The Applications of Lattice Light-sheet Microscopy for Functional Volumetric Imaging of Hippocampal Neurons in a Three-Dimensional Culture System.
The characterization of individual cells in three-dimensions (3D) with very high spatiotemporal resolution is crucial for the development of organs-on-chips, in which 3D cell cultures are integrated with microfluidic systems. In this study, we report the applications of lattice light-sheet microscopy (LLSM) for monitoring neuronal activity in three-dimensional cell culture. We first established a 3D environment for culturing primary hippocampal neurons by applying a scaffold-based 3D tissue engineering technique. Fully differentiated and mature hippocampal neurons were observed in our system. With LLSM, we were able to monitor the behavior of individual cells in a 3D cell culture, which was very difficult under a conventional microscope due to strong light scattering from thick samples. We demonstrated that our system could study the membrane voltage and intracellular calcium dynamics at subcellular resolution in 3D under both chemical and electrical stimulation. From the volumetric images, it was found that the voltage indicators mainly resided in the cytosol instead of the membrane, which cannot be distinguished using conventional microscopy. Neuronal volumetric images were sheet scanned along the axial direction and recorded at a laser exposure of 6 ms, which covered an area up to 4800 μm2, with an image pixel size of 0.102 μm. When we analyzed the time-lapse volumetric images, we could quantify the voltage responses in different neurites in 3D extensions.


Measurement of Urea in the Saliva of Healthy Mice - a Pilot Study.
Salivary urea is studied as a non-invasive alternative for screening and monitoring of renal diseases. Its high variability prevents a wider clinical use. Animal experiments are needed to identify factors affecting this marker. The aim of this study was to describe the inter-individual variability of salivary urea in healthy mice, establish reference intervals, and analyse the effects of sex, age and body weight. Plasma and saliva samples were obtained from 37 male and 41 female healthy adult CD1 mice aged 13-69 weeks (body weight 22-51 g). The reference interval for salivary urea in heathy mice based on our results is 2.7-8.4 mmol/l (CV = 23 %). Multivariate analysis did not show any significant effect of age, sex, or body weight. In addition, salivary urea did not correlate with its plasma concentrations. The high variability of the promising salivary marker of kidney function in healthy mice requires further research before its use to diagnose or monitor renal failure in animal models of kidney diseases. Other potential confounders should be analysed, including intra-individual and pre-analytical variability. In addition, a normalization factor such as total salivary proteins or salivation rate is likely needed.


[Prevention of cancer].
Both the cancer incident rate and mortality rate are increasing in Japan. Well-balanced and strategic measures effectively combining primary and secondary preventions are required. In this article, primary prevention measures, such as smoking control and improvement of dietary habits, and secondary prevention measures, such as new methods of cancer screening are discussed. The importance of establishing a Center for Cancer Prevention and Screening is also discussed.


Emergency peripartum hysterectomy.
A total of 54 166 mothers delivered at the Riyadh Armed Forces Hospital between 1990 and 1997, including 6119 (11.3%) caesarean sections. Emergency peripartum hysterectomy for obstetric haemorrhage was carried out in 16 cases (0.3/1000 deliveries). The operation followed major degrees of placenta praevia in 12 (75%) cases and atonic postpartum haemorrhage in four (25%). All patients required blood transfusion. There was one neonatal death and no maternal deaths. Although the operation was straightforward, bladder injury occurred in five (31%) cases which was repaired with no residual damage. Placenta accreta was confirmed histologically in 12 (75%) patients. In conclusion, all obstetricians should be aware of the strong association between a scarred uterus, placenta praevia and placenta accreta which can be very adherent and difficult to remove causing bleeding and necessitating hysterectomy. The operation should be performed by an experienced obstetrician before the patient's condition is extreme.


Polymeric Dental Nanomaterials: Antimicrobial Action.
This review aims to describe and critically analyze studies published over the past four years on the application of polymeric dental nanomaterials as antimicrobial materials in various fields of dentistry. Nanoparticles are promising antimicrobial additives to restoration materials. According to published data, composites based on silver nanoparticles, zinc(II), titanium(IV), magnesium(II), and copper(II) oxide nanoparticles, chitosan nanoparticles, calcium phosphate or fluoride nanoparticles, and nanodiamonds can be used in dental therapy and endodontics. Composites with nanoparticles of hydroxyapatite and bioactive glass proved to be of low efficiency for application in these fields. The materials applicable in orthodontics include nanodiamonds, silver nanoparticles, titanium(IV) and zinc(II) oxide nanoparticles, bioactive glass, and yttrium(III) fluoride nanoparticles. Composites of silver nanoparticles and zinc(II) oxide nanoparticles are used in periodontics, and nanodiamonds and silver, chitosan, and titanium(IV) oxide nanoparticles are employed in dental implantology and dental prosthetics. Composites based on titanium(IV) oxide can also be utilized in maxillofacial surgery to manufacture prostheses. Composites with copper(II) oxide nanoparticles and halloysite nanotubes are promising materials in the field of denture prosthetics. Composites with calcium(II) fluoride or phosphate nanoparticles can be used in therapeutic dentistry for tooth restoration.


Association between Maternal Periodontitis and Development of Systematic Diseases in Offspring.
Periodontal disease (PD) is one of the most common oral conditions affecting both youths and adults. There are some research works suggesting a high incidence of PD in pregnant women. As an inflammatory disease of bacterial origin, PD may result in the activation of the pathways affecting the course and the pregnancy outcome. The authors, based on the literature review, try to answer the PICO question: Does maternal periodontitis (exposure) influence the incidence of complications rates in pregnancy and the development of systemic diseases in childhood and adult offspring (outcome) in the humans of any race (population) compared to the offspring of mothers with healthy periodontium (comparison)? The authors try to describe the molecular pathways and mechanisms of these interdependencies. There is some evidence that maternal periodontitis may affect the pregnancy course and outcome, resulting in preeclampsia, preterm delivery, vulvovaginitis and low birth weight. It can be suggested that maternal periodontitis may affect offspring epigenome and result in some health consequences in their adult life.


Antigenic variation of gonococcal pilus involves assembly of separated silent gene segments.
The pilus is a major outer-membrane protein of Neisseria gonorrhoeae that undergoes phase and antigenic variation. In strain MS11 pilus expression is regulated at two expression loci on the chromosome, pilE1 and pilE2, although many other regions contain silent pilin information. A comparison of variant pilin sequences has revealed that the gene can be divided into a constant, a semivariable, and a hypervariable region. We report here that complete pilin genes are found only at the expression loci. Silent constant and variable region pilin gene segments are located on separate and distinct restriction fragments, and the generation of a complete pilin gene within the expression loci is the result of multiple recombination events. Conserved sequences within and flanking the pilin gene are proposed to act as recombination sites during the gene conversion events needed to produce a functional pilin gene.


The Logician in the Archive: John Venn's Diagrams and Victorian Historical Thinking.
Like the overlapping circles of his famous diagrams, English probability theorist, logician, and historian John Venn (1834-1923) operated at a site of productive intersection. Across a career comprising seemingly disparate pursuits, Venn exhibited an epistemic apparatus shaped by a mathematical probability, formal logic, and British historicism. Scholarly interest in Venn has tended to isolate these elements; I argue that a deep continuity joined his projects. The unappreciated coherence of his work reveals larger convergent currents in Victorian historical thinking, a kind of statistical attitude according to which large series of elite individuals constituted the most illuminating historical subject.


Oral bis(tri-n-butyltin) oxide in pregnant mice. I. Potential influence of maternal behavior on postnatal mortality.
Pregnant Swiss mice were treated with 0, 5, 10, 20, and 30 mg/kg body weight of bis(tri-n-butyltin) oxide (TBTO) on d 6-15 of gestation. At birth litters were normalized to eight pups, and postnatal evaluation of pup growth rate and behavioral observations of dams were carried out. Litters were sacrificed on postnatal days (pnd) 7, 14, and 21, to perform hematological analysis, in connection with another study. Dam weight gain was impaired in all the treated groups (except at the lowest dose level) in the late phase of gestation. A high incidence of anticipated or delayed parturitions, without any correlation with fetal mass, was observed in the treated groups. All the treated dams showed a significant increase in resorptions, and a decrease in body weight gain between gestational day (gd) 6 and pnd 1. At birth, only the 20 and 30 mg/kg dose groups showed reduced litter size and reduced pup weight. Body weight gain reduction of pups persisted in wk 1 of life only in the 10 and 20 mg/kg dose groups. In addition, the maternal weight trend was affected during the lactation period in the higher dose groups. Postnatal death rate and growth rate of treated pups were affected by an altered maternal behavior; pups, apparently viable and with normal weight, were found often scattered throughout the cage with signs of wounds, and the percentage of dams that had not built a nest increased in the 10, 20, and 30 mg/kg dose groups. Total absence of parental care was noted in many litters, and many infanticidal events were reported. Our results seem to confirm low TBTO embryofetotoxicity, and strongly support the assumption that TBTO's toxicity to the mother is much stronger than its embryo-fetotoxic potential. Most of the reproductive parameters examined in this study were unaffected in the low-dose group, while some indices, such as gestation length and maternal weight gain between gd 6 and pnd 1, were markedly altered also at the 5 mg/kg dose level and appear to be sensitive parameters in assessing maternal toxicity.


Pleiotrophin interacts with glycosaminoglycans in a highly flexible and adaptable manner.
Pleiotrophin (PTN) is a potent mitogenic cytokine whose activities are controlled by its interactions with glycosaminoglycan (GAG). We examined the specificity of PTN for several types of GAG oligosaccharides. Our data indicate that the interaction of PTN with GAGs is dependent on the sulfation density of GAGs. Surprisingly, an acidic peptide also had similar interactions with PTN as GAGs. This shows that the interaction of PTN with anionic polymers is flexible and adaptable and that the charge density is the main determinant of the interaction. In addition, we show that PTN can compensate for the loss of its termini in interactions with heparin oligosaccharides, allowing it to maintain its affinity for GAGs in the absence of the termini. Taken together, these data provide valuable insight into the interactions of PTN with its proteoglycan receptors.


