Enhanced tumor localization of radiolabeled Fab fragments of monoclonal antibody A7 in nude mice bearing human pancreatic carcinoma xenografts.
Much recent research has been directed toward the use of monoclonal antibodies (MAb) for the immunodetection of solid tumors. In pancreatic cancer, the results of conventional immunoscintigraphy using intact MAb remain disappointing. Clear immunoscintigraphy with radiolabeled MAb requires a high tumor tissue/blood ratio of radioactivity and a low normal tissue/blood ratio of radioactivity. In this study, 125I-labeled Fab fragments produced by papain digestion of MAb A7 were injected intravenously into nude mice bearing a human pancreatic cancer (HPC-YS) xenograft previously shown to react specifically with MAb A7. The radioactivity of tumors and normal organs was subsequently measured. The tumor tissue/blood ratio of 125I-labeled Fab fragments of MAb A7 was 1.00 +/- 0.24 and 9.68 +/- 2.54 at 2 and 24 h after injection, respectively. The tumor tissue/blood ratio of radioactivity was significantly higher than those of normal organs at 24 h after injection. Moreover, the tumor tissue/blood ratio of 125I-labeled Fab fragments of MAb A7 was greater than that of intact MAb A7, although the 125I-labeled Fab accumulation level was much less than that of 125I-labeled intact MAb A7 in the tumor. When mice bearing tumors which did not react with MAb A7 were studied, 125I-labeled Fab fragments did not specifically localize to the tumors. These results suggest that Fab fragments of MAb A7 may be suitable carriers of radionuclides for the immunodetection of human pancreatic cancer.


Limited Cross-Variant Immunity after Infection with the SARS-CoV-2 Omicron Variant Without Vaccination.
SARS-CoV-2 Delta and Omicron strains are the most globally relevant variants of concern (VOCs). While individuals infected with Delta are at risk to develop severe lung disease 1 , Omicron infection causes less severe disease, mostly upper respiratory symptoms 2,3 . The question arises whether rampant spread of Omicron could lead to mass immunization, accelerating the end of the pandemic. Here we show that infection with Delta, but not Omicron, induces broad immunity in mice. While sera from Omicron-infected mice only neutralize Omicron, sera from Delta-infected mice are broadly effective against Delta and other VOCs, including Omicron. This is not observed with the WA1 ancestral strain, although both WA1 and Delta elicited a highly pro-inflammatory cytokine response and replicated to similar titers in the respiratory tracts and lungs of infected mice as well as in human airway organoids. Pulmonary viral replication, pro-inflammatory cytokine expression, and overall disease progression are markedly reduced with Omicron infection. Analysis of human sera from Omicron and Delta breakthrough cases reveals effective cross-variant neutralization induced by both viruses in vaccinated individuals. Together, our results indicate that Omicron infection enhances preexisting immunity elicited by vaccines, but on its own may not induce broad, cross-neutralizing humoral immunity in unvaccinated individuals.


Palpitations and lifestyle: impact of depression and self-rated health. The Nordland Health Study.
On the basis of a questionnaire in a population study in the county of Nordland, Norway, the prevalence of palpitations and its associations to some lifestyle factors, depression and self-rated health were analysed. All the 10,497 residents aged 40 to 42 years were invited to participate, 82% attended, 87% of the attenders returned a questionnaire by mail, and 6436 subjects were included in this report. The prevalence of palpitations was 15% in men and 25% in women. Palpitations were significantly associated with coffee consumption, smoking, alcohol intoxication, physical inactivity, depression and poor self-rated health in the univariate analyses. In a logistic regression analysis, the relations between palpitations and lifestyle were weakened. Significant predictors for palpitations were depression and poor self-rated health in both sexes, in addition to heavy coffee drinking and physical inactivity in men and alcohol intoxication in women. In conclusion, palpitations were more firmly linked to depression and self-evaluated health than to lifestyle.


What Therapeutic Regimen Will Be Optimal for Initial Clinical Trials of Pig Organ Transplantation?
We discuss what therapeutic regimen might be acceptable/successful in the first clinical trial of genetically engineered pig kidney or heart transplantation. As regimens based on a calcineurin inhibitor or CTLA4-Ig have proved unsuccessful, the regimen we administer to baboons is based on induction therapy with antithymocyte globulin, an anti-CD20 mAb (Rituximab), and cobra venom factor, with maintenance therapy based on blockade of the CD40/CD154 costimulation pathway (with an anti-CD40 mAb), with rapamycin, and a corticosteroid. An anti-inflammatory agent (etanercept) is administered for the first 2 wk, and adjuvant therapy includes prophylaxis against thrombotic complications, anemia, cytomegalovirus, and pneumocystis. Using this regimen, although antibody-mediated rejection certainly can occur, we have documented no definite evidence of an adaptive immune response to the pig xenograft. This regimen could also form the basis for the first clinical trial, except that cobra venom factor will be replaced by a clinically approved agent, for example, a C1-esterase inhibitor. However, none of the agents that block the CD40/CD154 pathway are yet approved for clinical use, and so this hurdle remains to be overcome. The role of anti-inflammatory agents remains unproven. The major difference between this suggested regimen and those used in allotransplantation is the replacement of a calcineurin inhibitor with a costimulation blockade agent, but this does not appear to increase the complications of the regimen.


Paternal Uniparental Disomy of the Entire Chromosome 20 in a Child with Beckwith-Wiedemann Syndrome.
Epigenetic alterations at imprinted genes on different chromosomes have been linked to several imprinting disorders (IDs) such as Beckwith-Wiedemann syndrome (BWS) and pseudohypoparathyroidism type 1b (PHP1b). Here, we present a male patient with these two distinct IDs caused by two independent mechanisms-loss of methylation (LOM) at chromosome 11p15.5 associated with multi-locus imprinting disturbances (MLID and paternal uniparental disomy of chromosome 20 (patUPD20). A clinical diagnosis of BWS was made based on the clinical features of macrosomia, macroglossia, and umbilical hernia. The diagnosis of PHP1b was supported by the presence of reduced growth velocity and mild learning disability as well as hypocalcemia and hyperphosphatemia at 14 years of age. Molecular analyses, including genome-wide DNA methylation (Illumina 450k array), bisulfite pyrosequencing, single nucleotide polymorphism (SNP) array and microsatellite analysis, demonstrated loss of methylation (LOM) at IC2 on chromosome 11p15.5, and paternal isodisomy of the entire chromosome 20. In addition, imprinting disturbances were noted at the differentially methylated regions (DMRs) associated with DIRAS3 on chromosome 1 and PLAGL1 on chromosome 6. This is the first case report of PHP1b due to patUPD20 diagnosed in a BWS patient with LOM at IC2 demonstrating etiologic heterogeneity for multiple imprinting disorders in a single individual.


[Study on HPV infection and p53 protein expression in laryngeal carcinoma].
In order to evaluate the role of human papillomavirus (HPV) infection and p53 protein expression in laryngeal squamous cell carcinoma (LSCC), the in situ hybridization and the labelled streptavidin biotin (LSAB) immunohistochemical method were used to detect the presence of HPV genomes 6B, 11, 16, 18 and expression of p53 protein respectively in 44 specimens of LSCC. And 16 specimens of laryngeal polyp were selected as controls. 1. HPV genomes 16/18 were detected in 19 (43.2%) of 44 LSCCs and in 2 (12.5%) of 16 laryngeal polyps (P < 0.05). 2.25 (56.9%) of 44 specimens of LSCC were p53 protein positive whereas the laryngeal polyps were all p53 negative. 3. 12 (63.2%) of 19 HPV 16/18 DNA-positive specimens of LSCC showed p53 protein expression and 12 (48%) of 25 p53 protein positive specimens of LSCC showed HPV 16/18 infection. Expression of p53 protein and infection of HPV 16, 18 may play a role in carcinogenesis of LSCC, respectively or simultaneously.


[To improve minimally invasive gastrointestinal surgery based on high quality in China].
Laparoscopic surgery for gastrointestinal diseases had a remarkable achievement in the past 20 years. To ensure the high quality of minimally invasive gastrointestinal surgery, several issues should be addressed, including correct guidelines and standard based on the consensus, high quality evidence from multi-center randomized control studies, proper training system for the technique, and constant innovations to improve the technique. We believe that with the great efforts of gastrointestinal surgeons, the minimally invasive gastrointestinal surgery in China is promising in the near future.


Detailed theoretical investigation of bending properties in solid-core photonic bandgap fibers.
In this paper, detailed properties of bent solid-core photonic bandgap fibers (SC-PBGFs) are investigated. We propose an approximate equivalent straight waveguide (ESW) formulation for photonic bandgap (PBG) edges, which is convenient to see qualitatively which radiation (centripetal or centrifugal radiation) mainly occurs and the impact of bend losses for an operating wavelength. In particular, we show that cladding modes induced by bending cause several complete or incomplete leaky mode couplings with the core mode and the resultant loss peaks. Moreover, we show that the field distributions of the cladding modes are characterized by three distinct types for blue-edge, mid-gap, and red-edge wavelengths in the PBG, which is explained by considering the cladding Bloch states or resonant conditions without bending. Next, we investigate the structural dependence of the bend losses. In particular, we demonstrate the bend-loss dependence on the number of the cladding rings. Finally, by investigating the impacts of the order of PBG and the core structure on the bend losses, we discuss a tight-bending structure.


Conductive and antimicrobial macroporous nanocomposite hydrogels generated from air-in-water Pickering emulsions for neural stem cell differentiation and skin wound healing.
Electro-active conducting hydrogels have shown promising applications in promoting soft tissue regeneration. However, achieving good conductive performance while simultaneously imparting macroporous structures to these hydrogels still remains challenging. In this study, we report the development of multifunctional conductive macroporous nanocomposite hydrogels (MNHs) prepared by an air-in-water emulsion template that is stabilized by colloidal hybrids of carbon nanotubes (CNTs) and gelatin methacryloyl. The MNH hydrogels demonstrated tunable pore size, electrical conductivity and mechanical properties with various CNT concentrations in the crosslinking matrices. An in vitro cell assay showed that the MNH hydrogels could promote the spreading and differentiation of NE-4C neural stem cells. Furthermore, sustainable release of antimicrobial peptides (AMPs) from the MNH hydrogel can be achieved and the released AMPs maintained high S. aureus killing activity. An in vivo evaluation of the MNH hydrogel using a murine dorsal skin model further showed that the conductive MNH hydrogel loaded with AMPs demonstrated appealing antimicrobial and wound healing performance in two weeks.


