The Role of Completion Surgery in Ovarian Cancer.
Patients referred with inadequately staged ovarian malignancies present a clinical dilemma. We report our experience with completion surgery in ovarian cancer. To determine the benefits and risks of completion surgery in women with ovarian cancer who presented after having had inadequate primary surgery. A retrospective case series of 30 women with ovarian cancer and one with fallopian tube cancer who had inadequate primary surgery underwent completion surgery at gynaecologic oncology unit in a tertiary level hospital in Tamil Nadu, India. Electronic medical records of patients with ovarian cancer who underwent completion surgery between January 2011 and September 2014 for ovarian were reviewed. Forty-five patients with initial inadequate surgery were identified of whom 31 underwent completion surgery; the remaining 14 did not return to our hospital. Thirty-one women with a mean age of 37 years (17-53) and median parity of 2 (0-4) with inadequately staged ovarian malignancy underwent completion surgery. Complex ovarian mass was the most common indication for initial surgery (94 %). The tumours were epithelial in 27 (87 %), germ cell in 3 (10 %) and sex cord stromal in 1 (3 %). In view of extensive disease at presentation, 19 % (6/31) were referred for neoadjuvant chemotherapy and underwent interval debulking. With regard to surgical complexity, 52 % (16/31), 38 % (12/31) and 10 % (3/31) underwent simple, intermediate and complex surgeries, respectively. Optimal cytoreduction (R0 and R1) was performed in 25 patients (81 %). Twelve (39 %) had upstaging of disease. Six patients required no further adjuvant treatment following surgical restaging. Complications included bladder injury (1), iliac vessel injury (1) and surgical site infections (2). During the study period of 45 months, 7 patients (23 %) presented with disease recurrence. There were 2 recorded deaths. In inadequately staged ovarian malignancies, completion surgery should be considered based on the patients' performance status and disease assessment. Considering the low specificity of imaging and Ca 125, completion surgery provides information to plan adjuvant therapy, besides allowing optimal cytoreduction but delays initiation of adjuvant therapy.


Synthesis of 'reactive' and covalent polymeric multilayer coatings with durable superoleophobic and superoleophilic properties under water.
Bioinspired underwater super-oil-wettability (superoleophilic/superoleophobic) properties are emerging as a potential avenue for developing smart materials for addressing issues related to healthcare, environment, energy, etc. However, the inherent poor durability of the materials that are mostly developed using polymeric hydrogel, metal oxide coatings and electrostatic multilayers often challenges the application of these wettability properties in practical scenarios. Here, 'amine-reactive' polymeric multilayers of nano-complex were developed to fabricate 'internal' underwater superoleophobic/superoleophilic coatings with impeccable physical/chemical durability. This allows the super-wetting properties to exist beyond the surface of the material and remain intact even after severe physical damage including erosion of the material and continuous exposure to an artificial-marine environment for more than 80 days. Moreover, this current design allowed for independent revalidation of some key hypotheses with direct experimental demonstrations, and provided a basis to develop highly durable super-oil-wettability properties under water. It is believed that this contemporary study will make a worthwhile contribution on developing multifunctional materials for widespread practical applications by exploiting these super-oil-wetting properties.


Patients with oropharyngeal cancer: a comparison of adults living independently and patients living in long-term care facilities.
The low survival rate of persons with oropharyngeal cancer (OPC) is directly related to the size of the primary tumor, lymph node involvement and to the smoking history. The association between medical independence and the survival rate of oral cancer is unclear. The purpose of this study was to assess the survival rate of institutionalized patients with oral cancer compared to those living independently. Information regarding gender, age, tobacco habits, disease characteristics, and survival status were recorded and statistically analyzed from 30 patients with oral cancer who were institutionalized compared to 543 patients with oral cancer who were non-institutionalized. Patients living in long-term care facilities (LTC) were significantly older than the independent patients (67% were 70 years or older versus 28% of independent patients) (p = 0.0001). No differences in smoking habits were noted between the two groups but more patients who were institutionalized stopped smoking at the time of diagnosis (p = 0.47). More patients who were institutionalized were diagnosed with positive lymph node involvement (p = 0.09). Significantly higher all-cause and disease-free 5-year survival rates were noted in the patients living independently, compared to the adults who were institutionalized (32% and 60% compared to 7% and 26% respectively; p < 0.05). The disease-specific 5-year survival was directly related to age (p = 0.001), size of the tumor (p = 0.001), and lymph node involvement (p < 0.001). Significant longer survival rates were observed for patients living independently. The more advanced disease seen in the patients who were institutionalized may be due to a delay in diagnosis, which may be associated with fewer symptoms, limited report of symptoms, a lack of attention or a misdiagnosis of the oral lesion.


Health benefits of yogurt among infants and toddlers aged 4 to 24 months: a systematic review.
Health benefits of yogurt are well documented in adults and older children, but less is known about the effects of yogurt in infants and toddlers (aged 4 to 24 months). The aim of this qualitative systematic review was to assess the effects of yogurt and fermented milk products on the health of infants and toddlers. PubMed was searched for English-language papers. No date restrictions were applied. Randomized controlled trials, observational studies, and prospective cohort studies were included. Systematic or narrative reviews, conference abstracts, and dissertations were excluded. In total, 1624 abstracts were screened, of which 1614 were excluded. Full texts of the remaining 10 abstracts were independently reviewed by both authors, who reached consensus about relevance, methods, findings, quality, and conclusions of the included studies. The included studies (published between 1987 and 2017) were heterogeneous with respect to sample size, study population, and type of yogurt used. Five of six studies showed a positive effect of yogurt consumption on infectious diarrhea. Two studies reported a positive effect on gut microbiota composition. Two cohort studies reported a positive effect on reducing the incidence of atopic dermatitis, one of which also reported a positive impact on food sensitivity. Published evidence, much of it decades old, supports a health benefit of yogurt consumption in infants and children. New short- and long-term studies are needed to better evaluate the impact of yogurt consumption in contemporary settings.


Tinnitus in occupational hearing loss: nosological aspects.
Tinnitus is a frequent and annoying accompaniment of occupational hearing loss. Detailed case histories of 2,442 workers claiming compensation for hearing impairment were analyzed with respect to the incidence and characteristics of tinnitus. It was present in 58% of claimants, and was rated as a major problem in 19%. It was usually bilateral, and there was no evidence of ear differences in incidence or severity. Most commonly, it was tonal and of high pitch. There was no apparent relationship of tinnitus incidence to hearing loss severity, but the data suggest a higher incidence in workers exposed to impulse noise.


Comparative investigation of the cleavage step in the synthesis of model peptide resins: implications for Nalpha-9-fluorenylmethyloxycarbonyl-solid phase peptide synthesis.
Based on our studies of the stability of model peptide-resin linkage in acid media, we previously proposed a rule for resin selection and a final cleavage protocol applicable to the Nalpha-tert-butyloxycarbonyl (Boc)-peptide synthesis strategy. We found that incorrect choices resulted in decreases in the final synthesis yield, which is highly dependent on the peptide sequence, of as high as 30%. The present paper continues along this line of research but examines the Nalpha-9-fluorenylmethyloxycarbonyl (Fmoc)-synthesis strategy. The vasoactive peptide angiotensin II (AII, DRVYIHPF) and its [Gly8]-AII analogue were selected as model peptide resins. Variations in parameters such as the type of spacer group (linker) between the peptide backbone and the resin, as well as in the final acid cleavage protocol, were evaluated. The same methodology employed for the Boc strategy was used in order to establish rules for selection of the most appropriate linker-resin conjugate or of the peptide cleavage method, depending on the sequence to be assembled. The results obtained after treatment with four cleavage solutions and with four types of linker groups indicate that, irrespective of the circumstance, it is not possible to achieve complete removal of the peptide chains from the resin. Moreover, the Phe-attaching peptide at the C-terminal yielded far less cleavage (50-60%) than that observed with the Gly-bearing sequences at the same position (70-90%). Lastly, the fastest cleavage occurred with reagent K acid treatment and when the peptide was attached to the Wang resin.


The origins of the Lacto-Bolo reflex: the mythology of lactate in sepsis.
The use of lactate as a marker of the severity of circulatory shock was popularized by Dr. Weil in the 1970's. Dr. Weil promoted the idea that blood lactate concentration increased in circulatory shock due to anaerobic metabolism following decreased oxygen delivery. This concept becomes entrenched with 1992 ACCP/SCCM consensus conference definition of sepsis. Since then, the central role of lactate in the definition and management of septic shock has only been expanded and become more ingrained. This review will discuss the wisdom of such an approach, an updated model describing the origins of hyperlactatemia in sepsis, and how such improvements in our knowledge of the underlying physiology should change our approach to resuscitation in patients presenting with septic shock.


[A method of comparison of DNA polynucleotide sequences].
The results of a comparative analysis of the kinetic curves of reassociation of DNA of closely related species of Microtus (Microtus arvalis, Microtus oeconomus oeconomus, Microtus oeconomus Chachlovi) are presented. A five power polynomial was used as a mathematical model of the kinetic DNA reassociation curves. The values of polynomial coefficients and the theoretical value, both with statistical deviations dispersion, have been estimated with the help of a standard computer programme. The modified Fischer criterium was used for comparing the model kinetic curves of reassociation of the above species and of subspecies of Microtus, and to estimate the significance of the difference between two random means. A pair-wise comparison of the model curves shows that the similarity of the DNA polynucleotide sequences in two subspecies is less expressed than in two species of Microtus. A method of comparison of DNA nucleotide sequences is suggested on the basis of mathematical models of kinetic curves of DNA reassociation.


Non-motor symptoms in Parkinson's disease: An explorative network study.
Research on the association between non-motor symptoms (NMS) of Parkinson's disease (PD) and patients' quality of life (QoL) has given insight into the burden of NMS. Most studies investigate NMS by assessing the contribution of individual symptoms to QoL. However, symptoms could also have an interactive relationship, which might not be fully taken into account when only studying these individual contributions. Recently, a network approach has been developed that treats symptoms as nodes and associations between symptoms as edges in a network, providing the opportunity to investigate the dimensional spectrum of NMS. In the current cross-sectional study, we investigated NMS with both approaches: first, we assessed individual contributions of NMS to QoL. Second, we aimed to assess NMS using a network approach. Seventy PD patients completed questionnaires on NMS and QoL. Our primary analysis shows that the domains Mood and Pain are significant contributors to QoL. Our secondary network analysis suggests that Mood and Sleep play central roles in the NMS-network, and that Mood and Cognition are strongly related. Because of power issues, the generalizability of our explorative results is limited. However, complementary information from the network analysis does suggest that focusing on sleep problems might help both mood and pain symptoms, which negatively affect QoL. Investigating symptoms not only as individual and independent entities but rather as part of a connected network could show how treating one symptom affects other symptoms.