Plant-Derived Natural Non-Nucleoside Analog Inhibitors (NNAIs) against RNA-Dependent RNA Polymerase Complex (nsp7/nsp8/nsp12) of SARS-CoV-2.
The emergence of fast-spreading SARS-CoV-2 mutants has sparked a new phase of COVID-19 pandemic. There is a dire necessity for antivirals targeting highly conserved genomic domains on SARS-CoV-2 that are less prone to mutation. The nsp12, also known as the RNA-dependent RNA-polymerase (RdRp), the core component of 'SARS-CoV-2 replication-transcription complex', is a potential well-conserved druggable antiviral target. Several FDA-approved RdRp 'nucleotide analog inhibitors (NAIs)' such as remdesivir, have been repurposed to treat COVID-19 infections. The NAIs target RdRp protein translation and competitively block the nucleotide insertion into the RNA chain, resulting in the inhibition of viral replication. However, the replication proofreading function of nsp14-ExoN could provide resistance to SARS-CoV-2 against many NAIs. Conversely, the 'non-nucleoside analog inhibitors (NNAIs)' bind to allosteric sites on viral polymerase surface, change the redox state; thereby, exert antiviral activity by altering interactions between the enzyme substrate and active core catalytic site of the RdRp. NNAIs neither require metabolic activation (unlike NAIs) nor compete with intracellular pool of nucleotide triphosphates (NTPs) for anti-RdRp activity. The NNAIs from phytonutrient origin are potential antiviral candidates compared to their synthetic counterparts. Several in-silico studies reported the antiviral spectrum of natural phytonutrient-NNAIs such as Suramin, Silibinin (flavonolignan), Theaflavin (tea polyphenol), Baicalein (5,6,7-trihydroxyflavone), Corilagin (gallotannin), Hesperidin (citrus bioflavonoid), Lycorine (pyrrolidine alkaloid), with superior redox characteristics (free binding energy, hydrogen-bonds, etc.) than antiviral drugs (i.e. remdesivir, favipiravir). These phytonutrient-NNAIs also exert anti-inflammatory, antioxidant, immunomodulatory and cardioprotective functions, with multifunctional therapeutic benefits in the clinical management of COVID-19.


Using the american board of internal medicine practice improvement modules to teach internal medicine residents practice improvement.
Although residency programs must prepare physicians who can analyze and improve their practice, practice improvement (PI) is new for many faculty preceptors. We describe the pilot of a PI curriculum incorporating a practice improvement module (PIM) from the American Board of Internal Medicine for residents and their faculty preceptors. Residents attended PI didactics and completed a PIM during continuity clinic and outpatient months working in groups under committed faculty. All residents participated in PI group projects. Residents agreed or strongly agreed that the projects and the curriculum benefited their learning and patient care. A self-assessment revealed significant improvement in PI competencies, but residents were just reaching a "somewhat confident" level. A PI curriculum incorporating PIMs is an effective way to teach PI to both residents and faculty preceptors. We recommend the team approach and use of the PIM tutorial approach especially for faculty.


National health expenditures, 1983.
Although growing more slowly than in recent years, spending for health continued to account for an increasing share of the Nation's gross national product. In 1983, spending for health amounted to 10.8 percent of the gross national product, or $1,459 per person. Public programs financed 40 percent of all personal health care spending. Medicare and Medicaid expended $91 billion in benefits, 29 percent of all spending for personal health. New estimates of spending in calendar year 1983, along with revised measures of the benefits paid by private health insurers, are presented here.


Risk factors for workplace sexual harassment and violence among a national cohort of women in Iceland: a cross-sectional study.
Sexual harassment and violence in the workplace are a serious public health concern for women worldwide with substantial costs due to sick leave and personnel turnover. Yet little is known about the prevalence of sexual harassment and violence at a population level, especially across work sectors. The aim of this study was to investigate the prevalence of workplace sexual harassment and violence by demographic factors and work sectors among Icelandic women. For this cross-sectional study we analysed nationally representative, de-identified individual-level data from women who had responded to an online survey item about self-labelled current and lifetime workplace sexual harassment or violence as part of the Stress and Gene Analysis (SAGA) study, a cross-sectional nationally representative study done from March 1, 2018, to July 1, 2019. Eligible participants were women who resided in Iceland, were aged between 18 and 69 years, spoke Icelandic, and had a registered address from the Icelandic Population Register or a telephone number from the online 1819 service. We used binomial and Poisson regression analysis to study the cross-sectional association between workplace sexual harassment and violence and demographic factors (eg, age, sexual orientation, and education) and factors relating to the workplace (eg, work schedule), across works sectors. Of 113 814 eligible women, 104 197 were invited to complete the online survey, of whom 30 403 women responded and were included in the SAGA cohort. 15 799 women answered the item about exposure to workplace sexual harassment or violence. 11 286 [71·4%] of 15 799 women answered the question about sexual orientation that were included in the survey from June, 2018. 5291 (33·5%) of 15 799 of participants reported having experienced workplace sexual harassment or violence during their lifetime, and 1178 (7·5%) in their current workplace. Such exposure in the current workplace was most common among women who were young (age 18-24 years: prevalence ratio [PR] 3·89 [95% CI 2·66-5·71]; age 25-34 years: 3·66 [2·53-5·31]), single (1·27 [1·12-1·43]), and worked shifts (2·32 [2·02-2·67]), with the highest prevalence rates observed among women in work sectors of public figures (15·67 [9·34-25·12]), tourism (15·01 [11·01-20·13]), and the legal system and security (13·56 [7·00-24·66]). Lifetime exposure to workplace sexual harassment or violence was more common among women who belonged to sexual minorities than among heterosexual women (PR 1·35 [1·24-1·46]). Lifetime exposure to workplace sexual harassment or violence seems common among women in a Nordic welfare state. These findings provide nuanced targets for prevention and for public policies aimed at promoting women's safety in the work environment. Icelandic Gender Equality Fund, European Research Council, and Icelandic Centre for Research.


The impact of advanced age on trauma triage decisions and outcomes: a statewide analysis.
Physiologic variables used in trauma triage criteria may be significantly affected by age, decreasing their predictive value in geriatric trauma. The study population was all adult patients in the Washington State Trauma Registry from 2000 to 2004. Elderly patients were defined as those aged >65 years. Multivariate analyses were conducted to evaluate the relationship between age and trauma triage decisions, need for emergent interventions, and outcomes. Of 51,227 trauma admissions, 13,820 (27%) were for elderly patients. Elderly patients were significantly less likely to have trauma team activation (14% vs 29%, P <.01), despite a similar percentage of severe injuries (injury severity score > 15), and more often required urgent craniotomy (10% vs 6%, P <.01) and orthopedic procedures (67% vs 51%, P <.01). Heart rate and blood pressure were not predictive of severe injury for those aged >65 years. Undertriaged elderly patients had 4 times the mortality rate and discharge disability of younger patients (both P values <.001). Elderly trauma victims are less likely to undergo rapid trauma evaluation and have significantly worse outcomes compared with younger patients. Standard physiologic triage variables may not identify severe injury in older patients.


Rectal Metastases of Breast Carcinoma: A Case Report.
The scarcely reported hematogenous rectal metastases from breast cancer are rare and the diagnosis is challenging. They may be recognized before, concomitantly with, or after the diagnosis of the primary site of breast cancer. Invasive lobular cancer is the histological type more frequently described, and most of the affected patients have a late diagnosis. Tardive recognition is associated with poor outcomes, despite the management options. Endoscopic and imaging evaluations, mainly magnetic resonance studies, are useful, but the anatomopathological findings are mandatory to confirm the diagnostic hypothesis. We describe a middle-aged woman with advanced rectal metastases of unsuspected breast cancer found during the evaluation of manifestations due to intestinal implants. One must highlight long-term follow-up of breast cancers even if seeming in remission. The aim of this report is to enhance the suspicion index of primary health care workers.


Reporting unethical research behavior.
Scientists, as professionals, have a responsibility to self-regulate. However, whistleblowing is rare. We investigated scientists' infrequent disclosure of unethical behavior by studying their responses to scenarios describing unethical research acts and compared their responses to those of research administrators. A cross-sectional survey was administered to National Science Foundation-funded principal investigators and their institutions' representatives (IRs) to the Office of Research Integrity. Both scientists and IRs proposed to respond to nearly all research behaviors that they rated as unethical. Scientists more often proposed responses limited to the research team (58% vs. 25% of cases, p < .001) whereas IRs more often proposed to inform an administrator or dean, journal editor, funding agency, professional society, or reporter. The prior behavior and academic rank of the scenario protagonist were associated with responses, but consequences of the unethical behavior were not. Scientists appear to perceive that they uphold their responsibility to respond to unethical behavior by disclosures within the research team, whereas administrators propose to report to externally accountable individuals, raising the question of whether scientists' behavior constitutes professional self-regulation or cover up.


Neighboring sp-Hybridized Carbon Participated Molecular Oxygen Activation on the Interface of Sub-nanocluster CuO/Graphdiyne.
Activation of O2 is a crucial step in oxidation processes. Here, the concept of sp-hybridized C≡C triple bonds as an electron donor is adopted to develop highly active and stable catalysts for molecular oxygen activation. We demonstrate that the neighboring sp-hybridized C and Cu sites on the interface of the sub-nanocluster CuO/graphdiyne are the key structures to effectively modulate the O2 activation process in the bridging adsorption mode. The as-prepared sub-nanocluster CuO/graphdiyne catalyst exhibited the highest CO oxidation activity and readily converted 50% CO at around 133 °C, which is 34 and 94 °C lower than that for CuO/graphene and CuO/active carbon catalysts, respectively. In situ diffused reflectance infrared Fourier transform spectroscopy and density functional theory calculation results proved that the neighboring sp-hybridized C is more favorable to promote the rapid dissociation of carbonate than sp2-hybridized C without overcoming any energy barrier. The gaseous CO directly reacts with the active molecular oxygen and tends to proceed through the E-R mechanism with a relatively low energy barrier (0.20 eV). This work revealed that sp-hybridized C of graphdiyne-based materials could effectively improve the O2 activation efficiency, which could facilitate the low-temperature oxidation processes.


A case of factor VIII inhibitor-positive acquired hemophilia treated by plasmapheresis.
We report on a case of factor VIII inhibitor-positive acquired hemophilia in which combined therapy of plasma exchange (PE) and steroids was effective. The patient, a 68-year-old man, had undergone hemodialysis since April 1998, due to chronic renal failure caused by diabetic nephropathy. The hemostasis of blood access sites gradually became difficult after the initiation of dialysis and the prolongation of activated partial thromboplastin time (APTT) (74.5 s), and a decrease in factor VIII (0.02%) and an abnormally high concentration of factor VIII inhibitor (111 U/ml) were found. Under the diagnosis of factor VIII inhibitor-positive acquired hemophilia, 3 consecutive PE were performed, followed by a large dose administration of gamma globulin. However, the effect of this therapy disappeared within 20 days. Then the PE therapy was performed again accompanied by pulse methylprednisolone therapy. After that, factor VIII inhibitor was suppressed and the patient's hemostatic defect continued to improve even after the reduction of the steroid dose. These results suggest that PE is very effective in treating factor VIII inhibitor-positive acquired hemophilia.