Oxazolidine Nitroxide Transformation in a Coordination Sphere of the Ln3+ Ions.
Upon the interaction of the hydrated lanthanide(III) salts found in acetonitrile solution with a tripodal paramagnetic compound, 4,4-dimethyl-2,2-bis(pyridin-2-yl)-1,3-oxazolidine-3-oxyl (Rad), functionalized by two pyridyl groups, three neutral, structurally characterized complexes with diamagnetic polydentate ligands-[Dy(RadH)(hbpm)Cl2], [Yb2(ipapm)2(NO3)4], and [Ce2(ipapm)2(NO3)4(EtOAc)2]-were obtained. These coordination compounds are minor uncolored crystalline products, which were formed in a reaction mixture due to the Rad transformation in a lanthanide coordination sphere, wherein the processes of its simultaneous disproportionation, hydrolysis, and condensation proceed differently than in the absence of Ln ions. The latter fact was confirmed by the formation of the structurally characterized product of the oxazolidine nitroxide transformation during its crystallization in toluene solution. Such a conversion in the presence of 4f elements ions is unique since no similar phenomenon was observed during the synthesis of the 3d-metal complexes with Rad.


Iron-sulfur clusters: biogenesis, molecular mechanisms, and their functional significance.
Iron-sulfur clusters [Fe-S] are small, ubiquitous inorganic cofactors representing one of the earliest catalysts during biomolecule evolution and are involved in fundamental biological reactions, including regulation of enzyme activity, mitochondrial respiration, ribosome biogenesis, cofactor biogenesis, gene expression regulation, and nucleotide metabolism. Although simple in structure, [Fe-S] biogenesis requires complex protein machineries and pathways for assembly. [Fe-S] are assembled from cysteine-derived sulfur and iron onto scaffold proteins followed by transfer to recipient apoproteins. Several predominant iron-sulfur biogenesis systems have been identified, including nitrogen fixation (NIF), sulfur utilization factor (SUF), iron-sulfur cluster (ISC), and cytosolic iron-sulfur protein assembly (CIA), and many protein components have been identified and characterized. In eukaryotes ISC is mainly localized to mitochondria, cytosolic iron-sulfur protein assembly to the cytosol, whereas plant sulfur utilization factor is localized mainly to plastids. Because of this spatial separation, evidence suggests cross-talk mediated by organelle export machineries and dual targeting mechanisms. Although research efforts in understanding iron-sulfur biogenesis has been centered on bacteria, yeast, and plants, recent efforts have implicated inappropriate [Fe-S] biogenesis to underlie many human diseases. In this review we detail our current understanding of [Fe-S] biogenesis across species boundaries highlighting evolutionary conservation and divergence and assembling our knowledge into a cellular context.


Rural children's attitudes to people with HIV/AIDS in Mali: the causes of stigma.
Qualitative research among young people and other community members in rural Mali elicited knowledge and attitudes with regard to HIV/AIDS. Findings indicated that rumours concerning methods of infection are likely to increase the stigmatization of those with the disease. The most frequently stated mode of transmission involved urinating in a place where someone with AIDS had already urinated. Shared clothes, food and water were seen as sources of infection. Both children and teachers recommended that people with AIDS be isolated. Even talking to them would lead to a risk of infection. Discriminatory views were likely to have been reinforced by parents and community elders who possessed the same misinformation. The notion that AIDS results from sexual encounters between young women and dogs belonging to white people in Côte d'Ivoire was also widespread. These discourses may reflect perceived xenophobia and risk to migrants associated with current tensions between the two countries, together with misgivings about Western sexual liberalism. A holistic educational programme is proposed to address not simply HIV/AIDS, but the social context in which infection occurs, with view to combating stigma and discrimination associated with not just HIV but also with migration in this setting.


Use of high-volume haemodiafiltration in patients with refractory septic shock and acute kidney injury.
High-volume haemofiltration (HVHF) has been used successfully in animal models with sepsis, and preliminary data have shown that this technique may improve the haemodynamics in patients with refractory septic shock. We used high-volume continuous venovenous haemodiafiltration (CVVHDF) in patients with acute kidney injury (AKI) and refractory septic shock to evaluate their outcome when compared with their prognosis predicted by scores of severity. This is a cohort study in a Medical and Surgical Intensive Care Unit. Fifty-five patients with refractory septic shock and AKI were included in the study. High-volume CVVHDF was started in patients with AKI and septic shock requiring norepinephrine dose >0.2 µg/kg/min. AKI was classified according to the RIFLE criteria. Treatment was implemented within the first 24 h of refractory septic shock with a dialysis dose of 70 mL/kg/h until reversal of shock or death. Fifty-five patients were treated with high-volume CVVHDF with an observed mortality of 63%, similar to the mortality predicted by the APACHE II and SAPS II scores. Survival rate in our patients with AKI and refractory septic shock treated with high-volume CVVHDF was identical to survival predicted by the severity scores. Treatment with high-volume haemodiafiltraton is applicable to severely ill patients with septic shock but does not confer any clear advantage in terms of survival. This therapy should not be implemented on a routine basis in patients with AKI and refractory septic shock.


Structural organization and chromosomal assignment of the swine endothelin-1 gene.
Cosmid clone containing swine endothelin-1 (EDN1) gene, cosEDN1, was isolated from swine cosmid library using swine EDN1 cDNA as a probe. The sequence analysis of cosEDN1 DNA revealed that the swine EDN1 gene consists of 5 exons, spanning approximately 6.5 kb. In the 5'-upstream region of the EDN1 gene, AP-1 and NF-1 elements were found, suggesting the possibility that the expression of swine EDN1 gene is controlled by protooncogene products Fos and Jun, and TGF-beta. Fluorescence in situ hybridization (FISH) using cosEDN1 DNA as a probe demonstrated that EDN1 gene resides on swine chromosome 7p13- > pter.


Myocardial Dysfunction Is Independently Associated With Mortality in Pediatric Septic Shock.
Circulatory dysfunction has been associated with mortality in children with septic shock. However, the mortality risk attributable to myocardial dysfunction per se has not been established, and the association between myocardial dysfunction and mortality is confounded by illness severity. The objective was to determine if sepsis-associated myocardial dysfunction defined by low left ventricular ejection fraction or global longitudinal strain is associated with mortality in pediatric septic shock after adjusting for baseline mortality probability. Retrospective, observational study. Single-center, quaternary-care PICU. Children less than 18 years old admitted to the PICU from 2003 to 2018 who had an echocardiogram performed within 48 hours of septic shock identification and Pediatric Sepsis Biomarker Risk Model II data available. None. All echocardiograms were reread by a cardiologist blinded to patient data for left ventricular ejection fraction and global longitudinal strain. Low left ventricular ejection fraction was defined as less than 45%, and low global longitudinal strain was defined as greater than z score of -2 for body surface area. Multivariable logistic regression separately analyzed the associations of low left ventricular ejection fraction and low global longitudinal strain with mortality, adjusting for Pediatric Sepsis Biomarker Risk Model II mortality risk. A post hoc logistic regression analyzed the association of left ventricular ejection fraction as a continuous variable with mortality, where linearity was maintained for left ventricular ejection fraction less than 65%. Eighteen percent of 181 children had low left ventricular ejection fraction. After adjusting for baseline mortality risk, low left ventricular ejection fraction remained independently associated with mortality (odds ratio, 4.4 [1.0-19.8]; p = 0.0497). Likewise, left ventricular ejection fraction was associated with mortality (odds ratio, 0.96 [0.93-0.99]; p = 0.037) on multivariable analysis for left ventricular ejection fraction less than 65%. Thirty-six percent of 169 children had low global longitudinal strain, and low global longitudinal strain was also independently associated with mortality (odds ratio, 4.6 [1.2-18.0]; p = 0.027). Sepsis-associated myocardial dysfunction, whether defined by low left ventricular ejection fraction or low global longitudinal strain, is an independent risk factor for mortality in pediatric septic shock after accounting for the confounding effects of septic shock severity.


A novel use of AIDS surveillance data to assess the impact of initial treatment regimen on survival.
The expense in time and money limit the use of randomized clinical trials (RCT) and cohort studies for evaluating long-term AIDS treatment outcomes. We conducted a case-control study to characterize predictors of AIDS mortality after the availability of highly active antiretroviral therapy (HAART) in San Francisco, in which cases were matched with controls on stage of disease, year of AIDS diagnosis and year of HAART initiation. Overall, 266 cases and 1173 controls were included, representing >90% of eligible patients. The class of initial HAART regimen was not associated with mortality. Predictors of mortality were older age ([adjusted odds ratio] AOR 1.23, 95% [confidence interval] CI: 1.13-1.35), public versus private health insurance (AOR 2.80, 95% CI: 1.77-4.42), no versus private insurance (AOR 1.45, 95% CI: 1.02-2.07) and unboosted saquinavir (AOR 2.50, 95% CI: 1.34-4.65). Survival benefit was found in following the 2004 US Department of Health and Human Services preferred treatment guidelines; borderline survival benefits were found in following the guidelines from other years. Similar predictors were found for all-cause and AIDS-specific mortality. Our findings mirrored those of RCT and multi-centre cohort studies, and may be applicable to other settings. Our findings support similar survival benefit to persons initiating HAART with non-nucleoside reverse transcriptase inhibitor- or protease inhibitor-based regimens.


Pain management at the end of life in a patient with renal failure.
Literature indicates that an essential element of a 'good' death is the absence of pain. Achieving a pain-free death for the patient who discontinues dialysis is a goal shared by patient, family and care providers. Pain management at end of life can be challenging, especially in the setting of renal failure. Aspects of assessment and pharmacological management of pain in the dying patient are explored through the use of a case study. Through investment in ongoing relationships with their patients, and striving to build knowledge and skills in pain management, nephrology nurses promote excellence in end-of-life patient care.


Phase stability of the ice XVII-based CO2 chiral hydrate from molecular dynamics simulations.
We computed the phase diagram of CO2 hydrates at high pressure (HP), from 0.3 to 20 kbar, by means of molecular dynamics simulations. The two CO2 hydrates known to occur in this pressure range are the cubic structure I (sI) clathrate and the HP hydrate, whose water framework is the recently discovered ice XVII. We investigated the stability of both hydrates upon heating (melting) as well as the phase changes upon compression. The CO2-filled ice XVII is found to be more stable than the sI clathrate and than the mixture of ice VI and dry ice at pressure values ranging from 6 to 18 kbar and in a wide temperature range, although a phenomenological correction suggests that the stability should more realistically range from 6.5 to 13.5 kbar. Our simulation results support the current hypothesis that the HP hydrate is stable at temperatures above the melting curve of ice VI.


