Deep sequencing identifies two genotypes and high viral genetic diversity of human pegivirus (GB virus C) in rural Ugandan patients.
Human pegivirus (HPgV), formerly 'GB virus C' or 'hepatitis G virus', is a member of the genus Flavivirus (Flaviviridae) that has garnered significant attention due to its inhibition of HIV, including slowing disease progression and prolonging survival in HIV-infected patients. Currently, there are six proposed HPgV genotypes that have roughly distinct geographical distributions. Genotypes 2 and 3 are the most comprehensively characterized, whereas those genotypes occurring on the African continent, where HPgV prevalence is highest, are less well studied. Using deep sequencing methods, we identified complete coding HPgV sequences in four of 28 patients (14.3%) in rural Uganda, east Africa. One of these sequences corresponds to genotype 1 and is the first complete genome of this genotype from east Africa. The remaining three sequences correspond to genotype 5, a genotype that was previously considered exclusively South African. All four positive samples were collected within a geographical area of less than 25 km(2), showing that multiple HPgV genotypes co-circulate in this area. Analysis of intra-host viral genetic diversity revealed that total single-nucleotide polymorphism frequency was approximately tenfold lower in HPgV than in hepatitis C virus. Finally, one patient was co-infected with HPgV and HIV, which, in combination with the high prevalence of HIV, suggests that this region would be a useful locale to study the interactions and co-evolution of these viruses.


Autogenic biofeedback treatment for migraine.
Autogenic biofeedback training appears to be a promising technique for the treatment of migraine headaches, as reflected in the literature reviewed herein and in the data from 21 patients who were followed up for an average of 10 months. Autogenic biogeedback training exemplifies an important trend in psychosomatic medicine, in shifting a major portion of responsibility for treatment process both depends on and facilitates greater understanding on the part of the part of the patient of psychosomatic events relevant to symptom development. Autogenic biofeedback training may also provide a useful tool for investigators exploring the relation between psychology and somatic medicine.


The 'other' London effect: the diversification of London's suburban grammar schools and the rise of hyper-selective elite state schools.
This paper examines the rise of a new elite of 'super-state' schools in London, revealing a growing divide within the state sector which problematizes claims that the capital is a 'hotspot' for social mobility (Social Mobility Commission ). Although recent research has revealed a 'London effect' in which students in the capital on Free School Meals outperform their peers in other regions (Greaves, Macmillan and Sibieta ), inequalities between London's schools in access to elite universities have been overlooked. Drawing on a case study of a suburban London grammar school, 'King Henry's School', I show how ethnic-minority suburbanization has combined with an institutional strategy to compete with elite private schools. Strategies of selection have been mobilized alongside elements of elite 'gentlemanly' educational culture in order to reposition the school within the hierarchy of London's schools. The result is a hyper-selective school which provides a conduit to elite universities for upwardly mobile British-Asian students. I show that this strategy has strong parallels with the school's attempts in the early twentieth century to compete with London's fee-paying 'public' schools. The continuing symbolic value of 'traditional' forms of elite educational culture to a school seeking to reposition itself within the field reflects deep structural patterns of inequality in English education. To understand how apparent improvements in social mobility can sit alongside deepening inequalities between state schools, there is a need for a historical sociological approach that takes account of long-term processes of institutional change (Savage ; Inglis ).


Small airway hyperreactivity among lifelong non-atopic non-smokers exposed to isocyanates.
The development of isocyanate asthma is little understood. To gain more knowledge in this area, a group of 20 workers occupationally exposed to isocyanates, five subjects with clinical isocyanate asthma, and a control group of 10 people not exposed to isocyanate were examined with lung function tests and a methacholine provocation test. Forced expiratory volume in one second and tests aimed at detecting small airways obstruction such as volume of trapped gas, closing volume, and wash out volume were made. To detect abnormal airway reactivity, tests were made before and after inhalation of methacholine and of salbutamol. A significant increased reactivity to methacholine in the exposed and asthma groups was seen compared with the control group as measured by volume of trapped gas. The increase was reversed by inhaling salbutamol. In neither group could a statistically significant reaction be shown in the large airways. The study group had increased small airways reactivity of the same magnitude as the group with isocyanate asthma. The subjects in the study group had no clinical symptoms or spirometric abnormalities. The volume of trapped gas in combination with methacholine seems to disclose significantly altered reactivity of the small airways in workers exposed to isocyanate with no subjective symptoms of disease.


Identification of monocytes in suspensions of mononuclear cells.
A new histochemical technique for morphological studies of mononuclear cells and granulocytes, based on fluorescent staining with methyl green, pyronine Y, and stilbene-isothiocyanato disulfonic acid (MPS stain) is described. The method was applied to mononuclear cells isolated from the blood of normal human subjects by Ficoll-Isopaque density centrifugation. Three cell populations were distinguished, mainly on the basis of differences in morphology and cytochemistry, utilizing the MPS stain. One of the cell types had many of the morphological characteristics of the monocyte. This technique, augmented by lysosomal content and endocytosis capacity studies, revealed contimination of the cell suspension with a larger percentage of monocytes than has usually been reported in the literature.


A Comparative Evaluation of the Influence of Command Set Methods on Microleakage of Glass Ionomer Cement: An In Vitro Study.
A major challenge when using glass ionomer cement in clinical situation particularly in paediatric dentistry is to overcome the problem of microleakage. Fast or command setting of Type IX glass ionomer cement using external energy source enhances the setting reaction and results in improved initial physical and mechanical properties. To compare and evaluate the influence of ultrasonic activation, halogen light irradiation and combined effect of both on microleakage of enamel adjacent to Type IX glass ionomer restorations. For forty premolar teeth, standard Class V cavities prepared were restored with GC Gold Label Type IX glass ionomer cement in vitro. The specimens were randomly divided into four groups: 1) Control group; 2) halogen group; 3) ultrasonic group; 4) ultrasonic with halogen group. The teeth were kept in distilled water for 24 hours. Teeth were exposed to 1500 thermocycles at temperature of 12°C ±2 and 60°C ±2 with alternate immersion in hot and cold water for one minute. First teeth were immersed in dye solution for four hours and then in developing solution for four hours. The samples were sectioned buccolingually through centre of the restorations and degree of dye penetration was assessed under stereomicroscope and scored. One-Way ANOVA model was constructed followed by post-hoc Tukey's test for multiple pair wise comparison of mean values. Statistically significant differences were found in microleakage among the four groups (p<0.001) with respect to dye penetration. Halogen group showed least microleakage followed by control but differences between them were statistically not significant (p>0.05). Similarly the differences between Ultrasonic plus halogen group and ultrasonic group were not significant (p>0.05). The differences between ultrasonic and halogen group were statistically significant (p<0.05). Halogen light decreases the microleakage of enamel adjacent to GC Type IX glass ionomer restorations, when used to accelerate the setting reaction of glass ionomers and can be used as command set method in paediatric dentistry.


Relation of platelet and leukocyte inflammatory transcripts to body mass index in the Framingham heart study.
Although many genetic epidemiology and biomarker studies have been conducted to examine associations of genetic variants and circulating proteins with cardiovascular disease and risk factors, there has been little study of gene expression or transcriptomics. Quantitative differences in the abundance of transcripts has been demonstrated in malignancies, but gene expression from a large community-based cohort examining risk of cardiovascular disease has never been reported. On the basis of preliminary microarray data and previously suggested genes from the literature, we measured expression of 48 genes by high-throughput quantitative reverse-transcriptase polymerase chain reaction in 1846 participants of the Framingham Offspring cohort from RNA derived from isolated platelets and leukocytes. A multivariable stepwise regression model was used to assess clinical correlates of quantitative RNA expression. For specific inflammatory platelet-derived transcripts, including ICAM1, IFNG, IL1R1, IL6, MPO, COX2, TNF, TLR2, and TLR4, there were significant associations with higher body mass index (BMI). Compared with platelets, fewer leukocyte-derived transcripts were associated with BMI or other cardiovascular risk factors. Select transcripts were found to be highly heritable, including GPIBA and COX1. Almost uniformly, heritable transcripts were not those associated with BMI. Inflammatory transcripts derived from platelets, particularly those part of the nuclear factor kappa B pathway, are associated with BMI, whereas others are heritable. This is the first study, using a large community-based cohort, to demonstrate clinical correlates of gene expression and is consistent with the hypothesis that specific peripheral-blood transcripts play a role in the pathogenesis of coronary heart disease and its risk factors.


Identification of Agrobacterium tumefaciens genes that direct the complete catabolism of octopine.
Agrobacterium tumefaciens R10 was mutagenized by using the promoter probe transposon Tn5-gusA7, and a library of approximately 5,000 transcriptional fusions was screened for octopine-inducible patterns of gene expression. Twenty-one mutants carrying strongly inducible gusA fusions, 20 of which showed defects in the catabolism of octopine or its metabolites, were obtained. One group of mutants could not use octopine as a carbon source, while a second group of mutants could not utilize arginine or ornithine and a third group could not utilize octopine, arginine, ornithine, or proline as a carbon source. Utilization of these compounds as nitrogen sources showed similar but not identical patterns. Fifteen fusions were subcloned together with adjacent DNA. Sequence analysis and further genetic analysis indicated that insertions of the first group are localized in the occ region of the Ti plasmid. Insertions of the second group were localized to a gene encoding ornithine cyclodeaminase. This gene is very similar to, but distinct from, a homolog located on the Ti plasmid. This gene is located immediately downstream from a gene encoding an arginase. Genetic experiments indicated that this arginase gene is essential for octopine and arginine catabolism. Insertions of the third group was localized to a gene whose product is required for degradation of proline. We therefore have identified all steps required for the catabolism of octopine to glutamate.