Superconducting nanowires fabricated using molecular templates.
The application of single molecules as templates for nanodevices is a promising direction for nanotechnology. We use suspended deoxyribonucleic acid molecules or single-walled carbon nanotubes as templates for fabricating superconducting devices and then study these devices at cryogenic temperatures. Because the resulting nanowires are extremely thin, comparable in diameter to the templating molecule itself, their electronic state is highly susceptible to thermal fluctuations. The most important family of these fluctuations are the collective ones, which take the form of Little's phase slips or ruptures of the many-electron organization. These phase slips break the quantum coherence of the superconducting condensate and render the wire slightly resistive (i.e., not fully superconducting), even at temperatures substantially lower than the critical temperature of the superconducting transition. At low temperatures, for which the thermal fluctuations are weak, we observe the effects of quantum fluctuations, which lead to the phenomenon of macroscopic quantum tunneling. The modern fabrication method of molecular templating, reviewed here, can be readily implemented to synthesize nanowires from other materials, such as normal metals, ferromagnetic alloys, and semiconductors.


COVID-19 and the Kidneys, Implications and Outcomes.
Coronavirus disease (COVID-19), declared as a pandemic has affected millions of people and caused unprecedented number of death. The disease is caused by a severe acute respiratory syndrome related coronaviruses-2 virus which enters cells by binding with the host angiotensin converting enzyme-2 and CD147 protein. Among COVID-19 patients admitted to a hospital, hypertension, diabetes and obesity are the most common co-morbidities. A majority of COVID-19 hospitalized patients are found to have proteinuria and hematuria which is associated with higher risk of in-hospital mortality. Studies have reported high incidence of acute kidney injury (AKI) among COVID-19 patients admitted to hospital (10 to 43%) and intensive care unit (43-75%). These patients with AKI have much higher need for mechanical ventilation, vasopressor use and critical care. In addition, proportion of patients with AKI who require renal replacement (RRT) therapy is greatly increased. Acute tubular injury, cytokine storm induced systemic inflammatory response, endothelial injury and dysfunction are the main mechanisms of AKI. In addition, direct viral invasion of tubules, lymphocytic infiltration and complement mediated (C5b- 9) related injury is also seen. Mortality risk among patients with AKI and those in need of RRT is greatly amplified. Appropriate timing and choice of RRT for these patients is not well defined but will need to take in account the clinical condition, anticipation of their clinical course and availability of dialysis resources. Risk of AKI and death is also increased among kidney recipients and patients with chronic kidney disease.


Analysis of the distribution of magnetic fluid inside tumors by a giant magnetoresistance probe.
Magnetic fluid hyperthermia (MFH) therapy uses the magnetic component of electromagnetic fields in the radiofrequency spectrum to couple energy to magnetic nanoparticles inside tumors. In MFH therapy, magnetic fluid is injected into tumors and an alternating current (AC) magnetic flux is applied to heat the magnetic fluid- filled tumor. If the temperature can be maintained at the therapeutic threshold of 42 °C for 30 minutes or more, the tumor cells can be destroyed. Analyzing the distribution of the magnetic fluid injected into tumors prior to the heating step in MFH therapy is an essential criterion for homogenous heating of tumors, since a decision can then be taken on the strength and localization of the applied external AC magnetic flux density needed to destroy the tumor without affecting healthy cells. This paper proposes a methodology for analyzing the distribution of magnetic fluid in a tumor by a specifically designed giant magnetoresistance (GMR) probe prior to MFH heat treatment. Experimental results analyzing the distribution of magnetic fluid suggest that different magnetic fluid weight densities could be estimated inside a single tumor by the GMR probe.


Genes involved in the evolution of herbivory by a leaf-mining, Drosophilid fly.
Herbivorous insects are among the most successful radiations of life. However, we know little about the processes underpinning the evolution of herbivory. We examined the evolution of herbivory in the fly, Scaptomyza flava, whose larvae are leaf miners on species of Brassicaceae, including the widely studied reference plant, Arabidopsis thaliana (Arabidopsis). Scaptomyza flava is phylogenetically nested within the paraphyletic genus Drosophila, and the whole genome sequences available for 12 species of Drosophila facilitated phylogenetic analysis and assembly of a transcriptome for S. flava. A time-calibrated phylogeny indicated that leaf mining in Scaptomyza evolved between 6 and 16 million years ago. Feeding assays showed that biosynthesis of glucosinolates, the major class of antiherbivore chemical defense compounds in mustard leaves, was upregulated by S. flava larval feeding. The presence of glucosinolates in wild-type (WT) Arabidopsis plants reduced S. flava larval weight gain and increased egg-adult development time relative to flies reared in glucosinolate knockout (GKO) plants. An analysis of gene expression differences in 5-day-old larvae reared on WT versus GKO plants showed a total of 341 transcripts that were differentially regulated by glucosinolate uptake in larval S. flava. Of these, approximately a third corresponded to homologs of Drosophila melanogaster genes associated with starvation, dietary toxin-, heat-, oxidation-, and aging-related stress. The upregulated transcripts exhibited elevated rates of protein evolution compared with unregulated transcripts. The remaining differentially regulated transcripts also contained a higher proportion of novel genes than the unregulated transcripts. Thus, the transition to herbivory in Scaptomyza appears to be coupled with the evolution of novel genes and the co-option of conserved stress-related genes.


The complementarity-determining region-like loops of CD8 alpha interact differently with beta 2-microglobulin of the class I molecules H-2Kb and thymic leukemia antigen, while similarly with their alpha 3 domains.
The murine CD8 glycoprotein interacts with both classical MHC class I molecules and some nonclassical molecules, including the thymic leukemia Ag (TL). TL binds preferentially to CD8alphaalpha homodimers with a 10-fold higher affinity than H-2K(b) class I molecules. To understand the molecular basis for this difference, we created a panel of CD8alpha mutants and tested the ability of the CD8alphaalpha homodimers to bind to H-2K(b) tetramers and TL tetramers. Mutations in three CD8 residues located on the complementarity-determining region-like loops contacting the negatively charged loop in the alpha3 domain of MHC class I greatly reduced binding to both tetramers. Because TL and H-2K(b) class I sequences are highly conserved in the alpha3 domain of MHC class I, this suggests that CD8 contacts the alpha3 domain of TL and H-2K(b) in a similar manner. In contrast, mutations in residues on the A and B beta strands of CD8 that are involved in contact with beta(2)-microglobulin affected interaction with the H-2K(b) tetramer, but not the TL tetramer. Therefore, the orientation of interaction of TL with CD8 appears to be different from that of H-2K(b). The unique high affinity binding of TL with CD8alphaalpha is most likely a result of amino acid differences in the alpha3 domain between TL and H-2K(b), particularly at positions 198 (K to D) and 228 (M to T), which are contact residues in the CD8alphaalpha-H-2K(b) cocrystal.


Synthesis and Evaluation of Potent KCNQ2/3-Specific Channel Activators.
KQT-like subfamily (KCNQ) channels are voltage-gated, noninactivating potassium ion channels, and their down-regulation has been implicated in several hyperexcitability-related disorders, including epilepsy, neuropathic pain, and tinnitus. Activators of these channels reduce the excitability of central and peripheral neurons, and, as such, have therapeutic utility. Here, we synthetically modified several moieties of the KCNQ2-5 channel activator retigabine, an anticonvulsant approved by the U.S. Food and Drug Administration. By introducing a CF3-group at the 4-position of the benzylamine moiety, combined with a fluorine atom at the 3-position of the aniline ring, we generated Ethyl (2-amino-3-fluoro-4-((4-(trifluoromethyl)benzyl)amino)phenyl)carbamate (RL648_81), a new KCNQ2/3-specific activator that is >15 times more potent and also more selective than retigabine. We suggest that RL648_81 is a promising clinical candidate for treating or preventing neurologic disorders associated with neuronal hyperexcitability.


Insecticidal roof barriers mounted on untreated bed nets can be as effective against Anopheles gambiae as regular insecticide-treated bed nets.
Barrier bednets (BBnets), regular bednets with a vertical insecticidal panel to target mosquitoes above the bednet roof, where they are most active, have the potential to improve existing Insecticidal Treated Bednets (ITNs), by reducing the quantity of insecticide required per net, reducing the toxic risks to those using the net, potentially increasing insecticide choice. We evaluated the performance of PermaNet 3.0 (P3) and untreated (Ut) bed nets with and without pyrethroid and piperonyl butoxide roof barriers in killing pyrethroid-resistant and susceptible Anopheles gambiae, simultaneously video-recording mosquito flight tracks. Bioassay results showed that treated roof barriers, particularly the longitudinal P3 barrier (P3L) could be an effective addition to a bed net: P3 + P3L were consistently significantly more effective than the reference P3 bednet while performance of untreated nets could be raised to equal that of the reference P3 following the addition of a P3 barrier. The BBnet's potential to augment existing bednets and enhance their performance is considered.


Killing of skin-derived tumor cells by mouse dendritic epidermal T-cells.
Dendritic epidermal T-cells (DETC) are a unique population of T-cells that reside normally in mouse epidermis and express a gamma delta T-cell receptor. We have reported previously that DETC acquire in culture the capacity to lyse the YAC-1 lymphoma, a conventional target for natural killer cells. The aim of the present study was to characterize this cytotoxic potential, using a spectrum of skin-derived mouse tumors. Cytotoxicity was measured by a 51Cr release assay and by the visual assessment of target cell lysis. Long-term DETC lines, established from CBA, AKR, and BALB/c mice by mitogenic stimulation and repeated feeding with interleukin 2 (5 units/ml), were used as effectors. Skin-derived tumor targets included 5 melanoma lines and the transformed keratinocyte line Pam 212. Each DETC line lysed skin-derived tumors as well as YAC-1 targets effectively in the 18-h 51Cr release assay, and target lysis occurred in a non-major histocompatibility complex-restricted manner. By contrast, freshly isolated spleen cells lysed YAC-1 but not skin tumor targets. Moreover, confluent monolayers of melanoma or Pam 212 targets were disrupted completely by added DETC lines but not by spleen cells. The cytolytic activity of DETC appeared to be specific for tumor cells, since normal mouse keratinocyte monolayers remained intact under the same conditions. Finally, DETC freshly isolated from skin failed to exhibit significant cytotoxicity but acquired this capacity 10-14 days after mitogenic stimulation and feeding with interleukin 2 (5 units/ml). We conclude that DETC possess the potential to recognize, bind, and lyse tumor cells that originate in skin.