Polyproline Peptide Aggregation with Klebsiella pneumoniae Extracellular Polysaccharides Exposes Biofilm Associated Bacteria.
Klebsiella pneumoniae produces a thick capsule layer composed of extracellular polysaccharides protecting the bacterial cells from clearance by innate host immunity during infection. Here we characterize the interactions of a structurally diverse set of host defense peptides with K. pneumoniae extracellular polysaccharides. Remarkably, we found that all host defense peptides were active against a diverse set of K. pneumoniae strains, including hypermucoviscous strains with extensive capsule production, and aggregated with extracted capsule. Interestingly, the polyproline peptide bac7 (1-35), was the most potent antimicrobial and induced the most capsule aggregation. In addition to capsule aggregation, we found that bac7 (1-35) could also disrupt pre-formed hypermucoviscous K. pneumoniae biofilm. Further analysis using scanning electron microscopy revealed the biofilm matrix of a hypermucoviscous strain is removed by bac7 (1-35) exposing associated bacterial cells. This is the first description of a host defense peptide interacting with capsular and biofilm extracellular polysaccharides to expose cells from a K. pneumoniae biofilm matrix and suggests that features of polyproline peptides may be uniquely suited for extracellular polysaccharide interactions. IMPORTANCE Klebsiella pneumoniae bacterial infections are a major threat to human health as mortality rates are steadily on the rise. A defining characteristic of K. pneumoniae is the robust polysaccharide capsule that aids in resistance to the human immune system. We have previously discovered that a synthetic peptide could aggregate with capsule polysaccharides and disrupt the capsule of K. pneumoniae. Here we describe that host defense peptides also aggregate with capsule produced from hypermucoviscous K. pneumoniae, revealing this mechanism is shared by natural peptides. We found the polyproline peptide bac7 (1-35) had the greatest antimicrobial activity and caused the most capsule aggregation. Interestingly, bac7 (1-35) also removed the biofilm matrix of hypermucoviscous K. pneumoniae exposing the associated bacterial cells. This is the first description of a polyproline peptide interacting with capsular and biofilm polysaccharides to expose cells from a K. pneumoniae biofilm matrix.


Prevention of fungal infection in transplantation.
Despite significant advances in the diagnosis, prevention, and treatment of fungal infection in transplant recipients, this infection complication remains a major cause of morbidity and mortality. Our understanding of the pathogenesis of the different fungal microorganisms has enabled us to identify patients at risk for such infections. While Candida infection remains a major complication in patients with intra-abdominal solid organ transplantations in which the bowel is surgically manipulated, Aspergillus infection remains the main fungal complication in lung transplantation recipients. The incidence of all types of fungal infection remains around 5-10%, while mortality following Aspergillus infection remains around 70%. Suppression of Candida growth at the time of surgical manipulation of the bowel should be the mainstay of prevention of this infection in intra-abdominal organ transplantation. Fluconazole is effective and relatively safe at 100-400 mg daily for the first 1-3 months post-liver transplantation. Prevention strategies toward Aspergillus infections remain elusive, but a number of manipulations, such as inhaled liposomal preparations post-organ transplantation or the preemptive use or universal prophylaxis of itraconazole are being validated. The next step is to determine the clinical value of molecular diagnostic techniques for the identification and preemptive therapy of patients at risk for the variety fungal infections.


Fluorophobic effect for building up the surface morphology of electrodeposited substituted conductive polymers.
During the past decade, several works display the electrochemical polymerization of fluorinated monomers as a highly efficient method (one-pot method, mild conditions, various morphologies) to obtain superhydrophobic or superoleophobic surfaces. Here, we point out the fluorinated tails not only are useful to increase both hydrophobicity and oleophobicity but also are involved in the formation of surface structurations: two necessary conditions for liquid dewetting. To support this assertion, a series of fluorinated pyrrole derivatives and their hydrocarbon homologues were synthesized and electrochemically deposited in the same conditions. Whereas hydrocarbon pyrroles give rise to smooth films, structured films are achieved from fluorinated pyrroles. The abundance of the surface structurations depends on the length of the fluorinated tail.


The vascular pathogenesis of gastroschisis: intrauterine interruption of the omphalomesenteric artery.
Recognition of the disruptive vascular nature of the structural defects associated with gastroschisis and an appreciation of the embryology of the umbilical region suggest that gastroschisis results from an intrauterine interruption of the omphalomesenteric artery. This mechanism accounts for the usual location of gastroschisis to the right of the umbilical cord, the integrity of the rectus muscles in affected children, and many of the clinically observed differences between gastroschisis and omphalocele. The vascular basis of this defect explains its negligible recurrence risk and should alert the clinician to the possibility of concomitant structural defects of a similar pathogenesis.


Dynamic HIV-1 genetic recombination and genotypic drug resistance among treatment-experienced adults in northern Ghana.
There have been hardly any reports on the human immunodeficiency virus type 1 (HIV-1) drug-resistance profile from northern Ghana since antiretroviral therapy (ART) was introduced over a decade ago. This study investigated prevailing HIV-1 subtypes and examined the occurrence of drug resistance in ART-experienced patients in Tamale, the capital of the Northern Region of Ghana. A cross-sectional study was carried out on HIV-infected adult patients receiving first-line ART. HIV viral load (VL) and CD4+ T-cell counts were measured. The pol gene sequences were analysed for genotypic resistance by an in-house HIV-1 drug-resistance test; the prevailing HIV-1 subtypes were analysed in detail.Results/Key findings. A total of 33 subjects were studied. Participants comprised 11 males (33.3 %) and 22 (66.7 %) females, with a median age of 34.5 years [interquartile range (IQR) 30.0-40.3]. The median duration on ART was 12 months (IQR 8.0-24). Of the 24 subjects successfully genotyped, 10 (41.7 %) viruses possessed at least one mutation conferring resistance to nucleoside or non-nucleoside reverse-transcriptase inhibitors (NRTIs/NNRTIs). Two-class drug resistance to NRTI and NNRTI was mostly detected (25 %, 6/24). The most frequent mutations were lamivudine-resistance M184V and efavirenz/nevirapine-resistance K103N. HIV-1 subtype CRF02_AG was predominant (79.2 %). Other HIV-1 subtypes detected were G (8.3 %), A3 (4.2 %) and importantly two (8.3 %) unique HIV-1 recombinant forms with CRF02_AG/A3 mosaic. HIV-1 shows high genetic diversity and on-going viral genetic recombination in the study region. Nearly 42 % of the patients studied harboured a drug-resistant virus. The study underscores the need for continued surveillance of HIV-1 subtype diversity; and of drug-resistance patterns to guide selection of second-line regimens in northern Ghana.


The pathogenesis of pterygia.
Pterygium is an active, invasive, inflammatory process, a key feature of which is focal limbal failure. In a two-stage process, "conjunctivalization" of the cornea occurs with tissue characterized by extensive chronic-inflammation, cellular proliferation, connective tissue remodeling, and angiogenesis. An understanding of this process has resulted in efforts aimed at limbal reconstruction, which is considered the gold standard for surgical care. Although good results have been obtained with other treatment methods, a long-term approach to follow-up with at least 5-year survival figures is desirable. Sophisticated analyses of the tear film and surface epithelium in patients with pterygium may help explain symptoms. The efficacy, at least in the short term, of nonsteroidal anti-inflammatory drugs in the treatment of inflamed pterygia has been confirmed. Corneal topographic analysis has shown that surgery reduces induced astigmatism and also causes subtle changes that may explain postsurgical improvements in vision.


The FDA's Approach to the Prescription Opioid Problem.
Our nation's ongoing prescription opioid abuse crisis, amounting to over 78 billion dollars in health and social costs annually,1 is a critical priority for the US Food and Drug Administration (FDA). As a part of our mission to support the safe and effective use of prescription medicines, the FDA is taking a fresh look at potential scientific and regulatory actions we can take to address this crisis.


Judgment, 2 September 1987.
The Court held that the defendant had discriminated against the plaintiff flight hostesses in violation of Article VI of the Constitution when it paid them less in unemployment benefits than it paid men. The Court rejected an argument that, since flight hostesses were paid less than male employees, their unemployment benefits should be less, ruling that there was no valid reason related to sex to justify the difference in pay.


The heavy eye phenomenon: orthoptic and ophthalmic characteristics.
A series is presented of nine patients who demonstrate the heavy eye phenomenon. Illustrations of these patients show the salient features of the phenomenon, including hypotropia, exotropia and pseudoproptosis. The condition is summarized and the pathogenesis of the eye and lid positions are discussed. The indications for surgery and some examples with results are shown. The correct diagnosis may prevent unnecessary investigation of pseudoproptosis and pseudo third-nerve palsy.


Conjugated polymer/molten salt blend optimization.
Light-emitting electrochemical cells with low current threshold can be realized through mixing conjugated polymers and molten salts. Current drive capability is proportional to the overall interface perimeter of the planar, discotic molten salt domains inserted into the polymer matrix. Electric force microscopy indicates that this interface perimeter exhibits a specific dependence on the molten salt content in the active layer, with a well-defined maximum. We show that this maximum corresponds to an optimal current drive.


The influence of two functional genetic variants of GRK5 on tau phosphorylation and their association with Alzheimer's disease risk.
Our work explores the relationship between G protein-coupled receptor kinase-5 (GRK5) single nucleotide polymorphisms and Alzheimer's disease risk. We confirmed that GRK5 translocates from the cellular membrane to the cytosol in the hippocampus of Alzheimer's disease mice and that GRK5 deficiency promotes tau hyperphosphorylation, a hallmark of Alzheimer's disease pathology. Our results indicate that one functional variant, or mutant, of GRK5 (GRK5-Gln41Leu) decreased GRK5 translocation from the membrane to the cytoplasm and reduced tau hyperphosphorylation, whereas, another GRK5 mutant (GRK5-Arg304His) increased GRK5 translocation to the cytoplasm and promoted tau hyperphosphorylation. In addition, case-control studies revealed that GRK5-Gln41Leu is associated with a lower risk of late-onset Alzheimer's disease. Our findings suggest that the GRK5-Gln41Leu mutant may resist tau hyperphosphorylation by promoting GRK5 membrane stability and, in effect, may contribute to lower Alzheimer's disease risk.


