[Ultrastructure on imaginalDrosophila leg discs culturedin vitro].
Ultrastructural observations were made on imaginal leg discs ofDrosophila cultured in vitro in Mandaron's medium M in the presence of α- or β-ecdysone.During evagination of discs in vitro the tight epidermal folds of the disc flatten out progressively and the cells change their shape.As the discs evaginate, the pupal cuticle is secreted at the apex of the cells: it comprises a three-layered cuticulin, an epicuticle and a thick endocuticle. Secretion of pupal cuticle always starts by the appearance of dense deposits at the apex of microvilli. Only the latter apparently participate in the construction of the three successive layers of the pupal cuticle.During disc development an abundant rough endoplasmic reticulum is formed. Nuclei and nucleoli become progressively enlarged. At the same time, the nucleus, initially located near the base of the cell, moves closer to the apical cell surface. Microtubules become fragmented as soon as evagination begins and are reorientated parallel to the cell surface (i.e. parallel to the new long axis of the cell) at the end of evagination.


Charge transfer and tunable ambipolar effect induced by assembly of Cu(II) binuclear complexes on carbon nanotube field effect transistor devices.
Assembly of paramagnetic Cu(2) complexes with a Schiff base scaffold possessing extended electron delocalization together with a quasi-planar structure onto carbon nanotubes induces a diameter-selective charge transfer from the complex to the nanotubes leading to an interestingly large and tunable ambipolar effect. We used complementary techniques such as electron paramagnetic resonance, absorption spectroscopy, and photoluminescence to ensure the success of the assembly process and the integrity of the complex in the nanohybrid. We carried out density functional theory type calculations to rationalize the experimental results, evidencing the selective enhanced interaction of the metal complexes with one type of nanotube.


The role of butyrate in the reverse transformation reaction in mammalian cells.
The reverse transformation reaction of Chinese hamster ovary cells from compact, epithelial-like, randomly growing, heavily knobbed, lectin reactive cells into stretched, tighly adherent, smooth-surfaced, lectin resistant, fibroblast-like cells normally elicited by dibutyryl cAMP can be produced to its complete extent by N6-monobutyryl cAMP or 8-bromo-cAMP, O2'-monobutyryl cAMP is ineffective as is cAMP itself in the absence of an inhibitor of phosphodiesterase activity. In the presence of a phosphodiesterase inhibitor, cAMP is fully effective. These results indicate that the role of the butyryl groups of dibutyryl cAMP and, especially, the N6-butyryl, in the reverse transformation reaction is protection of the cAMP analogue from degradation. Butyrate at concentrations of about 1 mM does produce a response which to some extent mimics that of cAMP analogues. The cells, however, fail to assume a fibroblastic-like shape, but rather become flattened. The butyrate effect is much slower and less readily reversible than that evoked by cAMP analogues. Butyrate produces an approximately 2-fold increase in intracellular cAMP levels. These results are consistent with the hypothesis that butyrate effects, in part, are mediated by AMP.


Learning outcomes in medical informatics: comparison of a WebCT course with ordinary web site learning material.
The purpose of this study is to compare whether students' learning outcomes would be better in a designed learning environment (WebCT) than in a conventional web site (WWW) with similar course material but without special learning tools. Third-year medical students in an introductory course on medical informatics at the University of Helsinki, Finland. Students were randomly assigned to a WebCT group (n=39) and a WWW group (n=46). The students in the WebCT group utilized the course material in general discussion groups, special discussions about lectures, quizzes and students' own notes. The WWW group had access only to the course material. The learning outcome was assessed by administering an on-line examination and the learning experience of the students was assessed by an on-line quiz. The course grade was significantly higher in the WebCT group as compared to the WWW group. This finding was more prominent among females. The students of the WebCT group also experienced significantly more improvement in collaboration with the use of computers than the students in the WWW group. Based on our results, web-based learning seems to be more effective when students are provided with specially designed learning tools.


Antibody response following the third and fourth SARS-CoV-2 vaccine dose in individuals with common variable immunodeficiency.
The antibody response after vaccination is impaired in common variable immunodeficiency (CVID). We aimed to study the spike receptor-binding domain IgG antibody (anti-S-RBD) levels during a four-dose SARS-CoV-2 vaccination strategy and after monoclonal antibody (mAB) treatment in CVID. Moreover, we assessed the anti-S-RBD levels in immunoglobulin replacement therapy (IgRT) products. In an observational study, we examined anti-S-RBD levels after the second, third, and fourth dose of mRNA SARS-CoV-2 vaccines. Moreover, we measured anti-S-RBD after treatment with mAB. Finally, anti-S-RBD was assessed in common IgRT products. Antibody non-responders (anti-S-RBD < 7.1) were compared by McNemar's test and anti-S-RBD levels were compared with paired and non-paired Wilcoxon signed rank tests as well as Kruskal-Wallis tests. Among 33 individuals with CVID, anti-S-RBD levels increased after the third vaccine dose (165 BAU/ml [95% confidence interval: 85; 2280 BAU/ml], p = 0.006) and tended to increase after the fourth dose (193 BAU/ml, [-22; 569 BAU/ml], p = 0.080) compared to the previous dose. With increasing number of vaccinations, the proportion of patients who seroconverted (anti-S-RBD ≥ 7.1) increased non-significantly. mAB treatment resulted in a large increase in anti-S-RBD and a higher median level than gained after the fourth dose of vaccine (p = 0.009). IgRT products had varying concentrations of anti-S-RBD (p < 0.001), but none of the products seemed to affect the overall antibody levels (p = 0.460). Multiple SARS-CoV-2 vaccine doses in CVID seem to provide additional protection, as antibody levels increased after the third and fourth vaccine dose. However, anti-S-RBD levels from mAB outperform the levels mounted after vaccination. Boosting with SARS-CoV-2 vaccines seems to improve the antibody response in CVID patients. The third and possibly also the fourth dose of mRNA SARS-CoV-2 vaccine in CVID improve the antibody response as well as stimulate seroconversion in most non-responders.


The influence of hyperosmotic stress on the blood-retinal barrier effects on the electroretinogram.
Electroretinographic recordings were obtained from cat eyes before and after an intracarotid injection of a hypertonic NaCl-solution. It was found that after the injection the c-wave decreased in amplitude or disappeared, but reappeared within a period of four to six hours, suggesting that there is a reversible opening of the tight junctions following osmotic stress.


Phosphorothioate analogs of m7GTP are enzymatically stable inhibitors of cap-dependent translation.
We report synthesis and properties of a pair of new potent inhibitors of translation, namely two diastereomers of 7-methylguanosine 5'-(1-thiotriphosphate). These new analogs of mRNA 5'cap (referred to as m(7)GTPalphaS (D1) and (D2)) are recognized by translational factor eIF4E with high affinity and are not susceptible to hydrolysis by Decapping Scavenger pyrophosphatase (DcpS). The more potent of diastereomers, m(7)GTPalphaS (D1), inhibited cap-dependent translation in rabbit reticulocyte lysate approximately 8-fold and approximately 15-fold more efficiently than m(7)GTP and m(7)GpppG, respectively. Both analogs were also significantly more stable in RRL than unmodified ones.