Timing and Duration of Axillary Lymph Node Swelling After COVID-19 Vaccination: Japanese Case Report and Literature Review.
COVID-19 vaccination is now performed in most of the world to limit the spread of the disease. The first mRNA vaccine was approved in clinical settings and has specific side effects including axillary lymph node swelling, which can be misdiagnosed as breast cancer metastasis. The timing of axillary lymph node swelling and its duration are unclear. Here, we present a Japanese case and review of the existing literature. We report the case of a 67-year-old woman with breast calcification. She had regular follow ups in our hospital for this calcification and received ultrasonography of the breast and axilla at every visit. She visited 6 months before having her COVID-19 vaccination, and 7 days and 6 months after the first COVID-19 vaccination. She had a swollen axillary lymph node 7 days after the first vaccination, which although it was improved, remained for 6 months. Axillary lymph node swelling occurred 7 days after vaccination and remained up to 6 months after it.


[Addiction as a life style: on the social anthropology of addiction].
Regularly the unsolved problems of addiction- and dependence-research are discussed in the sense of the psycho-body-dichotomy, arguing that the biological mechanisms of reward-systems and their pathobiochemistry have to be confronted with the psychological and philosophical/anthropological dimensions within persons. The present paper, however, tries to demonstrate that this dichotomy is insufficient insofar as social-anthropological components of being addicted, which represent integrative constituents of a theory of addiction, are neglected within such a scheme. The developmental-psychological and philosophical-psychological aspects of socialization are considered and related to internal valuating systems and reality models regarding the problems of drugs and dependency. Herein it is shown that especially the model of René Girard, constituting "mimetic triangulation", is applicable to the understanding of the microsocialization of drug-consumers. This is also demonstrated in film-examples. It is shown that the problem of drug-addiction cannot be solved from a neurobiological/biochemical--and also a psychotherapeutic/psychoanalytic concept--without incorporating the dynamics and the value-worlds within groups which should also be considered to be therapeutically influenceable.


Selective agonist binding of (S)-2-amino-3-(3-hydroxy-5-methyl-4-isoxazolyl)propionic acid (AMPA) and 2S-(2alpha,3beta,4beta)-2-carboxy-4-(1-methylethenyl)-3-pyrrolidineacetic acid (kainate) receptors: a molecular modeling study.
Molecular models were constructed, using the published X-ray structure of rat glutamate receptor 2 (GluR2), for the ligand-binding domains of the human (S)-2-amino-3-(3-hydroxy-5-methyl-4-isoxazolyl)propionic acid (AMPA)- and kainate-selective ionotropic glutamate receptors (iGluRs): GluR1-7 and KA1-2. Based on the analysis of the known X-ray structures of GluR2 in complex with glutamate, kainate, and AMPA, we have constructed binding motifs (relative positioning of a ligand in the binding site and the physico-chemical interactions that take place) for selected agonist ligands and found explanations for ligand-binding selectivity to homomeric receptors among the different iGluRs. Even a single sequence difference can explain significant differences in ligand-binding affinities between two receptors. In total, there are seven residues surrounding the binding cavity that affect agonist selectivity: in GluR2, these residues are Pro478, Thr480, Leu650, Ser654, Thr686, Tyr702, and Met708. Each of these seven positions has been shown, or is predicted, to influence the presence of one or more water molecules that, when present, may form bridging hydrogen bonds between particular ligands and receptors. By using this knowledge it should be possible to design new selective agonist ligands with high affinity for any AMPA/kainate receptor.


Influence of the antifolate drug Methotrexate on the development of murine neural tube defects and genomic instability.
Impaired folate metabolism is considered a risk factor for neural tube defects (NTDs). However, the relationship between folate deficiency and the risk of NTDs remains unclear, because experimentally induced dietary folate deficiency is insufficient to cause NTDs in non-mutant mice. Methotrexate (MTX) is a specific folate antagonist that competitively inhibits dihydrofolate reductase (DHFR) activity. The objective of this study was to develop a folate dysmetabolism murine model, and study the development of NTDs and its mechanism. Pregnant mice were injected with different doses of MTX [0, 0.5, 1.0, 3.0, 4.5 and 6.0 mg kg(-1) body weight (b/w) intraperitoneally (i.p.)] on gestational day 7.5 and sacrificed on gestational day 11.5. DHFR activity in embryonic tissues was detected, and folate concentrations were analyzed using LC/MS/MS. Copy number variations (CNVs) in neural tube tissues were detected using array comparative genomic hybridization (aCGH). A dose of MTX 4.5 mg kg(-1) b/w, resulted in the highest incidence of NTDs (31.4%) compared with the other groups, and DHFR activities, 5-MeTHF and 5-FoTHF concentrations in embryonic tissues decreased significantly after MTX injection. Furthermore, we found three high-confidence CNVs on chromosome X using aCGH, which was confirmed by RT-PCR and MassARRAY. These results indicate that MTX could cause a folate-associated dysmetabolism, which is similar to that of dietary folate deficiency in mice. The presence of CNVs in neural tube tissues was associated with the development of NTDs.


[Treatment of vertical talus with the Dobbs method].
The widely accepted treatment of vertical talus after casting is correction by extensive surgery. Dobbs described a new method for the treatment of vertical talus by casting and minimally invasive surgery. The purpose of the present study was to evaluate the efficacy of this new method. Between 11/06 and 11/09 we treated 7 patients with 12 vertical tali. Treatment followed the protocol of Dobbs. The initiation of treatment, number of casts, surgery, as well as clinical and radiological results were documented. To evaluate the radiological result we used the Hamanishi score. From the beginning all feet could be treated successfully with the Dobbs method. According to the Hamanishi classification we have four excellent and five good results. Two feet had a relapse with subluxation or dislocation of the talonavicular joint. Treatment of vertical talus with the Dobbs method is successful. Extensive surgery could be reduced. We recommend the method as primary treatment for vertical talus.


Laser-generated broadband antireflection structures for freeform silicon lenses at terahertz frequencies.
We present a flexible technology to generate broadband antireflection (AR) structures for the terahertz (THz) frequency range on planar and curved surfaces of silicon optics. Ultrashort laser pulses are used to ablate the surface to form a pattern of conical pillars with a period of 30 μm. These subwavelength structures act as an effective medium with gradual transition of the refractive index from air to silicon, which reduces the Fresnel reflection losses. The characterization with the THz time-domain spectroscopy system shows an AR effect for a frequency range of 0.1-1.5 THz with a maximum enhancement of the spectral amplitude by ca. 32% at 0.4 THz for planar surfaces. In addition, we demonstrate laser-generated AR structures on convex silicon lenses of both photoconductive emitter and detector devices. Here, the THz pulse amplitude can be increased by about 28%, and single frequencies even show an improvement of the spectral amplitude up to 58%.


Proliferation-dependent and cell cycle regulated transcription of mouse pericentric heterochromatin.
Pericentric heterochromatin transcription has been implicated in Schizosaccharomyces pombe heterochromatin assembly and maintenance. However, in mammalian systems, evidence for such transcription is inconsistent. We identify two populations of RNA polymerase II-dependent mouse gamma satellite repeat sequence-derived transcripts from pericentric heterochromatin that accumulate at different times during the cell cycle. A small RNA species was synthesized exclusively during mitosis and rapidly eliminated during mitotic exit. A more abundant population of large, heterogeneous transcripts was induced late in G1 phase and their synthesis decreased during mid S phase, which is coincident with pericentric heterochromatin replication. In cells that lack the Suv39h1,2 methyltransferases responsible for H3K9 trimethylation, transcription occurs from more sites but is still cell cycle regulated. Transcription is not detected in quiescent cells and induction during G1 phase is sensitive to serum deprivation or the cyclin-dependent kinase inhibitor roscovatine. We demonstrate that mammalian pericentric heterochromatin transcription is linked to cellular proliferation. Our data also provide an explanation for inconsistencies in the detection of such transcripts in different systems.


Implementation of an academic detailing intervention to increase naloxone distribution and foster engagement in harm reduction from the community clinician.
Respond to Prevent (R2P) is a randomized clinical trial which sought to accelerate distribution of naloxone and other harm reduction materials from community pharmacies. R2P combined an online continuing education course with in-store materials, specifically designed for use in community pharmacies, and then supported implementation through the one-on-one educational technique of academic detailing. The objective of this paper is to describe and synthesize our experiences providing academic detailing as part of the R2P randomized trial. Closed-ended items from standardized post detailing questionnaires were analyzed with descriptive statistics. Open-ended items were content analyzed for key themes using immersion-crystallization qualitative methods. A total of 176 pharmacies participated in R2P with 175 receiving their initial academic detailing visit between August 2019 and May 2021. Initial visits were in-person and lasted a median of 35 minutes (interquartile range, 20-45 minutes). The R2P naloxone guide was the most common topic covered (n = 162, 92.6%). Following a fidelity check to assess adequacy of the R2P program implementation, 80 pharmacies (45.7%) required secondary academic detailing. Secondary detailing was more targeted and most frequently focused on the sale of nonprescription syringes (n = 28; 35.2%) or disposal container distribution (n = 30; 37.5%). Analysis of the open-ended items identified factors that the detailers perceived to affect the quality of academic detailing sessions, including the pharmacy environment, participant knowledge of and attitudes toward the subject matter, and ability of the detailer to remain flexible yet consistent. R2P provided a standardized process to foster naloxone distribution and engagement in harm reduction with demonstrated implementation in 175 community pharmacies across 4 states. Academic detailing was perceived to be well-received and effective at providing education and promoting distribution of naloxone and nonprescription syringes in community pharmacies. Additional research is needed to confirm these perceptions through evaluation post-intervention behavioral and attitude changes.