The biological activity in vivo of recombinant murine interleukin 1 in the rat.
The present study summarizes the biological response of rats to infusion with recombinant murine IL-1 (rIL-1) cloned in Escherichia coli. Thirty-seven male rats (135-180 g) were infused over a 6-hr period with either 0.008 M guanidine hydrochloride (the vehicle) or E. coli product (both groups are controls) or 1000, 3750, 7500, 15,000, or 37,500 LAF units/hr of rIL-1. The controls and the group receiving 1000 LAF units/hr of rIL-1 did not exhibit a change in body temperature during the experiment. A mild fever was noted with 3750 LAF units/hr which became significantly elevated with 7500 and 15,000 LAF units/hr. At a dose of 37,500 LAF units/hr of rIL-1 (in 0.08 M guanidine hydrochloride) the rats became hypothermic and died. An equivalent dose of guanidine hydrochloride alone (0.08 M) was not fatally toxic although the rats did become hypothermic. Plasma zinc levels were significantly depressed and white blood cell count elevated at 6 hr postinfusion onset. Resting energy expenditure (REE) was significantly depressed during an infusion of 7500 and 15,000 LAF units/hr of rIL-1 despite a concurrent elevation in body temperature. Whole-body leucine kinetics were unchanged by infusion with rIL-1. Plasma fibrinogen and serum haptoglobin and copper levels were not altered by rIL-1. In conclusion, murine rIL-1 is similar to monocytic-derived IL-1 in that it produces a fever, hypozincemia, and leukocytosis; however, rIL-1 does not induce changes in protein metabolism.


Pharmacological targeting of the Wdr5-MLL interaction in C/EBPα N-terminal leukemia.
The CEBPA gene is mutated in 9% of patients with acute myeloid leukemia (AML). Selective expression of a short (30-kDa) CCAAT-enhancer binding protein-α (C/EBPα) translational isoform, termed p30, represents the most common type of CEBPA mutation in AML. The molecular mechanisms underlying p30-mediated transformation remain incompletely understood. We show that C/EBPα p30, but not the normal p42 isoform, preferentially interacts with Wdr5, a key component of SET/MLL (SET-domain/mixed-lineage leukemia) histone-methyltransferase complexes. Accordingly, p30-bound genomic regions were enriched for MLL-dependent H3K4me3 marks. The p30-dependent increase in self-renewal and inhibition of myeloid differentiation required Wdr5, as downregulation of the latter inhibited proliferation and restored differentiation in p30-dependent AML models. OICR-9429 is a new small-molecule antagonist of the Wdr5-MLL interaction. This compound selectively inhibited proliferation and induced differentiation in p30-expressing human AML cells. Our data reveal the mechanism of p30-dependent transformation and establish the essential p30 cofactor Wdr5 as a therapeutic target in CEBPA-mutant AML.


Germ cell fate and seminiferous tubule development in bovine testis xenografts.
Spermatogenesis can occur in testis tissue from immature bulls ectopically grafted into mouse hosts; however, efficiency of sperm production is lower than in other donor species. To elucidate a possible mechanism for the impaired spermatogenesis in bovine testis xenografts, germ cell fate and xenograft development were investigated at different time points and compared with testis tissue from age-matched calves as controls. Histologically, an initial decrease in germ cell number was noticed in xenografts recovered up to 2 months post-grafting without an increase in germ cell apoptosis. From 2 months onward, the number of germ cells increased. In contrast, a continuous increase in germ cell number was seen in control tissue. Pachytene spermatocytes were observed in some grafts before 4 months, whereas in the control tissue they were not present until 5 months of age. Beyond 4 months post-grafting spermatogenesis appeared to be arrested at the pachytene spermatocyte stage in most grafts. Elongated spermatids were observed between 6 and 8 months post-grafting, similar to the controls, albeit in much lower numbers. Lumen formation started earlier in grafts compared with controls and by 6 months post-grafting tubules with extensively dilated lumen were observed. A donor effect on efficiency of spermatogenesis was also observed. These results indicate that the low efficiency of sperm production in bovine xenografts is due to an initial deficit of germ cells and impaired meiotic and post-meiotic differentiation. The characterization of spermatogenic efficiency will provide the basis to understand the control of spermatogenesis in testis grafts.


[Evaluation of Hymenoptera hypersensitivity including large local reactions among forest administration workers in Gunma prefecture].
We used a questionnaire to investigate Hymenoptera hypersensitivity in 715 forest administration workers in Gunma prefecture and measured venom specific IgE antibodies in those who had exhibited large local reactions (LLR). The results were as follows. 1) Almost all, i.e. 660 (92.3%), of the workers, including 156 (23.6%) hypersensitive workers, had been exposed to insect stings and 241 (36.5%) had experienced LLR. 2) Among the hypersensitive workers, 68.9% exhibited systemic reactions after having been stung no more than ten times and 18.2% experienced systemic reactions when they were stung for the first time. 3) About 60% of the hypersensitive workers had been stung on only one site when they exhibited systemic reactions. 4) An evaluation of venom specific IgE titer for the workers who experienced LLR revealed a relatively high rate of RAST positive results to yellow jackets (39.3%) and wasps (36.9%).


Fixed dose subcutaneous low molecular weight heparins versus adjusted dose unfractionated heparin for venous thromboembolism.
Low molecular weight heparins (LMWH) have been shown to be effective and safe in preventing venous thromboembolism (VTE), and may also be effective for the initial treatment of VTE. To determine the effect of LMWH compared with unfractionated heparin (UFH) for the initial treatment of VTE. Trials were identified from the Cochrane Peripheral Vascular Diseases Group's Specialised Register, CENTRAL and LILACS. Colleagues and pharmaceutical companies were contacted for additional information. Randomised controlled trials comparing fixed dose subcutaneous LMWH with adjusted dose intravenous or subcutaneous UFH in people with VTE. At least two reviewers assessed trials for inclusion and quality, and extracted data independently. Twenty-two studies were included (n = 8867). Thrombotic complications occurred in 151/4181 (3.6%) participants treated with LMWH, compared with 211/3941 (5.4%) participants treated with UFH (odds ratio (OR) 0.68; 95% confidence intervals (CI) 0.55 to 0.84, 18 trials). Thrombus size was reduced in 53% of participants treated with LMWH and 45% treated with UFH (OR 0.69; 95% CI 0.59 to 0.81, 12 trials). Major haemorrhages occurred in 41/3500 (1.2%) participants treated with LMWH, compared with 73/3624 (2.0%) participants treated with UFH (OR 0.57; 95% CI 0.39 to 0.83, 19 trials). In eighteen trials, 187/4193 (4.5%) participants treated with LMWH died, compared with 233/3861 (6.0%) participants treated with UFH (OR 0.76; 95% CI 0.62 to 0.92). Nine studies (n = 4451) examined proximal thrombosis; 2192 participants treated with LMWH and 2259 with UFH. Subgroup analysis showed statistically significant reductions favouring LMWH in thrombotic complications and major haemorrhage. By the end of follow up, 80 (3.6%) participants treated with LMWH had thrombotic complications, compared with 143 (6.3%) treated with UFH (OR 0.57; 95% CI 0.44 to 0.75). Major haemorrhage occurred in 18 (1.0%) participants treated with LMWH, compared with 37 (2.1%) treated with UFH (OR 0.50; 95% CI 0.29 to 0.85). Nine studies (n = 4157) showed a statistically significant reduction favouring LMWH with respect to mortality. By the end of follow up, 3.3% (70/2094) of participants treated with LMWH had died, compared with 5.3% (110/2063) of participants treated with UFH (OR 0.62; 95% CI 0.46 to 0.84). LMWH is more effective than UFH for the initial treatment of VTE. LMWH significantly reduces the occurrence of major haemorrhage during initial treatment and overall mortality at follow up.


The Emergency Room Medical Group: improving hospital efficiency.
With national health care expenditures in the United States consuming 14 percent of the gross domestic product, the U.S. health care industry faces a turbulent environment. Adding to this situation, health care executives are having a difficult time developing strategies for dealing with patients who use the emergency room for primary care. Hospital executives may consider forming an Emergency Room Medical Group (ERMG). ERMGs are defined (as well as their alternative health care alliances), and each is illustrated in a model called the Physician Alliance Continuum.


Tau, sigma, and delta. A family of repeated elements in yeast.
We report here the isolation and structure of a new repeated DNA element, tau. This element, from Saccharomyces cerevisiae, is 371 base pairs long and is flanked on either end by the same invertedly repeated sequence found at the ends of some Ty and sigma elements in yeast, copia elements in Drosophila and spleen necrosis virus. The tau inverted repeats are themselves flanked by a 5-base pair directly repeated genomic sequence that is present only once in a cognate tau-allele. These structural characteristics, the presence of multiple copies of tau in the genome, and the isolation of tau+ and tau- allelic pairs suggest that tau may be capable of transposition either alone or in association with some larger element. Detailed sequence analysis of the tau, sigma, and delta elements revealed that all three contain significant regions of homology, suggesting that they are probably members of a single family derived from a common progenitor.


Long-term effects of ambient air pollution on lung function: a review.
Lung function is an important measure of respiratory health and a predictor of cardiorespiratory morbidity and mortality. Over the past 2 decades, more than 50 publications have investigated long-term effects of ambient air pollution on lung function with most finding adverse effects. Several studies have also suggested effects from traffic-related air pollution. There is strong support for air pollution effects on the development of lung function in children and adolescents. It remains unclear whether subjects with slower development of lung function compensate by prolonging the growth phase, or whether they end their development at a lower plateau, thus entering the decline phase with a reduced lung function. In adults, the evidence for long-term air pollution effects is mostly based on cross-sectional comparisons. One recent longitudinal study observed that decreasing pollution attenuated the decline of lung function in adults. Earlier inconclusive cohort studies were based on limited data. There is great diversity in study designs, markers of air pollution, approaches to the measurement of exposure, and choices in lung function measures. These limit the comparability of studies and impede quantitative summaries. New studies should use individual-level exposure assessment to clarify the role of traffic and to preclude potential community-level confounding. Further research is needed on the relevance of specific pollution sources, particularly with regard to susceptible populations and relevant exposure periods throughout life.


In vivo alternative assessment of the chemicals that interfere with anterior pituitary POMC expression and interrenal steroidogenesis in POMC: EGFP transgenic zebrafish.
Adrenocorticotropin (ACTH) has been considered a classic adrenocorticotropic hormone and the key pituitary-derived peptide controlling steroidogenesis in the adult adrenal. ACTH is encoded by the propiomelanocortin (POMC) gene, and its active form is mainly synthesized and processed from the POMC-encoded multihormone precursor in the anterior pituitary. The ACTH level has always been precisely controlled in the signaling cascade of the hypothalamo-pituitary-adrenal (HPA) axis due to its central role. The purpose of this study was to investigate whether the transgenic zebrafish line with EGFP driven by the POMC promoter can be used as a surrogate marker to detect the interference effects on anterior pituitary POMC expression caused by chemicals in teleost. The Tg (POMC:EGFP) fish treated for 4days with the known adrenergic agents, dexamethasone (Dex) or aminoglutethimide (AG), exhibited altered levels of EGFP and POMC expression in the anterior domain of pituitary corticotrophs. Whole-mount in situ hybridization revealed impaired patterns of expression of the zebrafish ftz-fl gene (ff1b), a key molecular marker for early interrenal development. Next, several chemicals and six commonly used organophosphorus compounds (OPs) were tested for their effects on anterior pituitary POMC expression and early interrenal development. Our preliminary screening analyses indicated that simazine and 3,3',4,4'5-pentachlorobiphenyl (PCB126) could interfere with anterior pituitary POMC expression and interrenal development in fish. In summary, our results demonstrated that the Tg (POMC:EGFP) zebrafish line might be employed as a specific and reproductive in vivo assessment model for the effects of endocrine disruption on HPA signaling.