Presence of pulsations and reproducibility of waveform recording in the umbilical and left portal vein in normal pregnancies.
Reproducibility and inter-observer variability of intra- and extra-abdominal umbilical venous flow velocity and left portal venous flow velocity as well as heart-synchronous waveform pulsations in these vessels were studied in 23 women at 34-38 weeks of normal pregnancy.Limited reproducibility, expressed by large intra-patient coefficients and limits of agreement between two observers, was established for all standardized recording sites. Pulsations, defined as negative venous deflections of at least 10% of the mean velocity, were demonstrated at all locations ranging from 19.6% of the measurements at the free-floating loop of the umbilical vein to 78.4% of the measurements at the left portal vein. The present study shows that the limited reproducibility of venous flow velocity waveforms should be taken into consideration, and that the presence of pulsations can be demonstrated in normal late pregnancy.


Biosynthesis of α-Pinene by Genetically Engineered Yarrowia lipolytica from Low-Cost Renewable Feedstocks.
α-Pinene, an important biologically active natural monoterpene, has been widely used in fragrances, medicines, and fine chemicals, especially, in high-density renewable fuels such as jet fuel. The development of an α-pinene production platform in a highly modifiable microbe from renewable substitute feedstocks could lead to a green, economical avenue, and sustainable biotechnological process for the biosynthesis of α-pinene. Here, we report engineering of an orthogonal biosynthetic pathway for efficient production of α-pinene in oleaginous yeast Yarrowia lipolytica that resulted in an α-pinene titer of 19.6 mg/L when using glucose as the sole carbon source, a significant 218-fold improvement than the initial titer. In addition, the potential of using waste cooking oil and lignocellulosic hydrolysate as carbon sources for α-pinene production from the engineered Y. lipolytica strains was analyzed. The results indicated that α-pinene titers of 33.8 and 36.1 mg/L were successfully obtained in waste cooking oil and lignocellulosic hydrolysate medium, thereby representing the highest titer reported to date in yeast. To our knowledge, this is also the first report related to microbial production of α-pinene from waste cooking oil and lignocellulosic hydrolysate.


Cancer leads to calling.
A nursing student shares her adolescent experience of Hodgkin's lymphoma and calling from God into nursing.


2-[6-(4-Chloro-phen-yl)imidazo[2,1-b][1,3]thia-zol-2-yl]-N'-[(E)-4-meth-oxy-benzyl-idene]acetohydrazide.
In the imidazo[2,1-b][1,3]thia-zole group of the title compound, C(21)H(17)ClN(4)O(2)S, the dihedral angle between the thia-zole and imidazole rings is 1.9 (2)°. The mean plane of this group makes dihedral angles of 5.5 (2) and 39.9 (2)° with the benzene rings of the chloro-phenyl and meth-oxy-phenyl groups, respectively. The dihedral angle between these two benzene rings is 34.4 (2)°. In the crystal, mol-ecules are connected to each other by inter-molecular N-H⋯O hydrogen bonds along the b axis, generating a C(4) chain. Weak C-H⋯π inter-actions also occur.


[Regulation of the number of gonocytes in the genital ridges of duck embryos after partial destruction of the initial stock of germ cells].
X rays irradiation of anterior or posterior halves of Duck blastoderms at the non incubated stage is followed by a decrease of the number of germ cells in the germinal crescent at the stage of 10 somites. However, after 6 days of incubation, the genital ridges of such embryos contain the same number of gonocytes as those of normal embryos. A regulation of the number of gonocytes occures at the level of the genital ridges.


The varied adult psychopathologies of children's behavior disorders.
Thirteen percent of the general population show the traits of emotional over-reactivity, emotional lability and impulsiveness that appear to be genetically transmitted. The troublesome manifestation of these traits can often be medically controlled, thereby reducing their costs to society.


ChiS is a noncanonical DNA-binding hybrid sensor kinase that directly regulates the chitin utilization program in Vibrio cholerae.
Two-component signal transduction systems (TCSs) represent a major mechanism that bacteria use to sense and respond to their environment. Prototypical TCSs are composed of a membrane-embedded histidine kinase, which senses an environmental stimulus and subsequently phosphorylates a cognate partner protein called a response regulator that regulates gene expression in a phosphorylation-dependent manner. Vibrio cholerae uses the hybrid histidine kinase ChiS to activate the expression of the chitin utilization program, which is critical for the survival of this facultative pathogen in its aquatic reservoir. A cognate response regulator for ChiS has not been identified and the mechanism of ChiS-dependent signal transduction remains unclear. Here, we show that ChiS is a noncanonical membrane-embedded one-component system that can both sense chitin and directly regulate gene expression via a cryptic DNA binding domain. Unlike prototypical TCSs, we find that ChiS DNA binding is diminished, rather than stimulated, by phosphorylation. Finally, we provide evidence that ChiS likely activates gene expression by directly recruiting RNA polymerase. This work addresses the mechanism of action for a major transcription factor in V. cholerae and highlights the versatility of signal transduction systems in bacterial species.


Clinical and Cone-Beam Computed Tomography Features of Orthokeratinized Odontogenic Cysts and Odontogenic Keratocysts in the Mandible.
The aim of the study was to compare the clinical and cone-beam computed tomography features of orthokeratinized odontogenic cysts (OOCs) and odontogenic keratocysts (OKCs) and to fully understand features of these 2 odontogenic cysts. This retrospective cross-sectional study included patients with mandibular OOCs and OKCs. The predictor variables included age at the time of diagnosis, sex, anatomical location of the cysts, lesion size, cortical bone expansion rate, and presence of cortical bone destruction, impacted tooth, tooth displacement, and root resorption. The outcome variable was the type of cystic lesion. A 1-way analysis of variance test was used to analyze the differences among the cases of OOCs and OKCs. The specificity and sensitivity of the radiological features were calculated to differentiate OOCs from OKCs. The sample was composed of 12 patients with OOCs and 36 patients with OKCs. The mean ages of the patients with OOCs (30.50 ± 6.14 years) and OKCs (38.39 ± 19.44 years) were concentrated in the third decade. The cystic lesions occurring in areas II and III accounted for 66.67 and 52.78% of the OOC and OKC cases, respectively. The cortical bone expansion rate of the OOC was larger than that of the unilocular OKC (OOC, 2.20 ± 1.05; OKC, 1.48 ± 0.50; P < .05). The specificity and sensitivity of unilocular or multiocular cysts to differentiate OOC from OKC were 100%, 42%, 95% confidence interval of 0.1479 to 0.3892 (P < .05) and tooth displacement were 100%, 3%, 95% confidence interval of 0.1479 to 0.3892 (P < .05). The results of this study suggest clinical and radiological features of OOCs and OKCs mostly overlap, but OOC has distinctive characteristics. Most cystic lesions of OOC are unilocular cysts, rarely accompanied by tooth displacement. The cortical bone expansion rate is larger than that of unilocular cysts of OKC.


