWT. Whether this is due to sex differences in light sensitivity or if females respond with a different behavioural strategy in response to bright light, which could not be detected in the DWT, remains to be elucidated.


Efficiency dilution: long-term exergy conversion trends in Japan.
This analysis characterizes century-scale trends in exergy efficiency in Japan. Exergy efficiency captures the degree to which energy inputs (such as coal) are converted into useful work (such as electricity or power to move a vehicle). This approach enables the estimation of net efficiencies which aggregate different technologies. Sectors specifically analyzed are electricity generation, transport, steel production, and residential space heating. One result is that the aggregate exergy efficiency of the Japanese economy declined slightly over the last half of the 20th century, reaching a high of around 38% in the late 1970s and falling to around 33% by 1998. The explanation for this is that while individual technologies improved dramatically over the century, less exergy-efficient ones were progressively adopted, yielding a net stabilization or decline. In the electricity sector, for instance, adoption of hydropower was followed by fossil-fired plants and then by nuclear power, each technology being successively less efficient from an exergy perspective. The underlying dynamic of this trend is analogous to declining ore grades in the mining sector. Increasing demand for exergy services requires expended utilization of resources from which it is more difficult to extract utility (e.g., falling water versus coal). We term this phenomenon efficiency dilution.


Rapid identification of Bordetella avium and related organisms on the basis of their cellular carbohydrate patterns.
Whole cell hydrolysates of Bordetella avium, B. bronchiseptica, B. pertussis, B. parapertussis, Alcaligenes faecalis, A. xylosoxidans ssp. denitrificans, A. xylosoxidans ssp. xylosoxidans, and A. piechaudii were analysed for their cellular carbohydrates by capillary gas-chromatography of per-acetylated aldononitriles and O-methyloximes, respectively. All Alcaligenaceae species could be discriminated on the basis of their carbohydrate profiles and a few conventional features. Taxometric evaluation of the established carbohydrate patterns confirmed previous separation of the taxa and the genetic relatedness within the Alcaligenaceae. One of the advantages of the method is, that the analysis is easy to perform and can be completed within less than 5 h, starting from a pure culture and, therefore, it seems to be applicable as a rapid method in routine diagnostics.


Efficacy of surgical therapy for carotid body tumors.
To evaluate the efficacy of surgical therapy for carotid body tumors. A retrospective analysis was conducted, covering the diagnosis, surgical procedure, postoperative complications, and prognosis of 120 cases of carotid body tumors in Peking Union Medical College Hospital from 1949 to May, 2011. Surgical excision was successfully performed in 111 cases with 117 tumors. In all those cases, 50 underwent simple tumor resection, 42 underwent resection of tumors and ligation of the external carotid arteries, 7 underwent co-resection of tumors and common carotid arteries, internal carotid arteries, as well as external arteries without vascular reconstruction, and the other 12 cases experienced tumor resection and vascular reconstruction as internal carotid arteries were involved. After operation, 3 cases developed cerebral infarction, 30 cases showed cranial nerve palsy, including 15 cases of hypoglossal nerve damage, 10 cases of vagus paralysis, and 5 cases of Horner's syndrome. It is essential to make a proper surgical strategy, which can reduce postoperative complications.


External quality assessment of COVID-19 real time reverse transcription PCR laboratories in India.
Sudden emergence and rapid spread of COVID-19 created an inevitable need for expansion of the COVID-19 laboratory testing network across the world. The strategy to test-track-treat was advocated for quick detection and containment of the disease. Being the second most populous country in the world, India was challenged to make COVID-19 testing available and accessible in all parts of the country. The molecular laboratory testing network was augmented expeditiously, and number of laboratories was increased from one in January 2020 to 2951 till mid-September, 2021. This rapid expansion warranted the need to have inbuilt systems of quality control/ quality assurance. In addition to the ongoing inter-laboratory quality control (ILQC), India implemented an External Quality Assurance Program (EQAP) with assistance from World Health Organization (WHO) and Royal College of Pathologists, Australasia. Out of the 953 open system rRTPCR laboratories in both public and private sector who participated in the first round of EQAP, 891(93.4%) laboratories obtained a passing score of > = 80%. The satisfactory performance of Indian COVID-19 testing laboratories has boosted the confidence of the public and policy makers in the quality of testing. ILQC and EQAP need to continue to ensure adherence of the testing laboratories to the desired quality standards.