[Summarization of Prof. ZHANG Jia-Wei's experiences on clinical application of Suliao (GV 25)].
Suliao (GV 25) is the 25th acupoint of The Governor Vessel and is mostly used to treat various nasal diseases clinically. In light of the recordation about the therapeutic effect of Suliao (GV 25) in ancient medical books, combining with his own several years' clinical experiences, Prof. ZHANG Jia-Wei enlarges the clinical application of Suliao (GV 25) creatively, and treats hyperkinetic syndrome of childhood, three facial diseases and some diseases of the lower-jiao in combination with the unique flying needling therapy, attaining rapidly therapeutic effect.


Digestion rate of dietary starch affects systemic circulation of amino acids in weaned pigs.
The present study was conducted to evaluate the in vitro and in vivo digestibility of dietary starch and its digestive behaviour on the systemic circulating amino acids (AA) in weaned pigs. Eighteen weanling pigs surgically fitted with a catheter in the jugular vein were randomly assigned to three dietary treatment groups. Sticky rice starch (SRS) was hydrolysed more quickly in vitro (P < 0.05) than maize starch (MS) and resistant starch (RS), and was almost completely hydrolysed within 4 h. The in vivo digestibility of dietary starch in different segments of the small intestine was significantly different. SRS was digested (81.9 %; P < 0.05) in the anterior jejunum, but not more than half of the MS and RS was digested in the same segment of the small intestine. The digestibilities of isoleucine, leucine, methionine, phenylalanine, threonine, tryptophan, valine, alanine, aspartate and serine in the SRS group were higher than in the MS group (P < 0.05), and all nutritionally indispensable and dispensable AA in the SRS group were higher when compared with those in the RS group (P < 0.05). The serum concentrations of nutritionally indispensable AA, proline and serine in the three groups were increased to a peak point within 1.5 h postprandially then decreased gradually; however, the time that serum concentrations of alanine, aspartate, glutamate and glycine in each group increased to a peak point was different. The concentrations of nutritionally indispensable AA, including arginine, cystine, histidine, isoleucine, leucine, methionine, phenylalanine, threonine, tryptophan, tyrosine and valine at 09.30 hours and arginine, cystine, histidine, isoleucine, methionine, phenylalanine, threonine, tryptophan, tyrosine and valine at 13.30 hours in the SRS group were higher than in the MS group (P < 0.05); all nutritionally indispensable AA in the SRS group were higher than in the RS group at 09.30 and 13.30 hours (P < 0.05), respectively. We conclude that dietary starches digested rapidly in vitro have higher digestibility in the anterior small intestine of pigs. Diets containing rapidly digestible starch ameliorate the digestive and absorptive function and regulate AA metabolism to beneficially increase the entry of dietary AA into the systemic circulation in pigs.


Decreased insulin binding to adipocytes precedes both hyperinsulinemia and decreased insulin binding to erythrocytes in cafeteria-fed rats.
The relationship between food intake, obesity, insulin binding to adipocytes and erythrocytes, plasma insulin and plasma glucose was studied in an animal model of nutritional obesity--'the cafeteria-fed rats'--after 3 days, 10 days, and 3 weeks of cafeteria feeding. The antilipolytic effect of insulin was also studied. The cafeteria-fed rats ate more carbohydrates after 3 days of diet, while from the 10th day, as previously found, they ate about the same amount of carbohydrates but more lipids and increased in weight. Insulin binding to adipocytes started to decrease (P less than 0.05) 10 days after beginning the cafeteria diet despite the absence of hyperinsulinemia. This decrease in insulin binding to adipocytes was accompanied by a decrease in the responsiveness of adipocytes to the antilipolytic effect of insulin. Hyperinsulinemia (P less than 0.01) appeared only after 3 weeks. At the same time, insulin binding to erythrocytes started also to decrease (P less than 0.05). Plasma glucose levels in the cafeteria-fed rats were unchanged when compared to their controls at any time of the study. There was no correlation between body weight, plasma insulin and insulin binding, to adipocytes and to erythrocytes, at any time of the study. Thus it is possible that factors other than hyperinsulinemia could be involved in the decrease in insulin binding to both adipocytes and erythrocytes.


Late course accelerated hyperfractionation radiotherapy concomitant with cisplatin in patients with esophageal carcinoma.
The purpose of this study was to examine whether combined cisplatin and late course accelerated fractionation radiotherapy (LCAH) (the combined group) can confer a better outcome over LCAH alone in treating esophageal carcinoma. Eighty-one eligible patients were randomly entered into two groups: the LCAH alone group, and the combined group. There was a better outcome in the combined group compared to the LCAH group, but the difference was not significant. The combined therapy could significantly improve the survival rate and local control of the disease in the early stage, but not in the advanced stage, because of the possibility of invasion. More severe complications occurred in the combined group than in the LCAH group, but they were within tolerance. In conclusion, LCAH concomitant with cisplatin could improve the survival of patients with esophageal cancer, especially in the early stage, as long as the side effects of the treatment are within tolerable limits.


Metabolism of theophylline and its inhibition by fluoroquinolones in rat hepatic microsomes.
1. The effects of beta-naphthoflavone, dexamethasone, phenobarbitone and isosafrole on the metabolism of theophylline by rat liver microsomes have been studied. Only beta-naphthoflavone, a known P4501A inducer, increased the rate of 1-methylxanthine formation (3-fold), whereas all the inducers studied increased the rate of 1,3-dimethyluric acid production (2.5-3-fold). 2. To study the effects of a range of fluoroquinolones on theophylline metabolism, beta-naphthoflavone-induced microsomes were used, as the ratio for metabolite production rates was similar to that of untreated microsomes (4:1,3-dimethyluric acid: 1-methylxanthine at 2 mM theophylline). High concentrations of fluoroquinolones (0.5-1.5 mM) were required to affect microsomal theophylline metabolism. 1-Methylxanthine was more sensitive to fluoroquinolone inhibition by enoxacin, ciprofloxacin, norfloxacin and pipemidic acid than 1,3-dimethyluric acid; CP67015, had a significant effect on 1,3-dimethyluric acid production only; binfloxacin had no effect on either pathway. 3. Ethoxycoumarin, a rapidly metabolized substrate, was also investigated as a surrogate for theophylline in in vitro experiments. Fluoroquinolone inhibition of ethoxycoumarin O-de-ethylation in beta-naphthoflavone-induced microsomes was quantitatively greater but qualitatively similar to theophylline metabolism (IC50s 440-870 microM at 2 microM 7-ethoxycoumarin). 4. These data are comparable with previous rat experiments in vivo, indicating that enoxacin, ciprofloxacin and norfloxacin have similar intrinsic activity in the inhibition of theophylline metabolism.


The neuroprotective effect of resveratrol on retinal ganglion cells after optic nerve transection.
This study aimed to investigate the neuroprotective effect of resveratrol in an optic nerve transection (ONT) model and to identify the neuroprotective mechanism of resveratrol in retinal ganglion cells (RGCs). ONT and retrograde labeling were performed in Sprague-Dawley rats. Various concentrations of resveratrol were injected intravitreally immediately after ONT. The number of labeled RGCs was determined at 1 and 2 weeks after ONT. The effect of resveratrol and sirtinol (a sirtuin 1 inhibitor) co-injection was investigated. RGC-5 cells were cultured and treated with staurosporine to induce differentiation. 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay was performed to evaluate the effect of resveratrol on RGC-5 cell survival under serum-free conditions. RGC-5 cells were cultured with sirtinol to investigate the neuroprotective mechanism of resveratrol. A dose-response relationship was observed between resveratrol and RGC survival. A single intravitreal injection of resveratrol was neuroprotective in RGCs at 1 week after ONT (p<0.01). Repeated intravitreal injection of resveratrol showed a neuroprotective effect at 2 weeks after ONT (p<0.01). However, co-injection of resveratrol and sirtinol diminished the neuroprotective effect of resveratrol (p<0.05). The neuroprotective effect of resveratrol was observed in RGC-5 cells under serum-free conditions, and sirtinol diminished this neuroprotective effect. Resveratrol exerts its neuroprotective effect on RGCs via activation of the sirtuin 1 pathway in an ONT model. This finding demonstrates the therapeutic potential of resveratrol in treating optic nerve diseases.


Serum rotavirus neutralizing-antibody titers compared by plaque reduction and enzyme-linked immunosorbent assay-based neutralization assays.
Comparisons in rotavirus neutralizing-antibody responses were made with sera collected from vaccinated infants. The methods were a plaque reduction assay and a new enzyme-linked immunosorbent assay-based neutralization assay. Agreement of 94% was found in detecting at least fourfold seroresponses, and correlation coefficients between titers obtained by the two methods showed excellent agreement, indicating that either could be used reliably.


CD151 is associated with prostate cancer cell invasion and lymphangiogenesis in vivo.
CD151, a member of the tetraspanin family, is associated with regulation of migration of normal and tumour cells via cell surface microdomain formation. CD151 was found in our laboratory to have a prognostic value in prostate cancer and is a promoter of prostate cancer migration and invasion. These roles involve association with integrins on both cell-cell and cell-stroma levels. Furthermore, CD151 plays a role in endothelial cell motility. CD151 expression was examined in three commonly used prostate cancer cell lines. We investigated CD151 expression, angiogenesis (microvessel density; MVD) and lymphangiogenesis (lymphatic vessel density; LVD) in an orthotopic xenograft model of prostate cancer in matched tumours from primary and secondary sites. CD151 was found to be heterogeneously expressed across different prostate cancer cell lines and the levels of CD151 expression were significantly higher in the highly tumorigenic, androgen-insensitive cells PC-3 and DU-145 compared to the androgen-sensitive cell line LNCaP (P<0.05). The majority of in vivo xenografts developed pelvic lymph node metastases. Importantly, primary tumours that developed metastasis had significantly higher CD151 expression and MVD compared to those which did not develop metastasis (P<0.05). We identified, for the first time, that CD151 expression is associated with LVD in prostate cancer. These findings underscore the potential role of CD151 and angiogenesis in the metastatic potential of prostate cancer. CD151 has a prognostic value in this mouse model of prostate cancer and may play a role in lymphangiogenesis. CD151 is likely an important regulator of cancer cell communication with the surrounding microenvironment.