Real-time TaqMan RT-PCR for detection of maize chlorotic mottle virus in maize seeds.
Maize chlorotic mottle virus (MCMV) causes corn lethal necrosis disease, and can be transmitted through infected maize seeds. It remains a challenge to detect this virus in the seeds to prevent its introduction and infection. For this purpose, a real-time TaqMan RT-PCR procedure for efficient detection of MCMV was developed. The sensitivity of the method was 4 fg of total RNA or 25 copies of RNA transcripts, which was approximately ten-fold higher than conventional RT-PCR gel electrophoresis method. The successful detection of MCMV in maize seeds suggested the feasibility of this procedure for routine testing.


Roommate's race and the racial composition of white college students' ego networks.
We develop and test a new hypothesis about how the race of a college freshman's roommate affects the racial composition of the student's ego network. Together, three principles of social structure-proximity, homophily, and transitivity-logically imply that college students assigned a roommate of a given race will have more friends (other than their roommate) of that race than will students assigned a roommate not of that race. A test with data collected from 195 white freshmen at Stanford University in the spring of 2002 supports this prediction. Our analysis advances earlier work by predicting and providing evidence of race-specific effects: While students assigned a different-race roommate of a given race have more friends (other than their roommate) of their roommate's race, they do not have more different-race friends not of their roommate's race.


Responses of cats to nasal vaccination with a live, modified feline herpesvirus type 1.
Intranasal vaccination with a cold-adapted strain of feline herpesvirus type 1 (FHV-1) two days before challenge gave partial protection, and four days before challenge gave complete protection, against feline viral rhinotracheitis. Protection at this time appeared to be specific since vaccination with FHV-1 did not affect the disease caused by the unrelated feline calicivirus. The time course of onset of protection also confirmed that the protective mechanism was likely to be specific. However, six days after vaccination only low levels of FHV-specific IgA and IgM antibody and of interferon were found in serum and nasal washings. In lymphocyte transformation assays neither peripheral blood lymphocytes nor tonsil lymphocytes gave a significant proliferative response in the presence of FHV antigen. Pathogenesis experiments demonstrated that the tonsil and nasal turbinates were the most important sites of virulent FHV-1 replication. Vaccination significantly reduced levels of infectious virus found in both sites. The results provide evidence that no one mechanism is responsible for protection following vaccination but local specific responses are more likely to be involved.


Bilateral pelvic ganglioneuroma: clinico-pathological findings: a case report.
Ganglioneuroma is a rare benign neurogenic tumor originating from the autonomic nervous system, and is considered the benign counterpart of neuroblastoma, lacking the immature neuroblastic cells. A case of pelvic ganglioneuroma with bilateral pelvic spread is described.


Noninvasive targeted imaging of matrix metalloproteinase activation in a murine model of postinfarction remodeling.
Time-dependent activation of matrix metalloproteinases (MMPs) after myocardial infarction (MI) contributes to adverse left ventricular (LV) remodeling; however, noninvasive methods to monitor this process serially are needed. MMP-targeted radiotracers were developed that displayed selective binding kinetics to the active MMP catalytic domain. Initial nonimaging studies were performed with a (111)In-labeled MMP-targeted radiotracer ((111)In-RP782) and negative control compound ((111)In-RP788) in control mice (Ctrl) and in mice 1 week after surgically induced MI. Localization of (111)In-RP782 was demonstrated within the MI by microautoradiography. A 334+/-44% increase (P<0.001 versus Ctrl) in relative retention of (111)In-RP782 was confirmed by gamma well counting of myocardium. Subsequent high-resolution dual-isotope planar and hybrid micro-single-photon emission computed tomography/CT imaging studies with an analogous 99mTc-labeled MMP-targeted radiotracer (99mTc-RP805) and 201Tl demonstrated favorable biodistribution and clearance kinetics of 99mTc-RP805 for in vivo cardiac imaging, with robust retention 1 to 3 weeks after MI in regions of decreased 201Tl perfusion. Gamma well counting yielded a similar approximately 300% increase in relative myocardial retention of 99mTc-RP805 in MI regions (Ctrl, 102+/-9%; 1 week, 351+/-77%; 2 weeks, 291+/-45%; 3 weeks, 292+/-41%; P<0.05 versus Ctrl). Myocardial uptake in the MI region was also significantly increased approximately 5-fold when expressed as percentage injected dose per gram tissue. There was also a significant 2-fold increase in myocardial activity in remote regions relative to control mice, suggesting activation of MMPs in regions remote from the MI. This novel noninvasive targeted MMP radiotracer imaging approach holds significant diagnostic potential for in vivo localization of MMP activation and tracking of MMP-mediated post-MI remodeling.


The Cerebro-Renal System- Anatomical and Physiological Considerations.
The brain and kidney both uniquely are highly susceptible to vascular injury from shared vascular risk factors. However these are not sufficient to explain the complete extent of cerebrovascular disease especially small vessel disease in its myriad presentations that patients with chronic kidney disease manifest. They both require a large amount of blood supply to function optimally. Shared anatomical and physiological factors such as the presence of strain vessels, the local vascular autoregulation that control blood supply possible, results in the vulnerability of these organs to the vascular risk factors. Because it is a bidirectional system where each affects the other, it is best considered as a cerebro-renal unit.


Status Of Dysphagia After Ischemic Stroke: A Korean Nationwide Study.
To identify the incidence of dysphagia after ischemic stroke and determine factors affecting the presence of dysphagia. Retrospective case-control study. This was an interim analysis of a prospective multicenter Korean stroke cohort. Acute care university hospitals. Patients (N=6000) with first-ever acute ischemic stroke. Patients were divided into 2 groups according to the presence or absence of dysphagia confirmed at 7 days after onset using the American Speech-Language-Hearing Association National Outcomes Measurement System (ASHA-NOMS) scale, which was determined after conducting screening or standardized tests. Not applicable. Age at stroke onset, body mass index (BMI), premorbid modified Rankin Scale (mRS), brainstem lesions, National Institutes of Health Stroke Scale (NIHSS), poststroke mRS, and ASHA-NOMS swallowing level at poststroke day 7 were evaluated. Among patients with ischemic stroke, 32.3% (n=1940) had dysphagia at 7 days after stroke onset. At discharge, 80.5% (n=1561) still had dysphagia. The prediction model for the presence of dysphagia identified age at onset, underweight (BMI <18.5 kg/m2), premorbid mRS, brainstem lesions, and NIHSS as independent predictors. The odds ratio (OR) for the presence of dysphagia significantly increased with underweight (OR, 1.6684; 95% confidence interval [CI], 1.27-2.20), increased age at onset (OR, 1.0318; 95% CI, 1.03-1.04), premorbid mRS (OR, 1.1832; 95% CI, 1.13-1.24), brainstem lesions (OR, 1.6494; 95% CI, 1.39-1.96), and NIHSS (OR, 1.2073; 95% CI, 1.19-1.23). The incidence of dysphagia after ischemic stroke was 32.3%. The prediction model for the presence of dysphagia identified age, low BMI, premorbid disabilities, brainstem lesions, and NIHSS as predictive factors.