Composition-tuned Co(n)Si nanowires: location-selective simultaneous growth along temperature gradient.
We report the simultaneous and selective synthesis of single-crystalline Co(n)Si NWs (n = 1-3) and their corresponding crystal structures--simple cubic (CoSi), orthorhombic (Co(2)Si), and face-centered cubic (Co(3)Si)--following a composition change. Co(n)Si NWs were synthesized by placing the sapphire substrates along a temperature gradient. The synthetic process is a successful demonstration of tuning the chemical composition in Co(n)Si NWs. The synthesis and detailed crystal structure of single-crystalline Co(2)Si and Co(3)Si are reported for the first time including the bulk and the nanostructure phases. The electrical and magnetic properties of Co(2)Si NWs are investigated and compared with those of CoSi NWs.


Laboratory evaluation of the effect of compaction method and compaction work on the performance of SMA-13 mixture.
The influence of compaction methods such as the Marshall compaction method (MCM), vibration compaction method (VCM) and gyration compaction method (GCM), on the performance of stone mastic asphalt (SMA-13) mixture has yet to be explored. Therefore, to compare the influences of compaction methods and work on the physical and mechanical properties of SMA-13 mixture, the volume parameters, mechanical properties, and gradation changes of SMA-13 mixture specimens prepared under different vibration compaction times, Marshall double-compaction numbers, and gyration compaction numbers were studied. The compaction method for SMA-13 mixture design was also proposed under the principle of optimum properties. Results demonstrate that the asphalt aggregate ratio and compaction work directly affect the volumetric properties (VV, VFA, and VMA) of asphalt mixture specimens while the raw material and mineral aggregate gradation were fixed. The influence of compaction work on physical properties is greater than that of asphalt aggregate ratio. The mechanical strength of VCM and GCM specimens is higher than that of MCM specimens under the same compaction work and the optimum asphalt aggregate ratio. With the increase in compaction work, the mechanical properties of SMA-13 mixture are improved at the same compaction method and the optimum asphalt aggregate ratio. The aggregate gradation of the SMA-13 mixture before and after compacted using VCM and GCM changes minimally compared with that of the SMA-13 mixture compacted by MCM. Thus, the compaction methods of VCM65 and GCM130 were recommended for SMA-13 mixture design.


Highly selective and sensitive determination of dopamine using Nafion coated microelectrode arrays.
The present study concerns methodological issue of electrochemical recordings using Nafion-coated microelectrode arrays fabricated by MEMS technology for voltammetric and amperometric measurements of dopamine (DA). The properties of Nafion-coated different temperature dried microelectrodes were determined by cyclic voltammetry. The electrochemical characteristics of the 120 degrees C dried Nafion-coated microelectrode for measures of dopamine and ascorbic acid (AA) were studied by chronoamperometry. These studies showed that the 120 degrees C dried Nafion-coated microelectrode had better recording properties: enlarged electrochemical signal for DA and high selectivity for DA versus AA. The linear response was obtained in the range of 0.1 to 50 microM with a low detection limit. The modified microelectrode arrays providing 30 microm diameter multiple sites showed the capability to simultaneously detect DA from cells, neurons and brain slices.


[Value of diagnostic methods in conduction disorders for pacemaker indications and choice of a suitable stimulation mode].
Sinus node syndrome: In patients with sinus node dysfunction, additional conduction disturbances may be present in the AV-node thereby precluding the possibility for basically-desirable atrial stimulation. Systematic electrophysiologic studies have shown that, overall, conduction disturbances are uncommon, albeit more frequently than in normal subjects and most are incurred a high rate of stimulation. In practice, invasive electrophysiologic studies are not required to clarify this question. If there is no high-grade AV-block on Holter monitoring, diagnostic atrial stimulation can be carried out at the time of pacemaker implantation via the atrial electrode. A low rate should be used initially then increased gradually. On 1:1 conduction to 130 to 140 b/min permanent atrial pacing is possible since under these conditions it is very unlikely that high-grade AV-block will occur. If AV-block is observed at an atrial rate of 130 b/min, an additional ventricular electrode for two-chamber pacing should be implanted. If there is intact retrograde ventriculo-atrial (V-A) conduction, isolated ventricular stimulation should not be carried out because of the possibility of hemodynamically-unfavorable pacemaker syndrome. Possible problems with intact V-A conduction currently have only negligible importance since the development of modern programmable two-chamber systems. Carotid sinus syndrome: On manipulation of the hypersensitive carotid sinus, the invariably-present functional compromise of the AV-node is masked by the marked bradycardia but can be detected by atrial stimulation. This examination is not routinely necessary however, since in carotid sinus syndrome isolated atrial stimulation is not carried out.(ABSTRACT TRUNCATED AT 250 WORDS)