Regional lung function following upper sleeve lobectomy for bronchogenic carcinoma.
Regional lung function of the operated side following upper sleeve lobectomy (n = 8) and simple upper lobectomy (n = 7) for lung cancer was evaluated. Regional ventilation was studied with Krypton 81m and regional pulmonary blood flow was studied with Technetium 99m. Measurements were taken from 12 to 24 months after operation. The ventilation rate of the operated side following right upper sleeve lobectomy (n = 5) was 42.9 +/- 6.7% and the perfusion rate was 37.4 +/- 4.6%. The regional ventilation rate of the operated side after simple right upper lobectomy (n = 3) was 45.9 +/- 10.5% and the perfusion rate was 46.2 +/- 5.2%. For the patients with left upper sleeve lobectomy (n = 3), these ratios were 29.9 +/- 11.1% and 19.2 +/- 3.6%, respectively. For the patients with simple left upper lobectomy (n = 4), these ratios were 27.3 +/- 4.5% and 22.3 +/- 3.3%. There were no statistical differences between the group with upper sleeve lobectomy and that with simple upper lobectomy. Regional function improved gradually with time. In conclusion, the regional lung function of the operated side following sleeve lobectomy was well preserved and showed no difference when compared with the regional function after simple lobectomy for lung cancer.


Eculizumab in the treatment of atypical hemolytic uremic syndrome in an infant leads to cessation of peritoneal dialysis and improvement of severe hypertension.
Severe hypertension (HTN) and acute kidney injury frequently associated with atypical hemolytic uremic syndrome (aHUS) were refractory to various therapies in the pre-eculizumab era. Here we report the case of a 4-month-old boy who developed aHUS presenting with undetectable C3 protein, no predisposing mutations in complement factors, and no antibodies against factor H. Repeated plasma infusions and nine sessions of plasmapheresis were ineffective. The patient initially required continuous hemodiafiltration and thereafter peritoneal dialysis. Despite vigorous antihypertensive treatment and improved fluid overload with dialysis, HTN persisted. His low C3 level (<20 mg/dl) suggested unrestricted complement activation. Therefore, based on the suspicion of unrestricted complement cascade in the pathogenesis, treatment with eculizumab, a human anti-C5 monoclonal antibody, was initiated with the aim of controlling disease activity. Eculizumab therapy resulted in the control of severe HTN and cessation of peritoneal dialysis. This infant with HTN and acute kidney injury associated with aHUS was treated successfully with eculizumab.


In Vitro and In Vivo Evaluation of Two Hydroxychloroquine Tablet Formulations: HPLC Assay Development.
The relative in vitro and in vivo evaluation of two hydroxychloroquine (HCQ) products was conducted. In vitro studies involved assay, content uniformity and dissolution test, and a two-way crossover fashion were used for in vivo studies. Blood samples were collected at appropriate intervals and HCQ levels were measured using a validated reversed-phase high-performance liquid chromatography (HPLC) method. The drug and the internal standard, chloroquine (CQ), were extracted from blood with diethyl ether, separated and dried under nitrogen gas. Residues were reconstituted in the mobile phase and analyzed at 340 nm on a μ-bondapack C18 (250 × 4.6 mm) HPLC column with acetonitrile:methanol:KH2PO4 (10:10:80) mixture containing 0.01% triethylamine. The standard curve was linear within 50-1,500 ng/mL HCQ (R2 = 0.9996), relative errors were 1.6 to 5%, and the CV% ranged from 7 to 15.4. The resolution factor and RSD were 1.62 and 0.35% and in vitro data of both products met the USP requirements. The 90% confidence intervals for the ratios of the AUC0-96, Cmax and Tmax and their corresponding logarithmically transformed values of generic product over those of Plaquenil® were within the acceptable limit of 0.80-1.20 and 0.80-1.25, respectively. Therefore, the generic HCQ was bioequivalent to the innovator formulation.


Analytical and transfer characteristics of a fluorescent detection spray: Implications for subvisible and nanotrace particle transfers.
Fluorescent detection sprays are applied to objects to elucidate evidence of contact. Billed as an invisible powder, evidence of contact between objects may be visualized through illumination by ultra-violet light, which causes the fluorescent tracer to luminesce. While the presence of the fluorescent powder on a suspect or object is often used as evidence of direct contact, the fine nature of the powder, which is comprised of sub-visible particles that are generally less than 10 μm in diameter, lends itself to higher-order transfers that do not necessarily involve the original object. Due to the small particle size and light-yellow color, the particles are generally invisible to the unaided eye in white light. This increases the opportunity for unwanted or unanticipated transfers (i.e., contamination). This article provides a microanalytical characterization of a common fluorescent tracer and the approaches by which this powder (or analogous powders) may be applied, detected, and specifically identified in quantities that range from major to trace. This research illustrates the ease of higher order cross-transfers (up to the 10th order) and the considerations necessary to maximize the evidentiary value of sub-visible particles and nanotraces, while minimizing the chances of cross-contamination.


Structural, functional and evolutionary implications of the three-dimensional crystal structure of murine interferon-beta.
The crystal structure of recombinant murine interferon-beta as elucidated by Senda et al. (Proc. Jap. Acad. 66B: 77-80 (1990); EMBO J. 11: 3193-3201 (1992)) appears to represent the basic structural framework of all Type I interferons including interferons-beta and all subtypes of interferons-alpha of various mammalian origin. Now the huge accumulated data on the structure-activity relationship of Type I interferons using various chemical and genetic techniques can be systematically evaluated in terms of the three-dimensional structure. Structural comparison with other cytokines, for which three-dimensional structures have been established, including interferon-gamma and considerations on the evolution of cytokines and cytokine receptors are also given.


Oral drug delivery with polymeric nanoparticles: the gastrointestinal mucus barriers.
Oral delivery is the most common method for drug administration. However, poor solubility, stability, and bioavailability of many drugs make achieving therapeutic levels via the gastrointestinal (GI) tract challenging. Drug delivery must overcome numerous hurdles, including the acidic gastric environment and the continuous secretion of mucus that protects the GI tract. Nanoparticle drug carriers that can shield drugs from degradation and deliver them to intended sites within the GI tract may enable more efficient and sustained drug delivery. However, the rapid secretion and shedding of GI tract mucus can significantly limit the effectiveness of nanoparticle drug delivery systems. Many types of nanoparticles are efficiently trapped in and rapidly removed by mucus, making controlled release in the GI tract difficult. This review addresses the protective barrier properties of mucus secretions, how mucus affects the fate of orally administered nanoparticles, and recent developments in nanoparticles engineered to penetrate the mucus barrier.


Novel application of autologous micrografts in a collagen-glycosaminoglycan scaffold for diabetic wound healing.
Therapeutic strategies that successfully combine two techniques-autologous micrografting and biodegradable scaffolds-offer great potential for improved wound repair and decreased scarring. In this study we evaluate the efficacy of a novel modification of a collagen-glycosaminoglycan (collagen-GAG) scaffold with autologous micrografts using a murine dorsal wound model. db/db mice underwent a full thickness 1.0 cm2dorsal wound excision and were treated with a collagen-GAG scaffold (CGS group), a modified collagen-GAG scaffold (CGS + MG group) or simple occlusive dressing (Blank group). The modified scaffold was created by harvesting full thickness micrografts and transplanting these into the collagen-GAG membrane. Parameters of wound healing, including cellular proliferation, collagen deposition, keratinocyte migration, and angiogenesis were assessed. The group treated with the micrograft-modified scaffold healed at a faster rate, showed greater cellular proliferation, collagen deposition, and keratinocyte migration with higher density and greater maturity of microvessels. The grafts remained viable within the scaffold with no evidence of rejection. Keratinocytes were shown to migrate from the wound border and from the micrograft edges towards the center of the wound, while cellular proliferation was present both at the wound border and wound bed. We report successful treatment of diabetic wounds with a novel collagen-GAG scaffold modified with full-thickness automicrografts. Differences in cellular migration and proliferation offer maiden evidence on the mechanisms of wound healing. Clinically, the successful scaffold engraftment, micrograft viability and improved wound healing offer promising results for the development of a new therapeutic modality for wound repair.


Local Effects of Vaginally Administered Estrogen Therapy: A Review.
The results of the Women's Health Initiative (WHI) led to a distinct decline in the routine use of estrogen as preventive therapy for vasomotor symptoms, osteoporosis, and cardiovascular disease in postmenopausal women. Without estrogen replacement, one third of women experience symptoms of atrophic vaginitis including dryness, irritation, itching and or dyspareunia. Local application of estrogen has been shown to relieve these symptoms and improve quality of life for these women. In addition, local estrogen therapy may have a favorable effect on sexuality, urinary tract infections, vaginal surgery, and incontinence. This review examines the effects of vaginally applied estrogen on the vaginal epithelium, urethra and endometrium. An accompanying review examines the systemic effects of vaginally applied estrogen.


A Quantitative Analysis of Cellular Lipid Compositions During Acute Proteotoxic ER Stress Reveals Specificity in the Production of Asymmetric Lipids.
The unfolded protein response (UPR) is central to endoplasmic reticulum (ER) homeostasis by controlling its size and protein folding capacity. When activated by unfolded proteins in the ER-lumen or aberrant lipid compositions, the UPR adjusts the expression of hundreds of target genes to counteract ER stress. The proteotoxic drugs dithiothreitol (DTT) and tunicamycin (TM) are commonly used to induce misfolding of proteins in the ER and to study the UPR. However, their potential impact on the cellular lipid composition has never been systematically addressed. Here, we report the quantitative, cellular lipid composition of Saccharomyces cerevisiae during acute, proteotoxic stress in both rich and synthetic media. We show that DTT causes rapid remodeling of the lipidome when used in rich medium at growth-inhibitory concentrations, while TM has only a marginal impact on the lipidome under our conditions of cultivation. We formulate recommendations on how to study UPR activation by proteotoxic stress without interferences from a perturbed lipid metabolism. Furthermore, our data suggest an intricate connection between the cellular growth rate, the abundance of the ER, and the metabolism of fatty acids. We show that Saccharomyces cerevisiae can produce asymmetric lipids with two saturated fatty acyl chains differing substantially in length. These observations indicate that the pairing of saturated fatty acyl chains is tightly controlled and suggest an evolutionary conservation of asymmetric lipids and their biosynthetic machineries.