Demographics of disclosure of conflicts of interest at the 2011 annual meeting of the American Academy of Orthopaedic Surgeons.
There is growing concern regarding conflicts of interest in orthopaedic research and education. Because of their potential influence on orthopaedic practice, conflicts of interest among participants in the educational programs of the American Academy of Orthopaedic Surgeons (AAOS) are of particular interest. We analyzed the voluntarily disclosed conflicts of interest listed in the Final Program of the 2011 Annual Meeting of the AAOS for the relevant program committees as well as for presentations in the disciplines of pediatric orthopaedic surgery, spine, and sports medicine/arthroscopy. Conflicts of interest were disclosed by participants for each of the program committees and for over 75% of the presentations. Conflicts of interest were disclosed for 100% of the featured symposia, 80% of the scientific exhibits, 76% of the podium presentations, and 75% of the posters. Over half (53%) of the disclosures were for paid consultancy, 51% were for research support for the principal investigator, 41% were for paid presentations, 39% were for royalties, and 39% were for stock. The highest number of disclosures for an individual author was thirty-seven. The number of disclosures per author was significantly (p < 0.001) correlated to the number of presentations per author. Disclosures were associated with 379 different companies; relationships with a relatively small number (twenty-six, 7%) of these companies were listed in the disclosures for 67% of the presentations. Voluntarily disclosed conflicts of interest were common at the 2011 AAOS Annual Meeting, especially for the featured symposia. In view of the previously documented frequency of undisclosed conflicts of interest, as well as the previously documented effects of conflicts of interest on research design, conduct, and conclusion, it may be time to consider improved strategies for ensuring the accuracy and completeness of disclosure and for managing the biasing effects of conflicts of interest.


PARK10 is a major locus for sporadic neuropathologically confirmed Parkinson disease.
To minimize pathologic heterogeneity in genetic studies of Parkinson disease (PD), the Autopsy-Confirmed Parkinson Disease Genetics Consortium conducted a genome-wide association study using both patients with neuropathologically confirmed PD and controls. Four hundred eighty-four cases and 1,145 controls met neuropathologic diagnostic criteria, were genotyped, and then imputed to 3,922,209 variants for genome-wide association study analysis. A small region on chromosome 1 was strongly associated with PD (rs10788972; p = 6.2 × 10(-8)). The association peak lies within and very close to the maximum linkage peaks of 2 prior positive linkage studies defining the PARK10 locus. We demonstrate that rs10788972 is in strong linkage disequilibrium with rs914722, the single nucleotide polymorphism defining the PARK10 haplotype previously shown to be significantly associated with age at onset in PD. The region containing the PARK10 locus was significantly reduced from 10.6 megabases to 100 kilobases and contains 4 known genes: TCEANC2, TMEM59, miR-4781, and LDLRAD1. We confirm the association of a PARK10 haplotype with the risk of developing idiopathic PD. Furthermore, we significantly reduce the size of the PARK10 region. None of the candidate genes in the new PARK10 region have been previously implicated in the biology of PD, suggesting new areas of potential research. This study strongly suggests that reducing pathologic heterogeneity may enhance the application of genetic association studies to PD.


The cutaneous effects of blue light from electronic devices: a systematic review with health hazard identification.
The biologic effects of visible light, particularly blue light, on the skin at doses and irradiances representative of sunlight have been established. Recent research studies investigated the effects of blue light (BL) from electronic screen devices; however, it is unclear if the evidence can be generalized to real life. The aim of this systematic review was to evaluate available evidence regarding clinical effects of BL emitted from electronic devices on human skin using the framework established by the Office of Health Assessment and Translation (OHAT). A systematic literature search was conducted by two librarians in Ovid MEDLINE, Embase.com, and Web of Science for relevant articles published from 1946 to March 2022. In vitro and in vivo studies that investigated the effects of BL from electronic devices on skin were included. From the 87 articles gathered from database searches and 1 article identified from citation search, only 9 met the inclusion criteria (6 in vitro and 3 in vivo studies). Human and animal literature with the highest level of evidence ratings were considered with mechanistic data to form one of five human hazard identifications for each outcome category using the OHAT protocol: (1) known, (2) presumed, (3) suspected, (4) not classifiable, or (5) not identified to be a hazard to humans. Literature-based evidence integration did not identify exposure to BL from electronic devices as a hazard to skin pigmentation, redness, yellowness, or melasma exacerbation. Exposure to BL from electronic devices was not classified as a skin photoaging hazard. Low confidence in representative exposure characterization drove high OHAT risk-of-bias ratings for the majority of included studies. While these conclusions hold true for the limited existing data, a larger number of future studies with high-confidence evidence are needed to verify and strengthen hazard identification conclusions.


Molecular characterization of a calponin-like protein from Schistosoma japonicum.
The gene for a Schistosoma japonicum (Philippine strain origin) (Sjp) calponin-like protein has been cloned and characterised. The clone, designated P14, was isolated from a Sjp adult worm lambda ZAP cDNA library by immunoscreening, and was shown to contain a full-length cDNA encoding a 38.3 kDa protein that shared significant sequence similarity to a number of previously reported calponins and 22 kDa smooth-muscle proteins. Northern analysis indicated the P14 transcript was approximately 2.2 kb in both Sjp and Chinese strain S. japonicum (Sjc) adult worms. Southern blot analysis of genomic DNA suggested that several copies of the P14 gene are present in the Sjc and Sjp genomes but only one copy was evident in the S. mansoni (Sm) genome. Western blot analysis indicated that the product of P14 occurs as a 38 kDa protein in adult Sjp worms and homologues are present in adult worms of Sjc and Sm. At least six isoforms, all with a similar molecular size of approximately 38 kDa and isoelectric points ranging from 8.1 to 9.5, were present in adult Sjc worms. The protein was immunolocalized to the muscle of male and female Sjc adult worms. Recombinant protein was expressed in E. coli and purified under denaturing conditions, and in yeast to produce a soluble protein in purified form. The availability of purified, correctly folded protein will allow investigations into its biological functions and potential involvement in host immunity.


ACR Appropriateness Criteria® Myelopathy: 2021 Update.
Myelopathy is a clinical diagnosis with localization of the neurological findings to the spinal cord, rather than the brain or the peripheral nervous system, and then to a particular segment of the spinal cord. Myelopathy can be the result of primary intrinsic disorders of the spinal cord or from secondary conditions, which result in extrinsic compression of the spinal cord. While the causes of myelopathy may be multiple, the acuity of presentation and symptom onset frame a practical approach to the differential diagnosis. Imaging plays a crucial role in the evaluation of myelopathy with MRI the preferred modality. The American College of Radiology Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed annually by a multidisciplinary expert panel. The guideline development and revision include an extensive analysis of current medical literature from peer reviewed journals and the application of well-established methodologies (RAND/UCLA Appropriateness Method and Grading of Recommendations Assessment, Development, and Evaluation or GRADE) to rate the appropriateness of imaging and treatment procedures for specific clinical scenarios. In those instances where evidence is lacking or equivocal, expert opinion may supplement the available evidence to recommend imaging or treatment.


Findings from a survey on GIS use in the UK National Health Service: organisational challenges and opportunities.
The use of geographical information systems (GIS) in a variety of application areas points to an increasing interest in the spatial aspects of health policies. Despite the fact that most public sector organisations in the United Kingdom (UK) have access to such software tools, there has not been a comprehensive review of take-up within the health sector. In this paper, we report on a recently completed mixed-method research project that has examined the current levels of GIS use in the UK National Health Service, and focus our discussion on health authorities (HAs). Couched within the context of previous studies that have been concerned with outlining the types of factors influencing IT implementation in the health sector, we illuminate the importance of behavioural, cultural and organisational factors on the diffusion of GIS in the UK National Health Service. It is noted that very few organisations had a GIS strategy and we contend that if GIS is to play a wider role in addressing issues surrounding 'joined-up' government, more advice and guidance is needed on policies promoting the exchange of geographical data between agencies concerned with tackling health issues. We conclude by drawing attention to the perceived lack of national guidance on GIS matters, more generally, within the UK health sector.


Karyotyping in melon (Cucumis melo L.) by cross-species fosmid fluorescence in situ hybridization.
Chromosome identification is critical for cytogenetic research and will accelerate studies on genetic variation and breeding, especially for those species with relatively little sequence information. So far, no reliable cytological landmarks have been developed to distinguish individual chromosomes in melon. In this study, using FISH (fluorescence in situ hybridization) combined with comparative genome information, we selected 21 cucumber fosmids anchored by SSR markers as chromosome-specific cytological markers for melon chromosomes. Moreover, with the help of melon centromeric satellite DNA repeats CentM, 45S rDNA and 5S rDNA, sequential FISH with 3 sets of multi-fosmid cocktails were conducted on the same metaphase cell, which allowed us to simultaneously identify each of the 12 metaphase chromosomes of melon and a standardized melon karyotype of somatic metaphase chromosomes was constructed. Finally, we compared the distribution of 21 FISH-mapped fosmids between melon and cucumber chromosomes, which allows a better understanding of the evolutionary process shaping these 2 species. Our study provides a basis for cytological characterization of the melon genome and comparative genomics of Cucurbitaceae.


Low-Temperature Solution Synthesis of Transition Metal Dichalcogenide Alloys with Tunable Optical Properties.
Nanostructures of layered transition metal dichalcogenide (TMD) alloys with tunable compositions are promising candidates for a broad scope of applications in electronics, optoelectronics, topological devices, and catalysis. Most TMD alloy nanostructures are synthesized as films on substrates using gas-phase methods at high temperatures. However, lower temperature solution routes present an attractive alternative with the potential for larger-scale, higher-yield syntheses of freestanding, higher surface area materials. Here, we report the direct solution synthesis of colloidal few-layer TMD alloys, MoxW1-xSe2 and WS2ySe2(1-y), exhibiting fully tunable metal and chalcogen compositions that span the MoSe2-WSe2 and WS2-WSe2 solid solutions, respectively. Chemical guidelines for achieving the targeted compounds are presented, along with comprehensive structural characterizations (X-ray diffraction, electron microscopy, Raman, and UV-visible spectroscopies). High-resolution microscopic imaging confirms the formation of TMD alloys and identifies a random distribution of the alloyed elements. Analysis of the tilt-angle dependency of the intensities associated with atomic-resolution annular dark field imaging line scans reveals the types of point vacancies present in the samples, thus providing atomic-level insights into the structures of colloidal TMD alloy nanostructures that were previously only accessible for substrate-confined films. The A excitonic transition of the TMD alloy nanostructures can be readily adjusted between 1.51 and 1.93 eV through metal and chalcogen alloying, correlating the compositional modulation to the realization of tunable optical properties.


Cofilin rod formation in neurons impairs neuronal structure and function.
Cofilin-1 is a major actin depolymerizer in the central nervous system. It is a member of the ADF/cofilin family that regulates the dynamics of actin filaments. The activity of cofilin-1 is regulated by the modulation of phosphorylation at its Ser3 residue, and its proper function is crucial for the structure and proper function of neurons. Cofilin rods, pathological structures composed of cofilin and actin, form under stress conditions. A high cofilin/F-actin ratio, cofilin dephosphorylation and/or cofilin oxidation are three major mechanisms of cofilin rod formation. Cofilin rods can be divided into cytoplasmic rods and nuclear rods. Cytoplasmic rods have been proved to disrupt dendritic transportation, cause synaptic loss and impair synaptic function, which maybe associated with neurodegenerative diseases such as Alzheimer's disease. On the other hand, the role of nuclear rods remains largely unknown. Further studies are needed to investigate the relationship and the underlying mechanisms of cofilin rod formation during the progression of various neurological diseases.