Integrated pest management in the U.S.: progress and promise.
In the U.S., where heavy use of insecticides has been commonplace for years, the development of proper integrated insect pest control cannot get underway unless there is a changed use pattern for such chemicals. A changed use pattern, however, cannot be accomplished without much study to establish the requirements for integrated control for each major crop situation. In this paper recent developments in a number of crop areas in the U.S. in which the necessary study has been begun are reviewed. Important phases in the development of integrated control programs include: the single tactics phase, the multitactic phase, phase, the biological monitoring phase, the modeling phase, the management and optimization phase, and the implementation phase. Several crops are discussed in relation to how far along we are in the development of practical programs of insect pest control. These are cotton, apples, alfalfa, soybeans, citrus, corn, cereal grains, tobacco and pine forests. Several of these programs have already made substantial headway, e.g., those for cotton, alfalfa, apples, tobacco, and soybeans, although the accomplishments have not been even or parellel with respect to the phases of development where progress has been good. The review of developments in these crops suggests that programs of control for individual crops and perhaps for complexes of associated crops will be developed according to specific needs of the crop, the geographic area and the pests, the technologies available and the socioeconomic and political factors of relevance. The tendency will be toward greater use of science in pest control decision-making, with extensive use of biological monitoring to establish realistic levels of threatened damage to the crop, and greater concern given to possible profit reductions and environmental disturbances of applying an insecticide, as well as the possible gain from doing so.


Glycine-spacers influence functional motifs exposure and self-assembling propensity of functionalized substrates tailored for neural stem cell cultures.
The understanding of phenomena involved in the self-assembling of bio-inspired biomaterials acting as three-dimensional scaffolds for regenerative medicine applications is a necessary step to develop effective therapies in neural tissue engineering. We investigated the self-assembled nanostructures of functionalized peptides featuring four, two or no glycine-spacers between the self-assembly sequence RADA16-I and the functional biological motif PFSSTKT. The effectiveness of their biological functionalization was assessed via in vitro experiments with neural stem cells (NSCs) and their molecular assembly was elucidated via atomic force microscopy, Raman and Fourier Transform Infrared spectroscopy. We demonstrated that glycine-spacers play a crucial role in the scaffold stability and in the exposure of the functional motifs. In particular, a glycine-spacer of four residues leads to a more stable nanostructure and to an improved exposure of the functional motif. Accordingly, the longer spacer of glycines, the more effective is the functional motif in both eliciting NSCs adhesion, improving their viability and increasing their differentiation. Therefore, optimized designing strategies of functionalized biomaterials may open, in the near future, new therapies in tissue engineering and regenerative medicine.


Controlling Major Portal Vein Invasion Progression during Lenvatinib Treatment by Carbon-Ion Radiotherapy in Patients with Advanced Hepatocellular Carcinoma.
Macrovascular invasion (MVI), including portal vein tumor thrombosis (PVTT), is strongly associated with poor prognosis in patients with hepatocellular carcinoma (HCC). While recommended standard treatment for patients with advanced HCC is systemic therapy, various treatment approaches, including resection, transarterial chemoembolization, and radiation, have been empirically suggested to improve prognosis by eliminating or controlling MVI. Herein, we report our experience of a case with advanced HCC where MVI was controlled by carbon-ion radiotherapy (CIRT) while on systemic therapy, resulting in a prolonged survival. A female patient with HCC in her early 60s had multiple intrahepatic lesions (maximum 60 mm in diameter) with PVTT. The PVTT of this patient had reached the main trunk of the portal vein despite the use of lenvatinib. The other intrahepatic lesions of the patient, except PVTT, had been controlled by lenvatinib. Therefore, hoping to control PVTT, we attempted CIRT. The patient resumed lenvatinib therapy after the irradiation. During lenvatinib re-treatment, no evident progression of PVTT was observed in the patient.


Within-diver variability in venous gas emboli (VGE) following repeated dives.
Venous gas emboli (VGE) are widely used as a surrogate endpoint instead of decompression sickness (DCS) in studies of decompression procedures. Peak post-dive VGE grades vary widely following repeated identical dives but little is known about how much of the variability in VGE grades is proportioned between-diver and within-diver. A retrospective analysis of 834 man-dives on six dive profiles with post-dive VGE measurements was conducted under controlled laboratory conditions. Among these data, 151 divers did repeated dives on the same profile on two to nine occasions separated by at least one week (total of 693 man-dives). Data were analysed for between- and within-diver variability in peak post-dive VGE grades using mixed-effect models with diver as the random variable and associated intraclass correlation coefficients. Most divers produced a wide range of VGE grades after repeated dives on the same profile. The intraclass correlation coefficient (repeatability) was 0.33 indicating that 33% of the variability in VGE grades is between-diver variability; correspondingly, 67% of variability in VGE grades is within-diver variability. DCS cases were associated with an individual diver's highest VGE grades and not with their lower VGE grades. These data demonstrate large within-diver variability in VGE grades following repeated dives on the same dive profile and suggest there is substantial within-diver variability in susceptibility to DCS. Post-dive VGE grades are not useful for evaluating decompression practice for individual divers.


Spicing Up the N Gene: F. O. Holmes and Tobacco mosaic virus Resistance in Capsicum and Nicotiana Plants.
One of the seminal events in plant pathology was the discovery by Francis O. Holmes that necrotic local lesions induced on certain species of Nicotiana following rub-inoculation of Tobacco mosaic virus (TMV) was due to a specific interaction involving a dominant host gene (N). From this, Holmes had an idea that if the N gene from N. glutinosa was introgressed into susceptible tobacco, the greatly reduced titer of TMV would, by extension, prevent subsequent infection of tomato and pepper plants by field workers whose hands were contaminated with TMV from their use of chewing and smoking tobacco. The ultimate outcome has many surprising twists and turns, including Holmes' failure to obtain fertile crosses of N. glutinosa × N. tabacum after 3 years of intensive work. Progress was made with N. digluta, a rare amphidiploid that was readily crossed with N. tabacum. And, importantly, the first demonstration by Holmes of the utility of interspecies hybridization for virus resistance was made with Capsicum (pepper) species with the identification of the L gene in Tabasco pepper, that he introgressed into commercial bell pepper varieties. Holmes' findings are important as they predate Flor's gene-for-gene hypothesis, show the use of interspecies hybridization for control of plant pathogens, and the use of the local lesion as a bioassay to monitor resistance events in crop plants.


Naturally produced outer membrane vesicles from Pseudomonas aeruginosa elicit a potent innate immune response via combined sensing of both lipopolysaccharide and protein components.
Pseudomonas aeruginosa is a prevalent opportunistic human pathogen that, like other Gram-negative pathogens, secretes outer membrane vesicles. Vesicles are complex entities composed of a subset of envelope lipid and protein components that have been observed to interact with and be internalized by host cells. This study characterized the inflammatory responses to naturally produced P. aeruginosa vesicles and determined the contribution of vesicle Toll-like receptor (TLR) ligands and vesicle proteins to that response. Analysis of macrophage responses to purified vesicles by real-time PCR and enzyme-linked immunosorbent assay identified proinflammatory cytokines upregulated by vesicles. Intact vesicles were shown to elicit a profoundly greater inflammatory response than the response to purified lipopolysaccharide (LPS). Both TLR ligands LPS and flagellin contributed to specific vesicle cytokine responses, whereas the CpG DNA content of vesicles did not. Neutralization of LPS sensing demonstrated that macrophage responses to the protein composition of vesicles required the adjuvantlike activity of LPS to elicit strain specific responses. Protease treatment to remove proteins from the vesicle surface resulted in decreased interleukin-6 and tumor necrosis factor alpha production, indicating that the production of these specific cytokines may be linked to macrophage recognition of vesicle proteins. Confocal microscopy of vesicle uptake by macrophages revealed that vesicle LPS allows for binding to macrophage surfaces, whereas vesicle protein content is required for internalization. These data demonstrate that macrophage sensing of both LPS and protein components of outer membrane vesicles combine to produce a bacterial strain-specific response that is distinct from those triggered by individual, purified vesicle components.


The effect of spinal instrumentation on lumbar intradiscal pressure.
The purpose of this study was to investigate the effect of spinal instrumentation on the intradiscal pressure (IDP) within the fixed motion segment. In vitro biomechanical testing was performed in six single functional spinal units of fresh calf lumbar spines using a pressure needle transducer. Various loads were applied by a materials testing system device. In addition to intact spine (control), anterior spinal instrumentation (ASI) and pedicle screw fixation (PS) constructs, as well as destabilized spine were tested. Relative to the control, the destabilized spine tended to have an increased IDP; by 15% in axial compression and by 9-36% in flexion-extension. Compared to the control, PS decreased the IDP by 23% in axial loading and 51% in extension loading and increased it by 60% in flexion for each loading. ASI decreased the IDP by 32% in flexion and 1% in extension. Lateral bending produced symmetrical changes of IDP in the control and destabilized spine, but no change in the PS construct. The IDP of the ASI construct was decreased by 77% in ipsilateral bending and increased by 22% in contralateral bending. These results demonstrated that eccentric loading from the spinal instruments increased IDP and significant disc pressure may still exist despite an increase in motion segment stiffness after lumbar stabilization.


Improvements in clinical pain and experimental pain sensitivity after cognitive functional therapy in patients with severe persistent low back pain.
Multidisciplinary care is recommended for disabling persistent low back pain (pLBP) nonresponsive to primary care. Cognitive functional therapy (CFT) is a physiotherapy-led individualised intervention targeting psychological, physical, and lifestyle barriers to recovery, to self-manage pLBP. This pilot study investigated clinical outcomes and pain thresholds after a 12-week CFT pathway in patients with severe pLBP referred to a University Pain Center. Exploratory analyses compared changes in clinical outcomes, opioid consumption, and costs after CFT with changes after a multidisciplinary pain management (MPM) pathway. In total, 47 consecutively referred pLBP patients consented to the CFT pathway. At baseline, 3 and 6 months, clinical outcomes and PPTs were assessed. Control patients (n = 99) who had completed an MPM pathway in the last 3 years were matched from the clinical pain registry used in the Pain Center in a 3:1 ratio based on propensity scores derived from relevant baseline variables of the CFT cases. Most clinical outcomes and low back pressure pain threshold were improved at 3 and 6 months after the CFT pathway. Compared with MPM, CFT patients had significantly larger reductions in disability and improved quality of life after the interventions at a lower cost (-3688€ [confidence interval: -3063 to -4314€]). Reduction in pain intensity and proportion of patients withdrawing from opioids (18.2% vs 27.8%) were similar between CFT and MPM groups. Improvements in clinical and experimental pain were found after the CFT pathway. Fully powered randomized controlled trials comparing CFT with an MPM program in patients with disabling pLBP are warranted to control for the current limitations.