Comparison of Pure Palm Olein Oil, Hydrogenated Oil-Containing Palm, and Canola on Serum Lipids and Lipid Oxidation Rate in Rats Fed with these Oils.
Due to increased consumption of canola oil and hydrogenated oil containing palm and palm olein, and their possible effects on serum lipoproteins, the present study was conducted to determine the effects of these oils on lipids and lipid oxidation level. In this experimental study, 88 Wistar rats were randomly assigned to four groups. Control group (A) was on a normal diet. Groups B, C, and D, in addition to normal diet, were fed with hydrogenated oil-contained palm oil, pure palm olein oil, and canola oil, respectively for 4 weeks. Serum Biochemical factors [total cholesterol (TC), triglyceride (TG), LDL, HDL, LDL/HDL ratio, oxLDL, paraoxanase-1 (PON1), and malondialdehyde (MDA)] were measured. The lowest mean serum TC was seen in the control group and the highest in the group B. There were differences in TC, TG, HDL, MDA, and PON1 between the control group and other groups (P<0.001). The lowest and highest LDL/HDL ratios were observed in the group C and the control group, respectively. Significant differences were seen in OxLDL and PON1 between the control group and other three groups (P<0.05), while there were no significant differences in oxLDL and PON1 among the other three groups (P>0.05). MDA was higher in groups C and D. Canola oil, hydrogenated oil-containing palm and palm olein may increase atherosclerosis risk through decreasing PON1 activity and elevating oxLDL. Palm olein oils in rats' diets cause a considerable decrease in LDL and help to increase HDL.


Nitrogen Nutrition of Nodules in Relation to ;N-Hunger' in Cowpea (Vigna unguiculata L. Walp).
Early growth, nodule development, and nitrogen fixation by two cultivars of cowpea (Vigna unguiculata L. Walp), one large-seeded (Vita 3; 146.0 +/- 0.9 milligrams seed dry weight, 4.1 +/- 0.2 milligrams seed N), the other small-seeded (Caloona; 57.5 +/- 2.5 milligrams seed dry weight, 1.8 +/- 0.1 milligrams seed N), were compared under conditions of sand culture with nutrient solution free of combined N. The seed stocks used had been obtained from plants uniformly labeled with (15)N, thus enabling changes with time in distribution of cotyledon and fixed N among plant parts to be measured by isotope dilution. Caloona, but not Vita 3, showed physiological symptoms of ;N hunger,' i.e. transient loss of chlorophyll (visible yellowing) and N from the first-formed unifoliolate leaves at or around the onset of symbiotic functioning and N(2) fixation. The smaller-seeded Caloona showed higher early nitrogenase activity than the larger-seeded Vita 3 and by 28 days had fixed 6.6 milligrams of N per milligram of seed N [mg N . (mg seed N)(-1)] versus only 3.5 mg N . (mg seed N)(-1) in Vita 3. Both cultivars lost around 30% of their initial seed N at germination, mostly as fallen cotyledons. Abscised cotyledons of Caloona contained 1.21 +/- 0.17% N; those of Vita 3 contained 2.61 +/- 0.37% N. When compared on the basis of cotyledon N available for seedling growth, Caloona was shown to have fixed 10.6 mg N . (mg seed N)(-1) and Vita 3 only 5.3 mg N . (mg seed N)(-1). Most of the cotyledon N withdrawn from the unifoliolate leaf pair of Caloona during ;N-hunger' was committed to early nodule growth and, in total, 20 to 25% of the cotyledon N resource of this cultivar was ultimately invested in establishment of symbiosis compared with only 7% in Vita 3.


Treating Chronic Fatigue states as a disease of the regulation of energy metabolism.
Chronic Fatigue Syndrome is a physiological state in which the patient feels high levels of fatigue without an obvious organic cause, which affects around 1 in 400 people in the developed world. A wide range of causes have been suggested, including immune or hormonal dysfunction, viral or bacterial infection, and psychological somatization. It is likely that several causes are needed to trigger the disease, and that the triggers are different from the mechanisms that maintain fatigue over months or years. Many treatments have been tested for CFS, with very limited success - a programme of combined CBT and graded exercise shows the most effect. I suggest that patients with CFS have a reduced ability to increase mitochondrial energy production when exertion requires it, with fewer mitochondria that are each more efficient, and hence nearer to their maximum energy output, than normal. A range of indirect evidence suggests that the renin-angiotensin system stimulates mitochondrial responsiveness and reduces mitochondrial efficiency: chronic under-stimulation of this system could contribute to CFS aetiology. If correct, this means that CFS can be successfully treated with RAS agonists (eg angiotensin mimetics), or adrenergic agonists. It also suggests that there will be a positive link between the use of adrenergic- and RAS-blocking drugs and CFS incidence, and a negative link between adrenergic agonist use and CFS.


Ring chromosome 22: a case report.
A three year old girl with ring chromosome 22 is described. The clinical findings include epicanthus, flat nasal bridge, hypertelorism, long eye-lashes, lymphoedema, hypoplastic toe nails, hydrocephalus and muscular hypotonia. Speech and language development is delayed. At three years the child begins to walk.


Assessment of the Morphology and Degenerative Changes in the Temporomandibular Joint Using CBCT according to the Orthodontic Approach: A Scoping Review.
Available knowledge about disorders of temporomandibular joint structures and their association with orthodontic variables are still lacking. This article is aimed at to identifying studies and presenting current information on the relationship between morphology diversity and the occurrence of degenerative changes in structures of the temporomandibular joint (TMJ) assessed by cone-beam computed tomography (CBCT) in the context of craniofacial morphology and malocclusion. Search Methods. The review was conducted by analyzing the PubMed (including Medline), Cochrane Library, Web of Science, and Scopus electronic databases up to November 2021 using two different comprehensive search strategies based on keywords as well as additional manual searches. Eligibility Criteria. Selection of the literature was carried out according to the PRISMA-ScR checklist. Methodological quality of the selected studies was evaluated using JBI Critical Appraisal Tool. The electronic databases search revealed 3331 records. After applying the eligibility criteria and JBI assessment, a total of 33 studies were extracted and selected to the study. The review was divided into 4 parts, in which the following correlations were assessed in terms of orthodontic variables: TMJ degenerative changes, joint space and condylar position, condylar shape, TMJ articular eminence, and fossa. Skeletal and dental class II malocclusion with a retrognathic mandible, a hypodivergent skeletal pattern with a steep mandibular plane, and significant lateral mandibular displacement can be risk factors for developing radiographically detectable degenerative changes. Patients with skeletal and dental class III malocclusion as well as a hyperdivergent skeletal pattern may be at greater risk of TMD occurrence compared with other groups. Further studies are necessary to clarify the relationship between the position of the condylar processes and the presence of degenerative changes in the temporomandibular joints among orthodontic patients.


The elephant in the room.
Nurses of color refrain from speaking up when facing racism in their nursing practice from patients, White peers, coworkers, and higher-ups. Racism is the elephant in the room that no one wants to talk about. This article examines the barriers that may prevent nurses of color from speaking openly about racism and encourages all nurses to speak up and out against racism in nursing.


Variable-focus liquid microlenses with adjustable 3-D curved housings.
This paper reports two novel types of variable-focus liquid microlenses with adjustable sensitivity, which consist of a poly(dimethylsiloxane) (PDMS) lens housing with circular sidewall and a liquid with tunable volume stored in it. The type-I lens housing ("in" bridge structure) is molded from water droplet sandwiched between two plates with identical wettability and the type-II lens housing ("out" bridge structure) is molded from solid microsphere. Because of the variable slope of the sidewall, the altitude of the liquid/air interface, which can be regulated by hydrostatic pressure, determines the curvature of the meniscus and hence the focal length (f). The curvature radius of sidewall, which determines the sensitivity, depends on the surface wettability or the radius of solid microsphere, thus, it is adjustable. Both of the two types of lenses have wide dynamic range, and their tuning tendencies are opposite. The experimental demonstrations and theoretical simulations yield good agreement in the key aspects of the optics.


Clinicopathological aspects of liver diseases associated with early history of tattooing.
No matter whether it is the B type or non-A, non-B type, chronic infection with the hepatitis virus often causes chronic hepatitis, which may ultimately lead to cirrhosis and even hepatocellular carcinoma. From an epidemiological point of view, it was considered that tattooing might be an important mode of transmission of hepatitis virus through tattoo needles even at the time when hepatitis-B-virus related antigens and antibodies were not yet utilized as clinical markers in practice. Since HBV related antigens and antibodies in serum came into routine use as clinical markers, several articles on the outbreak of hepatitis B from tattooing have appeared in consideration of the correlation between the appearance and disappearance of the clinical markers and the clinical course of liver diseases. Nevertheless, a perusal of the literature to date failed to reveal any mention of clinical, pathological and prognostic aspects of liver disease with tattooing. These aspects are certainly ready for clarification. On the basis of clinicopathological observations of 26 patients with tattooing and liver diseases, it can be concluded that tattooing might be an important route of infection for hepatitis viruses including both the B type and non-A, non-B type, which can lead to chronic inflammatory liver diseases.


Prevention of postoperative wound haematomas and hyperperfusion following carotid endarterectomy.
To study the incidence of wound haematomas and hyperperfusion following carotid endarterectomy and the effect of changes in perioperative management. We undertook a prospective audit of the postoperative outcome of 300 consecutive carotid endarterectomies performed for a symptomatic stenosis of the internal carotid artery, under the care of a single consultant. audit of the first 100 operations between 1990-93 resulted in 4 changes to clinical practice. These included the use of Dacron instead of vein because of 3 vein patch blowouts, invasive postoperative monitoring of blood pressure, and the use of intravenous beta-blockers to control hypertension, because of 4 hyperperfusion injuries. The use of 10F suction drains was discontinued, because they did not prevent 8 wound haematomas. The results of the second 100 cases between 1994-97 and the third 100 cases between 1998-2000 confirmed no further hyperperfusion injuries or patch blowouts (p =0.01 and 0.04 respectively). Larger 14F suction drains were reintroduced for the third series because of thirteen haematomas in the second series (p =0.09). Only 4 haematomas occurred in the third series ( p =0.05). The need for beta-blockers fell in the third series due to the introduction of local anaesthesia (p =0.0001). The use of Dacron patches and postoperative control of hypertension has reduced the incidence of haemorrhage and hyperperfusion after carotid endarterectomy. Larger suction drains may also help.