The value of ultrasound in predicting non-visualization of the gall-bladder on OCG: implications for imaging strategies in patient selection for non-surgical therapy of gallstones.
Gall-bladder visualization on oral cholecystography (OCG) is required for most non-surgical therapies of gallstones. In this study we attempted to establish sonographic criteria which will predict non-visualization of the gall-bladder on OCG. For this purpose we compared the results of ultrasound (US) and OCG in 171 patients with gallstones being assessed for non-surgical therapy. Sonographic criteria for non-visualization were a contracted gall-bladder and stone impaction in the gall-bladder neck or cystic duct. In detecting findings which predict non-visualization on OCG, US had a sensitivity of 78.3% and a specificity of 97.6%. The predictive values were: positive findings 92.3% and negative findings 92.4%. The overall accuracy was 92.4%. We conclude that US can be used as a first step in selecting patients for non-surgical therapy and if US indicates a contracted gall-bladder, 11% of the patients can be excluded from further diagnostic imaging.


Vulvar leiomyoma in an adolescent girl: a case report and review of the literature.
Vulvar leiomyoma is a rare soft tissue tumor, with only around 300 cases described in the literature. Owing to its low incidence of just 0.03% of all gynecological tumors, it often poses a great diagnostic challenge, especially in teenagers. We report this rare occurrence of vulvar leiomyoma in a teenage girl who was primarily left untreated due to cultural taboos and fear of loss of virginity. The main aim in presenting such rare case studies is to raise awareness and expand the diagnostic horizon of the surgeon for appropriate management. We describe a case of a 15-year-old North Indian, sexually inactive unmarried girl, who presented with a history of painless swelling in the left labia majora for the last 1 year, which gradually increased in size. There was no associated pain or any other difficulty. Local examination revealed a 14 × 10 cm solid, unilateral nonpedunculated mass on the left labia majora with superficial vascularity. Differential diagnoses of sarcoma, lipoma, Bartholin cyst, and fibroid were kept in mind. Ultrasonography revealed a solid mass with superficial vascularity with normal internal genitalia. The mass was enucleated with an intact capsule under anesthesia. Histopathology confirmed it to be benign vulvar leiomyoma. The patient was discharged after 3 days in a satisfactory condition. Leiomyoma of the vulva is an exceptionally rare tumor and is seldom seen in teenagers. It is often misinterpreted as a Bartholin cyst and should be kept as one of the differential diagnosis in teenage girls presenting with unilateral vulvar swelling. Vulvar leiomyoma can be completely cured by surgical removal if diagnosed timely without compromising virginity, so should never be missed in adolescents.


Responsiveness of patient reported outcomes including fatigue, sleep quality, activity limitation, and quality of life following treatment with abatacept for rheumatoid arthritis.
To evaluate the responsiveness of patient reported outcomes (PROs), including fatigue, sleep, activity limitation, and quality of life, in patients with rheumatoid arthritis (RA). Data were considered from a randomised controlled trial comparing abatacept (n = 258) with placebo (n = 133) on a background of DMARD treatment in RA patients who were inadequate responders to anti-TNF therapy (ATTAIN study). PROs assessed included SF-36, activity limitation, fatigue, and sleep. For each outcome the treatment difference, relative per cent improvement, standardised response mean (SRM), and relative efficiency for assessing an outcome's ability to detect a treatment effect relative to tender joint count (TJC) were calculated. A relative efficiency >1 suggests a measure that is more efficient than TJC in detecting treatment effect. Moderate to large SRMs (>or=0.6) were observed for the PRO measures. In particular, SRMs (95% confidence interval) were: physician global, 0.72 (0.51 to 0.94); HAQ, 0.63 (0.42 to 0.85); SF-36 physical component score, 0.62 (0.40 to 0.83); SF-36 bodily pain, 0.68 (0.46 to 0.90); and fatigue, 0.59 (0.38 to 0.81). Relative efficiencies for physician global (1.6), SF-36 bodily pain domain (1.4), pain intensity (1.4), HAQ (1.2), SF-36 physical component score (1.2), fatigue (1.1), and patient global assessment (1.04) were all more responsive than TJC. The SF-36 mental component score (0.3), swollen joint count (0.6), activity limitation (0.8), sleep (0.7), and C reactive protein (0.9) were less responsive. Using PROs for evaluating treatments for RA can detect improvements and will identify changes that are important to patients. In general, physical assessments are more responsive to an effective treatment than mental assessments.


Adjuvant radiation therapy for adenocarcinoma of the rectum.
This article reviews the indications and techniques for adjuvant radiation therapy for rectal cancer. Adjuvant radiation therapy can significantly reduce the risk of local recurrence for rectal cancer.


Comparative genomics of Rothia species reveals diversity in novel biosynthetic gene clusters and ecological adaptation to different eukaryotic hosts and host niches.
Rothia species are understudied members of the phylum Actinobacteria and prevalent colonizers of the human and animal upper respiratory tract and oral cavity. The oral cavity, including the palatine tonsils, is colonized by a complex microbial community, which compete for resources, actively suppress competitors and influence host physiology. We analysed genomic data from 43 new porcine Rothia isolates, together with 112 publicly available draft genome sequences of Rothia isolates from humans, animals and the environment. In all Rothia genomes, we identified biosynthetic gene clusters predicted to produce antibiotic non-ribosomal peptides, iron scavenging siderophores and other secondary metabolites that modulate microbe-microbe and potentially microbe-host interactions. In vitro overlay inhibition assays corroborated the hypothesis that specific strains produce natural antibiotics. Rothia genomes encode a large number of carbohydrate-active enzymes (CAZy), with varying CAZy activities among the species found in different hosts, host niches and environments. These findings reveal competition mechanisms and metabolic specializations linked to ecological adaptation of Rothia species in different hosts.