Overnight cross-coverage on hospital medicine services: perceived workload based on patient census, pager volumes, and patient acuity.
Little is understood about what contributes to perceived workload for those providing overnight coverage to hospitalized patients overnight, which limits the ability to modify these factors or to proactively identify appropriate staffing levels. The objective of this study is to understand the major contributors to perceived overnight cross-coverage workload. Cross-covering advanced practice providers (APPs) in a large academic hospitalist group completed the National Aeronautics and Space Administration Task Load Index (NASA-TLX) at the end of each night shift. Other shift characteristics were collected, including patient load, assigned action items, watcher/unstable patients, newly admitted patients, number of units covered, total pages, peak pager density, rapid response team (RRT) activations, and intensive care unit (ICU) transfers. For 14 APP participants, who completed 271 post-shift surveys, the mean (SD) patient load was 49.9 (6.4) patients per night, and providers received a mean (SD) of 40.8 (13.7) total pages per shift. Mean (SD) NASA-TLX score was 35.1 (19.0). In multivariate modeling, total pages, action items, and any RRT or ICU transfer were associated with significant increases in the mean NASA-TLX score, with estimated effect sizes of 0.5, 0.8, and 14.3, respectively, per 1-unit increase in each shift characteristic. The greatest cumulative contributor to perceived workload was total number of pages, followed by the presence of any RRT activation/ICU transfer, with estimated effect sizes of 20.4 and 14.9, respectively. Total number of pages was the greatest contributor to perceived workload. This study suggests that quality improvement initiatives designed to improve pager communication may considerably improve provider-perceived workload.


Tuberculosis vaccine BCG: the magical effect of the old vaccine in the fight against the COVID-19 pandemic.
Bacillus Calmette-Guérin (BCG) is a live attenuated M. bovis vaccine that was developed about 100 years ago by Albert Calmette and Camille Guérin. Many countries have been using the vaccine for decades against tuberculosis (TB). The World Health Organization (WHO) recommends a single dose of BCG for infants in TB endemic as well as leprosy high risk countries, and globally almost 130 million infants are vaccinated yearly. The role of BCG is well known in reducing neonatal and childhood death rates. Epidemiological and retrospective cross-sectional studies demonstrated that the BCG vaccination protects the children against respiratory tract infections and lowers the risk of malaria in children. In addition, BCG enhances IFN-γ and IL-10 levels, thus providing immunity against respiratory tract infection even in elderly people. The BCG is also known to provide nonspecific innate immunity against viruses and parasites, through an innate immune mechanism termed 'trained immunity' and is defined as the immunological recall of the innate immune system by epigenetic reprogramming. Based on these studies it is suggested that the BCG has the potential to act as a protective agent against COVID-19. Further proven safety records of BCG in humans, its adjuvant activity and low-cost manufacturing make it an attractive option to stop the pandemic and reduce the COVID-19 related mortality. In this review we discuss the heterologous effects of BCG, induction of trained immunity and its implication in development of a potential vaccine against COVID-19 pandemic.


Glycemic control in critically ill patients: What to do post NICE-SUGAR?
Until recently, stress hyperglycemia was considered to be a beneficial adaptive response, with raised blood glucose providing a ready source of fuel for the brain, skeletal muscle, heart and other vital organs at a time of increased metabolic demand. Following the Leuven Intensive Insulin Therapy Trial in 2001, tight glycemic control became rapidly adopted as the standard of care in intensive care units (ICU's) throughout the world. However, four randomized controlled studies and the recently published NICE-SUGAR study have subsequently been unable to replicate the findings of the Leuven Intensive Insulin Therapy Trial. This paper offers an explanation for these discordant findings, and provides a practical approach to glucose control in the ICU.


Tetragonal versus Hexagonal: Structure-Dependent Catalytic Activity of Co/Zn Bimetallic Metal-Organic Frameworks.
Tetragonal and hexagonal phases of monometallic Zn and bimetallic Co/Zn metal-organic frameworks (MOFs), with secondary building units (SBUs) containing a M3O (M = metal) cluster, were synthesized from identical constituents using a benzenetricarboxylate (BTC(3-)) linker that forms decorated 3,6- and 3,5-connected networks, respectively. There exist subtle differences between the SBUs; one of the metal atoms in the M3O cluster in the tetragonal phase has one dissociable DMF solvent molecule while that in the hexagonal phase has three. Connectivities between the SBUs form one-dimensional channels in both MOFs. These MOFs catalyze the chemoselective addition of amines to epoxides, giving exclusively β-hydroxyamine under heterogeneous conditions. A ring-opening reaction of a symmetrical epoxide showed that the hexagonal phase diastereoselectively yields trans-alcohol, exhibiting an exquisite model for structure-dependent activity.


Multi-resBind: a residual network-based multi-label classifier for in vivo RNA binding prediction and preference visualization.
Protein-RNA interactions play key roles in many processes regulating gene expression. To understand the underlying binding preference, ultraviolet cross-linking and immunoprecipitation (CLIP)-based methods have been used to identify the binding sites for hundreds of RNA-binding proteins (RBPs) in vivo. Using these large-scale experimental data to infer RNA binding preference and predict missing binding sites has become a great challenge. Some existing deep-learning models have demonstrated high prediction accuracy for individual RBPs. However, it remains difficult to avoid significant bias due to the experimental protocol. The DeepRiPe method was recently developed to solve this problem via introducing multi-task or multi-label learning into this field. However, this method has not reached an ideal level of prediction power due to the weak neural network architecture. Compared to the DeepRiPe approach, our Multi-resBind method demonstrated substantial improvements using the same large-scale PAR-CLIP dataset with respect to an increase in the area under the receiver operating characteristic curve and average precision. We conducted extensive experiments to evaluate the impact of various types of input data on the final prediction accuracy. The same approach was used to evaluate the effect of loss functions. Finally, a modified integrated gradient was employed to generate attribution maps. The patterns disentangled from relative contributions according to context offer biological insights into the underlying mechanism of protein-RNA interactions. Here, we propose Multi-resBind as a new multi-label deep-learning approach to infer protein-RNA binding preferences and predict novel interactions. The results clearly demonstrate that Multi-resBind is a promising tool to predict unknown binding sites in vivo and gain biology insights into why the neural network makes a given prediction.


Standardization of a Siddha formulation Amukkara curanam by HPTLC.
Amukkara curanam, a Siddha formulation, currently used in all types of gastric disorders, rheumatic pain, insomnia and sexual insufficiency, was investigated for the estimation of the marker compounds, withaferine A and piperine contents in a prepared standard formulation and a commercial formulation by using HPTLC method of analysis. The two formulations were subjected to methanol, ethyl acetate and chloroform extractions by using Soxhhlet apparatus The chromatogram was developed using chloroform: methanol (8.5:1.5 v/v) and toluene: ethyl acetate (7:3 v/v) as mobile phases for the estimation of withferine A and piperine respectively. The detection and quantification were performed at a wavelength of 220 nm for withaferine A and 254 nm for piperine. The linear regression analysis of calibration plots of withferine A and piperine exhibited linear relationship in the range of 5-15 microg and 50-150 ng respectively, while the % recovery was found to be 94.52% w/w of withaferine A and 98.73% w/w of piperine, thus proving the accuracy and precision of the analysis. Methanol and ethyl acetate were found to be the suitable solvents for the extraction of withaferin A and piperine respectively. The withaferine A content in standard formulation was found to be much higher in all the three extracts than that of the commercial sample. However, the piperine content in all the three extracts of standard formulation was slightly lower than the respective extracts of commercial formulation. The proposed HPTLC method was found to be rapid, simple and accurate for quantitative estimation of withferine A and piperine in different formulation extracts.


Discovery and initial analysis of novel viral genomes in the soybean cyst nematode.
Nematodes are the most abundant multicellular animals on earth, yet little is known about their natural viral pathogens. To date, only two nematode virus genomes have been reported. Consequently, nematode viruses have been overlooked as important biotic factors in the study of nematode ecology. Here, we show that one plant parasitic nematode species, Heterodera glycines, the soybean cyst nematode (SCN), harbours four different RNA viruses. The nematode virus genomes were discovered in the SCN transcriptome after high-throughput sequencing and assembly. All four viruses have negative-sense RNA genomes, and are distantly related to nyaviruses and bornaviruses, rhabdoviruses, bunyaviruses and tenuiviruses. Some members of these families replicate in and are vectored by insects, and can cause significant diseases in animals and plants. The novel viral sequences were detected in both eggs and the second juvenile stage of SCN, suggesting that these viruses are transmitted vertically. While there was no evidence of integration of viral sequences into the nematode genome, we indeed detected transcripts from these viruses by using quantitative PCR. These data are the first finding of virus genomes in parasitic nematodes. This discovery highlights the need for further exploration for nematode viruses in all tropic groups of these diverse and abundant animals, to determine how the presence of these viruses affects the fitness of the nematode, strategies of viral transmission and mechanisms of viral pathogenesis.


Magnetic Attributes of NiFe2O4 Nanoparticles: Influence of Dysprosium Ions (Dy3+) Substitution.
This paper reports the influence of dysprosium ion (Dy3+) substitution on the structural and magnetic properties of NiDyxFe2-xO4 (0.0 ≤ x ≤ 0.1) nanoparticles (NPs) prepared using a hydrothermal method. The structure and morphology of the as-synthesized NPs were characterized via X-ray diffraction (XRD), scanning and transmission electron microscope (SEM, and TEM) analyses. 57Fe Mössbauer spectra were recorded to determine the Dy3+ content dependent variation in the line width, isomer shift, quadrupole splitting, and hyperfine magnetic fields. Furthermore, the magnetic properties of the prepared NPs were also investigated by zero-field cooled (ZFC) and field cooled (FC) magnetizations and AC susceptibility measurements. The MZFC (T) results showed a blocking temperature (TB). Below TB, the products behave as ferromagnetic (FM) and act superparamagnetic (SPM) above TB. The MFC (T) curves indicated the existence of super-spin glass (SSG) behavior below Ts (spin-glass freezing temperature). The AC susceptibility measurements confirmed the existence of the two transition temperatures (i.e., TB and Ts). Numerous models, e.g., Neel-Arrhenius (N-A), Vogel-Fulcher (V-F), and critical slowing down (CSD), were used to investigate the dynamics of the systems. It was found that the Dy substitution enhanced the magnetic interactions.