Adaptive control of bivalirudin in the cardiac intensive care unit.
Bivalirudin is a direct thrombin inhibitor used in the cardiac intensive care unit when heparin is contraindicated due to heparin-induced thrombocytopenia. Since it is not a commonly used drug, clinical experience with its dosing is sparse. In earlier work [1], we developed a dynamic system model that accurately predicts the effect of bivalirudin given dosage over time and patient physiological characteristics. This paper develops adaptive dosage controllers that regulate its effect to desired levels. To that end, and in the case that bivalirudin model parameters are available, we develop a Model Reference Control law. In the case that model parameters are unknown, an indirect Model Reference Adaptive Control scheme is applied to estimate model parameters first and then adapt the controller. Alternatively, direct Model Reference Adaptive Control is applied to adapt the controller directly without estimating model parameters first. Our algorithms are validated using actual patient data from a large hospital in the Boston area.


Kidney vascular congestion exacerbates acute kidney injury in mice.
Heart failure is frequently accompanied by kidney failure and co-incidence of these organ failures worsens the mortality in patients with heart failure. Recent clinical observations revealed that increased kidney venous pressure, rather than decreased cardiac output, causes the deterioration of kidney function in patients with heart failure. However, the underlying pathophysiology is unknown. Here, we found that decreased blood flow velocity in peritubular capillaries by kidney congestion and upregulation of endothelial nuclear factor-κB (NF-κB) signaling synergistically exacerbate kidney injury. We generated a novel mouse model with unilateral kidney congestion by constriction of the inferior vena cava between kidney veins. Intravital imaging highlighted the notable dilatation of peritubular capillaries and decreased kidney blood flow velocity in the congestive kidney. Damage after ischemia reperfusion injury was exacerbated in the congestive kidney and accumulation of polymorphonuclear leukocytes within peritubular capillaries was noted at the acute phase after injury. Similar results were obtained in vitro, in which polymorphonuclear leukocytes adhesion on activated endothelial cells was decreased in flow velocity-dependent manner but cancelled by inhibition of NF-κB signaling. Pharmacological inhibition of NF-κB for the mice subjected by both kidney congestion and ischemia reperfusion injury ameliorated the accumulation of polymorphonuclear leukocytes and subsequent exacerbation of kidney injury. Thus, our study demonstrates the importance of decreased blood flow velocity accompanying activated NF-κB signaling in aggravation of kidney injury. Hence, inhibition of NF-κB signaling may be a therapeutic candidate for the vicious cycle between heart and kidney failure with increased kidney venous pressure.


Failure of oral DHEA treatment to increase local salivary androgen outputs of female patients with Sjögren's syndrome.
Sjögren's syndrome (SS) is a female-dominant autoimmune disease characterized by androgen depletion and defective dehydroepiandrosterone (DHEA) processing enzymatic machinery in the salivary glands. We hypothesized that, because of these local failures, DHEA replacement therapy would be unable to improve the local androgen deficiency in SS salivary glands. DHEA-deficient female SS patients (n = 12) were treated with placebo for 4 months followed by DHEA 50 mg q.d. for 4 months. Serum and saliva, collected in the morning before the trial and after both periods, were analysed for pro-hormones, androgens, and androgen metabolite using an enzyme-linked immunosorbent assay (ELISA). DHEA treatment increased serum DHEA-sulfate from 1.3 ± 0.1 to 6.4 ± 1.3 µM (p = 0.005), DHEA from 16.5 ± 2.8 to 34.8 ± 8.2 nM (p = 0.012), androstenedione from 3.1 ± 0.3 to 17.2 ± 1.9 nM (p = 0.002), free testosterone from 2.2 ± 0.1 to 7.7 ± 1.1 pM (p = 0.002), DHT from 275.5 ± 24.4 to 834.6 ± 122.8 pM (p = 0.002) and 3-α-diol-G from 3.8 ± 0.6 to 13.6 ± 2.0 nM (p = 0.001). However, only salivary DHEA and DHT outputs increased significantly and 25% of the patients showed no increases, except for DHEA itself. Outputs of active androgens (T, DHT) and 3-α-diol-G metabolite correlated with salivation. The local androgen deficiency in SS salivary glands is not only caused by low serum DHEA(-S) because restoration of systemic androgen levels by DHEA treatment did not correct local androgen depletion. This could be explained by low or no capacity of DHEA-substituted patients to convert the pro-steroid to active androgen metabolites. Such intracrine failures affect women in particular, who must produce their salivary T and DHT locally from DHEA.


Renal function outcomes after nephrectomy for kidney cancer in elderly patients.
The kidneys are organs with multiple functions and essential to maintain life. Ablative procedures, such as nephrectomy, diminish nephron mass and can have a potentially negative impact on renal function. We investigated renal function outcome in patients who underwent nephrectomy for renal cell cancer with special emphasize on elderly patients. Data from 104 patients who underwent nephrectomy for kidney cancer in the Department of Urology, University Hospital Rijeka from January 2005 to December 2010 were retrospectively analyzed. All patients had a normal concentration of serum creatinine and a normal contralateral kidney before surgery. Renal function, as estimated by the glomerular filtration rate (eGFR), was determined before and after nephrectomy using the abbreviated Modification of Diet in Renal Disease equation. We compared the eGFR before and after nephrectomy in the patients of different age. The mean preoperative eGFR was 75.2 mL/min, and the mean postoperative eGFR was 52.7 mL/min (p < 0.0001). In the group of patients > or = 65 years old, the mean preoperative GFR was 69.2 mL/min, and the mean postoperative eGFR was 47.4 mL/min (p < 0.0001). Our data indicate that the eGFR significantly decreased after nephrectomy for kidney cancer. In elderly patients, diminished renal function following nephrectomy was more prominent.


[Clinical analysis of 11 cases of juvenile dermatomyositis and polymyositis].
Juvenile dermatomyositis (JDM) is characterized by microvasculopathy of the striated muscle, which indicates different etiology, clinical manifestation and prognosis from the adult-onset dermatomyositis. We experienced 10 cases of JDM and 1 case of juvenile polymyositis (JPM) in the recent 14 years, and analyzed clinical manifestation, laboratory findings, treatment anrognosis. The cases were 9 girls and 2 boys. The onset of the disease was 2 years of age in 2 patients, and 9 to 13 years of age in 9 patients. During the follow-up courses, no cases were dead or complicated with neoplasm. Skin rash was the most frequent manifestation at the onset, and facial erythema was common. Muscle weakness was observed only in 4 cases at the onset, and in all cases muscle enzymes including creatine kinase and aldolase were elevated. The clinical course was classified into three groups; monocyclic (5 cases), chronic and recurrent (4 cases), and fulminant (2 cases). Prognosis depended not on the degree of the elevated serum muscle enzymes, but on the initial therapy employed at the onset of the disease. Five cases including 2 cases of fulminant type were initially treated with methylprednisolon pulse therapy, and all of these had no recurrence. On the other hand, 6 cases were started the therapy with p.o. prednisolone. Four of them had frequent recurrences in accordance with tapering of prednisolone. These cases were effectively treated with the combination with immunosuppressants. In previous reports, JDM and JPM were reported to be a disorder which had relatively favorable prognosis. But we found that one third of the cases had chronic and recurrent courses. Methylprednisolone pulses as initial therapy may be effective in preventing the chronicity and recurrence of the disease.


Pharmacokinetics-Based Optimization of Phototherapy in Neonates Undergoing Treatment for Hyperbilirubinemia.
Introduction: Neonatal jaundice results from combined effects of both increased production of bilirubin and decreased hepatic excretory capacity in neonates. Since its discovery, phototherapy is the most widespread treatment used in neonatal jaundice. In this work, we try to search for a relationship between exposure to phototherapy and decrease in serum bilirubin (linearity vs proportionality). Methods:The present research was non-randomized prospective study conducted in the Neonatal Intensive Care Unit (NICU), Department of Paediatrics, AIIMS, New Delhi, and the Department of Pharmacology, AIIMS, New Delhi, India. Subjects were recruited from neonates admitted in NICU AIIMS, which meets our selection criteria. Infants were given a low dose of either phototherapy continuously or phototherapy for the first six hours and a double dose of phototherapy for the next six hours. Samples were collected before the beginning of the study (0 hours) and then at six and 12 hours. Bilirubin concentration was measured using HPLC and (LC-MS/MS). Results and conclusion:The percentage of reduction during the 6-12-hour interval was compared with that during the 0-6-hour interval if all experimental conditions were kept unchanged. A relationship curve between percentage of reduction and irradiance was created based on the percentage of reduction in serum bilirubin during the 0-6-hour and 0-12-hour intervals. The present study suggests that the relationship between efficacy, as measured by percentage of reduction in serum bilirubin, and irradiance is unlikely to be linear. Collected data are insufficient to clearly distinguish between proportionality and saturation point, considering that the results may be possible with both of these hypotheses.


Characterization of GDP-Fucose: Polysaccharide Fucosyl Transferase in Corn Roots (Zea mays L.).
The peripheral root cap cells of corn (cv. SX-17A) secrete a fucose-rich, high molecular weight, polysaccharide slime via the dictyosome pathway. To study the synthesis of this polysaccharide, a technique for isolating and assaying GDP-fucose:polysaccharide fucosyl transferase activity was developed. Corn roots were excised from germinated seeds, incubated 12 hours at 10 C in water, and ground in 100 millimolar Tris or Pipes buffer (pH 7.0) with or without 0.5 molar sucrose. The membrane-bound enzyme was solubilized by sonication in the presence of 2 molar urea and 1.5% (v/v) Triton X-100 and assayed by monitoring the incorporation of GDP-[(14)C]fucose into endogenous acceptors. Optimum enzyme activity is expressed at pH 7.0 and 30 C in the presence of 0.8% (v/v) Triton X-100. The enzyme does not require divalent cations for activation and is inhibited by concentrations of MnCl(2) or MgCl(2) greater than 1 millimolar. Corn root cap slime will serve as an exogenous acceptor for the enzyme if it is first hydrolyzed in 5 millimolar trifluoroacetic acid for 60 minutes at 18 pounds per square inch, 121 C. This procedure prepares the acceptor by removing terminal fucose residues from the slime molecule. Kinetics of fucose release during hydrolysis of native slime and in vitro synthesized product suggests that the two polymers possess similar linkages to fucose.


Burst fractures of the thoracic and lumbar spine.
A burst fracture may be defined as an unstable compression fracture of the posterior wall of the vertebral body that allows fragments to be retropulsed into the spinal canal. Computerized axial tomography evaluation of these injuries often reveals posterior element fracture heretofore not stressed in the literature. In surgical treatment for these injuries four important considerations must be met; (1) the coronal and sagittal alignment of the spine; (2) patency of the neural canal; (3) the two-column concept of spinal stability; and (4) bony vertebral body reconstitution. An algorithm for treatment may be developed with the aid of these principles. Distraction and the creation of spinal lordosis are necessary for reduction.