High-level expression of adeno-associated virus (AAV) Rep78 or Rep68 protein is sufficient for infectious-particle formation by a rep-negative AAV mutant.
Adeno-associated virus (AAV) codes for four closely related nonstructural proteins (Rep) required for AAV DNA replication and gene regulation. In vitro studies have revealed that either Rep78 or Rep68 alone is sufficient for AAV DNA replication. Rep52 and Rep40 are not required for DNA replication but have been reported to enhance the efficiency of accumulation of single-stranded progeny DNA. Previous studies on rep-expressing cell lines had indicated that only a subset of the four Rep proteins are required for the production of infectious AAV. We therefore set out to determine the minimal set of Rep proteins sufficient for the generation of infectious AAV. Transient cotransfections in HeLa cells of constructs for high-level expression of individual Rep proteins with a rep-negative AAV genome revealed that either Rep78 or Rep68 alone could complement for a full replication cycle yielding infectious virus. This result was confirmed by transfection studies in the cell line HeM2, which selectively expresses Rep78 at rather low levels under the control of the glucocorticoid-responsive mouse mammary tumor virus long terminal repeat (C. Hölscher, M. Hörer, J. A. Kleinschmidt, H. Zentgraf, A. Bürkle, and R. Heilbronn, J. Virol. 68:7169-7177, 1994). Increasing the level of Rep78 expression by transfection of a glucocorticoid receptor expression construct resulted in a higher level of DNA replication of a cotransfected rep-negative AAV genome and in the production of infectious rep-negative AAV particles. We further report on the generation of a new rep-expressing cell line, HeCM1, which was obtained by stable supertransfection of a construct for constitutive Rep40 expression into HeM1 cells (Hölscher et al., J. Virol. 68:7169-7177). Transfection of rather large amounts of rep-negative AAV DNA led to detectable virus production in HeCM1 cells even in the absence of the cotransfected glucocorticoid receptor expression construct, but higher yields were obtained after increasing the Rep78 level by coexpression of the glucocorticoid receptor. These data demonstrate that all Rep functions required for the productive replication of AAV in HeLa cells are contained within both Rep78 and Rep68.


Drug-resistant Nocardia asteroides infection in a patient with acquired immunodeficiency syndrome.
We have reported what we believe to be the first case of disseminated infection due to a multiply drug resistant strain of Nocardia asteroides in a patient with the acquired immunodeficiency syndrome and concomitant disseminated histoplasmosis. This strain of the organism fits a pattern of susceptibility that is rare among N asteroides isolates in general and has been called the type 5 pattern, described as a resistance to broad spectrum cephalosporins, ciprofloxacin, and all aminoglycosides except amikacin. The recognition of disease due to this group of organisms is especially important in patients with AIDS because sulfonamides, considered the drugs of choice for treatment of N asteroides infection, are associated with a high incidence of adverse effects in these patients.


Sexuality: a challenge for nursing practice.
Nursing has made significant progress towards individualised, holistic patient care. Yet caring for patients who have concerns about sexuality and body image remains a challenge, despite considerable literature on the subject. This article explores reasons for this and suggests learning exercises to enable nurses to examine their own attitudes to body image and sexuality.


Prostaglandin E2, thromboxane B2, and leukotriene B4 release from peritoneal macrophages by different osmotic agents in nonuremic guinea pigs.
Interleukin-1 (Il-1), prostaglandins, and leukotrienes have been identified as inflammatory parameters in the setting of peritoneal dialysis. Recently, it was postulated that chronic overstimulation of peritoneal macrophages (PM) may result in fibrosis and loss of ultrafiltration. The aim of the present study was to investigate whether alternative osmotic agents (polyglucose, amino acids, glycerol, bicarbonate/glucose, gelatine, hydroxyethyl starch) provoke greater eicosanoid release by PMs than glucose. Fifty milliliters of sterile dialysate containing different osmotic agents were injected intraperitoneally into nonuremic guinea pigs. After 4 hours of dwell time, prostaglandin E2 (PGE2), thromboxane B2 (TXB2), and leukotriene B4 (LTB4) production was analyzed in peritoneal effluents using specific radioimmunoassays (RIA) after liquid extraction. Cyclooxygenase products were generated with all osmotic agents: PGE2 concentrations ranged from 0.9 to 2.8 ng/4h, and TXB2 levels ranged from 39 to 49 ng/4h. In addition, the lipoxygenase product LTB4 was found in concentrations between 1.8 and 3.5 ng/4h. There were no significant differences in eicosanoid release among the osmotic agents. Thus, in this experimental setting, the capacity of PM to release inflammatory mediators did not correlate with the chemical composition of the dialysis solutions.


Dye-induced stabilization of bleached holograms.
A number of organic dyes have been found to be capable of desensitizing AgBr phase holograms against printout darkening by the light of an argon ion laser. The greatest lifetime extensions observed to date are approximately 500% and 3300% for 488 nm and 515 nm irradiation, respectively, referred to control samples produced by a bleaching process reported to give high stability. The most successful desensitizing dyes showed negligible absorption of the laser light.