Highly selective, facile NO2 reduction to NO at cryogenic temperatures on hydrogen precovered gold.
We have discovered that NO(2) is reduced to NO at 77 K by hydrogen precovered gold in vacuum. Here, we investigate the partial reduction of NO(2) to NO on an atomic-hydrogen populated model gold catalyst for a more fundamental understanding of the surface chemistry of hydrogenation. Gold-based catalysts have been found to be active for many hydrogenation reactions, but few related fundamental studies have been conducted. Our experimental results reveal a high catalytic activity for gold: indeed, NO(2) is reduced to NO with 100% conversion and 100% selectivity at temperatures lower than 120 K. Density functional theory calculations and reflection-absorption infrared spectroscopy measurements indicate that HNO(2) and N(2)O(3) are intermediates which are highly dependent on surface hydrogen concentrations; subsequent hydrogenation of HNO(2) and dissociation of N(2)O(3) upon annealing induces the production of NO and H(2)O.


Should we abandon Kielland's forceps?
To assess the risks associated with the use of Kielland's forceps 2708 consecutive deliveries were studied prospectively and the neonatal outcome related to the mode of delivery. Of the 1191 primigravidas, 279 (23.4%) underwent instrumental delivery, of whom 65 (5.5%) were delivered with Kielland's forceps. There was no difference in early neonatal outcome (as judged by Apgar scores, intubations, and admission to the special care baby unit) between these babies and those delivered normally or by non-rotational forceps, but a higher proportion of the 127 (10.7%) delivered by emergency caesarean section were compromised. Of the 1517 multigravid patients, only 57 (3.8%) underwent instrumental delivery, 15 (1.0%) by Kielland's forceps. Among these babies, also, the outcome was no worse than for those delivered normally, but the babies delivered by caesarean section showed a greatly increased incidence of low Apgar scores, intubations, and admission to the special care baby unit. There were no stillbirths or neonatal deaths among babies delivered by Kielland's forceps, nor were there any cases of severe birth trauma or of obvious neonatal morbidity.


[Causes of complications and fatal outcome after combat gunshot wounds of the internal organs].
Under examination there were 110 wounded with battle gunshot injuries of organs of the abdominal cavity. Among them there were 14 patients with thoracoabdominal wounds. Injuries of the internal and other organs were diagnosed in 39 wounded. Ten patients had injuries of the internal organs and upper extremity, 11 patients had injuries of the lower extremity, 4 patients had wounds in the pelvic area, 7--of the trunk, 2--of the skull and face, 5--of the chest. Postoperative complications developed in 28%. Relaparotomy was performed in 13.6% of the patients. Postoperative lethality was 15.3%.


A computational assessment of the permeability and salt rejection of carbon nanotube membranes and their application to water desalination.
Membranes made from nanomaterials such as nanotubes and graphene have been suggested to have a range of applications in water filtration and desalination, but determining their suitability for these purposes requires an accurate assessment of the properties of these novel materials. In this study, we use molecular dynamics simulations to determine the permeability and salt rejection capabilities for membranes incorporating carbon nanotubes (CNTs) at a range of pore sizes, pressures and concentrations. We include the influence of osmotic gradients and concentration build up and simulate at realistic pressures to improve the reliability of estimated membrane transport properties. We find that salt rejection is highly dependent on the applied hydrostatic pressure, meaning high rejection can be achieved with wider tubes than previously thought; while membrane permeability depends on salt concentration. The ideal size of the CNTs for desalination applications yielding high permeability and high salt rejection is found to be around 1.1 nm diameter. While there are limited energy gains to be achieved in using ultra-permeable CNT membranes in desalination by reverse osmosis, such membranes may allow for smaller plants to be built as is required when size or weight must be minimized. There are diminishing returns in further increasing membrane permeability, so efforts should focus on the fabrication of membranes containing narrow or functionalized CNTs that yield the desired rejection or selection properties rather than trying to optimize pore densities.


Sensitive Scalp and Trichodynia: Epidemiology, Etiopathogenesis, Diagnosis, and Management.
Sensitive scalp (SSc) is considered a sensitive skin on the scalp, with its particularities. Although it is not rare in the dermatological practice and the term is commonly present in personal care products, this entity is poorly investigated in the medical literature. The etiopathogenesis is still uncertain, and the sensitivity may be associated with hair loss. Clinical manifestations are subjective symptoms of pruritus, burning, pain, pricking, and/or trichodynia, often with scalp erythema. SSc can be triggered by several factors (endogenous or exogenous). The diagnosis is guided by the anamnesis, and there are still no specific trichoscopic features. Trigeminal trophic syndrome and postherpetic neuralgia are the main differential diagnosis to be considered. We organized the therapeutical approach in three steps: scalp care, topical and systemic treatment.


Genetic and familial aspects of narcolepsy.
Narcolepsy-cataplexy is a disabling sleep disorder characterized by excessive daytime sleepiness and abnormal REM sleep. The development of human narcolepsy involves environmental factors acting on a specific genetic background. The importance of environmental factors is evidenced by the reported 25 to 31% of monozygotic twins who are concordant for narcolepsy. One of the predisposing genetic factors is located in the MHC DQ region. More than 85% of all narcoleptic patients with definite cataplexy share a specific HLA allele, HLA DQB1*0602 (most often in combination with HLA DR2), compared with 12 to 38% of the general population, as evaluated in various ethnic groups. Genetic factors other than HLA are also likely to be involved. Even if genuine multiplex families are rare, 1 to 2% of the first-degree relatives of narcolepsy patients manifest the disorder, compared with 0.02 to 0.18% in the general population. Studies using a canine model of narcolepsy illustrate the importance of non-MHC genes in disease predisposition. In this model, narcolepsy is transmitted as a single autosomal recessive trait, canarc-1. In spite of an association with immune-related polymorphisms, narcolepsy does not appear to be a classic autoimmune disease. Other pathophysiologic models involving the microglia and the release of specific cytokines in the CNS may be involved and are being explored. This approach, together with positional cloning studies in humans and canines, should reveal the cause of narcolepsy and open new therapeutic avenues.


Fetus-in-fetu in the cranium of a 4-month-old boy: histopathology and short tandem repeat polymorphism-based genotyping. Case report.
Fetus-in-fetu is a very rare condition in which one fetus is contained within another. About 100 cases have been reported, and in most of these the fetus was located in the retroperitoneum. The authors describe an extremely rare case of an intracranial fetus-in-fetu in an extraaxial location. This is the eighth intracranial fetus-in-fetu to be reported, the first intracranial extraaxial case, and involves the oldest documented patient with this condition. Histopathological analysis of the mass revealed a degenerated amnionic membranelike tissue, well-differentiated extremities (including fingerlike structures), skin, matured lungs, well-formed intestines, cerebellar and cerebral tissue, and a notochord with ganglion cells. DNA analysis using short tandem repeat polymorphisms confirmed that the fetus-in-fetu mass and the host infant had heterozygous alleles and were of identical sex and genotype.


Docetaxel/2-Hydroxypropyl β -Cyclodextrin Inclusion Complex Increases Docetaxel Solubility and Release from a Nanochannel Drug Delivery System.
Breast cancer remains the second leading cause of cancer deaths for women in the U.S. The need for new and alternative strategies to treat this cancer is imperative. Here we show the optimization of our nanochannel delivery system (nDS) for constant and sustained delivery of docetaxel (DTX) for thetreatment of triple negative breast cancer. DTX is a highly hydrophobic drug, making it difficult to reach the therapeutic levels when released in aqueous solutions from our implantable delivery system. To overcome this challenge and test the release of DTX from nDS, we prepared DTX/2-hydroxypropyl β-cyclodextrin (DTX/HPCD) inclusion complexes in different molar ratios. The 1:10 DTX/HPCD complex achieved 5 times higher solubility than the 1:2 complex and 3 times higher in vitrorelease of DTX than with free DTX. When released in SCID/Beige mice from nanochannel system, the DTX/HPCD complex showed reduced tumor growth, comparable to the standard bolus injections of DTX, indicating that the structural stability and biological activity of DTX were retained in the complex, after its diffusion through the nanochannel system.


Structure-based drug designing and identification of Woodfordia fruticosa inhibitors targeted against heat shock protein (HSP70-1) as suppressor for Imiquimod-induced psoriasis like skin inflammation in mice model.
Heat shock proteins (HSPs) emerged as a therapeutic target and it was observed that inhibition of HSP70-1 plays a pivotal role in the management of psoriasis. In-silico investigation involving techniques like molecular docking and molecular dynamics (MD) simulation analysis was performed against HSP70-1. Further, anti-psoriatic activity of bioactive immunomodulatory compounds present in ethanolic extract of Woodfordia fruticosa flowers (Wffe) using combination of bioinformatics together with ethnopharmacological approach has been explored in this study. Myricetin (-8.024), Quercetin (-7.368) and Ellagic acid (-7.311) were the top three compounds with minimum energy levels as well as high therapeutic value/ADMET as compared to currently available marketed anti-psoriatic drug Tretinoin (-7.195). ADMET prediction was used to screen ligands for drug-likeness and efficacy. Further, biogenically Woodfordia fruticosa gold nanoparticles (WfAuNPs) were synthesized and characterized by UV-Visible Spectroscopy (UV-vis), Dynamic Light Scattering (DLS), Zeta Potential, X-Ray Diffraction (XRD) and High Resolution Transmission Electron Microscopy (HRTEM) techniques. Synthesized WfAuNPs observed in the size range of 10-20 nm and were used to develop WfAuNPs-Carbopol®934 ointment gel. Subsequently, the therapeutic efficacy of WfAuNPs-Carbopol® 934 was checked against 5% Imiquimod-induced psoriasis like skin inflammation. WfAuNPs-Carbopol® 934 was found to be exerting better therapeutic effect in reducing the mean DAI score (0.63 ± 0.08), serum cytokines (TNF-α, IL-22 and IL-23) levels along with reduced epidermal thickness, parakeratosis and marked decrease in the hyperproliferation of keratinocytes. Results of the study revealed that the WfAuNPs-Carbopol® 934 could be an effective alternative treatment for psoriasis in near future.