Impact of a programme of autologous blood donation on the incidence of infection in patients with colorectal cancer.
To assess the effects of both autologous and homologous blood transfusion on the incidence of infective complications after elective operations for colorectal cancer. Prospective open study. University hospital, Italy. Recording of variables known to influence the development of infection. Infective morbidity and mortality. Fifty-three patients (33%) deposited their own blood. Eighty-six of the 161 (53%) patients were transfused, 36 were given autologous blood, 48 homologous blood and 2 both autologous and homologous blood. These two were excluded from the analysis. Infective complications developed in 28 patients (17%), of which 7/75 (9%) were in patients who had not been transfused, 5/56 (14%) in patients given autologous transfusion, and 16/48 (33%) in patients given homologous transfusions (p < 0.001). Multivariate analysis identified homologous blood transfusion as the only variable significantly associated with the development of postoperative infective complications. No patient died. Transfusion of autologous blood was associated with significantly fewer postoperative infective complications than transfusion of homologous blood or no blood transfusion.


Gamma-aminobutyric acid agonists for neuroleptic-induced tardive dyskinesia.
Chronic antipsychotic drug treatment may cause tardive dyskinesia (TD), a long-term movement disorder. The gamma-aminobutyric acid (GABA) agonist drugs have been trialed as a treatment for TD, but these drugs have intense sedative properties and may exacerbate psychotic symptoms. To determine the effects of GABA agonist drugs (baclofen, gamma-vinyl-GABA, gamma-acetylenic-GABA, progabide, muscimol, sodium valproate and tetrahydroisoxazolopyridine (THIP)) for people with neuroleptic-induced tardive dyskinesia (TD) and schizophrenia or other chronic mental illnesses. Electronic searches of Biological Abstracts (1982-2000), The Cochrane Library (Issue 4, 2000), Cochrane Schizophrenia Group's Register of Trials (2000), EMBASE (1980-2000), LILACS (1982-2000), MEDLINE (1966-2000), PsycLIT (1974-2000), and SCISEARCH were undertaken. References of all identified studies were searched for further trial citations. First authors of each included trial were contacted. The inclusion criteria for all relevant randomised studies were that they should focus on people with schizophrenia or other chronic mental illnesses, with neuroleptic-induced TD and compare the use of non-benzodiazepine GABA agonist drugs to placebo or no intervention. The reviewers extracted the data independently and the relative risk (RR) and its 95% confidence interval (CI) or the weighted mean difference with 95% CI were estimated. The reviewers assumed that people who dropped out had no improvement. Eight small, short, poorly reported studies were included. For the outcome of 'no clinically important improvement in tardive dyskinesia' GABA agonist drugs were not clearly better than placebo (n=108, RR 0.83 CI 0.6 to 1.1). Deterioration in mental state was more likely to occur for people receiving GABA medication (n=95, RR 2.55 CI 1.17 to 5.59), but this effect was influenced by the decision to assign a negative outcome to those who dropped out before the end of the study. A greater proportion of people allocated GABA medication may fail to complete the trial compared with those allocated placebo (20% versus 9%) but, this difference was not statistically significant (n=136, RR 1.99 CI 0.84 to 4.68). There is a suggestion of an increase in ataxia for both baclofen and sodium valproate (n=95, RR 3.26 CI 0.4 to 30), and in sedation (n=113, RR 2.12 CI 0.8 to 5.4) compared with placebo. Withdrawal of THIP may cause seizures. Currently, evidence of effect of baclofen, progabide, sodium valproate, or THIP for people with neuroleptic-induced TD is inconclusive and unconvincing. Any possible benefits are likely to be outweighed by the adverse effects associated with the use of these drugs.


Power Doppler Sonography: Applications in Musculoskeletal Imaging.
Power Doppler sonography (PDS) is a recently developed technique that depicts moving blood volume within tissues. The enhanced sensitivity of PDS makes it possible to depict soft tissue vascularity, facilitating its role in the evaluation of musculoskeletal inflammatory diseases. A broad range of new and potential applications of PDS in the musculoskeletal system will be described including its use in the setting of bursal, tendon, articular, and muscle diseases, and in the evaluation of fluid collections and soft tissue masses.


Molecular characterization of nuclear small subunit (18S)-rDNA pseudogenes in a symbiotic dinoflagellate (Symbiodinium, Dinophyta).
For the dinoflagellates, an important group of single-cell protists, some nuclear rDNA phylogenetic studies have reported the discovery of rDNA pseudogenes. However, it is unknown if these aberrant molecules are confined to free-living taxa or occur in other members of the group. We have cultured a strain of symbiotic dinoflagellate, belonging to the genus Symbiodinium, which produces three distinct amplicons following PCR for nuclear small subunit (18S) rDNA genes. These amplicons contribute to a unique restriction fragment length polymorphism pattern diagnostic for this particular strain. Sequence analyses revealed that the largest amplicon was the expected region of 18S-rDNA, while the two smaller amplicons are Symbiodinium nuclear 18S-rDNA genes that contain single long tracts of nucleotide deletions. Reverse transcription (RT)-PCR experiments did not detect RNA transcripts of these latter genes, suggesting that these molecules represent the first report of nuclear 18S-rDNA pseudogenes from the genome of Symbiodinium. As in the free-living dinoflagellates, nuclear rDNA pseudogenes are effective indicators of unique Symbiodinium strains. Furthermore, the evolutionary pattern of dinoflagellate nuclear rDNA pseudogenes appears to be unique among organisms studied to date, and future studies of these unusual molecules will provide insight on the cellular biology and genomic evolution of these protists.


Rainfall erosivity index for the Ghana Atomic Energy Commission site.
Rainfall erosivity is the potential ability for rainfall to cause soil loss. The purpose of this study was to estimate the rainfall erosivity index for the Ghana Atomic Energy Commission site in order to compute the surface erosion rate. Monthly rainfall data, for the period 2003-2012 were used to compute annual rainfall erosivity indices for the site, using the Modified Fournier index. Values of the annual rainfall erosivity indices ranged from 73.5 mm for 2004 to 200.4 mm for the year 2003 with a mean annual erosivity index of 129.8 mm for the period. The Pearson's Coefficient of Correlation was used to establish the relationship between annual rainfall and annual rainfall erosivity. This showed a high degree of positive relationship (r = 0.7) for the study area. The computed mean annual erosivity index revealed that the site is in the high erosion risk zone. Therefore, it is necessary to develop soil protection and management strategies to protect the soil from erosion.


Cephalosporins in surgery. Prophylaxis and therapy.
Prophylactic antibiotics in surgery are intended to prevent morbidity and mortality, as well as to reduce the duration and cost of hospitalisation. The indications for prophylaxis, and its effectiveness, should be evaluated with these criteria in mind. The basis for antibiotic prophylaxis in surgery is either provision of an effective concentration of antibiotic in the tissue site at the time of potential contamination, or (primarily in the case of colorectal surgery) to reduce the inoculum of potentially contaminating bacteria. Cephalosporins are the antibiotics most widely used for prophylaxis in surgery, and have clearly been shown to reduce postoperative morbidity in vaginal hysterectomy, resection of head and neck cancers, vascular grafting, total joint replacement, repair of hip fractures, and high risk gastroduodenal surgery. They are probably also useful in cardiac surgery, abdominal hysterectomy, caesarean section, and colorectal surgery. For orthopaedic, cardiac, gynaecological, and gastroduodenal procedures it is important to select an antibiotic with proven clinical activity against Gram-positive organisms. For head and neck surgery, the spectrum of activity should also include oral anaerobes and Enterobacteriaceae. For biliary surgery an antibiotic effective against both Gram-positive and Gram-negative organisms may offer at least theoretical advantages, while for appendicectomy a cephamycin represents the most appropriate choice. In colorectal procedures, activity against B. fragilis is the major consideration in selecting an antibiotic for systemic prophylaxis. When intra-abdominal sepsis occurs following surgery, a potentially wide range of bacteria may be implicated, but in practice such infections are due to a small number of species, with B. fragilis most commonly implicated. The most useful cephalosporins in this setting are those active against both aerobic Gram-negative bacteria and anaerobes, especially B. fragilis. In practice, an aminoglycoside is often administered concomitantly. Importantly, prompt surgical treatment is the cornerstone of management of abdominal sepsis, and empirical antibiotic therapy should be adjusted as needed when culture and sensitivity tests become available.


An overview of antibody-drug conjugates in oncological practice.
Antibody-drug conjugates (ADCs) are designed to manipulate the toxic efficacy of specific chemotherapeutic compounds, employing the high affinity of antibody-mediated delivery so as to drive them selectively to target cancer cells. These immunoconjugates encompass the general tendency towards precision medicine and avert the systemic toxicities of conventional chemotherapy, accomplishing an improved therapeutic index. Cumulative experience acquired from first-generation ADCs offers new perspectives to these promising therapeutic modalities for various hematological and solid cancers and propels their clinical development in a faster-than-ever pace, as indicated by the approval of four novel ADCs during the last year. This paper aims to provide an up-to-date overview of the eight ADCs approved by the US Food and Drug Administration and their current indications in oncological practice. Starting from their bio-pharmaceutical background, we track their clinical evolution, with an emphasis on the pivotal trials that led to their commercial release. Late-stage studies examining these eight ADCs in other-than-approved settings as well as the investigation of potential new candidates are also reviewed. In the close future, more data are expected to expand ADCs' oncological utility and to further reshape their role in cancer therapeutics.


Evaluation of bleeding risk and measurement methods in dental patients.
The present study explores bleeding manifestations in routine dental surgical procedures, evaluates the influence of antithrombotic drugs upon bleeding risk, and validates the efficiency of a clinical method for the measurement of bleeding. A prospective observational study was made involving a cohort of 99 patients in the setting of normal clinical practice, with the added conduction of prior hematological tests including baseline hemostasis and platelet function, based on a new method (Multiplate System®). For evaluation of the bleeding manifestations, a clinical method was selected that evaluates bleeding on the basis of its duration and the hemostatic measures needed to resolve the problem. Almost one-third of the patients (27.3%) were receiving treatment with oral antiplatelet drugs, while 19.2% received oral anticoagulants and 9% received combined therapy with acetylsalicylic acid plus clopidogrel. In turn, an 8% incidence of moderate bleeding episodes was detected correlated to the ASPI platelet function test and to advanced patient age. The incorporation of platelet function tests increases the safety of oral surgery in elderly patients subjected to antiplatelet treatment, particularly with acetylsalicylic acid and clopidogrel.