Developmental continuity in the processes that underlie spatial recall.
This study investigated whether children's spatial recall performance shows three separable characteristics: (1) biases away from symmetry axes (geometric effects); (2) systematic drift over delays; and (3) biases toward the exemplar distribution experienced in the task (experience-dependent effects). In Experiment 1, the location of one target within each geometric category was varied. Children's responses showed biases away from a midline axis that increased over delays. In Experiment 2, multiple targets were placed within each category at the same locations used in Experiment 1. After removing geometric effects, 6-year-olds'--but not 11-year-olds'--responses were biased toward the average remembered location over learning. In Experiment 3, children responded to one target more frequently than the others. Both 6- and 11-year-olds showed biases toward the most frequent target over learning. These results provide a bridge between the performance of younger children and adults, demonstrating continuity in the processes that underlie spatial memory abilities across development.


Piezoelectric ceramic disks with thickness-graded material properties.
A system of two-dimensional, first-order equations for electroded piezoelectric crystal plates with general symmetry and thickness-graded material properties recently was deduced from the three-dimensional equations of linear piezoelectricity. These equations are simplified for the two limiting cases of thickness-graded piezoelectric properties, i.e., the homogeneous plate and bimorph of piezoelectric ceramics. Closed-form solutions are obtained from these reduced equations for the flexural and thickness-shear vibrations and static response of bimorph disks as well as for the extensional and thickness-stretch vibrations of homogeneous disks. Frequency spectra and modes are computed and examined. Resonance frequencies for both homogeneous and bimorph disks of PZT-857 are computed and measured. The comparison of the results shows that the agreement is close.


Extrastriate visual cortex in idiopathic occipital epilepsies: The contribution of retinotopic areas to spike generation.
To provide insight into the pathophysiology of idiopathic childhood occipital epilepsies (ICOEs), by mapping the contribution of retinotopic visual areas to the generation and sustainment of epileptic activity. Thirteen patients affected by ICOEs (mean age = 10.9 years) underwent a video electroencephalography-functional magnetic resonance imaging (EEG-fMRI) study. A flexible-related fMRI analysis was applied to estimate the shape of the blood oxygen level-dependent (BOLD) response in each patient. Second-level analysis was performed using the interictal EEG discharge (IED)-specific response shape for the ICOE group. The resulting fMRI t-maps were warped to the Population-Average, Landmark- and Surface-based (PALS)-B12 atlas in Caret. For localization purposes, functional results were plotted and compared against 19 retinotopic areas for each hemisphere. A correlation analysis was performed between the hemodynamic maps and electroclinical variables. The shape of the group-averaged hemodynamic response in ICOE patients showed an earlier time-to-peak and a more pronounced undershoot than the canonical hemodynamic response function (HRF). The random-effect analysis showed positive hemodynamic changes in the bilateral temporooccipital network. With regard to the retinotopic subdivision of the visual cortex, the primary visual area was consistently spared. Conversely, an extensive involvement of the occipitotemporal cortex, including the fusiform gyrus, and the occipitoparietal areas was observed. Moreover, a linear relationship was detected between the occipital spike-density and BOLD increases at the postcentral gyrus and temporooccipital cortex. Our data indicate that both the ventral and dorsal visual pathways are involved in spike generation in ICOEs, to extents that vary between patients, and reinforce the concept of benign childhood seizure susceptibility syndrome as a substrate for ICOEs. Finally, these results underscore the need for appropriate neuropsychological testing in these children, aimed at revealing selective impairments in functions subserved by both visual pathways.


The Bifactor S-1 Model: a Psychometrically Sounder Alternative to Test the Structure of ADHD and ODD?
Questions persist about whether attention deficit hyperactivity disorder (ADHD), oppositional defiant disorder (ODD), and conduct disorder are in fact distinct from one another. When such questions arise, ODD is often suggested to be subsumed under one or the other condition. Modeling approaches that can evaluate whether specific subfactors can be distinguished from general psychopathology are of great interest, and the general bifactor model has been increasingly applied in studies evaluating the structure of psychopathology. However, evidence for bias in the model, the frequency of anomalous indicators, and theoretical concerns about the applicability of the general bifactor model to these questions raise doubts about whether it is reliable or appropriate to do so. Burns and colleagues propose the bifactor S-1 model as a psychometrically sounder alternative. Their systematic examination provides a compelling argument that it is psychometrically sounder, but it is not clear that it is a true alternative. It may not be answering the same questions, cannot test hypotheses regarding the same sets of specific subfactors, and relies on a priori decisions on the part of the researcher that may change the interpretation of the results. The bifactor S-1 model approach appears to be a valuable, psychometrically sound approach to test the structure of psychopathology, particularly in regard to ADHD and ODD.


Suicidal behavior in patients with schizophrenia and other psychotic disorders.
Patients with schizophrenia are known to be at high risk for suicide attempts and dying by suicide. However, little research has been conducted to determine whether the risk for suicidal behavior is elevated among patients with psychosis in general. This study evaluated 1-month and lifetime rates of suicidal behavior among 1,048 consecutively admitted psychiatric inpatients (ages 18 to 55 years) with DSM-III-R psychotic disorders. Demographic, clinical, and diagnostic correlates of suicidal behavior were examined. A high rate of suicidal behavior was found in the group: 30.2% reported a lifetime history of suicide attempts, and 7.2% reported a suicide attempt in the month before admission. The highest 1-month and lifetime rates were found in patients with schizoaffective disorder and major depression with psychotic features. Ratings of the medical dangerousness of the most recent suicide attempt on the basis of the extent of physical injury were higher in patients with schizophrenia spectrum psychoses. Agreement was high between emergency room assessments and semistructured interview assessments of suicidal behavior. Rates of suicidal behavior were high across a broad spectrum of patients with psychotic disorders; patients with a history of a current or past major depressive episode (as a part of major depressive disorder or schizoaffective disorder) were at a greater risk for suicide attempts, but patients with schizophrenia, on average, made more medically dangerous attempts. Risk factors for suicidal behavior in patients with psychosis appear to vary compared to those for the general population.


Case-control study of galactorrhea and its relationship to the use of oral contraceptives.
A case-control study was performed to determine the relationship between galactorrhea and the use of oral contraceptives as well as other risk factors. The cases included all 109 Olmsted County residents who satisfied the diagnostic criteria for galactorrhea between 1970 and 1980. Control subjects were selected from a sampling frame of all medical registrations and matched to the cases by age, year, and residency. Pituitary adenomas were strongly associated with galactorrhea, as the relative risk was 23.2 (95% confidence interval 2.0 to 90.0). In galactorrhea cases without pituitary adenomas there was an association with oral contraceptives (ever use versus never use), as the relative risk was 2.3 (95% confidence interval 1.3 to 4.4). Among current users of oral contraceptives, the risk of galactorrhea was not increased, but there was a trend of diminishing risk with duration of use. The estimate of relative risk was 3.1 after discontinuation of oral contraceptive use and was highest for the first year after discontinuation (5.5), compared with a year or more after discontinuation (2.1). Thus, galactorrhea was associated with the cessation of oral contraceptives.


Lymphoepithelial carcinoma of the minor salivary gland.
Undifferentiated carcinoma of the minor salivary glands has been rarely reported in the world literature. Lymphoepithelial carcinoma, which is a variant of undifferentiated carcinoma, is distinguished from small cell and large cell undifferentiated carcinoma by its association with benign lymphoepithelial lesions. We report a case of a lymphoepithelial carcinoma developing in a minor salivary gland of the oral cavity in a 69-year-old woman. To our knowledge, this is the first reported case of a lymphoepithelial carcinoma arising from a minor salivary gland.


A review of the scientific basis and practical application of a new test of utricular function--ocular vestibular-evoked myogenic potentials to bone-conducted vibration.
This is a review of recently published papers showing that bone-conducted vibration of the head causes linear acceleration stimulation of both inner ears and this linear acceleration is an effective way of selectively activating otolithic afferent neurons. This simple stimulus is used in a new test to evaluate clinically the function of the otoliths of the human inner ear. Single neuron studies in animals have shown that semicircular canal neurons are rarely activated by levels of bone-conducted vibration at 500 Hz which generate vigorous firing in otolithic irregular neurons and which result in a variety of vestibulo-spinal and vestibulo-ocular responses, and the latter is the focus of this review. In humans, 500 Hz bone-conducted vibration, delivered at the midline of the forehead, at the hairline (Fz), causes simultaneous and approximately equal amplitude linear acceleration stimulation at both mastoids and results in ocular-evoked myogenic potentials (oVEMPs) beneath both eyes. The first component of this myogenic potential, at a latency to peak of about 10 ms is a negative potential and is called n10 and, in healthy subjects, is equal in amplitude beneath both eyes, but after unilateral vestibular loss, the n10 potential beneath the eye opposite to the lesioned ear is greatly reduced or totally absent. n10 is a myogenic potential due to a crossed otolith-ocular pathway. In patients with total unilateral superior vestibular neuritis, in whom saccular function is largely intact (as shown by the presence of cervical vestibular evoked myogenic potentials (cVEMPs), but utricular function is probably compromised, there is a reduced n10 response beneath the contralesional eye, strongly indicating that n10 is due to utricular otolithic function.


Integrin-mediated signalling through the MAP-kinase pathway.
The mitogen activated protein (MAP) kinase cascade, leading to extracellular-regulated kinase (ERK) activation, is a key regulator of cell growth and proliferation. The effects of ERK are mediated by differences in ERK signalling dynamics, including magnitude and duration. In vivo, ERK signalling is stimulated by both growth factors and adhesion signals. A model for adhesion-mediated ERK activation is presented. Outputs of the model such as ERK and FAK activation, as well as responses to different ligand densities, are compared with published experimental data. The model then serves as a basis for understanding how adhesion may contribute to ERK signalling through changes in the dynamics of focal adhesion kinase activation. The main parameters influencing ERK are determined through screening analyses and parameter variation. With these parameters, key points in the pathway that give rise to changes in downstream signalling dynamics are identified. In particular, oncogenic Raf and Ras promote cell growth by increasing the magnitude and duration, respectively, of ERK activity.