How to stop tobacco use? Tobacco user's perspective.
To explore the tobacco-dependent subject's perspectives of what measures are likely to work for tobacco cessation. Nicotine-dependent male subjects attending a tertiary level de-addiction center in North India were recruited. Demographic and clinical data was recorded. Open-ended questions were asked to know user's perspective about the measures by which tobacco use can be effectively stopped in the country. The subjects were allowed as many responses as they desired. A total of 46 subjects were recruited. The median age of the sample was 35 years, with median duration of tobacco use being 12 years. All subjects were males, and most were married, employed, and had urban residence. Supply reducing measures were the most commonly reported to stop tobacco (67.4% of subjects) followed by people quitting tobacco use by themselves (19.6%) and raising awareness through media (13.1%). This pilot study reflects the perspectives of tobacco users for the measures likely to be effective in tobacco cessation. Evaluating the effect of implementation of individual policies may help focusing towards measures that yield greatest benefits.


Toward a Better Understanding of Dural Arteriovenous Fistula Angioarchitecture: Superselective Transvenous Embolization of a Sigmoid Common Arterial Collector.
Our aim was to propose a conceptually new angioarchitectural model of some dural arteriovenous fistulas based on subset analysis of transverse and sigmoid type lesions. The "common collector" notion argues for convergence of multiple smaller caliber arterial vessels on a common arterial collector vessel within the sinus wall. Communication of this single collector (or constellation of terminal collectors) with the sinus proper defines the site of arteriovenous fistula, which can be closed by highly targeted embolization, preserving the sinus and avoiding unnecessary permeation of indirect arterial feeders. One hundred consecutive dural arteriovenous shunts were examined. Thirty-six transverse/sigmoid fistulas were identified within this group and analyzed for the presence of a common arterial collector as well as other parameters, including demographics, grade, treatment approach, and outcome. A common collector was identified in nearly all Cognard type I lesions (15 fistulas with 14 single collector vessels seen) and progressively less frequently in higher grade fistulas. Identification of the common collector requires careful angiographic analysis, including supraselective and intraprocedural angiographies during treatment, and final embolic material morphology. Detailed evaluation of imaging studies allows frequent identification of a vascular channel in the sinus wall, which we argue reflects a compound, common arterial channel (rather than a venous collector) with 1 or several discrete fistulous points between this vessel and the sinus proper. Targeted closure of this channel is often feasible, with sinus preservation and avoidance of embolic material penetration into arteries remote from fistula site.


Selective reduction of a disulphide bridge in hen ovotransferrin.
Brief treatment of iron-saturated hen ovotransferrin with dithiothreitol selectively cleaves the disulphide bridge between residues 478 and 671, which is in the C-terminal domain of the protein. The reduced alkylated protein is less stable than the native protein, and its iron-binding properties are different. A fluorescent derivative was prepared by coupling N-iodoacetyl-N'-(5-sulpho-1-naphthyl)ethylenediamine to the thiol groups.


Two-Dimensional Massless Dirac Fermions in Antiferromagnetic AFe_{2}As_{2} (A=Ba,Sr).
We report infrared studies of AFe_{2}As_{2} (A=Ba, Sr), two representative parent compounds of iron-arsenide superconductors, at magnetic fields (B) up to 17.5 T. Optical transitions between Landau levels (LLs) were observed in the antiferromagnetic states of these two parent compounds. Our observation of a sqrt[B] dependence of the LL transition energies, the zero-energy intercepts at B=0 T under the linear extrapolations of the transition energies and the energy ratio (∼2.4) between the observed LL transitions, combined with the linear band dispersions in two-dimensional (2D) momentum space obtained by theoretical calculations, demonstrates the existence of massless Dirac fermions in the antiferromagnet BaFe_{2}As_{2}. More importantly, the observed dominance of the zeroth-LL-related absorption features and the calculated bands with extremely weak dispersions along the momentum direction k_{z} indicate that massless Dirac fermions in BaFe_{2}As_{2} are 2D. Furthermore, we find that the total substitution of the barium atoms in BaFe_{2}As_{2} by strontium atoms not only maintains 2D massless Dirac fermions in this system, but also enhances their Fermi velocity, which supports that the Dirac points in iron-arsenide parent compounds are topologically protected.


Cholinergic modulation of the Ca2+ response to bradykinin in neuroblastoma cells.
Fura 2 imaging was used to measure intracellular Ca2+ signals in N1E-115 mouse neuroblastoma cells during combined activation of bradykinin (BK) and cholinergic receptors. BK and carbachol (CCh) both activate phospholipase C (PLC) and cause Ca2+ release from inositol 1,4,5-trisphosphate (IP3)-sensitive Ca2+ stores. The Ca2+ signal in response to CCh is prolonged by the activation of Ca2+ influx, but BK does not appear to activate the influx pathway. When BK and CCh are applied together (BK+CCh), the Ca2+ response is composed of both Ca2+ release and Ca2+ influx. Ca2+ influx is also activated by BK+CCh in a subset of cells that does not respond with a intracellular Ca2+ concentration increase when CCh is presented by itself. This suggests that CCh stimulates a Ca(2+)-silent cholinergic receptor that is not coupled to Ca2+ release but acts synergistically with BK receptors to activate Ca2+ influx. Pertussis toxin reduces influx without affecting release, indicating that the G protein that modulates the influx pathway is different from the G protein responsible for activating PLC. Cholinergic stimulation also causes progressive heterologous desensitization of BK-evoked Ca2+ release. Desensitization has the unique property of continuing to develop after the cholinergic agonist is removed and the cholinergic Ca2+ response has fully recovered. Heterologous desensitization is not the result of Ca2+ store depletion or a long-lasting inhibition of PLC or IP3-dependent Ca2+ release. Instead, it appears to involve an early step in the BK-signaling cascade, possibly at the level of the B2 receptor or associated G proteins.


[Electroencephalographic changes induced by baclofen].
Electroencephalographic and clinical effects of baclofen were investigated in 46 neurological patients and 7 healthy volunteers. 27 cases showed an increase of slow EEG activity. Patients with spinal disease, brain-stem disease, disturbed vibratory sensation and also with renal insufficiency showed pronounced EEG-slowing. Baclofen depresses the activity in primary afferents and reticulocortical afferents. These effects can lead to EEG slowing. One patient developed a reversible organic brain syndrome and myoclonias with marked EEG-slowing and bilateral synchronous sharp and slow waves. This was interpreted as an epileptic stupor induced by Baclofen. The patient had renal insufficiency and accumulated Baclofen. Both conditions may have contributed to the epileptic manifestation.


Dual CNN cross-teaching semi-supervised segmentation network with multi-kernels and global contrastive loss in ACDC.
The cross-teaching based on Convolutional Neural Network (CNN) and Transformer has been successful in semi-supervised learning; however, the information interaction between local and global relations ignores the semantic features of the medium scale, and at the same time, the information in the process of feature coding is not fully utilized. To solve these problems, we proposed a new semi-supervised segmentation network. Based on the principle of complementary modeling information of different kernel convolutions, we design a dual CNN cross-supervised network with different kernel sizes under cross-teaching. We introduce global feature contrastive learning and generate contrast samples with the help of dual CNN architecture to make efficient use of coding features. We conducted plenty of experiments on the Automated Cardiac Diagnosis Challenge (ACDC) dataset to evaluate our approach. Our method achieves an average Dice Similarity Coefficient (DSC) of 87.2% and Hausdorff distance ([Formula: see text]) of 6.1 mm on 10% labeled data, which is significantly improved compared with many current popular models. Supervised learning is performed on the labeled data, and dual CNN cross-teaching supervised learning is performed on the unlabeled data. All data would be mapped by the two CNNs to generate features, which are used for contrastive learning to optimize the parameters.


Nasopalpebral lipoma-coloboma syndrome.
An autosomal dominant dysplasia-malformation syndrome affecting seven individuals in one family is reported. The components of the syndrome include congenital nasopalpebral lipoma, telecanthus, and bilateral colobomas of upper and lower lids without midface hypoplasia. It appears to be the second recorded example resulting from an autosomal dominant gene fully penetrant in both sexes.


Distal tibial fractures in dogs and cats.
A total of 43 fractures of the distal tibia in dogs and cats were evaluated for fracture patterns, methods of stabilization, and time to bone union. Fractures of the metaphysis (9.3%), physis (30.9%), epiphysis (2.3%), and malleoli (58.2%) were classified. Open reduction and internal fixation, with combinations of Kirschner wire, orthopedic wire, and bone screws, were the methods of fixation used in the majority of fractures. These relatively simple methods of fixation were applied to all sizes of dogs and cats and resulted in an average bone healing time of 6 weeks.


Survival and years of life lost in various aetiologies of dementia, mild cognitive impairment (MCI) and subjective cognitive decline (SCD) in Norway.
Alzheimer's disease patients are reported to have higher survival rate compared to patients with vascular dementia or dementia with Lewy bodies. There is a paucity of studies investigating survival including persons with cognitive decline and dementia of various aetiologies. We aimed to compare survival for patients with subjective cognitive decline, mild cognitive impairment, Alzheimer's disease, vascular dementia, mixed Alzheimer's/vascular dementia, dementia with Lewy bodies/Parkinson's disease, and other dementias compared to the general Norwegian population, taking into account the role of gender, cognitive function, function in everyday activities, comorbidity and education. Patients (N = 4682), ≥65 years, in the The Norwegian register of persons assessed for cognitive symptoms (NorCog) during 2009-2017 were followed for mortality in the National Registry until January 2018. Flexible parametric survival models were applied to estimate relative survival, life expectancy and years of life lost for diagnostic groups compared with the general population. Patients with vascular dementia or dementia with Lewy bodies/Parkinson's had the shortest survival, followed by mixed dementia, Alzheimer's disease, unspecified dementia, mild cognitive impairment and subjective cognitive decline. At age 70 years, men with vascular dementia or dementia with Lewy bodies/Parkinson's had life expectancy of 4.7 years, which corresponded to 10.3 years of life lost compared to the general population. Years of life lost for other diagnoses were 10.0 years for mixed dementia, 9.2 years for Alzheimer's disease, 9.3 years for other dementias, 5.2 years for mild cognitive impairment and 2.2 years for subjective cognitive decline. Corresponding years of life lost in women were: 12.7 years, 10.5 years, 9.8 years, 10.6 years, 7.8 years, and 2.6 years. Poor relative survival among dementia patients was associated with male gender, comorbidity, low cognitive function, and low function in activities of daily living. Compared with the general population, patients with subjective cognitive decline had no significant loss in life expectancy, while patients with mild cognitive impairment and all dementia subtypes had large losses, especially those with a diagnosis of vascular dementia or dementia with Lewy bodies/Parkinson's.