COVID-19 in health-care workers: lessons from SARS and MERS epidemics and perspectives for chemoprophylaxis and vaccines.
Introduction: The world is now facing the COVID-19 pandemic. Experience with SARS-CoV and MERS-CoV, and early reports about SARS-CoV-2 infection suggest that health-care settings and health-care workers (HCWs) are vulnerable in the context of the emergence of a new coronavirus. Areas covered: To highlight the need for prophylactic strategies particularly for HCWs, we identified SARS-CoV, MERS-CoV, and SARS-CoV-2 outbreaks in health-care settings and the incidence of infections in HCWs by a search on MEDLINE and MEDxRIV (for SARS-Cov-2). To identify prophylactic strategies against, we conducted a search on MEDLINE and clinicaltrials.gov about studies involving SARS-CoV, MERS-CoV, and SARS-CoV-2. Expert opinion: HCWs account for a great part of SARS, MERS, and SARS-CoV-2 infections, they may also contribute to the spread of the disease, particularly in health-care settings, and contribute to nosocomial outbreaks. Some preventive strategies were evaluated in previous emerging coronavirus epidemics, particularly in MERS-CoV. For COVID-19 prevention, different chemoprophylaxis with drug repositioning and new agents are under evaluation, and different vaccine candidates entered clinical development, with clinical trials. HCWs are a crucial target population for pre-exposure and post-exposure prophylaxis.


A diastereoselective and concise synthesis of functionalised vinyl epoxides with a Morita-Baylis-Hillman backbone.
A highly diastereoselective organocatalytic synthesis of unique functionalised vinyl epoxides, displaying a Morita-Baylis-Hillman backbone, has been developed by means of an user friendly sulfonium ylide epoxidation of aldehydes from a readily available alpha-(bromomethyl)acrylamide derivative. The first result in the asymmetric version is discussed.


Molecular Mechanisms and Cellular Contribution from Lung Fibrosis to Lung Cancer Development.
Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive, fibrosing interstitial lung disease (ILD) of unknown aetiology, with a median survival of 2-4 years from the time of diagnosis. Although IPF has unknown aetiology by definition, there have been identified several risks factors increasing the probability of the onset and progression of the disease in IPF patients such as cigarette smoking and environmental risk factors associated with domestic and occupational exposure. Among them, cigarette smoking together with concomitant emphysema might predispose IPF patients to lung cancer (LC), mostly to non-small cell lung cancer (NSCLC), increasing the risk of lung cancer development. To this purpose, IPF and LC share several cellular and molecular processes driving the progression of both pathologies such as fibroblast transition proliferation and activation, endoplasmic reticulum stress, oxidative stress, and many genetic and epigenetic markers that predispose IPF patients to LC development. Nintedanib, a tyrosine-kinase inhibitor, was firstly developed as an anticancer drug and then recognized as an anti-fibrotic agent based on the common target molecular pathway. In this review our aim is to describe the updated studies on common cellular and molecular mechanisms between IPF and lung cancer, knowledge of which might help to find novel therapeutic targets for this disease combination.


Dysregulation of ferroptosis may involve in the development of non-small-cell lung cancer in Xuanwei area.
The Xuanwei area of Yunnan Province, China, is one of the regions suffering from the highest occurrence and mortality rate of lung cancer in the world. Local residents tend to use bituminous coal as domestic fuel, which causes serious indoor air pollution and is established as the main carcinogen. After the local government carried out furnace and stove reform work, lung cancer rate including incidence and mortality among residents remains high. We herein wonder if there are specific mechanisms at protein level for the development of non-small-cell lung cancer (NSCLC) in this area. We investigated the changes of protein profiling in tumour of the patients from Xuanwei area. Tandem mass tag (TMT) was employed to screen the differential proteins between carcinoma and para-carcinoma tissues. We identified a total of 422 differentially expressed proteins, among which 162 proteins were significantly up-regulated and 260 were downregulated compared to para-carcinoma tissues. Many of the differentially expressed proteins were related to extracellular matrix (ECM)-receptor interaction, focal adhesion, PI3K/AKT pathway and ferroptosis. Further experiments on the two differential proteins, thioredoxin 2 (TXN2) and haptoglobin (HP), showed that the change of their expressions could make the lung cancer cell lines more resistant to erastin or RSL-induced ferroptosis in vitro, and promote the growth of tumour in nude mice. In conclusion, this study revealed that aberrant regulation of ferroptosis may involve in the development of lung cancer in Xuanwei area.


Utility of 3D transoesophageal echocardiography for the assessment of tricuspid and pulmonary valves in carcinoid heart disease.
We report on the case of a 45-year-old lady with metastatic carcinoid tumour and carcinoid syndrome who develops severe valvulopathy involving the tricuspid and pulmonary valve. The use of three-dimensional transoesophageal echocardiography allowed more detailed morphological assessment of tricuspid and pulmonary valve pathology, sub-valvular apparatus and improved delineation of the relationship between these structures and surrounding cardiac chambers.


Return to work of breast cancer survivors: a systematic review of intervention studies.
Breast cancer management has improved dramatically in the past three decades and as a result, a population of working age women is breast cancer survivor. Interventions for breast cancer survivors have shown improvements in quality of life and in physical and psychological states. In contrast, efforts aimed at stimulating re-employment and return-to-work interventions for breast cancer survivors have not kept pace. The objective of this review was to study the effects and characteristics of intervention studies on breast cancer survivors in which the outcome was return to work. The Cochrane Controlled Trials Register (The Cochrane Library, Issue 4, 2006), Medline, Ovid, EMBASE and PsychInfo were systematically searched for studies conducted between 1970 to February 2007. Intervention studies for female breast cancer survivors that were focused on return to work were included. Our search strategy identified 5219 studies. Four studies out of 100 potentially relevant abstracts were selected and included 46-317 employed women who had had mastectomy, adjuvant therapy and rehabilitation, with the outcome return to work. The intervention programs focused on improvement of physical, psychological and social recovery. Although a substantial percentage (between 75% to 85%) of patients included in these studies returned to work after rehabilitation, it is not clear whether this proportion would have been lower for patients without counseling or exercise, or any other interventions, as three out of four studies did not include a comparison group. The most important finding of this review is the lack of methodologically sound intervention studies on breast cancer survivors with the outcome return to work. Using evidence from qualitative and observational studies on cancer and the good results of intervention studies on return to work programs and vocational rehabilitation, return to work interventions for breast cancer survivors should be further developed and evaluated.


Electron-accepting conjugated materials based on 2-vinyl-4,5-dicyanoimidazoles for application in organic electronics.
We report the Heck coupling of 2-vinyl-4,5-dicyanoimidazole (vinazene) with selected di- and trihalo aromatics in an effort to prepare linear and branched electron-accepting conjugated materials for application in organic electronics. By selecting the suitable halo-aromatic moiety, it is possible to tune the HOMO-LUMO energy levels, absorption, and emission properties for a specific application. In this regard, materials with strong photoluminescence from blue --> green --> red are reported that may have potential application in organic light-emitting diodes (OLEDs). Furthermore, derivatives with strong absorption in the visible spectrum, coupled with favorable HOMO-LUMO levels, have been used to prepare promising organic photovoltaic devices (OPVs) when combined with commercially available semiconducting donor polymers.


[Bioethical and legal aspects of patient education].
In the last 35 years, patient education has started to gradually develop at hospitals as well as in primary health care. Now, it is an integral part of communication in health care. Due to the expanding application of technology in the field of medicine, it is difficult to achieve appropriate and extensive patient education. Patient dissatisfaction with the given information on the illness, treatment and prognosis has contributed to professionalization of patient education. Nevertheless, patient education has not yet been acknowledged as a discipline. Patient education by health care professionals while providing health care services and through the process of informed consent requires professional and bioethical education of health care professionals and also patient commitment to actively cooperate with their doctors.


Risk factors for developing seizures after a stroke.
We evaluated development of seizures in 219 consecutive patients who had ischemic or hemorrhagic stroke. Subjects with transitory ischemic attacks, subarachnoid, subdural, and epidural hemorrhages or those with previous history of epilepsy were excluded. Mean follow-up time was 11.5 months (range 1-72 months). Twenty-two of 219 stroke patients (10.04%) had seizures. Twelve (54.55%) were of early onset (< 1 month after the stroke), and 10 (45.45%) were of late onset. No statistically significant differences were evident between the early- and late-onset seizure group in comparisons of type of stroke, localization, and size of the lesion. Six of 22 patients (27%) had seizure recurrence. Seizures developed in (a) 13 of 183 patients with ischemic stroke (7.1%) and 9 of 36 patients with hemorrhagic stroke (25%) (p = 0.01); (b) 16 of 93 patients with cortical lesions (17%) and 6 of 126 patients with subcortical lesions (4.7%) (p = 0.01); and (c) 14 of 66 patients with a lesion comprising more than one lobe (21.2%) and 8 of 153 patients with a lesion comprising less than one lobe (5.2%) (p < 0.01). We conclude that patients with hemorrhagic stroke, cortical lesions, and lesions involving more than one lobe are at higher risk of developing seizures.


Calcium Channel Blockers Impair the Antitumor Activity of Anti-CD20 Monoclonal Antibodies by Blocking EGR-1 Induction.
Direct cell death induction, in addition to immune-effector cell-mediated mechanisms, is one of the key mechanisms of action of anti-CD20 antibodies, and yet the signaling pathways implicated remain poorly investigated. Here we show that the transcription factor EGR-1 is rapidly induced by anti-CD20 antibodies and is a key mediator for CD20-induced cell death. EGR-1 induction results from an increased calcium influx induced by anti-CD20 antibodies. We show that both rituximab and obinutuzumab induce calcium influx, albeit through different mechanisms, and this influx is crucial for cell death induction. Inhibition of the calcium flux with calcium channel blockers (CCB) abolished EGR-1 induction and impaired the efficacy of anti-CD20 antibodies in preclinical in vitro and in vivo models. Finally, we investigated the impact of CCBs in patients treated with anti-CD20 antibodies included in the clinical trials GOYA and REMARC, and found that patients simultaneously receiving CCBs and anti-CD20 therapy have a shorter progression-free survival and overall survival. These results reveal EGR-1 as a key mediator of the direct cytotoxic activity of anti-CD20 antibodies and provide a rationale to evaluate EGR-1 expression as a new biomarker to predict response to anti-CD20 treatment. In addition, our findings show that calcium influx is required for anti-CD20-mediated tumor cell death and suggest that simultaneous administration of calcium channel blocking agents could be deleterious in patients receiving anti-CD20-based immunotherapy.