Software standards and the laboratory information system.
Software standards simplify communication and cooperation between applications provided by different software vendors. However, adherence to a rigid standard can stifle innovation. Open standards, which are not proprietary to any particular vendor, are particularly useful. Many standard-setting organizations have provided useful tools for laboratory informatics, including the American Society for Testing and Materials (ASTM), Institute of Electrical and Electronics Engineers, National Committee for Clinical Laboratory Standards, and the College of American Pathologists. Data communication standards, such as ASTM 1238, HL7, and Digital Image Communication of Medicine, have reduced the cost and improved the timeliness of interfaces. Nomenclatures, particularly the Systematized Nomenclature of Medicine (SNOMED), have facilitated the structuring of medical information, and decision rules can be communicated with ASTM E1460. Laboratory Observation Identifier Names and Codes has eased the problem of identifying tests during interchange of laboratory data. Implementation standards are useful references for those deploying information systems. Standards have provided multiple benefits to laboratories and to the health care organizations of which they are a component.


Leukemic myeloblasts expressing lymphoid markers.
Out of 60 patients with acute myeloid leukemia not preceded by chronic myelocytic leukemia or any preleukemic phase, 7 had both lymphoid and myeloid markers. All patients expressed common acute lymphatic leukemia antigen (CALLA) in 20% or more of their leukemic cells, which also showed positive peroxidase reaction. In addition, 4 patients had Auer rods. Two additional patients had morphologically clear acute monocytic leukemia (FAB M5b) and cells expressing CALLA. In 4 of the 7 patients the sum of the percentages of peroxidase or Leu M1 + and CALLA-positive blast cells exceeded 100%, suggesting that at least some of the cells had both myeloid and lymphoid markers. Moreover, out of 3 patients where double staining with the CALLA antibody J5 and the myeloid marker Leu M1 was performed, 2 had both markers on the same cells.


First-principles studies on the efficient photoluminescent iridium(III) complexes with C^N═N ligands.
The electronic structures and photophysical properties of several homoleptic iridium complexes IrL(3) with C^N═N ligands, including 1 (L = 3,6-diphenylpyridazine), 2 (L = 1,4-diphenylphthalazine), 3 (L = 3-phenyl-5H-indeno[1,2-c]pyridazine), and 4 (L = 3-phenylbenzo[h]cinnoline), are investigated using the density functional method. The comparison between the calculated results of the four complexes shows that the assumed complex 4 may possess higher photoluminescent quantum efficiency than complexes 1-3 and is the potential candidate to be an efficient green-emitting material. The photophysical properties of the assumed complex 3 can be comparable to that of experimentally found complex 1. For 1 and 3, the emission energies are nearly the same, consistent with their similar HOMO-LUMO energy gaps. Their emission characters are also similar and mainly dominated by one ligand. For 4 and the experimentally found complex 2, although they have similar HOMO-LUMO energy gaps, and their luminescent nature is nearly the same and dominated by the three ligands, the emission spectrum of 4 is blue-shifted as compared to that of 2.


An integrated literature review on sexuality of elderly nursing home residents with dementia.
This study presents an integrative literature review on sexuality among elderly people with dementia living in nursing homes. Original research studies published from 1980 to 2012 were included in the review. Sexual expressions ranged from holding hands to sexual intercourse. These behaviours were sometimes directed towards caregivers while the latter were providing daily care. Sexual expressions were sometimes assessed and reported subjectively without context. Responses to sexual expressions varied from positive to negative. Some sexual expressions were dealt with inconsistently, and some were considered to be problematic due to a lack of policy or privacy. It is important to assess and report sexual expressions objectively, preferably with a standardized form, and to consider context in doing so. Effort is required to provide privacy for residents' sexual expressions and a safe environment for all residents and caregivers. It is important that a policy and guidelines for care be established regarding issues related to sexuality among elderly people with dementia.


On array design for matched-field processing
Conventional plane-wave beamforming array design guidelines are motivated by the desire to obtain particular beampattern characteristics, such as main lobe width and side lobe levels. These design guidelines are appropriate for arrays employed for beamforming, where a plane-wave signal model is utilized to derive both the array design parameters and the beamforming algorithm. However, matched-field processing utilizes full-field acoustic propagation models to exploit the complexities of ocean acoustic propagation. As a result, there may be more appropriate design guidelines for arrays employed for matched-field processing. In this paper, general guidelines for matched-field processing array design utilizing a normal mode propagation model are proposed. Various line array configurations are evaluated with respect to source localization performance, and the results suggest that arrays designed for matched-field processing should provide a unique representation of each propagating mode along the extent of the array. Further, the empirical analyses support the guidelines suggested by the theoretical analyses and show that arrays which are far from meeting conventional beamforming array design requirements may be more than sufficient for matched-field processing.


Roles of p53 in various biological aspects of hematopoietic stem cells.
Hematopoietic stem cells (HSCs) have the capacity to self-renew as well as to differentiate into all blood cell types, and they can reconstitute hematopoiesis in recipients with bone marrow ablation. In addition, transplantation therapy using HSCs is widely performed for the treatment of various incurable diseases such as hematopoietic malignancies and congenital immunodeficiency disorders. For the safe and successful transplantation of HSCs, their genetic and epigenetic integrities need to be maintained properly. Therefore, understanding the molecular mechanisms that respond to various cellular stresses in HSCs is important. The tumor suppressor protein, p53, has been shown to play critical roles in maintenance of "cell integrity" under stress conditions by controlling its target genes that regulate cell cycle arrest, apoptosis, senescence, DNA repair, or changes in metabolism. In this paper, we summarize recent reports that describe various biological functions of HSCs and discuss the roles of p53 associated with them.


[Clinical evaluation of donor renal artery reconstruction in kidney transplantation].
This retrospective study describes the experience of arterial reconstruction of donor kidney in our institute since 1982. Of total 56 living related kidney transplantations 15 required renal arterial reconstruction or ligation of donor kidneys. Renal arterial reconstruction was employed for 11 cases (end to side anastomosis [4 cases], conjoined anastomosis [3], hypogastric artery graft interposition [3], other [1], while simple ligation was employed for 4. Bench surgery with microsurgical techniques was employed for the repair. Elective surgery was done for preoperatively defined multiple renal arteries [10] and aneurysm [1], while imperative surgery for intraoperatively detected accessory arteries [2] and surgical injuries [2]. Postoperative patency of arteries and renal function (GFR) and evaluated by 99mTc-DTPA renoscintigraphy. The mean total ischemic time of reconstructed cases was 135 min., while that of ligated ones was 67 min. None of them required hemodialysis due to acute tubular necrosis. Postoperative graft arterial patency was impaired in 2 of 11 reconstructed cases (18%), while it was impaired in 3 of 4 ligated cases (75%). Two failure attempts of arterial reconstruction cases were all imperative ones. Postoperative GFR of the graft was well preserved in all cases. We conclude that (1) Ligation and imperative surgery tend to be associated with renal infarction, although it does not affect GFR. (2) Renal artery reconstruction was highly successful in preserving renal mass (or normal cortical image), albeit longer ischemic time than simple ligation. (3) Considering importance of preserved nephron mass in clinical renal transplantation every attempt should be made to repair the donor arterial anomalies when expected (elective) or found (imperative). (4) Thorough preoperative evaluation of donor renal arteries is mandatory.


[Comparison of three methods of antithrombotic therapy in elderly patients with nonvalvular atrial fibrillation].
We compared efficacy and safety of warfarin, direct thrombin inhibitor dabigatran and clopidogrel in prevention of stroke in 210 patients with nonvalvular atrial fibrillation (AF) aged 65-80 years. The use of dabigatran (110 mg twice daily) for 12 months or warfarin was associated with similar rate of ischemic stroke but caused less bleeding (2.8 vs. 16.9%, p<0.05). Treatment with clopidogrel prevented stroke no less successfully, than those with warfarin and dabigatran and turned out to be sufficiently safe. When chosing antithrombotic therapy in gerontological patients with nonvalvular AF dabigatran and clopidogrel can be considered acceptable alternative to warfarin.


Intravenous implanted neural stem cells migrate to injury site, reduce infarct volume, and improve behavior after cerebral ischemia.
Stroke represents one of the leading causes of death and disability in humans, but despite intense research, only a few options exist for the treatment of stroke-related infarction of brain tissue. Thus far, in experimental strokes, cell therapy appears to partly reverse some behavioral deficits. However, the mechanisms of action remain uncertain as most studies reveal only little, if any, evidence for neuronal replacement and observed behavioral improvements. This present study was performed to test rodent fetus forebrain derived neural stem cells (NSCs) implantation into rats subjected to suture-induced middle cerebral artery occlusion (MCAO). Efficacy of cell therapy was studied regarding behavior recovery, infarct volume, and protection possibility of related molecular mechanisms. Here, we show that grafted cells can home in on damaged regions by MCAO and significantly improve behavior of ischemic rats. Infarct volumes and brain atrophy were diminished after grafted NSCs treatment. Furthermore, we detected inflammation related molecules such as COX-2 and IL-1beta and found that grafted NSCs treatment after ischemic stroke could repress expression of inflammation molecular protein levels. We also detected protein levels of heat shock protein 27 (HSP27) as a protective protein against apoptosis. The results showed that grafted NSCs treatment induced the protein level of HSP27 and down-regulated activity of caspase-3 compared with the vehicle control. Our results demonstrate that transplanted NSCs provide benefits in behavioral function recovery after MCAO and increase neuroprotection whilst repressing inflammatory destruction. These data reveal another essential explanation of cellular transplantation therapy in damage recovery from ischemic stroke and offer new therapeutic possibilities.


Development of a new hybrid approach combining AFM and SEM for the nanoparticle dimensional metrology.
At this time, there is no instrument capable of measuring a nano-object along the three spatial dimensions with a controlled uncertainty. The combination of several instruments is thus necessary to metrologically characterize the dimensional properties of a nano-object. This paper proposes a new approach of hybrid metrology taking advantage of the complementary nature of atomic force microscopy (AFM) and scanning electron microscopy (SEM) techniques for measuring the main characteristic parameters of nanoparticle (NP) dimensions in 3D. The NP area equivalent, the minimal and the maximal Feret diameters are determined by SEM and the NP height is measured by AFM. In this context, a kind of new NP repositioning system consisting of a lithographed silicon substrate has been specifically developed. This device makes it possible to combine AFM and SEM size measurements performed exactly on the same set of NPs. In order to establish the proof-of-concept of this approach and assess the performance of both instruments, measurements were carried out on several samples of spherical silica NP populations ranging from 5 to 110 nm. The spherical nature of silica NPs imposes naturally the equality between their height and their lateral diameters. However, discrepancies between AFM and SEM measurements have been observed, showing significant deviation from sphericity as a function of the nanoparticle size.