Targeting of a Nicotiana plumbaginifolia H+ -ATPase to the plasma membrane is not by default and requires cytosolic structural determinants.
The structural determinants involved in the targeting of multitransmembrane-span proteins to the plasma membrane (PM) remain poorly understood. The plasma membrane H+ -ATPase (PMA) from Nicotiana plumbaginifolia, a well-characterized 10 transmembrane-span enzyme, was used as a model to identify structural elements essential for targeting to the PM. When PMA2 and PMA4, representatives of the two main PMA subfamilies, were fused to green fluorescent protein (GFP), the chimeras were shown to be still functional and to be correctly and rapidly targeted to the PM in transgenic tobacco. By contrast, chimeric proteins containing various combinations of PMA transmembrane spanning domains accumulated in the Golgi apparatus and not in the PM and displayed slow traffic properties through the secretory pathway. Individual deletion of three of the four cytosolic domains did not prevent PM targeting, but deletion of the large loop or of its nucleotide binding domain resulted in GFP fluorescence accumulating exclusively in the endoplasmic reticulum. The results show that, at least for this polytopic protein, the PM is not the default pathway and that, in contrast with single-pass membrane proteins, cytosolic structural determinants are required for correct targeting.


Genetic landscape of external auditory canal squamous cell carcinoma.
External auditory canal squamous cell carcinoma (EACSCC) is an extremely rare and aggressive malignancy. Due to its rarity, the molecular and genetic characteristics of EACSCC have not yet been elucidated. To reveal the genetic alterations of EACSCC, we performed whole exome sequencing (WES) on 11 primary tumors, 1 relapsed tumor and 10 noncancerous tissues from 10 patients with EACSCC, including 1 with a rare case of synchronous bilateral EACSCC of both ears. WES of the primary tumor samples showed that the most frequently mutated gene is TP53 (63.6%). In addition, recurrent mutations in CDKN2A, NOTCH1, NOTCH2, FAT1 and FAT3 were detected in multiple samples. The mutational signature analysis of primary tumors indicated that the mutational processes associated with the activation of apolipoprotein B mRNA-editing enzyme catalytic polypeptide-like (APOBEC) deaminases are the most common in EACSCC, suggesting its similarity to SCC from other primary sites. Analysis of arm-level copy number alterations detected notable amplification of chromosomes 3q, 5p and 8q as well as deletion of 3p across multiple samples. Focal chromosomal aberrations included amplifications of 5p15.33 (ZDHHC11B) and 7p14.1 (TARP) as well as deletion of 9p21.3 (CDKN2A/B). The protein expression levels of ZDHHC11B and TARP in EACSCC tissues were validated by immunohistochemistry. Moreover, WES of the primary and relapsed tumors from a case of synchronous bilateral EACSCC showed the intrapatient genetic heterogeneity of EACSCC. In summary, this study provides the first evidence for genetic alterations of EACSCC. Our findings suggest that EACSCC mostly resembles other SCC.


Controlled growth and form of precipitating microsculptures.
Controlled self-assembly of three-dimensional shapes holds great potential for fabrication of functional materials. Their practical realization requires a theoretical framework to quantify and guide the dynamic sculpting of the curved structures that often arise in accretive mineralization. Motivated by a variety of bioinspired coprecipitation patterns of carbonate and silica, we develop a geometrical theory for the kinetics of the growth front that leaves behind thin-walled complex structures. Our theory explains the range of previously observed experimental patterns and, in addition, predicts unexplored assembly pathways. This allows us to design a number of functional base shapes of optical microstructures, which we synthesize to demonstrate their light-guiding capabilities. Overall, our framework provides a way to understand and control the growth and form of functional precipitating microsculptures.


ERCP in patients with prior Billroth II gastrectomy: report of 30 years' experience.
Endoscopic retrograde cholangiopancreatography (ERCP) is difficult in patients with altered anatomy following Billroth II gastrectomy. Afferent loop intubation, selective cannulation, and sphincterotomy are the main issues. Experience from a tertiary referral endoscopy center is reported. A total of 713 patients with Billroth II reconstruction who underwent ERCP between October 1982 and October 2012 were retrospectively identified from a prospectively collected database (mean age 69 ± 27 years; 567 males). The main indications for ERCP were common bile duct stones (51.2 %) and obstructive jaundice (24.8 %). Procedures were always started with a duodenoscope; in cases of failure to reach the papilla the duodenoscope was changed to a gastroscope. Endoscopic sphincterotomy was performed using a long-nose sigmoid inverted sphincterotome. The successful duodenal intubation rate was 86.7 % (618/713 patients). The main reason for intubation failure was a long and angulated afferent loop. Successful cannulation/opacification of the desired biliopancreatic duct was 93.8 % (580/618). Biliary and/or pancreatic sphincterotomy were performed in 490 (84.5 %) and 23 (4.0 %) patients, respectively. The adverse event rate was 4.3 % (45/1050 procedures). Peritoneal perforation occurred in 1.8 % of the cases (19/1050 procedures) and always required immediate surgery. Two patients died after surgery (overall mortality 0.3 %). The other adverse events resolved following conservative management or endoscopic reintervention. In experienced centers, ERCP in Billroth II patients had morbidity and mortality rates that were comparable to patients with normal anatomy. The main reasons for failure were related to the inability to reach the papilla. Peritoneal perforation was the most common adverse event, and required a prompt surgical approach.


Molecular approaches in the diagnosis of sepsis in neutropenic patients with haematological malignances.
Sepsis is a major cause of significant morbidity and mortality in neutropenic patients. Blood culture remains the gold standard in the microbiological diagnosis of bacterial or fungal bloodstream infections, but it has clear limits of rapidity and sensitivity. The objective of the study was to compare the real-time polymerase chain reaction (RT-PCR) with automated blood cultures (BC) method in detection in whole blood of pathogens in febrile neutropenic patients with hematological malignancies. A total of 166 consecutive febrile neutropenic patients were enrolled. Blood samples for cultures and SeptiFast testing were obtained at the onset of fever, before the implementation of empirical antibiotic therapy. Forty (24.1%) samples out of the 166 blood samples tested, were positive by at least one method. Twenty-three (13.9%) samples were positive by blood culture and 38 (22.9%) by multiplex real-time PCR. The analysis of concordance evidenced a low correlation between the two methods (n = 21; 52.5%), mainly due to samples found negative by culture but positive with the Septi-Fast assay. Sensitivity, specificity, and positive and negative predictive values of RT-PCR were 91.3%, 88.1%, 55.3%, and 98.4%, respectively, compared with BC. Multiplex real-time PCR assay improved detection of the most bacteria associated with febrile neutropenia episodes. Further studies are needed to assess the real advantages and clinical benefits that molecular biology tests can add in diagnosis of sepsis.


Queering Environmental Justice: Unequal Environmental Health Burden on the LGBTQ+ Community.
The LGBTQ+ (lesbian, gay, bisexual, transgender/-sexual, queer or questioning, intersex, asexual, and all subsects) population has been the target of federal and state discriminatory policies leading to high levels of institutional discrimination in the housing, employment, and health sectors. Social determinants of health such as housing conditions, economic opportunities, and access to health care may negatively and disproportionately affect the LGBTQ+ population and reduce their capacity to respond to environmental harm (e.g., obtaining necessary medical care). Social determinants of health have been shown to be associated with unequal harmful environmental exposure, primarily along lines of race/ethnicity and socioeconomic status. However, chronic diseases, such as respiratory diseases, cardiovascular disease, and cancer, associated with environmental exposure have been shown to occur in higher rates in the LGBTQ+ population than in the cisgender, heterosexual population. We explore how environmental exposures may disproportionately affect the LGBTQ+ population through examples of environmental exposures, health risks that have been linked to environmental exposures, and social institutions that could affect resilience to environmental stressors for this population. We provide recommendations for policymakers, public health officials, and researchers. (Am J Public Health. 2022;112(1):79-87. https://doi.org/10.2105/AJPH.2021.306406).


Integration of amorphous ferromagnetic oxides with multiferroic materials for room temperature magnetoelectric spintronics.
A room temperature amorphous ferromagnetic oxide semiconductor can substantially reduce the cost and complexity associated with utilizing crystalline materials for spintronic devices. We report a new material (Fe0.66Dy0.24Tb0.1)3O7-x (FDTO), which shows semiconducting behavior with reasonable electrical conductivity (~500 mOhm-cm), an optical band-gap (2.4 eV), and a large enough magnetic moment (~200 emu/cc), all of which can be tuned by varying the oxygen content during deposition. Magnetoelectric devices were made by integrating ultrathin FDTO with multiferroic BiFeO3. A strong enhancement in the magnetic coercive field of FDTO grown on BiFeO3 validated a large exchange coupling between them. Additionally, FDTO served as an excellent top electrode for ferroelectric switching in BiFeO3 with no sign of degradation after ~1010 switching cycles. RT magneto-electric coupling was demonstrated by modulating the resistance states of spin-valve structures using electric fields.


Noninvasive time and frequency predictors of long-standing atrial fibrillation early recurrence after electrical cardioversion.
Several clinical factors have been studied to predict atrial fibrillation (AF) recurrence after electrical cardioversion (ECV) with limited predictive value. A method able to predict robustly long-standing AF early recurrence by characterizing noninvasively the electrical atrial activity (AA) with parameters related to its time course and spectral features is presented. To this respect, 63 patients (20 men and 43 women; mean age 73.4 ± 9.0 years; under antiarrhythmic drug treatment with amiodarone) who were referred for ECV of persistent AF were studied. During a 4-week follow-up, AF recurrence was observed in 41 patients (65.1%). RR variability and the studied AA spectral features, including dominant atrial frequency (DAF), its first harmonic and their amplitude, provided poor statistical differences between groups. On the contrary, f waves power (fWP) and Sample Entropy (SampEn) of the AA behaved as very good predictors. Patients who relapsed to AF presented lower fWP (0.036 ± 0.019 vs 0.081 ± 0.029 n.u.(2) , P < 0.001) and higher SampEn (0.107 ± 0.022 vs 0.086 ± 0.033, P < 0.01). Furthermore, fWP presented the highest predictive accuracy of 82.5%, whereas SampEn provided a 79.4%. The remaining features revealed accuracies lower than 70%. A stepwise discriminant analysis (SDA) provided a model based on fWP and SampEn with 90.5% of accuracy. The fWP has proved to predict long-standing AF early recurrence after ECV and can be combined with SampEn to improve its diagnostic ability. Furthermore, a thorough analysis of the results allowed outlining possible associations between these two features and the concomitant status of atrial remodeling.