Nitric oxide synthase (NOS) expression in the myenteric plexus of streptozotocin-diabetic rats.
Nitric oxide (NO) is an important inhibitory neurotransmitter in the gut. Alterations in NO mediated responses have been described in diabetic animals. The presence of nitric oxide synthase (NOS) reflects the potential for NO synthesis and is found in neurons in the myenteric plexus. The aim of this study was to determine changes in nitric oxide synthase (NOS) expression in the myenteric plexus of the gastrointestinal tract of diabetic rats at three months of streptozotocin-induced diabetes, compared to age matched controls, using immunohistochemistry. Diabetic animals showed a decrease in NOS expression in the antrum, with 59.1 +/- 7.3% of neurons being positive for NOS in diabetes compared to 81.2 +/- 4.7% in controls (P < 0.05). NOS expression in duodenum, ileum, and colon of diabetic animals was not statistically different from controls. Decreased expression of NOS in antrum may contribute to altered gastric emptying observed in diabetics.


[Atraumatic approach in myocardial perfusion, metabolism and receptors by positron emission tomography].
Positron emission tomography (PET) is a noninvasive visualization method that provides a quantitative representation of radioactive molecule distribution on a tissue section within an organ. PET may be compared to the quantitative autoradiography performed in animals on heart sections with carbon 14- or tritium-labelled molecules, but it has the advantages of being applicable to human beings and enabling time-related concentration studies to be carried out on various substances. By using mathematical models fatty acid consumption or cholinergic receptor density can then be measured in e.g. the interventricular septum. Myocardial perfusion is routinely measured using such tracers as rubidium 82, nitrogen 13-labelled ammonia or even oxygen 15 water or gallium 68-labelled albumin microspheres. 82 Rb and 13NH3 ammonia are strongly taken up by the myocardium. 82 Rb has properties that are similar to those of 201Tl used in nuclear medicine, and the kinetics of 13NH3 depend on both myocardial perfusion and myocardial metabolism. The myocardium can metabolize fatty acids, glucose, ketone-bodies and lactic acid. 11C-palmitate is ideal to evaluate the regional utilization of fatty acids. It has been extensively studied in dogs, where a good correlation was found between the size of experimental infarcts and that of the region where a reduction in palmitate concentration was observed. Glucose metabolism is studied by means of an 18F-labelled analogue: fluoro-deoxyglucose. Using this analogue and 11C-palmitate jointly in animals or patients with myocardial ischaemia showed an increase of glucose myocardial extraction and a decrease of palmitate uptake in the ischaemic areas. In necrotic areas, both fluoro-deoxyglucose and palmitate uptakes were extremely low.(ABSTRACT TRUNCATED AT 250 WORDS)


Effect of nuclear mutation in maize on photosynthetic activity and content of chlorophyll-protein complexes.
A number of new nuclear mutants have been isolated from maize by selection for high chlorophyll (Chl) fluorescence. These mutants show reduced rates of photosynthesis and/or are deficient in Chl. Electrophoretic examination of wild type thylakoid membranes revealed five Chl-protein complexes, two containing only Chl a and three containing Chl a and Chl b. A class of nonviable, photosystem I-deficient mutants was found to be lacking one (A-1) of the two Chl a-protein complexes. A second class of nonviable, photosystem I-lacking mutants was found to be missing not only this A-1 complex but also one or more of the three Chl a and b-containing, light-harvesting Chl-protein complexes. Viable mutants were obtained which appeared to have lost just one of the Chl b-containing complexes, whereas a second class of viable mutants was missing all three of the Chl b-complexes. The results confirm that the A-1 band is associated with the P700-Chl a-protein complex characterized previously. The data also indicate the existence of structurally different forms of the light-harvesting Chl a- and b-containing complexes. The results also show a lower molecular weight band (A-2) containing primarily Chl a and which appears to be required for viability.


ER-Mitochondria Communication in Cells of the Innate Immune System.
In cells the interorganelle communication comprises vesicular and non-vesicular mechanisms. Non-vesicular material transfer predominantly takes place at regions of close organelle apposition termed membrane contact sites and is facilitated by a growing number of specialized proteins. Contacts of the endoplasmic reticulum (ER) and mitochondria are now recognized to be essential for diverse biological processes such as calcium homeostasis, phospholipid biosynthesis, apoptosis, and autophagy. In addition to these universal roles, ER-mitochondria communication serves also cell type-specific functions. In this review, we summarize the current knowledge on ER-mitochondria contacts in cells of the innate immune system, especially in macrophages. We discuss ER- mitochondria communication in the context of macrophage fatty acid metabolism linked to inflammatory and ER stress responses, its roles in apoptotic cell engulfment, activation of the inflammasome, and antiviral defense.


Sex-Specific Associations of Genetically Predicted Circulating Lp(a) (Lipoprotein(a)) and Hepatic LPA Gene Expression Levels With Cardiovascular Outcomes: Mendelian Randomization and Observational Analyses.
Elevated Lp(a) (Lipoprotein(a)) levels are associated with coronary artery disease (CAD), ischemic stroke (IS), and calcific aortic valve stenosis (CAVS). Studies investigating the association between Lp(a) levels and these diseases in women have yielded inconsistent results. To investigate the association of Lp(a) with sex-specific cardiovascular outcomes, we determined the association between genetically predicted Lp(a) levels (using 27 single nucleotide polymorphisms at the LPA locus) and hepatic LPA expression (using 80 single nucleotide polymorphisms at the LPA locus associated with LPA mRNA expression in liver samples from the Genotype-Tissue Expression dataset) on CAD, IS, and CAVS using individual participant data from the UK Biobank: 408 403 participants of European ancestry (37 102, 4283, and 2574 with prevalent CAD, IS, and CAVS, respectively). The long-term association between Lp(a) levels and incident CAD, IS, and CAVS was also investigated in European Prospective Investigation into Cancer and Nutrition-Norfolk: 18 721 participants (3964, 846, and 424 with incident CAD, IS, and CAVS, respectively). Genetically predicted plasma Lp(a) levels were positively and similarly associated with prevalent and incident CAD and CAVS in men and women. Genetically predicted plasma Lp(a) levels were associated with prevalent and incident IS when we studied men and women pooled together, and in men only. Genetically predicted LPA expression levels were associated with prevalent CAD and CAVS in men and women but not with IS. Genetically predicted blood Lp(a) and hepatic LPA gene expression as well as serum Lp(a) levels predict the risk of CAD and CAVS in men and in women. Whether RNA interference therapies aiming at lowering Lp(a) levels could be useful in reducing cardiovascular disease risk in both men and women with high Lp(a) levels needs to be determined in large-scale cardiovascular outcomes trials.


Sodium Dichloroacetate Pharmacological Effect as Related to Na-K-2Cl Cotransporter Inhibition in Rats.
The study objective was to investigate a possible sodium dichloroacetate (DCA) pharmacological mechanism causing an increase in diuresis in rats. The aim was to define characteristics of 24-hour urinary Na+, K+, Cl-, Ca2+, and Mg2+ excretion in Wistar male rats and to evaluate effect of a single-dose DCA and repeated DCA dosage on diuresis. Six control and 6 DCA-treated male rats aged 5 to weeks after a single DCA dose and repeated dosage were tested. The single DCA dose treatment caused a significantly higher 24-hour diuresis when compared to control (P < .05), and it was related to increased Cl-, Na+, and K+ urine excretion and a significant increase in Ca2+ and Mg2+ excretion (P < .05); after the repeated 4-week DCA dosage, the diuresis was not increased, but the excretion of the Na+, Cl-, Ca2+, and Mg2+ ions was significantly higher. Kidney immunohistochemistry has revealed that DCA continuous treatment results in an increase in the size of Henle loop thick ascending limb epithelial cells (P < .001). The study results show a significantly reduced RNA expression of Na-K-2Cl co-transporter (NKCC1) in thymus of 4-week DCA-treated rats (P < .03). The study data have indicated a possible mechanism of such pharmacological effect to be NKCC inhibition.


[How I treat ... surgically benign uterine lesions in 2002].
For 20 years, pre-operative investigations have increasingly improved the gynaecological diagnosis, allowing to have an accurate idea on the size and the nature of the lesion to be treated when the matter is to carry out the surgical treatment. In the meantime, the gynaecological surgery has seen its endoscopic surgical techniques improved due to the development of these diagnostic techniques itself. The operative hysteroscopy allows to decrease considerably the amount of hysterectomies for benign lesions. The operative laparoscopy has become the first intended treatment for many pathologies. This latter allows performing either laparoscopic assisted vaginal hysterectomies or complete laparoscopic hysterectomies. On the other hand, even though these endoscopic techniques were developing, the vaginal hysterectomy strongly returned, in such a way that it became the dominating way, so that the rule is to perform abdominal hysterectomy only when it is impossible to carry out a low way hysterectomy. Consequently, the gynaecologist surgeon has to be capable, in 2002, to perform all these surgical techniques in order to offer to the patient the best treatment, matching as good as feasible according to the pathology to be treated and her anatomical status.


Total lymphocyte count and subpopulation lymphocyte counts in relation to dietary intake and nutritional status of peritoneal dialysis patients.
Dietary deficiency causes abnormalities in circulating lymphocyte counts. For the present paper, we evaluated correlations between total and subpopulation lymphocyte counts (TLC, SLCs) and parameters of nutrition in peritoneal dialysis (PD) patients. Studies were carried out in 55 patients treated with PD for 22.2 +/- 11.4 months. Parameters of nutritional status included total body mass, lean body mass (LBM), body mass index (BMI), and laboratory indices [total protein, albumin, iron, ferritin, and total iron binding capacity (TIBC)]. The SLCs were evaluated using flow cytometry. Positive correlations were seen between TLC and dietary intake of niacin; TLC and CD8 and CD16+56 counts and energy delivered from protein; CD4 count and beta-carotene and monounsaturated fatty acids 17:1 intake; and CD19 count and potassium, copper, vitamin A, and beta-carotene intake. Anorexia negatively influenced CD19 count. Serum albumin showed correlations with CD4 and CD19 counts, and LBM with CD19 count. A higher CD19 count was connected with a higher red blood cell count, hemoglobin, and hematocrit. Correlations were observed between TIBC and TLC and CD3 and CD8 counts, and between serum Fe and TLC and CD3 and CD4 counts. Patients with a higher CD19 count showed a better clinical-laboratory score, especially less weakness. Patients with a higher CD4 count had less expressed insomnia. Quantities of ingested vitamins and minerals influence lymphocyte counts in the peripheral blood of PD patients. Evaluation of TLC and SLCs is helpful in monitoring the effectiveness of nutrition in these patients.