Determination of testosterone in serum by liquid chromatography-tandem mass spectrometry.
Commercial direct immunoassays for serum testosterone sometimes result in inaccuracies in samples from women and children, leading to misdiagnosis and inappropriate treatment. The diagnosis of male hypogonadism also requires an accurate testosterone assay method. We therefore developed a sensitive and specific stable-isotope dilution liquid chromatography-tandem mass spectrometric (LC-MS/MS) method for serum testosterone at the concentrations encountered in women and children. Testosterone was extracted with ether-ethyl acetate from 250 microL or 500 microL of serum. Instrumental analysis was performed on an API 2000 tandem mass spectrometer in the multiple-reaction monitoring (MRM) mode after separation on a reversed-phase column. The MRM transitions (m/z) were 289/97 for testosterone and 291/99 for d(2) testosterone. The calibration curves exhibited consistent linearity and repeatability in the range 0.2-100 nmol/L. Interassay CVs were 4.2-7.6 % at mean concentrations of testosterone of 3.3-45 nmol/L. Total measurement uncertainty (U, k = 2) was 12.9 % and 13.4 % at testosterone levels of 2.0 nmol/L and 20 nmol/L, respectively. The limit of detection was 0.05 nmol/L (signal-to-noise ratio = 3) and the overall method recovery of testosterone was 95 %. Correlation (r) with our in-house extraction RIA was 0.98 and with a commercial RIA 0.92. Reference intervals for adult males and females in age groups 18-30, 31-50, 51-70 and over 70 years were established. Sensitivity and specificity of the LC-MS/MS method offer advantages over immunoassay and make it suitable for use as a high-throughput assay in routine clinical laboratories. The high equipment costs are balanced by higher throughput together with shorter chromatographic run times.


In vitro control of blastema cell proliferation by extracts from epidermal cap and mesenchyme of regenerating limbs of axolotls.
The presence of a mitogenic activity in limb blastemas of axolotls was detected in crude extracts of blastemas at the mid-bud stage. The mitogenicity of the extracts was estimated from the mitotic index of blastema cells grown for 6 days in the presence of limb blastema extracts, with colchicine present for the last 2 days. All the extracts tested (whole blastema, blastemal mesenchyme, epidermal cap) significantly enhanced proliferation of blastema cells. The highest stimulation factors we observed were 7 × with 7 μg protein/ml whole blastema extracts, 5.2 × with 14 μg/ml blastemal mesenchyme extracts, and 11 x with 3.5 μg/ml epidermal cap extracts. Hence the epidermal cap extracts appeared to be the most mitogenic. Extracts from the blastemal mesenchyme, although less mitogenic than the epidermal cap extracts, were more potent than nerve extracts [Albert P, Boilly B (1986) Biol Cell 58:251-262]. These results are discussed with regard to the production of growth factors during limb regeneration.


Leiomyomas of the rectum and anal canal: report of six cases and review of the literature.
Since 1872, 168 rectal leiomyomas have been reported in the world literature. Their incidence, therefore, is very low. It is estimated that one leiomyoma may be seen for every 2,000 or more rectal tumors. Those leiomyomas located in the anal canal and sphincter are the rarest. A case is reported here that appears to be the eleventh in such a location. The incidence of these lesions is highest between the ages of 40 and 59 years. Most patients have a combination of symptoms rather than a single one, the most frequent of these being the presence of a mass, bleeding, and constipation. Almost always, the chain of events that leads to the diagnosis starts when the tumor is discovered by digital examination of the rectum. The lack of reliable criteria of malignancy and the marked tendency to recur shown by these tumors are the two main problems the surgeon faces when selecting the operative procedure to be used. We believe that those tumors with an original size of 5 cm or more in largest diameter are the ones that have shown the highest tendency to recur, mostly as sarcomas. Therefore it is thought that these lesions should be treated radically from the beginning, especially when they recur. More adequate follow-up studies are needed.


Topical use of alcohol in ophthalmology - Diagnostic and therapeutic indications.
Alcohol (ethanol) has been used in medicine since time immemorial. In ophthalmic practice, besides as an antiseptic, it was given as retrobulbar injections to relieve severe ocular pain. Alcohol can be applied topically to the surface of neoplastic or suspicious lesions to kill cells that might desquamate and seed during surgical excision, to treat epithelial ingrowth that can occur following corneal surgeries, particularly laser in situ keratomileusis (LASIK), and to treat superficial infectious keratitis. In view of its ability to achieve a smooth cleavage plane between the epithelium and the Bowman's layer, alcohol-assisted delamination (ALD) of the corneal epithelium has been used widely and effectively for a variety of diagnostic and therapeutic indications, at times delivering both outcomes. Diagnostically, ALD yields an intact epithelial sheet which can be fixed flat to provide excellent orientation for histopathological evaluation. Therapeutically, it is most commonly used to treat recurrent corneal erosion syndrome, where its efficacy is comparable to that of phototherapeutic keratectomy but with several advantages. It has also been used to treat various forms of epithelial/anterior stromal dystrophies, which can obviate or delay the need for corneal transplantation for several years. In addition, ALD is performed in corneal collagen cross-linking and corneal refractive surgery for relatively atraumatic removal of the epithelium. In this review, we aimed to provide a comprehensive overview of the diagnostic and therapeutic use of topical alcohol in ophthalmology, to describe the surgical and fixation techniques of ALD, and to highlight our experience in ALD over the past decade.


Direct activation of platelets by heat is the possible trigger of the coagulopathy of heat stroke.
The trigger of the coagulopathy that complicates heat stroke is obscure, but direct platelet activation by heat is a possibility we set out to study. Platelet rich plasma (PRP), prepared from blood donors, was incubated at increasing temperatures (38-45 degrees C) and then platelet aggregation was undertaken in response to decreasing low doses of ADP (less than 2.0 mumol/l). Hyperaggregability was manifested when the incubation temperature reached 43 degrees C and was maximum at 44 degrees C before complete inhibition of responses at 45 degrees C. The platelet hyperactivity induced by heating at 44 degrees C persisted after reincubating PRP samples at 37 degrees C. These platelet responses could not be triggered in PRP samples prepared from subjects after the overnight ingestion of aspirin or after the addition of aspirin to PRP before starting the heating procedure. However, aspirin was less effective when added to PRP after the appearance of the heat-induced hyperaggregability. In conclusion, these results indicate that platelets can be activated directly by heat. This mechanism which may be operational in heat stroke, is unaffected by cooling (body cooling being basic in the management of heat stroke) but can be prevented by the early administration of aspirin.