Simultaneous 3D imaging of sound-induced motions of the tympanic membrane and middle ear ossicles.
Efficient transfer of sound by the middle ear ossicles is essential for hearing. Various pathologies can impede the transmission of sound and thereby cause conductive hearing loss. Differential diagnosis of ossicular disorders can be challenging since the ossicles are normally hidden behind the tympanic membrane (TM). Here we describe the use of a technique termed optical coherence tomography (OCT) vibrography to view the sound-induced motion of the TM and ossicles simultaneously. With this method, we were able to capture three-dimensional motion of the intact TM and ossicles of the chinchilla ear with nanometer-scale sensitivity at sound frequencies from 0.5 to 5 kHz. The vibration patterns of the TM were complex and highly frequency dependent with mean amplitudes of 70-120 nm at 100 dB sound pressure level. The TM motion was only marginally sensitive to stapes fixation and incus-stapes joint interruption; however, when additional information derived from the simultaneous measurement of ossicular motion was added, it was possible to clearly distinguish these different simulated pathologies. The technique may be applicable to clinical diagnosis in Otology and to basic research in audition and acoustics.


Molecular approaches for the diagnosis and epidemiological investigation of Aspergillus infection.
Molecular techniques have been applied to the diagnosis of invasive aspergillosis and to investigate the ecology and epidemiology of Aspergillus. Recent advances in diagnosis include the development of PCRs targeting either panfungal or Aspergillus-specific sequences, using whole blood or serum samples. When a sensitive PCR is used, invasive aspergillosis in bone marrow transplant patients can be detected several weeks before antigen tests become positive, and a positive PCR often pre-dates the institution of antifungal therapy. The role of PCR in monitoring response to therapy in immunocompromised patients is unclear. No prospective studies have yet demonstrated that management incorporating PCR alters the poor outcome of invasive aspergillosis in immunocompromised patients. Molecular typing of Aspergillus fumigatus has shown wide geographical dispersal of indistinguishable strains. This, combined with the observation that multiple strains may be isolated from individual colonised patients with cystic fibrosis and from immunocompromised patients with disseminated disease, makes the elucidation of the epidemiology of aspergillosis relatively complex.


Design and synthesis of some new 1-phenyl-3/4-[4-(aryl/heteroaryl/alkyl-piperazine1-yl)-phenyl-ureas as potent anticonvulsant and antidepressant agents.
A series of 1-phenyl-3/4-[4-(aryl/heteroaryl/alkyl-piperazine1-yl)-phenyl-urea derivatives (29-42) were designed, synthesized and evaluated for their anticonvulsant activity by using maximal electroshock (MES), subcutaneous pentylenetetrazole (scPTZ) seizure tests. The acute neurotoxicity was checked by rotarod assay. Most of the test compounds were found effective in both seizure tests. Compound 30 (1-{4-[4-(4-chloro-phenyl)-piperazin-1-yl]-phenyl}-3-phenyl-urea) exhibited marked anticonvulsant activity in MES as well as scPTZ tests. The phase II anticonvulsant quantification study of compound 30 indicates the ED50 value of 28.5 mg/kg against MES induced seizures. In addition, this compound also showed considerable protection against pilocarpine induced status epilepticus in rats. Seizures induced by 3-mercaptopropionic acid model and thiosemicarbazide were significantly attenuated by compound 30, which suggested its broad spectrum of anticonvulsant activity. Interestingly, compound 30 displayed better antidepressant activity than standard drug fluoxetine. Moreover, compound 30 appeared as a non-toxic chemical entity in sub-acute toxicity studies.


[Effectiveness of the use of solcoseryl after surgery of acute hemorrhage in gastroduodenal ulcer].
The experience of solcoseryl application in 70 patients, operated on for an acute hemorrhage from gastroduodenal ulcer, was summarized. The preparation was injected intravenously in the dose of 10 ml in 5% solution of glucose every other day during 6 days and then in the dose of 5 ml intramuscularly during 4-5 days. High efficacy of solcoseryl, manifesting by more earlier elimination of pain and oedema, healing of mucosa by first intention, shortening of the treatment duration in stationary by 3-5 days, was established.


A small, differentially regulated family of farnesyl diphosphate synthases in maize (Zea mays) provides farnesyl diphosphate for the biosynthesis of herbivore-induced sesquiterpenes.
Of the three functional FPPS identified in maize, fpps3 is induced by herbivory to produce FDP important for the formation of the volatile sesquiterpenes of plant defense. Sesquiterpenes are not only crucial for the growth and development of a plant but also for its interaction with the environment. The biosynthesis of sesquiterpenes proceeds over farnesyl diphosphate (FDP), which is either used as a substrate for protein prenylation, converted to squalene, or to volatile sesquiterpenes. To elucidate the regulation of sesquiterpene biosynthesis in maize, we identified and characterized the farnesyl diphosphate synthase (FPPS) gene family which consists of three genes. Synteny analysis indicates that fpps2 and fpps3 originate from a genome duplication in an ancient tetraploid ancestor. The three FPPSs encode active enzymes that produce predominantly FDP from the isopentenyl diphosphate and dimethylallyl diphosphate substrates. Only fpps1 and fpps3 are induced by elicitor treatment, but induced fpps1 levels are much lower and only increased to the amounts of fpps3 levels in intact leaves. Elicitor-induced fpps3 levels in leaves increase to more than 15-fold of background levels. In undamaged roots, transcript levels of fpps1 are higher than those of fpps3, but only fpps3 transcripts are induced in response to herbivory by Diabrotica virgifera virgifera. A kinetic of transcript abundance in response to herbivory in leaves provided further evidence that the regulation of fpps3 corresponds to that of tps23, a terpene synthase, that converts FDP to the volatile (E)-ß-caryophyllene. Our study indicates that the differential expression of fpps1 and fpps3 provides maize with FDP for both primary metabolism and terpene-based defenses. The expression of fpps3 seems to coincide with the herbivore-induced emission of volatile sesquiterpenes that were demonstrated to be important defense signals.


Planar covariation of limb elevation angles during bipedal locomotion in common quails (Coturnix coturnix).
In human bipedal walking, temporal changes in the elevation angle of the thigh, shank and foot segments covary to form a regular loop within a single plane in three-dimensional space. In this study, we quantified the planar covariation of limb elevation angles during bipedal locomotion in common quails to test whether the degree of planarity and the orientation of the covariance plane differ between birds, humans and Japanese macaques as reported in published accounts. Five quails locomoted on a treadmill and were recorded by a lateral X-ray fluoroscopy. The elevation angle of the thigh, shank and foot segments relative to the vertical axis was calculated and compared with published data on human and macaque bipedal locomotion. The results showed that the planar covariation applied to quail bipedal locomotion and planarity was stronger in quails than in humans. The orientation of the covariation plane in quails differed from that in humans, and was more similar to the orientation of the covariation plane in macaques. Although human walking is characterized by vaulting mechanics of the body center of mass, quails and macaques utilize spring-like running mechanics even though the duty factor is >0.5. Therefore, differences in the stance leg mechanics between quails and humans may underlie the difference in the orientation of the covariation plane. The planar covariation of inter-segmental coordination has evolved independently in both avian and human locomotion, despite the different mechanical constraints.


Assessment of Airborne Bacterial and Fungal Communities in Shahrekord Hospitals.
This paper presents information about airborne microorganisms (bacteria and fungi) in the indoor air of two hospitals (Kashani and Hajar) in the city of Shahrekord, Iran. The settle plate technique using open Petri dishes containing different culture media was employed to collect a sample and using Quick Take 30 Sample Pump three days per week for a period of 8 weeks. Standard microbiological methods were employed for the identification of bacterial and fungal isolates. The results showed that the concentration of bacteria in the study area ranged from 0 to 70 cfu/plate/h, while the concentration of fungi was 0 to 280 cfu/plate/h. Also, 12 bacterial and 3 fungal species were isolated and identified with varying frequencies of occurrence, including Staphylococcus spp., Escherichia coli, Salmonella, Enterobacter, Pseudomonas, Serratia Citrobacter, Proteus, and Klebsiella, while the fungal genera isolated included Yeast, Aspergillus flavus, and Penicillium. While the bacterial isolates Staphylococcus aureus (20.50%) and Pseudomonas (9.10%) were the most predominant airborne bacteria, yeast (22.70%) and Penicillium (20.50%) were the most frequently isolated fungal species. The population of microorganisms was the highest during the afternoon. The statistical analysis showed a significant difference between the microbial loads of the two hospitals at P < 0.05. The generated data underline the usefulness of monitoring the air quality of the indoor hospital.


Desmoplastic melanoma associated with an intraepidermal lentiginous lesion: case report and literature review.
Desmoplastic melanoma tends to present as firm, amelanotic papules. Microscopically, it reveals a proliferation of fusiform cells in the dermis and variable collagen deposition, as well as intraepidermal melanocytic proliferation of lentiginous type in most cases. Biopsy in a 61-year-old white male patient, who had received a diagnosis of lentigo maligna on his face 10 years before, revealed a proliferation of dermal pigmented spindle cells and collagen deposition, reaching the deep reticular dermis, with a lentiginous component. Immunohistochemistry with S-100, Melan-A and WT1 showed positivity, but it was weak with HMB45. Desmoplastic melanoma associated with lentigo maligna was diagnosed. Several authors discuss whether desmoplastic melanoma represents a progression from the lentiginous component or arises "de novo". Desmoplastic melanoma represents a minority of cases of primary cutaneous melanoma (less than 4%). Identification of lentigo maligna indicates that desmoplastic melanoma should be carefully investigated.