Heme oxygenase-1 inducing constituent of Prunella vulgaris in HepG2 cells.
Inducible heme oxygenase (HO)-1 is known to play a major role in the pathogenesis of several diseases, and it protects cells against oxidant-mediated injury. The bioassay-guided fractionation of the EtOH extract of the flowered fruit-spike of Prunella vulgaris L. (Labiatae) yielded two ursane-type triterpenes, 3beta,23-dihydroxyurs-12-en-28-oic acid (23-hydroxyursolic acid) (1) and 3beta-hydroxyurs-12-en-28-oic acid (ursolic acid) (2). Western blotting demonstrated that treatment with compound 1 increased the expression of HO-1 in a dose-dependent manner in human liver-derived HepG2 cells. Investigation of structure-related HO-1 inducing activity suggested that the hydroxyl group at the C-23 position in the ursane skeleton is important for this activity.


Europium sulfide nanoprobes predict antiretroviral drug delivery into HIV-1 cell and tissue reservoirs.
Background: Delivery of long-acting nanoformulated antiretroviral drugs (ARVs) to human immunodeficiency virus type one cell and tissue reservoirs underlies next generation antiretroviral therapeutics. Nanotheranostics, comprised of trackable nanoparticle adjuncts, can facilitate ARV delivery through real-time drug tracking made possible through bioimaging platforms. Methods: To model HIV-1 therapeutic delivery, europium sulfide (EuS) nanoprobes were developed, characterized and then deployed to cells, tissues, and rodents. Tests were performed with nanoformulated rilpivirine (NRPV), a non-nucleoside reverse transcriptase inhibitor (NNRTI) used clinically to suppress or prevent HIV-1 infection. First, CD4+ T cells and monocyte-derived macrophages were EuS-treated with and without endocytic blockers to identify nanoprobe uptake into cells. Second, Balb/c mice were co-dosed with NRPV and EuS or lutetium177-doped EuS (177LuEuS) theranostic nanoparticles to assess NRPV biodistribution via mass spectrometry. Third, single photon emission computed tomography (SPECT-CT) and magnetic resonance imaging (MRI) bioimaging were used to determine nanotheranostic and NRPV anatomic redistribution over time. Results: EuS nanoprobes and NRPV entered cells through dynamin-dependent pathways. SPECT-CT and MRI identified biodistribution patterns within the reticuloendothelial system for EuS that was coordinate with NRPV trafficking. Conclusions: EuS nanoprobes parallel the uptake and biodistribution of NRPV. These data support their use in modeling NRPV delivery to improve treatment strategies.


[Epidemiological profile of maternal deaths in Rio Grande do Sul, Brazil: 2004-2007].
This study analyzed the epidemiological profile of maternal deaths that occurred from 2004 to 2007 in Rio Grande do Sul, by means of Maternal Mortality Rates and Specific Maternal Mortality Ratio. Data was obtained from the Health Information System database and 323 maternal deaths were identified. In order to analyze indicators, Poisson regression and statistical tests were carried out. A decrease in maternal mortality rates (0.98) was identified, although there was no difference in estimate measures (CI95% 0.87-1.10). Maternal deaths were more frequent in women who were over 40 years old, had low schooling, black skin and no partners. The period of highest risk of maternal death was during pregnancy and birth, and the main direct causes were arterial hypertension and bleeding. Maternal mortality is an important issue to be confronted and reduced, given most maternal deaths could have been avoided.


Culturally competent healthcare systems. A systematic review.
Culturally competent healthcare systems-those that provide culturally and linguistically appropriate services-have the potential to reduce racial and ethnic health disparities. When clients do not understand what their healthcare providers are telling them, and providers either do not speak the client's language or are insensitive to cultural differences, the quality of health care can be compromised. We reviewed five interventions to improve cultural competence in healthcare systems-programs to recruit and retain staff members who reflect the cultural diversity of the community served, use of interpreter services or bilingual providers for clients with limited English proficiency, cultural competency training for healthcare providers, use of linguistically and culturally appropriate health education materials, and culturally specific healthcare settings. We could not determine the effectiveness of any of these interventions, because there were either too few comparative studies, or studies did not examine the outcome measures evaluated in this review: client satisfaction with care, improvements in health status, and inappropriate racial or ethnic differences in use of health services or in received and recommended treatment.


Human Leukocyte Antigen-A, B, C, DRB1, and DQB1 Allele and Haplotype Frequencies in a Subset of 237 Donors in the South African Bone Marrow Registry.
Human leukocyte antigen- (HLA-) A, HLA-B, HLA-C, HLA-DRB1, and HLA-DQB1 allele and haplotype frequencies were studied in a subset of 237 volunteer bone marrow donors registered at the South African Bone Marrow Registry (SABMR). Hapl-o-Mat software was used to compute allele and haplotype frequencies from individuals typed at various resolutions, with some alleles in multiple allele code (MAC) format. Four hundred and thirty-eight HLA-A, 235 HLA-B, 234 HLA-DRB1, 41 HLA-DQB1, and 29 HLA-C alleles are reported. The most frequent alleles were A∗02:02g (0.096), B∗07:02g (0.082), C∗07:02g (0.180), DQB1∗06:02 (0.157), and DRB1∗15:01 (0.072). The most common haplotype was A∗03:01g~B∗07:02g~C∗07:02g~DQB1∗06:02~DRB1∗15:01 (0.067), which has also been reported in other populations. Deviations from Hardy-Weinberg equilibrium were observed in A, B, and DRB1 loci, with C~DQB1 being the only locus pair in linkage disequilibrium. This study describes allele and haplotype frequencies from a subset of donors registered at SABMR, the only active bone marrow donor registry in Africa. Although the sample size was small, our results form a key resource for future population studies, disease association studies, and donor recruitment strategies.


Living conditions, including life style, in primary-care patients with nonacute, nonspecific spinal pain compared with a population-based sample: a cross-sectional study.
Nonspecific spinal pain (NSP), comprising back and/or neck pain, is one of the leading disorders behind long-term sick-listing, including disability pensions. Early interventions to prevent long-term sick-listing require the identification of patients at risk. The aim of this study was to compare living conditions associated with long-term sick-listing for NSP in patients with nonacute NSP, with a nonpatient population-based sample. Nonacute NSP is pain that leads to full-time sick-listing >3 weeks. One hundred and twenty-five patients with nonacute NSP, 2000-2004, were included in a randomized controlled trial in Stockholm County with the objective of comparing cognitive-behavioral rehabilitation with traditional primary care. For these patients, a cross-sectional study was carried out with baseline data. Living conditions were compared between the patients and 338 nonpatients by logistic regression. The conditions from univariate analyses were included in a multivariate analysis. The nonsignificant variables were excluded sequentially to yield a model comprising only the significant factors (P < 0.05). The results are shown as odds ratios (OR) with 95% confidence intervals. In the univariate analyses, 13 of the 18 living conditions had higher odds for the patients with a dominance of physical work strains and Indication of alcohol over-consumption, odds ratio (OR) 14.8 (95% confidence interval [CI] 3.2-67.6). Five conditions qualified for the multivariate model: High physical workload, OR 13.7 (CI 5.9-32.2); Hectic work tempo, OR 8.4 (CI 2.5-28.3); Blue-collar job, OR 4.5 (CI 1.8-11.4); Obesity, OR 3.5 (CI 1.2-10.2); and Low education, OR 2.7 (CI 1.1-6.8). As most of the living conditions have previously been insufficiently studied, our findings might contribute a wider knowledge of risk factors for long-term sick-listing for NSP. As the cross-sectional design makes causal conclusions impossible, our study should be complemented by prospective research.


Hawaiian Drosophila as an Evolutionary Model Clade: Days of Future Past.
The Hawaiian Drosophila have been a model system for evolutionary, ecological, and ethological studies since the inception of the Hawaiian Drosophila Project in the 1960s. Here we review the past and present research on this incredible lineage and provide a prospectus for future directions on genomics and microbial interactions. While the number of publications on this group has waxed and waned over the years, we assert that recent systematic, biogeographic, and ecological studies have reinvigorated Hawaiian Drosophila as an evolutionary model system. The characteristics that distinguish good model clades from good model organisms (e.g., Drosophila melanogaster) are somewhat different so we first define what constitutes a good evolutionary model. We argue that the Hawaiian Drosophila possess many desired aspects of a good evolutionary model, describe how this group of geographically isolated flies have been used in the past, and propose some exciting avenues for future evolutionary research on this diverse, dynamic clade of Drosophila.


The role of purinergic signaling on deformation induced injury and repair responses of alveolar epithelial cells.
Cell wounding is an important driver of the innate immune response of ventilator-injured lungs. We had previously shown that the majority of wounded alveolus resident cells repair and survive deformation induced insults. This is important insofar as wounded and repaired cells may contribute to injurious deformation responses commonly referred to as biotrauma. The central hypothesis of this communication states that extracellular adenosine-5' triphosphate (ATP) promotes the repair of wounded alveolus resident cells by a P2Y2-Receptor dependent mechanism. Using primary type 1 alveolar epithelial rat cell models subjected to micropuncture injury and/or deforming stress we show that 1) stretch causes a dose dependent increase in cell injury and ATP media concentrations; 2) enzymatic depletion of extracellular ATP reduces the probability of stretch induced wound repair; 3) enriching extracellular ATP concentrations facilitates wound repair; 4) purinergic effects on cell repair are mediated by ATP and not by one of its metabolites; and 5) ATP mediated cell salvage depends at least in part on P2Y2-R activation. While rescuing cells from wounding induced death may seem appealing, it is possible that survivors of membrane wounding become governors of a sustained pro-inflammatory state and thereby perpetuate and worsen organ function in the early stages of lung injury syndromes. Means to uncouple P2Y2-R mediated cytoprotection from P2Y2-R mediated inflammation and to test the preclinical efficacy of such an undertaking deserve to be explored.