Strengths and limitations of current pediatric blood pressure nomograms: a global overview with a special emphasis on regional differences in neonates and infants.
The availability of robust nomograms is essential for the correct evaluation of blood pressure (BP) values in children. A literature search was conducted by accessing the National Library of Medicine by using the keywords BP, pediatric and reference values/nomograms. A total of 43 studies that evaluated pediatric BP nomograms were included in this review. Despite the accuracy of the latest studies, many numerical and methodological limitations still remain. The numerical limitations include the paucity of data for neonates/infants and for some geographic areas (Africa/South America/East Europe/Asia) and ethnicities. Furthermore, the data on ambulatory BP and response to exercise are extremely limited, and the criteria for stress-test interruption are lacking. There was heterogeneity in the methodologies employed to perform the measurements, in the inclusion/exclusion criteria (often not reported), in the data normalization and the data expression (Z-scores/percentiles/mean values). Although most studies adjusted the measurements for age and/or height, the classification by specific age/height subgroups varied. Gender differences were generally considered, whereas other confounders (that is, ethnicity/geographic area/environment) were seldom evaluated. As a result, nomograms were heterogeneous, and when comparable, at times showed widely different confidence intervals. These differences are most likely because of both methodological limitations and differences among the populations studied. Some robust nomograms exist (particularly those from the USA); however, it has been demonstrated that if adopted in other countries/continents, they may generate an unpredictable bias in the evaluation of BP values in children. Actual pediatric BP nomograms present consistent limitations that affect the evaluation of BP in children. Comprehensive nomograms, which are based on a large population of healthy children (including neonates/infants) and use standardized methodology, are warranted for every country/region.


Using Small Angle X-Ray Scattering (SAXS) to Characterize the Solution Conformation and Flexibility of Matrix Metalloproteinases (MMPs).
Small angle X-ray scattering (SAXS) provides information about the conformation and flexibility of proteins in solution, and hence provides complementary structural information to that obtained from X-ray crystallography and nuclear magnetic resonance spectroscopy. In this chapter, we describe the methods for the preparation of matrix metalloproteinase (MMP) samples for SAXS analyses, and for the acquisition, processing and interpretation of the SAXS data.


Nanostructured micro particles as a low-cost and sustainable catalyst in the recycling of PET fiber waste by the glycolysis method.
Magnetic Mg-Al-O@Fe3O4 micro particles were synthesized by coating nanosized Mg-Al double oxides onto Fe3O4 micro particles. The formed hierarchical structure gave Mg-Al-O@Fe3O4 micro particles a high active surface area, which enabled these micro particles to work efficiently as a catalyst in the glycolysis of poly(ethylene terephthalate) (PET). The bis(hydroxyethyl) terephthalate (BHET) yield reached above 80 mol% in the presence of 0.5 wt% of Mg-Al-O@Fe3O4 micro catalyst in the reaction system within 90 min at 240 °C. After the reaction, Mg-Al-O@Fe3O4 micro catalyst was easily retrieved by a magnetic decantation and can be repetitively used for two times with a high catalytic efficiency. After that, the deactivated Mg-Al-O@Fe3O4 micro catalyst can be regenerated by heat treatment. The regenerated Mg-Al-O@Fe3O4 micro catalyst displays a comparable catalytic performance as that of the virgin catalyst. In addition, the Mg-Al double oxides and Fe3O4 micro particles are low-cost and environmentally benign. Therefore, the Mg-Al-O@Fe3O4 micro catalyst may contribute to an economically and environmentally improved large-scale circular recycling of PET fiber waste.


Arginase-1 Released into CSF After Aneurysmal Subarachnoid Hemorrhage Decreases Arginine/Ornithine Ratio: a Novel Prognostic Biomarker.
We hypothesized that the enzyme arginase-1 is released into the cerebrospinal fluid (CSF) during red blood cell lysis and contributes to dysregulated metabolism of the nitric oxide (NO) precursor L-arginine during aneurysmal subarachnoid hemorrhage (SAH). This prospective case-control study included 43 patients with aneurysmal SAH and ventricular drainage for clinical reasons. Longitudinal CSF samples (99) were obtained in the course of SAH. Patients were dichotomized regarding the occurrence of cerebral vasospasm syndrome (CVS) (N = 19). Arginase-1 and the amino acids L-arginine and L-ornithine were quantified in CSF. Outcome assessments included delayed cerebral ischemia (DCI) and functional status after 3 months using the modified Rankin Scale (mRS). Arginase-1 was released into the CSF of SAH patients whereas this enzyme was undetectable in controls. Compared to patients without CVS, arginase-1 levels were higher in CVS patients until day 14 after clinical event. The well-known surrogate parameter for arginase acitivity, the L-arginine to L-ornithine ratio (Arg/Orn), correlated with CSF arginase-1 levels. Arg/Orn was reduced in patients with CVS from disease onset (days 1-3, p = 0.0009) until day 14. Logistic regression analysis of early Arg/Orn was predictive for CVS (p = 0.008) and DCI (p = 0.035), independent of age, Hunt and Hess grade, and intraventricular blood. Arg/Orn < 2.71 at disease onset predicted CVS with a sensitivity of 86.7% and specificity of 72.2%. Arg/Orn ≥ 2.71 predicted excellent functional outcome. We propose a novel mechanism contributing to NO deprivation during SAH: arginase-1 is released from erythrocytes into the CSF, leading to L-arginine consumption and reduced NO bioavailability. Furthermore, Arg/Orn is a robust predictor for occurrence of CVS, DCI, and functional outcome 3 months after aneurysmal SAH. Our data provide a novel prognostic biomarker and may contribute to the development of novel therapeutic strategies in SAH. Clinical Trial Registration-URL: http://www.drks.de . Unique identifier: DRKS00015293, date of registration: 13.09.2018.


Discovery of pyrrolo[2,3-d]pyrimidin-4-ones as corticotropin-releasing factor 1 receptor antagonists with a carbonyl-based hydrogen bonding acceptor.
A new class of pyrrolo[2,3-d]pyrimidin-4-one corticotropin-releasing factor 1 (CRF(1)) receptor antagonists has been designed and synthesized. In general, reported CRF(1) receptor antagonists possess a sp(2)-nitrogen atom as hydrogen bonding acceptor (HBA) on their core scaffolds. We proposed to use a carbonyl group of pyrrolo[2,3-d]pyrimidin-4-one derivatives as a replacement for the sp(2)-nitrogen atom as HBA in classical CRF(1) receptor antagonists. As a result, several pyrrolo[2,3-d]pyrimidin-4-one derivatives showed CRF(1) receptor binding affinity with IC(50) values in the submicromolar range. Ex vivo (125)I-sauvagine binding studies showed that 2-(dipropylamino)-3,7-dimethyl-5-(2,4,6-trimethylphenyl)-3,7-dihydro-4H-pyrrolo[2,3-d]pyrimidin-4-one (16b) (30 mg/kg, p.o.) was able to penetrate into the brain and inhibit radioligand binding to CRF(1) receptors (frontal cortex, olfactory bulb, and pituitary) in mice. We identified pyrrolo[2,3-d]pyrimidin-4-one derivatives as the first CRF(1) antagonists with a carbonyl-based HBA.