The Effects of Total Mixed Ration Feeding with High Roughage Content on Growth Performance, Carcass Characteristics, and Meat Quality of Hanwoo Steers.
This study investigated the dietary effect of total mixed ration (TMR) based on high roughage content on the growth performance, carcass characteristics, and meat quality of Hanwoo steers. Twenty-four Hanwoo steers (average body weight, 195.3±4.7 kg; age, 8.5 mon) were randomly allocated to three experimental groups according to forage and concentrate ratio (DM basis): 25:75 (control), 50:50 (T50), and 70:30 (T70). Productivity in the fattening period and final body weight were significantly higher in the control. Average daily gain and feed conversion ratio were the same among treatments. Serum parameters, cholesterol, blood urea nitrogen, and total protein were higher in the control. Carcass weight was comparable in the control and T50 but feeding more roughage was significantly correlated with a higher intramuscular fat. Shear strength and drip loss were higher while n-6/n-3 was lower in T70 compared to the other groups. However, meat color was not significantly different among treatments. In terms of free amino acid contents, glutamic acid and glycine were higher in the control than T50 and T70. Overall, feeding Hanwoo steers with high forage content TMR had the lowest n-6/n-3 ratio of fatty acid content but highest intramuscular fat, shear strength, and drip loss. High forage content TMR is the best feed for Hanwoo steers that gives more benefits for human health and consumption but also provides the best meat grade and quality, which is important in the beef market in Korea.


Factors influencing lid pressure on the cornea.
To investigate the effects of eyelid pressure on corneal topography in different angles of gaze and under different eye movement conditions. Ten young subjects with healthy eyes were recruited for the study. Corneal topography of the right eye was measured with a videokeratoscope before and after four 15-minute visual tasks (downward gaze of 25 degrees or 45 degrees , both with no eye movements or 1 Hz eye movements). The four tasks were conducted on four separate mornings. RESULTS.: All subjects showed significant regions of topographic change after each of the four tasks. In general, eye movements were found to cause greater topographic changes than tasks without eye movements, and the larger angle of downward gaze led to greater changes in topography. The topographic changes were located close to the lid margin position during each task. The pressure exerted by the eyelid is capable of altering corneal topography. These changes are enhanced when the eye looks downward and when the eye moves laterally.


Low dose subcutaneous heparin and wound hematoma formation in inguinal hernia operations--a double-blind randomized clinical trial.
Postoperative wound bleeding and wound hematoma formation were studied in a prospective double-blind randomized clinical trial in selected patients undergoing surgery for inguinal hernia. With careful surgical technique, prophylactic administration of low dose subcutaneous heparin did not result in a significant increase in wound hematoma formation or wound bleeding. The postoperative decrease in the hemoglobin concentration, resulting from operative and postoperative blood loss, was -0.59 mmol/l, +/- 0.54 SD, in the control group and -0.60 mmol/l, +/- 0.57 SD, in the heparin group.


Nomenclature of Genetic Movement Disorders: Recommendations of the International Parkinson and Movement Disorder Society Task Force - An Update.
In 2016, the Movement Disorder Society Task Force for the Nomenclature of Genetic Movement Disorders presented a new system for naming genetically determined movement disorders and provided a criterion-based list of confirmed monogenic movement disorders. Since then, a substantial number of novel disease-causing genes have been described, which warrant classification using this system. In addition, with this update, we further refined the system and propose dissolving the imaging-based categories of Primary Familial Brain Calcification and Neurodegeneration with Brain Iron Accumulation and reclassifying these genetic conditions according to their predominant phenotype. We also introduce the novel category of Mixed Movement Disorders (MxMD), which includes conditions linked to multiple equally prominent movement disorder phenotypes. In this article, we present updated lists of newly confirmed monogenic causes of movement disorders. We found a total of 89 different newly identified genes that warrant a prefix based on our criteria; 6 genes for parkinsonism, 21 for dystonia, 38 for dominant and recessive ataxia, 5 for chorea, 7 for myoclonus, 13 for spastic paraplegia, 3 for paroxysmal movement disorders, and 6 for mixed movement disorder phenotypes; 10 genes were linked to combined phenotypes and have been assigned two new prefixes. The updated lists represent a resource for clinicians and researchers alike and they have also been published on the website of the Task Force for the Nomenclature of Genetic Movement Disorders on the homepage of the International Parkinson and Movement Disorder Society (https://www.movementdisorders.org/MDS/About/Committees--Other-Groups/MDS-Task-Forces/Task-Force-on-Nomenclature-in-Movement-Disorders.htm). © 2022 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson Movement Disorder Society.


A neurocognitive approach for recovering upper extremity movement following subacute stroke: a randomized controlled pilot study.
[Purpose] This study aims to describe a protocol based on neurocognitive therapeutic exercises and determine its feasibility and usefulness for upper extremity functionality when compared with a conventional protocol. [Subjects and Methods] Eight subacute stroke patients were randomly assigned to a conventional (control group) or neurocognitive (experimental group) treatment protocol. Both lasted 30 minutes, 3 times a week for 10 weeks and assessments were blinded. Outcome measures included: Motor Evaluation Scale for Upper Extremity in Stroke Patients, Motricity Index, Revised Nottingham Sensory Assessment and Kinesthetic and Visual Imagery Questionnaire. Descriptive measures and nonparametric statistical tests were used for analysis. [Results] The results indicate a more favorable clinical progression in the neurocognitive group regarding upper extremity functional capacity with achievement of the minimal detectable change. The functionality results are related with improvements on muscle strength and sensory discrimination (tactile and kinesthetic). [Conclusion] Despite not showing significant group differences between pre and post-treatment, the neurocognitive approach could be a safe and useful strategy for recovering upper extremity movement following stroke, especially regarding affected hands, with better and longer lasting results. Although this work shows this protocol's feasibility with the panel of scales proposed, larger studies are required to demonstrate its effectiveness.


[Use of polymer hemostatic cotton and plate in surgery of the lungs and pleura].
The article discusses the efficacy of using polymeric hemostatic wool and plate in operations on the lungs and pleura in experiments. From the results of experimental studies the authors concluded that a biodegradable polyamide based on hexamethylenediamine and derivatives of amino acids in a model of parenchymatous-capillary bleeding from the lungs and pleura is an effective hemostatic. The authors recommend these polymers for use in the clinic.


Does animal model on ventilator-associated pneumonia reflect physiopathology of sepsis mechanisms in humans?
Ventilator-associated pneumonia (VAP) is the leading cause of death in critically ill patients in intensive care units. In the last 20 years, different animal models have been a valuable tool for the study of pathophysiology and phenotypic characteristics of different lung infections observed in humans, becoming an essential link between ''in vitro'' testing and clinical studies. Different animal models have been used to study the mechanism of a deregulated inflammatory response and host tissue damage of sepsis in VAP, as well as different infection parameters such as clinical, physiological, microbiological and pathological facts in several large and small mammals. In addition, the dosage of inflammatory modulators and their consequences in local and systemic inflammation, or even the administration of antibiotics, have been evaluated with very interesting results. Although some bronchial inoculation ways do not resemble the common pathophysiologic mechanisms, the experimental model of VAP induced by the inoculation of high concentrations of pathogens in mechanically ventilated animals is useful for studying the local and systemic responses of sepsis in VAP and it reproduces biological mechanisms such as acute lung injury, distress response, cardiac events and immune modulation comparable with clinical studies.


Efficacy of two commercially available, low-magnesium, urine-acidifying dry foods for the dissolution of struvite uroliths in cats.
To compare the efficacy and safety of using 2 commercially available, low-magnesium, urine-acidifying dry foods to dissolve sterile struvite uroliths in cats. Prospective, multicenter, randomized clinical trial . 37 cats with presumed struvite uroliths. Cats were randomly assigned to be fed 1 of 2 low-magnesium, urine-acidifying dry foods (food A or B). For each cat, physical examination, urinalysis, and abdominal radiography were performed weekly to assess treatment response. 32 cats had complete urolith dissolution. Mean ± SD times for a 50% reduction in urolith size (0.69 ± 0.1 weeks) and complete urolith dissolution (13.0 ± 2.6 days) were significantly shorter for cats fed food A, compared with those (1.75 ± 0.27 weeks and 27.0 ± 2.6 days, respectively) for cats fed food B. At study termination, mean ± SD urine pH (6.083 ± 0.105) for cats fed food A was lower than that (6.431 ± 0.109) for cats fed food B. In 5 cats, uroliths did not dissolve and were subsequently determined to be composed of 100% ammonium urate (n = 4) or 100% calcium oxalate (1). Adverse events associated with diet were not observed in any of the cats. Results indicated that dietary dissolution is safe and effective for eradication of sterile struvite uroliths in cats. Cats fed food A had faster urolith dissolution than did cats fed food B. Lack of a reduction in urolith size at 2 weeks after diet initiation was indicative of misdiagnosis or noncompliance.


Stable over-expression of PPARβ/δ and PPARγ to examine receptor signaling in human HaCaT keratinocytes.
Peroxisome proliferator-activated receptor-β/δ (PPARβ/δ) function and receptor cross-talk with other nuclear receptors, including PPARγ and retinoic acid receptors (RARs), was examined using stable human HaCaT keratinocyte cell lines over-expressing PPARβ/δ or PPARγ. Enhanced ligand-induced expression of two known PPAR target genes, adipocyte differentiation-related protein (ADRP) and angiopoietin-like protein 4 (ANGPTL4), was found in HaCaT keratinocytes over-expressing PPARβ/δ or PPARγ. Over-expression of PPARβ/δ did not modulate the effect of a PPARγ agonist on up-regulation of ADRP or ANGPTL4 mRNA in HaCaT keratinocytes. All-trans retinoic acid (atRA) increased expression of a known RAR target gene, yet despite a high ratio of fatty acid binding protein 5 (FABP5) to cellular retinoic acid binding protein II, did not increase expression of ANGPTL4 or 3-phosphoinositide-dependent-protein kinase 1 (PDPK1), even in HaCaT keratinocytes expressing markedly higher levels of PPARβ/δ. While PPARβ/δ-dependent attenuation of staurosporine- or UVB-induced poly (ADP-ribose) polymerase (PARP) cleavage was not observed, PPARβ/δ- and PPARγ-dependent repression of UVB-induced expression and secretion of inflammatory cytokines was found in HaCaT keratinocytes over-expressing PPARβ/δ or PPARγ. These studies suggest that FABP5 does not transport atRA or GW0742 to PPARβ/δ and promote anti-apoptotic activity by increasing expression of PDPK1, or that PPARβ/δ interferes with PPARγ transcriptional activity. However, these studies demonstrate that stable over-expression of PPARβ/δ or PPARγ significantly increases the efficacy of ligand activation and represses UVB-induced expression of tumor necrosis factor α (TNFα), interleukin 6 (IL6), or IL8 in HaCaT keratinocytes, thereby establishing an excellent model to study the functional role of these receptors in human keratinocytes.