Transformations of N-confused porphyrin triggered by insertion of silicon(IV).
N-confused porphyrin, 5,10,15,20-tetraaryl-2-aza-21-carbaporphyrin, dissolved in triethylamine reacts with dichloromethylsilane yielding the methylsilicon(IV) complex of 5,10,15,20-tetraaryl-2-aza-21-hydroxy-21-carbaporphyrin. Addition of aldehydes or ketones (acetone, acetaldehyde acetophenone, butanone, propanal, benzaldehyde, p-methylbenzaldehyde, p-methoxybenzaldehyde, terephthaldehyde) into the insertion mixture triggered the profound transformation of N-confused porphyrin to form the methylsilicon(IV) complex of N-fused porphyrin derivative substituted at the inner C(9) position by a hydroxyalkyl moiety derived from aldehyde or ketone. The macrocyle is structurally related to an aromatic N-fused inner phlorin while the coordination polyhedron of bound silicon resembles the trigonal bipyramid. The macrocyclic ligand coordinates in the facial mode as the three pyrrolic nitrogen donors lie at the vertices of the single trigonal face. The meridional positions of the trigonal bipyramid are occupied by two pyrrolic nitrogen donors and a sigma-methyl ligand. The coordination sphere is completed by apical coordination of the alkoxy oxygen atom derived from alkanal or alkonone. The incorporation of aldehydes and ketones is stereoselective. Acidic desililation of alkanal compounds yields two aromatic N-confused porphyrin derivatives, that is, 3-(1-hydroxyalkyl)-5,10,15,20-tetraaryl-2-aza-21-carbaporphyrin and its oxidation product 3-alkanoyl-5,10,15,20-tetraaryl-2-aza-21-carbaporphyrin. The acid triggered desililation of ketone derivatives produces the equimolar amounts of N-confused porphyrin and ketone. The first spectroscopically identified step involves the protonation of the C(7) position affording the non-aromatic silicon(IV) complex. The density functional theory (DFT) has been applied to model the molecular and electronic structure of all species identified in the course of silicon insertion into the N-confused and N-fused porphyrin.


Carmi Syndrome in a Neonate: An Exacting Surgical Challenge.
Carmi syndrome is characterized by the concomitant presence of pyloric atresia and epidermolysis bullosa. Pyloric atresia routinely presents with symptoms of gastrointestinal obstruction, which include vomiting and feeding intolerance. On the other hand, epidermolysis bullosa presents with blistering skin lesions upon the slightest trauma. Due to these skin lesions, the affected patients are particularly susceptible to developing septicemia and adverse disease outcomes. We hereby delineate a case of Carmi syndrome in a neonate who was treated surgically. Postoperatively, the neonate began to deteriorate and eventually developed septicemia and passed away shortly thereafter.


Operative treatment of typical overuse injuries in sport.
In this report 670 operations, performed in 643 patients were analyzed. The indication for the surgery was a chronic symptomatic overuse injury caused by sports and physical activity. 552 (82.4%) of the operations were performed in men and 118 (17.6%) in women. The mean age of the patients was 24 years. Almost 90 per cent of the patients had presented following competitive sports and ten per cent recreational sports. More than 91 per cent of the operations were performed for lower extremity problems. The knee, foot and ankle regions needed surgical treatment most often in this series. Tendon and tendon sheath operations formed the majority (32%) of the operations. Chronic Achilles tendon problems (159) formed the biggest group of the diagnoses. Chronic overuse injuries do not respond always to conservative treatment. Surgery is often needed in the final stage of an overuse injury. The results of these operations are good.


Linking insomnia and suicide ideation in college females: The role of socio-cognitive variables and depressive symptoms in suicide risk.
Although insomnia symptoms are associated with risk of suicide ideation, the means by which insomnia influences ideation, as well as the role depression plays in these relationships, require further study. In this study, we examined whether certain socio-cognitive variables (fatigue, social problem-solving, and hopelessness) in conjunction with depression explained this relationship among female college students. 483 female students completed measures assessing insomnia and depressive symptoms, fatigue, social problem-solving ability, hopelessness, and suicide ideation. Path analyses indicated that socio-cognitive variables partially explained the insomnia-ideation relationship above the influence of depressive symptoms. Higher depressive symptoms exacerbated relationships between social problem-solving and hopelessness, heightening ideation risk. Our findings expand knowledge of intermediate socio-cognitive variables that may contribute to the insomnia-ideation relationship, and indicate that clinically-severe depressive symptoms compound the contribution of negative self and future appraisals to thoughts of suicide. Suicidal females with insomnia and depressive symptoms may benefit from interventions targeting problem-solving skills and improving sleep.


Does the degree of preoperative mitral regurgitation predict survival or the need for mitral valve repair or replacement in patients with anomalous origin of the left coronary artery from the pulmonary artery?
Anomalous origin of the left coronary artery from the pulmonary artery causes severe myocardial ischemia, global left ventricular dysfunction, and annular dilatation producing varying degrees of mitral regurgitation. Mitral regurgitation secondary to the left ventricular or papillary muscle dysfunction in infants will usually improve in the absence of ongoing ischemia. The aim of this study is to determine the influence of the degree of preoperative mitral regurgitation on the early and late outcomes of patients with anomalous origin of the left coronary artery from the pulmonary artery who underwent coronary reimplantation. Twenty-five patients underwent coronary reimplantation and 1 early patient had ligation during a 30-year period (median age, 4 months; range, 1 month to 16 years), with a median follow-up of 7 years (range, 4 months to 25 years). Before repair, 7 infants (27%) presented in extremis requiring ventilatory and inotropic support, and 17 patients (65%) presented with heart failure. Mitral regurgitation was present in all patients: trivial in 6 patients, mild in 12 patients, moderate in 5 patients, and severe in 3 patients. No patient underwent mitral valve repair or replacement at the time of anomalous origin of the left coronary artery from the pulmonary artery repair. Hospital survival was 92%. Three patients underwent mitral valve repair or replacement at the mean time of 3.5 years (all with severe preoperative mitral regurgitation). The degree of mitral regurgitation gradually improved in all remaining patients with preoperative mild and moderate mitral regurgitation. Echocardiographic studies demonstrated improvement in left ventricular function in all children. None of the patients showed any evidence of supravalvar pulmonary stenosis as a result of their pulmonary artery reconstruction. Long-term clinical outcome and left ventricular function are good despite severe left ventricular dysfunction at presentation. Mitral valve repair or replacement is generally not necessary at the time of anomalous origin of the left coronary artery from the pulmonary artery repair. Significant residual mitral regurgitation is present in some patients and can usually be managed surgically at a later date depending on its degree of severity.


Endoscopic therapy for gastric cancer in patients more than 80 years old.
We prospectively studied 17 gastric cancer patients who were more than 80 yr old, in whom endoscopic therapy was performed. The patients were divided into two groups: the first group included 13 patients in whom curative treatment was attempted, and in 11 (85%) a curative response was achieved. Two patients in this group showed a positive gastric biopsy after 1 and 2 yr, respectively, of therapy: one patient is under current treatment with laser therapy, and the other patient underwent surgery with resection of the stomach. The second group included four patients in whom treatment was aimed at prolonging survival or palliation, and in all four patients, a successful response was obtained. Therefore, our results demonstrate that endoscopic therapy is effective for the treatment of gastric cancer patients over 80 yr old.


T cell receptor V beta repertoire in the thymus and spleen of mice infected with Trypanosoma cruzi.
The T cell receptor (TCR) V beta repertoire was studied in BALB/c, CBA/HJ, and CBA/J mice experimentally infected with Trypanosoma cruzi. The percentage of expression of 14 V beta chains of the variable domain of the TCR in the thymus and spleen was evaluated. In the thymus of acutely infected with BALB/c and CBA/HJ mice there was an increase in the expression of positively selected V beta families. These changes in the V beta chains usage in the thymus paralleled the enrichment of CD4+ and CD8+ single-positive T cells. During the acute infection, several changes were observed in the peripheral expression of V beta families, such as of V beta 6 in BALB/c (a 36% increase in CD8+ T cells of the corresponding levels of V beta), of V beta 8 in CBA/HJ (a 37% decrease in CD8+ cells), and of V beta chains 8 and 14 in CBA/J mice (V beta 14+CD4+ cells increased 19%, and V beta 8 expression decreased 19 and 33% in CD4+ and CD8+ cells, respectively). In chronically infected BALB/c and CBA/HJ mice, no change in the V beta families was observed, neither in the thymus nor in the spleen. In acutely infected mice, the alterations of the peripheral expression of positively selected V beta families could be due to the stimulation by T. cruzi antigens and/or cytokines; the homeostatic mechanism/s that maintains the selection of the TCR V beta repertoire did not seem to be severely affected during the infections.


Radiation hardness of cadmium telluride solar cells in proton therapy beam mode.
We evaluated the durability of cadmium telluride (CdTe) solar cells upon proton beam irradiation as well as the possibility of achieving a dosimeter usable in proton beam therapy by applying 100 MeV of pencil beam scanning (PBS) irradiation. Specifically, a 100 MeV proton PBS beam was applied at irradiation doses of 0, 1012, 1013, 1014, and 1015 cm-2. According to the results, the remaining factors (defined as the ratio of the degraded value to the initial value) of open-circuit voltage (Voc), short-circuit current (Jsc), fill-factor (FF), and efficiency (ƞ) which are solar cell performance parameters, were approximately 89%, 44%, 69%, and 30%, respectively, compared to those of the reference cell (without irradiation) at the highest dose of 1×1015 cm-2. In particular, the conversion efficiency, which is the main factor, was approximately 70% of that of the reference cell even at a high fluence of 1×1014 cm-2. In addition, we observed the projected range of the hydrogen atoms based on the PBS beam energy using the Tool for Particle Simulation software and assessed the amount of fluence accumulated in a CdTe cell. As the energy increased, the fluence accumulated inside the cell tended to decrease owing to the characteristics of the Bragg peak of the proton. Thus, the radiation damage to the cell induced by the proton beam was reduced. The results of this study are expected to provide valuable reference information for research on dosimetry sensors composed of thin-film solar cells, serving as the basis for future application in proton beam therapy with CdTe solar cells.