Reduction of extracellular potassium ferricyanide by transmembrane NADH: (acceptor) oxidoreductase of human erythrocytes.
Reduction of extracellular ferricyanide by intact erythrocytes proceeds by a membrane bound, NADH-dependent reaction. It is depressed by a glycolysis inhibitor and a non penetrable sulfhydryl reagent, and activated by dehydroascorbate. Dehydroascorbate activation cannot be accounted for by release of reducing equivalents from the cells. It is concluded that the observed reaction is brought about by transmembrane NADH-acceptor oxidoreductase with donor binding at the inner and acceptor binding at the outer cell surface.


Effects of aromatase inhibitors on proliferation and apoptosis in eutopic endometrial cell cultures from patients with endometriosis.
To study the effect of letrozole (Let) and anastrozole (Anas) on apoptosis and cell proliferation in epithelial endometrial cells (EEC) from patients with endometriosis (EDT). Prospective study. Research institute and clinical fertility center. Eighteen women with untreated EDT. Biopsy specimens of eutopic endometrium were obtained from all subjects. Apoptosis and cell proliferation were examined in EEC after incubation with Let or Anas. Percentage of apoptotic cells (ApC) was evaluated by the acridine orange-ethidium bromide technique; cell proliferation was assessed by 3H-thymidine incorporation. Treatment with Let 10 nM and Let 100 nM enhanced values of ApC in cultures from EDT patients. Epithelial endometrial cells treated with Anas 100 nM or Anas 500 nM showed a statistically significant induction on apoptosis levels. Cultures treated with Let 1 nM or Anas 50 nM did not show any significant differences in ApC levels compared with basal conditions. 3H-Thymidine uptake was down regulated by Let 10 nM and Let 100 nM. Similarly, Anas 100 nM and Anas 500 nM showed a significantly lower degree of cell proliferation in EEC. Lower concentrations of Let and Anas did not induce any significant change in cell proliferation rates. Our results show that Let and Anas produced a significant and positive effect on apoptosis and cell proliferation on EEC from EDT patients. These findings support the further investigation of aromatase inhibitors as a treatment option in EDT.


Staged reconstruction of unilateral neglected hip dislocation through total hip arthroplasty and subsequent intramedullary femoral lengthening.
Total hip arthroplasty (THA) is a successful approach to treat unilateral symptomatic neglected hip dislocation (NHD). However, the extensive leg length discrepancy (LLD) can hereby only be partially corrected. In case of residual LLD of more than 2 cm, subsequent femoral lengthening can be considered. Retrospective analysis of clinical data and radiographs of five patients (age 38.1 (28-51) years) with unilateral NHD who underwent THA with (n = 3) or without (n = 2) subtrochanteric shortening osteotomy (SSO) and secondary intramedullary femoral lengthening through a retrograde magnetically-driven lengthening nail (follow-up 18.4 (15-27) months). LLD was 51.0 (45-60) mm before and 37.0 (30-45) mm after THA. Delayed bone union at one SSO site healed after revision with autologous bone grafting and plate fixation. Subsequent lengthening led to leg length equalisation in all patients. Complete consolidation was documented in all lengthened segments. Staged reconstruction via THA and secondary femoral lengthening can successfully be used to reconstruct the hip joint and equalise LLD. The specific anatomical conditions have to be taken into consideration when planning treatment, and patients ought to be closely monitored.


Long sleep duration is associated with higher mortality in older people independent of frailty: a 5-year cohort study.
Although general adult population studies show a U-shaped association between sleep duration and mortality, prolonged rather than short sleep duration was more consistently associated with higher mortality in older populations. Failing health or frailty is a possible mechanism. Thus, we examined the relationship among sleep duration, frailty status, and mortality in an elderly cohort. A total of 3427 community-living adults 65 years or older were examined for general health, mood, subjective sleep measures (insomnia, napping, sleep apnea, nighttime sleep duration, sleep medications), frailty, and 5-year mortality. After 5 years, 12.9% of men and 4.5% of women had died. Mean nighttime sleep duration was 7.3 hours. Proportion of participants who slept 10 or more hours increased with increasing frailty. Age-adjusted hazard ratio (HR) for 5-year mortality of long nighttime sleep (≥ 10 hours) was 2.10 (95% confidence interval [CI] 1.33-3.33) in men, and 2.70 (95% CI 0.98-7.46) in women. The HR in men was attenuated (HR 1.75; 95% CI 1.09-2.81) after adjustment for frailty and other covariates, whereas that of women strengthened (HR 2.88; 95% CI 1.01-8.18). Mortality increased sharply with nighttime sleep of 10 hours or more. Nighttime sleep of 10 or more hours (HR 1.75, men; HR 2.88, women) and frailty (HR 2.43, men; HR 2.08, P = .08 in women) were independently associated with 5-year mortality after full adjustment for covariates. Frailty and long nighttime sleep duration of 10 or more hours were independently associated with 5-year mortality in older adults.


Implementation and effect of life space crisis intervention in special schools with residential treatment for students with emotional and behavioral disorders (EBD).
The increase of violence in present-day society calls for adequate crisis interventions for students with behavioral problems. Life Space Crisis Intervention (LSCI) is a systematic and formatted response to a student's crisis, based on cognitive, behavioral, psychodynamic and developmental theory. The following research article evaluates a LSCI Program with students referred to special schools with residential treatment because of severe behavioral problems. The evaluation was conducted using a quasi experimental pre-test-post-test control group design. Thirty-one match paired students were pre-tested before the interventions started and post-tested after a period of 11 months. Five standardized questionnaires were examined to assess the effectiveness of the LSCI Program. General Linear Model (GLM) with repeated measures was used to analyze all data. For the total group of subjects (n = 62) it was found that students' perception about their athletic competence decrease significantly after 11 months in residential care. A positive effect of LSCI was found on direct aggression and social desirability.


Atypical presentation of abdominal group A streptococcal-necrotizing fasciitis after pessary removal.
Group A streptococcal (GAS) necrotizing fasciitis is a potentially life-threatening infection. We report on a patient with a history of prolonged pessary use with traumatic removal who developed ascending GAS infection in her gynecologic organs that tracked along the round ligament to her anterior abdominal wall.


Community medicine: an urban model.
The authors examine for relevance and current application what was learned in the building and progress of community medicine at the Mount Sinai School of Medicine, from 1968 to 1993. They look back on their twenty-five years' approach to service development, research and education in this field, as they worked in an urban-based academic medical center in New York and cooperated with universities and their schools of health sciences abroad. A claim is made that this approach, whether in the United States or abroad, while fostering community development produces a diversity of desirable population-oriented new role models for the medical profession.