The gp49B1 inhibitory receptor regulates the IFN-gamma responses of T cells and NK cells.
The magnitude and diversity of Ag-specific T cell effector activity have been proposed to be controlled by an integration of positive signals transduced by the TCR and negative signals originating from inhibitory cell surface molecules. Although the lectin family of NK cell-associated inhibitory receptors has been reported to regulate the function of murine CTLs, gp49B1, the Ig superfamily member is not known to be expressed on T cells. Moreover, the consequences of the lack of an endogenously expressed NK cell-associated inhibitory receptor on T cell functions are not known. We report that gp49B1 is expressed by nearly all activated CD8 and CD4 T cells in addition to NK cells during an immune response to viral, bacterial, or tumor challenge. Kinetics of gp49B1 expression parallel functional capability and subside in the memory phase. Following vaccinia viral infection, IFN-gamma production by both subsets of T cells and NK cells is enhanced in gp49B1-deficient mice compared with gp49B1(+/+) mice. The stimulation threshold for IFN-gamma production is also lower in gp49B1-deficient T cells. In contrast, no significant differences were observed in the cytotoxic responses. We conclude that gp49B1 is a unique inhibitory receptor that is induced in multiple lineages of innate and adaptive immune cells during an infection and controls their IFN-gamma, but not cytotoxic responses.


Rapamycin together with herceptin significantly increased anti-tumor efficacy compared to either alone in ErbB2 over expressing breast cancer cells.
The objective of this study was to assess the anti-tumor efficacy of rapamycin alone or in combination with herceptin in breast cancer. A total of 20 human breast cancer lines were examined for expression of various receptor tyrosine kinases and activation of their down stream signaling molecules, as well as for their invasion and colony forming ability. The ErbB2 and PI3 kinase pathway inhibitors were tested for the inhibition on breast cancer cell growth and tumor development. Seven of the 20 lines displayed an elevated level of ErbB2, others had varying level of EGF, IGF-1 or insulin receptor. Over 30% of the lines also had constitutive activation of Akt and MAP kinase. The lines displayed a wide range of colony forming and invasion ability. The PI3 kinase pathway inhibitors LY294002 and rapamycin inhibited the colony forming ability of all of the lines with the ErbB2 overexpressing lines having a higher sensitivity. A similar trend was observed for inhibition of invasion by LY294002. Rapamycin alone and additively together with herceptin inhibited the breast cancer cell growth especially in ErbB2 overexpressing cells. Rapamycin and herceptin synergistically inhibited tumor growth and endpoint tumor load in a xenograft model using a MCF-7 subline and in a MMTV-ErbB2 transgenic model. Rapamycin and herceptin significantly reduced the level of cyclin D1 and D3 and increased the cleavage of caspase 3 suggesting an increased apoptosis. Our results suggest that rapamycin together with herceptin has an enhanced anti-cancer effect and could be developed as an improved therapeutic regimen for breast cancer.


Quantitative and qualitative outcome measures after thalamic deep brain stimulation to treat disabling tremors.
We studied outcome measures after unilateral and bilateral thalamic stimulation to treat disabling tremor resulting from essential tremor and Parkinson's disease. The surgical technique, qualitative and quantitative tremor assessments, stimulation parameters, locations of active electrodes, complications, and side effects are described and analyzed. Forty-one patients with essential tremor or Parkinson's disease underwent implantation of 56 thalamic stimulators. Preoperative qualitative and quantitative tremor measurements were compared with those obtained after unilateral and bilateral surgery, with activated and deactivated stimulators. Stimulation parameters and stimulation-related side effects were recorded, and outcome measures were statistically analyzed. Qualitative measurements demonstrated significant improvement of contralateral upper-limb (P < 0.001), lower-limb (P < 0.01), and midline (P < 0.001) tremors after unilateral surgery. Ipsilateral arm tremor also improved (P < 0.01). No differences were observed with the Purdue pegboard task. Quantitative accelerometer measurements were correlated with qualitative assessments and confirmed improvements in contralateral resting (P < 0.001) and postural (P < 0.01) tremors and ipsilateral postural tremor (P < 0.05). Activities of daily living improved after unilateral surgery (P < 0.001) and additionally after bilateral surgery (P < 0.05). Adjustments of the pulse generator were required more frequently for tremor control than for amelioration of side effects. Bilateral thalamic stimulation caused more dysarthria and dysequilibrium than did unilateral stimulation. Stimulation-related side effects were reversible for all patients. Stimulation parameters did not change significantly with time. A significantly lower voltage and greater pulse width were used for patients with bilateral implants. Unilateral thalamic stimulation and bilateral thalamic stimulation are safe and effective procedures that produce qualitative and quantitative improvements in resting, postural, and kinetic tremor. Thalamic stimulation-related side effects are mild and reversible.


Comparison of bleomycin-induced pulmonary apoptosis between NMRI mice and C57BL/6 mice.
Apoptosis has a critical role in the pathogenesis of bleomycin induced-pulmonary fibrosis. The severity of fibrosis varies among different strains of mice. Recent studies have indicated that expression of apoptotic regulatory genes may be specific in different cell types in various strains. In this study, bleomycin-induced pulmonary apoptosis in NMRI (Naval Medical Research Institute, USA) albino mice were compared with C57BL/6 black mice. Pulmonary fibrosis induced by single intratracheal administration of bleomycin (3 U/kg). Control mice were instilled with the same volume of saline. After 2 weeks, fibrotic responses were studied by biochemical measurement of collagen deposition and histological examination of pathological lung changes. Apoptosis was detected and quantitated by terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) assay. Bleomycin significantly (P<0.05) increased lung collagen content and also induced fibrotic histological changes in both strains. Apoptosis was detected in the bronchiolar and alveolar epithelial cells after bleomycin instillation. TUNEL-positive alveolar epithelial cells in bleomycin-treated lungs of C57BL/6 and NMRI mice (19.5% + 2.7 and 17% + 2.0, respectively) were significantly (P<0.05) higher than that of saline-treated lungs (1.5% + 0.5) with no significant difference between two strains of mice (P>0.05). Despite some murine strain variation in the expression of apoptotic regulatory genes in bleomycin-induced pulmonary fibrosis, the results of the present study revealed no significant differences in alveolar epithelial apoptosis between NMRI and C57BL/6 black mice. However, these results confirm the role of apoptosis in the pathogenesis of pulmonary fibrosis and suitability of both strains as experimental models of lung fibrosis.


[Neurovegetative symptoms in infants with sleep-related respiratory disorders].
A relationship between neurovegetative symptoms and an increased risk of sudden infant death (SID) has been frequently described. Such symptoms are vomiting because of gastroesophageal reflux, breathing disorders while nutritive sucking, excessive sweating during sleep, prolonged apneas and apneas with associated symptoms, further unexplained episodes of cyanosis, pallor and loss of muscle tone. An acute decompensation of the cardiorespiratory autonomic system during sleep is currently discussed to be one of the causes of SID. Polysomnographic investigations are used to diagnose sleep related cardiorespiratory autonomic dysfunction. In this study, infants up to the age of 5 months were examined using polysomnography throughout their entire nocturnal sleep. The findings from 79 infants with neurovegetative symptoms were compared with the results from 163 healthy control children. Indications of an impaired respiratory regulation during sleep were shown to be significantly more frequent in infants with neurovegetative symptoms. In particular the occurrence of periodic breathing with a high frequency of periodic apnea plus a large number of acute decreases in oxygen saturation could be shown in infants with neurovegetative symptoms. The findings were most pronounced during the first 1.5 months after birth. The results of this investigations lead to the conclusion that, in the case of young infants with breathing abnormalities, neurovegetative symptoms can frequently be observed. The occurrence of such symptoms should therefore be a reason for a polysomnographic examination.


Nonoperative treatment of widely displaced patella fractures.
Eighteen patients with displaced patellar fractures were treated nonoperatively. All of the fractures were displaced by at least 1 cm. Ambulation and knee flexion were encouraged as soon as pain permitted. Twelve of the patients were limited in their activities by medical illnesses. Six of these patients died, and the remaining patients underwent follow-up for 2 years. No patient had severe pain, and only three had acquired significant limitations in their activities from their fractures. Nine patients had either minimal or moderate activity restrictions. There were no complications from treatment. Nonoperative treatment is a reasonable option for displaced fractures of the patella, particularly in patients whose activities are limited by chronic illness. Better results, however, are possible with operative treatment.


Super multi-view three-dimensional display technique for portable devices.
Portable display devices, such as intelligent telephones and panel PCs, have become parts of modern people's daily life. Their mainstream display interfaces are based on two-dimensional (2D) images. Although some three-dimensional (3D) technologies have been proposed for portable devices, comfortable visual effects are untouched until now. A super multi-view (SMV) system with comfortable 3D effects, constructed by a group of OLED microdisplay/projecting lens pairs, is proposed in this paper. Through gating different segments of each projecting lens sequentially and refreshing the virtual image of the corresponding microdisplay synchronously, the proposed SMV system greatly decreases the demand on the number of employed microdisplays and at the same time takes a thin optical structure, endowing great potential for portable devices.


Transplantation of dedifferentiated fat cells combined with a biodegradable type I collagen-recombinant peptide scaffold for critical-size bone defects in rats.
Tissue engineering is a promising approach to supplement existing treatment strategies for craniofacial bone regeneration. In this study, a type I collagen scaffold made from a recombinant peptide (RCP) with an Arg-Gly-Asp motif was developed, and its effect on regeneration in critical-size mandibular bone defects was evaluated. Additionally, the combined effect of the scaffold and lipid-free dedifferentiated fat (DFAT) cells was assessed. Briefly, DFAT cells were separated from mature adipocytes by using a ceiling culture technique based on buoyancy. A 3 cm × 4 cm critical-size bone defect was created in the rat mandible, and regeneration was evaluated by using RCP with DFAT cells. Then, cultured DFAT cells and adipose-derived stem cells (ASCs) were seeded onto RCP scaffolds (DFAT/RCP and ASC/RCP) and implanted into the bone defects. Micro-computed tomography imaging at 8 weeks after implantation showed significantly greater bone regeneration in the DFAT/RCP group than in the ASC/RCP and RCP-alone groups. Similarly, histological analysis showed significantly greater bone width in the DFAT/RCP group than in the ASC/RCP and RCP-alone groups. These findings suggest that DFAT/RCP is effective for bone formation in critical-size bone defects and that DFAT cells are a promising source for bone regeneration.