Few-photon multiple ionization of N2 by extreme ultraviolet free-electron laser radiation.
Few-photon multiple ionization of N2 was studied differentially in a reaction microscope using 44 eV, approximately 25 fs, intense ( approximately 10(13) W/cm(2)) photon pulses from FLASH. Sequential ionization is observed to dominate. For various intermediate charge states N(2)(n+0 we find a considerable excess of photons absorbed compared to the minimum number that would energetically be required. Photoionization of aligned N(2)(n+) ions, produced by photon absorption in sequential steps, is explored and few-photon absorption pathways are traced by inspecting kinetic energy releases and fragment-ion angular distributions.


The roles of microRNA-22 in myocardial infarction.
Myocardial infarction (MI) is the leading cause of morbidity and mortality worldwide. The regeneration capacity of the adult mammalian heart is very limited, so that the lost cells are replaced by fibrotic scar. This is followed by remodeling of the surrounding myocardium, which includes cardiac hypertrophy and fibrosis, and makes the ventricular wall thicken and stiffen. This adverse cardiac remodeling leads to impaired cardiac function and eventually leads to heart failure. Extensive studies have revealed that microRNAs (miRNAs) play an essential role in cardiovascular diseases. microRNA-22 (miR-22) is one of the most abundant miRNA in the heart. Many studies have demonstrated that miR-22 plays critical roles in MI and subsequent cardiac remodeling. In this review, we summarized the recent research progresses, including the regulatory effects of miR-22 in oxidative stress, cardiac apoptosis, autophagy, hypertrophy, fibrosis and regeneration.


A comparative study of electrochemical and electrostatic doping modulation of magnetism in Fe3O4via ultracapacitor structure.
Electric field control of magnetism can boost energy efficiency and have brought revolutionary breakthroughs in the development of widespread applications in spintronics. Electrolyte gating plays an important role in magnetism modulation. In this work, reversible room-temperature electric field control of saturation magnetization in Fe3O4via a supercapacitor structure is demonstrated with three types of traditional gate electrolytes for comparison. Different magnetization response and responsible mechanisms are revealed by Operando magnetometry PPMS/VSM and XPS characterization. The main mechanism in Na2SO4, KOH aqueous electrolytes is electrochemical effect, while both electrochemical and electrostatic effects were found in LiPF6organic electrolyte. This work offers a kind of reference basis for selecting appropriate electrolyte in magnetism modulation by electrolyte-gating in the future, meanwhile, paves its way towards practical use in magneto-electric actuation, voltage-assisted magnetic storage, facilitating the development of high-performance spintronic devices.


Activation of distinct motor cortex regions during ipsilateral and contralateral finger movements.
Previous studies have shown that unilateral finger movements are normally accompanied by a small activation in ipsilateral motor cortex. The magnitude of this activation has been shown to be altered in a number of conditions, particularly in association with stroke recovery. The site of this activation, however, has received limited attention. To address this question, functional magnetic resonance imaging (MRI) was used to study precentral gyrus activation in six control and three stroke patients during right index finger tapping, then during left index finger tapping. In each hemisphere, the most significantly activated site (P < 0.001 required) was identified during ipsilateral and during contralateral finger tapping. In the motor cortex of each hemisphere, the site activated during use of the ipsilateral hand differed from that found during use of the contralateral hand. Among the 11 control hemispheres showing significant activation during both motor tasks, the site for ipsilateral hand representation (relative to contralateral hand site in the same hemisphere) was significantly shifted ventrally in all 11 hemispheres (mean, 11 mm), laterally in 10/11 hemispheres (mean, 12 mm), and anteriorly in 8/11 hemispheres (mean, 10 mm). In 6 of 11 hemispheres, tapping of the contralateral finger simultaneously activated both the ipsilateral and the contralateral finger sites, suggesting bilateral motor control by the ipsilateral finger site. The sites activated during ipsilateral and contralateral hand movement showed similar differences in the unaffected hemisphere of stroke patients. The region of motor cortex activated during ipsilateral hand movements is spatially distinct from that identified during contralateral hand movements.


A Potential Role of Adhesion Molecules on Lung Metastasis Enhanced by Local Inflammation.
Local and systemic inflammations are associated with negative long-term outcomes; however, their precise mechanism of action remains unclear. We previously demonstrated that hepatocyte growth factor (HGF)/c-Met signaling contributed to the enhancement of liver metastasis associated with peritonitis model. The aim of this study is to investigate the effect of local inflammation on the development of lung metastasis. NL-17 cells were injected into BALB/c mice via the tail vein to produce a high potential model for lung metastasis. After injection of NL-17 cells, lipopolysaccharide (LPS) and live Pseudomonas aeruginosa, and phosphate-buffered saline were administered intratracheally to induce acute lung injury (ALI) and pneumonia, respectively. In both ALI and pneumonia mice, lung metastasis was significantly promoted compared to control mice. Concentrations of Interleukin-6, tumor necrosis factor-α, and HGF in the bronchoalveolar lavage fluid were significantly higher in ALI and pneumonia mice than in control mice. Neither administration of recombinant mouse HGF nor c-Met knockdown in NL-17 cells influenced the magnitude of lung metastasis. Yet stimulation with LPS increased the expression of α2 integrin, vascular cell-adhesion protein-1, and intercellular adhesion molecule-1 (ICAM-1) in the lung. Invasive activity of NL-17 cells was significantly up-regulated by LPS, but was suppressed by anti-ICAM-1 antibody. While LPS-stimulated NL-17 cells showed significantly promoted lung metastasis, E-selectin expression in the lungs of mice with ALI or pneumonia was significantly enhanced compared with control mice. Up-regulation of adhesion molecules, but not HGF/c-Met signaling, may contribute to the lung metastasis enhanced by local infection/inflammation.


The role of antibiotics in the evolution of microorganisms.
Bacteria were the first living beings to appear on our planet: the most ancient fossils available, all of them were procaryotic microorganisms, developed 4, 5 billion years ago. The paleomicrobiological studies made on that kind of fossils, which are by now several hundreds in each continent, proved bacteria to have constantly evolved and to have originated the modern Eubacteria as well as the Archebacteria and the Cianobacteria. These last appeared about 2 billion years ago and, having acquired the oxygen-type photosynthesis, have caused the formation of a large amount of organic material, afterwards used by the younger organisms, and have modified the atmosphere introducing oxygen in it and conditioning in this way the other living being's evolution. From Bacteriaceae and Cyanobacteria derive the eucaryotic microorganisms (algae, fungi, protozoa, mould) and, little by little, all the other organisms both vegetable and animal subjected to the evolutionary pressures. Nevertheless bacteria undergo more frequently than all the others the evolution law because of their short reproductive time; this is the reason why bacteria are favourite compared with the other organisms. In fact each species is subjected to a genetic mutation every 10(5)/10(6) generations: in the vegetables and animals the consequences of a genetic mutation will be evident after millennia whereas in the bacteria the mutation happens in a short time. We ourselves have witnessed the revolution which took place in the bacteria populations during the last half century when numerous antibiotic-resistant strains appeared.(ABSTRACT TRUNCATED AT 250 WORDS)


Therapy for lung failure using nitric oxide inhalation and surfactant replacement.
Nitric oxide inhalation and surfactant replacement therapy are relatively new concepts in the treatment of respiratory failure due to hypoxia and reperfusion injury after lung transplantation. We report on a patient in whom reperfusion injury of the lung developed after resuscitation and implantation of a biventricular assist device for sudden cardiac arrest. Lung failure developed within 12 hours after implantation of the biventricular assist device. Lung function was reestablished using combined therapy of nitric oxide and surfactant. Heart transplantation was performed successfully thereafter. This case indicates the potential role of a combined therapy of nitric oxide and surfactant in acute hypoxic lung failure.


Alternate trafficking of cathepsin L in dermal fibroblasts induced by UVA radiation.
UVA radiation is increasingly used to treat fibrotic skin disorders. However, the mechanisms underlying the therapeutic effects of UVA for these disorders are only partially understood. Cathepsin L is a lysosomal cysteine protease, which has been shown to degrade various matrix proteins thus contributing to extracellular remodeling. Therefore, we investigated whether UVA irradiation regulates the expression and release of cathepsin L in human dermal fibroblasts. No alterations were found after single irradiation; however, a significantly increased extracellular release of cathepsin L was observed after repeated irradiation up to four times. The transcript levels of cathepsin L were elevated after repetitive irradiation, leading to increased amounts of total cathepsin L protein. Furthermore, higher amounts of extracellular cathepsin L were associated with a significant reduction of intracellular processed cathepsin L and an accumulation of unprocessed procathepsin L. The use of specific inhibitors elucidated mannose phosphate-independent sorting pathways of cathepsin L leading to enhanced secretion and reduced intracellular processing. This is the first study which demonstrates that alternate trafficking mechanisms mediate the extracellular release of a cysteine protease induced by repetitive UVA irradiation.


Sensitivity, advantages, limitations, and clinical utility of targeted next-generation sequencing panels for the diagnosis of selected lysosomal storage disorders.
Lysosomal storage disorders (LSDs) constitute a heterogeneous group of approximately 50 genetic disorders. LSDs diagnosis is challenging due to variability in phenotype penetrance, similar clinical manifestations, and a high allelic heterogeneity. A powerful tool for the diagnosis of the disease could reduce the "diagnostic odyssey" for affected families, leading to an appropriate genetic counseling and a better outcome for current therapies, since enzyme replacement therapies have been approved in Brazil for Gaucher, Fabry, and Pompe diseases, and are under development for Niemann-Pick Type B. However, application of next-generation sequencing (NGS) technology in the clinical diagnostic setting requires a previous validation phase. Here, we assessed the application of this technology as a fast, accurate, and cost-effective method to determine genetic diagnosis in selected LSDs. We have designed two panels for testing simultaneously 11 genes known to harbor casual mutations of LSDs. A cohort of 58 patients was used to validate those two panels, and the clinical utility of these gene panels was tested in four novel cases. We report the assessment of a NGS approach as a new tool in the diagnosis of LSDs in our service.