Criminal poisoning of commuters in Bangladesh: prospective and retrospective study.
Travel-related poisoning is an emerging social and public health emergency in Bangladesh but its cause and significance have not been determined. To investigate this syndrome we performed a prospective clinical study and retrospective analysis of hospital records in a general medicine unit of a public tertiary care teaching hospital in Dhaka, Bangladesh, using toxicological analysis by fluorescence polarization immunoassay (FPIA) and liquid chromatography coupled to time-of-flight mass spectrometry (LC-TOF MS). The participants of the prospective study were 130 consecutive patients aged 16-80 years who were admitted with central nervous system depression (Glasgow Coma Score 3-14) after using public transportation, in the absence of other abnormalities, from January through June 2004, and a convenience sample of 15 such patients admitted during 3 days in May 2006. In 2004-2006, travel-related poisoning increased from 6.1 to 9.5% of all admissions (210-309 of 3266-3843 per year), representing 46.6-55.7% of all admitted poisoning cases. Incidents were associated with bus (76%), taxi, train, and air travel, or local markets; 98% of patients remembered buying or accepting food or drinks before losing consciousness. Direct financial damage (missing property) was diverse and frequently existential. Among 94 urine samples analyzed by FPIA, 74% tested positive for benzodiazepines. Among 15 urine samples analyzed by LC-TOF MS, lorazepam was detected in all; five also contained diazepam or metabolites; nitrazepam was present in three. FPIA results obtained for these 15 samples were below the recommended cut-off in eight (53%; lorazepam only). Our findings show that the massive medicosocial emergency of travel-related poisoning in Bangladesh is the result of drug-facilitated organized crime and that benzodiazepine drugs are used to commit these crimes, suggesting modifications to the local emergency management of the victims of this type of poisoning. They also highlight the need for more research in the neglected field of acute poisoning in Bangladesh, and for criminal investigations of the use of benzodiazepine drugs in this country.


The ovarian hyperstimulation syndrome in in-vitro fertilization: a Belgian multicentric study. II. Multiple discriminant analysis for risk prediction.
The considerable overlap of distributions of values for different parameters between control and ovarian hyperstimulation syndrome (OHSS) populations makes any single variable inefficient for risk prediction. Combinations of variables were studied in a discriminant function in order to increase predictivity and decrease the false negative rate. Such analyses were performed on two groups of in-vitro fertilization (IVF) patients: all OHSS cases (n = 128) (group A) and only severe OHSS cases (n = 92) (group B). Progressive introduction and automated stepwise selection of variables were applied to both groups. The best prediction (78.5%) was obtained in group A under post-oocyte retrieval conditions using log oestradiol, slope of log oestradiol increment, human menopausal gonadotrophin (HMG) dosage, number of oocytes retrieved and ratio of luteinizing hormone/follicle stimulating hormone (LH/FSH), in the formula. The corresponding false negative rate was 18.1%. However, effective prevention of OHSS implies the ability to withhold human chorionic gonadotrophin injection. Therefore a formula for pre-oocyte retrieval conditions was established yielding a prediction rate of 76.1% with a false negative rate of 18.1%. To be validated, such formulae have to be applied to another population of IVF cases used as a 'testing-set'.


Syphilis is a Rare Cause of Erythema Nodosum: A Case Report.
Erythema nodosum (EN) is a dermatological manifestation, the common etiologies of which are already widely described. Here, we report the case of a patient who presented an EN, where the etiology was found to be a rare diagnosis: syphilis, a sexually transmitted infection with various clinical presentations. A 42-year-old female patient without any medical condition presented with a clinical picture associating a maculopapular rash at first, and later on a well-defined hypodermic lesion, clinically suggestive of an EN, on the right forearm. The etiologic workup ruled out sarcoidosis, which was the first suspected diagnosis. Positive VDRL-TPHA and recovery within 15 days after benzathine benzylpenicillin administration allowed the diagnosis of syphilis to be made on the EN. EN is a rare manifestation of syphilis that should be kept in mind in these times of strong recrudescence of the disease among men who have sex with men in mainland France but also among heterosexuals in Reunion Island.


Halonium-initiated C-O bond formation via umpolung of α-carbon to the carbonyl: efficient access to 5-amino-3(2H)-furanones.
Highly efficient C-O bond formation has been developed via carboxylic acid catalyzed reaction of 1-acetylcyclopropanecarboxamides with N-halosuccinimide (NXS), which provides strategically novel and atom-economic access to biologically important 5-amino-3(2H)-furanones. The mechanism of halonium-initiated tandem oxa-cyclization and ring opening of cyclopropane was proposed. A variety of nucleophiles were found to open the cyclopropane.