Housing and food stress among transgender adults in the United States.
The purpose of the study was to assess housing and food-related stress in transgender and cisgender adults in the United States. Data from the 2014 and 2015 Behavioral Risk Factor Surveillance System were analyzed for 53,060 adults who responded to the Sexual Orientation and Gender Identity module and the Social Context module. We used multiple logistic regression to assess the association of gender identity with housing and food-related stress. There were no significant differences by gender identity in the odds of experiencing housing or food-related stress. A sensitivity analysis revealed that with a broader definition of food-related stress, transgender individuals had higher odds of experiencing food-related stress compared with cisgender individuals. The sample of transgender individuals who experienced food-related stress were young, single, racially diverse, sexual minorities, and the majority had a high school degree or less. Similarly, most transgender individuals who experienced housing-related stress were single, sexual minorities, and had a high school degree or less. More precise assessments of housing and food insecurity among probability-based samples of transgender individuals are needed to fully understand housing and food-related instability and the stress associated with these experiences.


Suppression effects of AICAR on insulin secretion involved in peroxisome proliferator-activated receptor gamma changes in INS-1 cells.
AMP-activated protein kinase (AMPK) activation is known to attenuate glucose-stimulated insulin secretion (GSIS) in pancreatic beta cells. However, the underlying mechanisms are poorly understood. The purpose of this study was to examine the effects of AMPK activation on insulin secretion and to determine whether peroxisome proliferator-activated receptors (PPAR) are involved in the effects on INS-1 cells. INS-1 cells, insulinoma cell lines, were treated with an activator (AICAR) or inhibitor (Compound C) of AMPK as well as inhibitors of PPAR [MK886 and biphenol A diglycidyl ether (BADGE)] for different treatment times. AICAR-induced AMPK activation significantly attenuated GSIS as well as insulin content. Meanwhile, AMPK activation increased the mRNA levels of both PPARalpha and PPARgamma. However, with regard to DNA binding, AMPK activation upregulated PPARgamma only, and it was possible to reduce the increment with the AMPK inhibitor. Moreover, the AICAR-induced suppression of insulin secretion can be counteracted by the PPARgamma inhibitor, BADGE but not the PPARalpha inhibitor. AICAR-induced glucose-stimulated insulin secretion reduction correlates mainly with PPARgamma changes.


Synthesis of 3-alkylbenzoxazolones from N-alkyl-N-arylhydroxylamines by contiguous O-trichloroacetylation, trichloroacetoxy ortho-shift, and cyclization sequence.
Benzoxazolone pharmacophore is present in clinical pharmaceuticals, drug candidates, and many compounds having a wide spectrum of biological activities. The methods available for the synthesis of benzoxazolones have limited diversity due to problems in accessibility and air-sensitivity of diversely substituted o-aminophenols from which they are generally prepared by cyclocarbonylation with phosgene or its equivalents. The present paper describes a mild method for the synthesis of 3-alkylbenzoxazolones from easily accessible and air-stable nitroarenes. Nitroarenes were converted to N-alkyl-N-arylhydroxylamines in two steps involving partial reduction to arylhydroxylamines followed by selective N-alkylation. Treatment of N-alkyl-N-arylhydroxylamines with trichloroacetyl chloride and triethylamine afforded 3-alkylbenzoxazolones generally in good yields through an uninterrupted three-step sequence involving O-trichloroacetylation, N→C(ortho) trichloroacetoxy shift, and cyclization in a single pot at ambient temperatures. The present method is mild, wide in scope, economical, and regioselective. Many sensitive groups like alkyl and aryl esters, amide, cyano, and the carbon-carbon double bond survive the reaction.


[Coeliac disease and problems associated with reproduction].
Coeliac patients taking a normal diet have a shortened reproductive period with delayed menarche and early menopause. Many studies have shown that coeliac women are susceptible to reproductive difficulties such as infertility and miscarriages. The disease is also associated with low birth weight in babies and short duration of breast feeding. Folic acid deficiency is present in the majority of patients with untreated disease and it might be a maternal risk factor for neural tube defects and orofacial clefts. Coeliac men may have reversible infertility, and as in women, if gastrointestinal symptoms are mild or absent the diagnosis may be missed. It is important to make diagnosis because the giving of gluten free diet may result in conception and favourable outcome of pregnancy.


The phenomenology and explanatory models of common mental disorder: a study in primary care in Harare, Zimbabwe.
In order to describe the explanatory models and the etic and emic phenomena of common mental disorder in Harare, Zimbabwe, 110 subjects were selected by general nurses in three clinics and by four traditional healers from their current clients. The subjects were interviewed using the Explanatory Model Interview and the Revised Clinical Interview Schedule. Mental disorder most commonly presented with somatic symptoms, but few patients denied that their mind or soul was the source of illness. Spiritual factors were frequently cited as causes of mental illness. Subjects who were selected by traditional healer, reported a greater duration of illness and were more likely to provide a spiritual explanation for their illness. The majority of subjects were classified as 'cases' by the etic criteria of the CISR. Most patients, however, showed a mixture of psychiatric symptoms that did not fall clearly into a single diagnostic group. Patients from a subgroup with a spiritual model of illness were less likely to conform to etic criteria of 'caseness' and they may represent a unique category of psychological distress in Zimbabwe. A wide variety of emic phenomena were elicited that have been incorporated in an indigenous measure of non-psychotic mental disorder. Kufungisisa, or thinking too much, seemed to be the Shona term closest to the Euro-American concept of neurotic illness.


The Evolution of World Health Organization's Initiatives for the Strengthening of Nursing and Midwifery.
To describe the evolution in the resolutions approved by World Health Organization (WHO)'s World Health Assembly (WHA) to strengthen nursing and midwifery. Qualitative and descriptive study, undertaken through a search of resolutions presented by WHA, on the WHO website, regarding the theme "strengthening of nursing and midwifery." The resolutions on the theme "nursing and midwifery" were included, whose titles were available and whose full texts were accessed, excluding those on general health themes. The key words used were resolutions, strengthening, and nursing and midwifery. Among the 20 resolutions found, 12 were selected, adopted between 1948 and 2013, in accordance with the study inclusion criteria. The data were interpreted using thematic qualitative analysis, identifying and grouping the data in categories related to the study theme. Based on the content analysis of the 12 resolutions studied, three thematic categories were defined: "nursing and midwifery in primary health"; "role of nursing and midwifery in health for all"; and "nurses and midwives' professional training." Based on the categories, the evolution in the strengthening of nursing and midwifery was demonstrated through the initiatives and resolutions approved by WHA, highlighting the importance of nurses and midwives as multiprofessional health team members and their fundamental role in the improvements of the health system. Therefore, in accordance with the needs of each country, the member states can implement strategies presented by the WHA resolutions to strengthen nursing and midwifery services. This study has relevance for the development of health policies considering the relevant contributions of nurses and midwives to healthcare systems and services, based on the analysis of WHO resolutions involving these professions.


A functional initiator element in the human beta-globin promoter.
Core promoters are defined by the presence of either a TATA box at approximately 30 base pairs upstream of the transcriptional start site (+1) and/or an initiator element centered around the +1 site. The prevalence, function, and significance of the various combinations of core promoter elements are as yet unclear. We describe here the identification and characterization of an initiator element in the TATA-containing human beta-globin promoter. Mutagenesis of the beta-globin initiator element at positions +2/+3 and +4/+5 abrogates transcription in a heterologous construct. Interestingly, we have found a beta-globin initiator binding activity in nuclear extracts whose presence or absence correlates with function of the beta-globin initiator. Accordingly, this binding activity may be part of the machinery required for beta-globin initiator-dependent transcription. Our analysis further describes a previously uncharacterized beta-thalassemia mutation at the +1 site as a mutation that decreases beta-globin initiator activity. Finally, consistent with other initiator elements, the beta-globin initiator requires a TFIID-containing fraction for in vitro activity. Thus, the human beta-globin promoter contains an initiator element whose function, as revealed by a beta-thalassemia mutation, is of physiological relevance.


Muscovy ducks as a source of Pasteurella anatipestifer infection in turkey flocks.
An outbreak of disease, characterised by neurological signs and increased mortality, occurred in 17 out of 50 turkey farms in a village. Virological tests were negative as were routine bacteriological tests of the organs. However, Pasteurella anatipestifer was repeatedly isolated from the brain. The source of the infection was probably a group of Muscovy ducks.


Is empathy an important attribute of midwives and other health professionals?: A review.
This paper is a report of a systematic review to identify and analyze studies of the measurement of empathy in midwives and other health professionals. Empathy has been recognized as an important factor in patient care, with positive outcomes for both patients and health professionals. There is a debate on the definition of empathy, on its measurement and on the possibility of improvement. Searches were made of the CINAHL, SCOPUS, PubMed and PsychINFO databases using the terms empathy, clinical, midwifery, nursing, medical students, measurement, and health professionals, singly or in combination, to identify literature published in English between 2002-2015. The included papers were critically reviewed and a narrative synthesis was conducted. In all, 22 papers met the inclusion criteria by studies that were conducted to measure the levels of empathy in a variety of health professionals and students. Their scores were analyzed in correlation with their sociodemographic factors. Despite numerous studies, many correlations but also differences exist, indicating the complexity of empathy and the need to further study it.


Retinoic acid inhibits cell growth in HPV negative cervical carcinoma cells by induction of insulin-like growth factor binding protein-5 (IGFBP-5) secretion.
Retinoids have been demonstrated to inhibit epithelial cell growth and differentiation. We examined the anti-proliferative effects of retinoic acid (RA) in an HPV positive and negative cervical carcinoma cell line. Our findings indicate that HPV-negative C33A cervical carcinoma cells are more sensitive to the growth inhibitory activity of retinoic acid (RA) than are HPV-positive CaSki cervical carcinoma cells. However, conditioned medium from RA-treated C33A cells displayed strong growth inhibitory activity in both C33A and CaSki cells. Since RA has been shown to modulate the expression of insulin-like growth factor binding proteins (IGFBPs) in many cells, we examined RA regulated expression of IGFBPs in medium isolated from RA treated C33A cells. IGFBP-5 was detectable in medium from C33A cells exposed to RA, and addition of purified exogenous IGFBP-5 resulted in growth inhibition of C33A cells. These results indicate that RA exerts it's anti-neoplastic effect in HPV negative cervical carcinoma cells via the overproduction of IGFBP-5.