Modeling a multivariable reactor and on-line model predictive control.
A nonlinear first principle model is developed for a laboratory-scaled multivariable chemical reactor rig in this paper and the on-line model predictive control (MPC) is implemented to the rig. The reactor has three variables-temperature, pH, and dissolved oxygen with nonlinear dynamics-and is therefore used as a pilot system for the biochemical industry. A nonlinear discrete-time model is derived for each of the three output variables and their model parameters are estimated from the real data using an adaptive optimization method. The developed model is used in a nonlinear MPC scheme. An accurate multistep-ahead prediction is obtained for MPC, where the extended Kalman filter is used to estimate system unknown states. The on-line control is implemented and a satisfactory tracking performance is achieved. The MPC is compared with three decentralized PID controllers and the advantage of the nonlinear MPC over the PID is clearly shown.


Are pioneer mangroves more vulnerable to oil pollution than later successional species?
Propagules of Avicennia marina, Bruguiera gymnorrhiza and Rhizophora mucronata were cultivated in rhizotrons (root observation chambers) and subjected to sediment oiling treatments for 409days to determine the effects of oil on root growth. Oiling reduced root length, specific root length, relative root growth rate and root diameter, while specific root volume increased. Oiling reduced root length by 96% in A. marina, 99% in B. gymnorrhiza and 80% in R. mucronata, while specific root volume increased by 34%, 29% and 23% respectively. Relative root growth rate decreased in the oiled treatments by 84%, 80% and 73% respectively. Avicennia exhibits typical root traits of a pioneer species compared to slower-growing later successional species like B. gymnorrhiza and R. mucronata. These traits of A. marina not only allow more rapid establishment of seedlings, but also expose a larger root surface area and therefore greater susceptibility to oil contamination than the other species.


Four reasons to confront crowding in the emergency department.
Emergency department crowding should be a board priority. Here are four reasons why.


Isolation of bioluminescent functions from Photobacterium leiognathi: analysis of luxA, luxB, luxG and neighboring genes.
Genes encoding luminescence of Photobacterium leiognathi have been cloned in Escherichia coli. The luminescent clones were readily apparent. Among them, a clone containing a recombinant plasmid with a 13.5-kb insertion was identified. This DNA fragment contained all of the luminescence-encoding genes. The luciferase-encoding genes (lux) in this DNA fragment were localized. We have sequenced a part of the cloned lux region and identified the luxA, luxB and luxG genes encoding the alpha and beta subunits of luciferase and a gamma protein with an Mr of 26,180, respectively. The analysis of deduced amino acid sequences and comparison with known luciferase sequences from Vibrio harveyi, indicate the common origin of these proteins.


Anodal Transcranial Direct Current Stimulation over the Cerebellum Enhances Sadness Recognition in Parkinson's Disease Patients: a Pilot Study.
Emotional processing impairments, resulting in a difficulty to decode emotions from faces especially for negative emotions, are characteristic non-motor features of Parkinson's disease (PD). There is limited evidence about the specific contribution of the cerebellum to the recognition of emotional contents in facial expressions even though patients with cerebellar dysfunction often lose this ability. In this study, we aimed to evaluate whether the recognition of facial expressions can be modulated by cerebellar transcranial direct current stimulation (tDCS) in PD patients. Nine PD patients were enrolled and received anodal and sham tDCS (2 mA, 20 min), for 5 consecutive days, in two separate cycles at intervals of at least 1 month. The facial emotion recognition task was administered at baseline (T0) and after cerebellar tDCS on day 5 (T1). Our preliminary study showed that anodal cerebellar tDCS significantly enhanced emotional recognition in response to sad facial expressions by about 16%, but left recognition of anger, happiness, and neutral facial expressions unchanged. Despite the small sample size, our preliminary results show that anodal tDCS applied for five consecutive days over the cerebellum modulates the way PD patients recognize specific facial expressions, thus suggesting that the cerebellum plays a crucial role in recognition of negative emotions and corroborating previous knowledge on the link between social cognition and the cerebellum.


Comparative efficacy of intraoperative extracorporeal irradiated and alcohol-inactivated autograft reimplantation for the management of osteosarcomas-a multicentre retrospective study.
Biologic bone reconstruction in limb salvage surgery for the treatment of malignant bone tumours has always been controversial. The various inactivation methods, their convenience and stability, the curative effects elicited and associated costs all need to be considered. This study aimed to compare the clinical efficacy of intraoperative extracorporeal irradiated reimplantation with alcohol-inactivated autograft reimplantation for limb salvage surgery in patients with osteosarcoma. We retrospectively analysed 28 patients with osteosarcoma, 14 patients treated with intraoperative cobalt 60 irradiation and reimplantation (group A), and 14 patients treated by alcohol-inactivated autograft reimplantation (group B). The postoperative complications and clinical efficacy of each treatment method were compared by statistical analysis. The local recurrence rate was 14.3% in each group. Complete bony union was achieved in 64.3% of patients in group A and 71.4% of patients in group B. The overall 5-year survival rate was 71.4% in group A and 78.6% in group B. The mean Musculoskeletal Tumor Society (MSTS) score was 25.33 ± 4.72 (range 15-30) in group A and 24.00 ± 5.85 (range 15-30) in group B, and the mean International Society of Limb Salvage (ISOLS) score was 25.79 ± 5.13 (range 20-36) in group A and 26.14 ± 5.33 (range 20-30) in group B. P < 0.05 was considered to indicate a significant difference. The results showed that the long-term clinical efficacy did not differ significantly between the two methods. In limb salvage surgery for osteosarcoma, intraoperative extracorporeal irradiation and alcohol-inactivated autograft reimplantation yielded equivalent outcomes. The alcohol-inactivated method may be a much more convenient and inexpensive way to reconstruct bone defects. Additional studies as well as more case studies are needed to fully evaluate the clinical efficacy and safety of this treatment method.


A systematic scoping study exploring opioid use across a variety of disability conditions.
Opioid use experiences among people with disability (PWD) as a group has not been clearly articulated in the current literature, despite links between pain and measures of disability. To conduct a systematic search and scoping study examining the characteristics of current literature focused on opioid use among PWD. Four databases were queried (i.e., Medline, PsycINFO, Embase, and CINAHL) for peer-reviewed, empirical, English-language, journal articles focused on long-term opioid use among PWD. Collected data points included: disability details (specific condition, onset of disability), opioid details (category of opioid use, and specified substance), study details, and design. A total of 196 articles were included, with 83.7% published since 2000 largely from the US. The majority of articles (70.4%) focused on the use of opioids as medical treatment, with fewer articles focusing on recreational opioid use or substance use disorders. The majority of included sources (73%) focused on opioid use in acquired conditions; neuropathic pain (21.9%) and attention deficit hyperactivity disorder (20.4%) were the most commonly studied. Differences were observed in the distribution of disability conditions across category of opioid use and study design classification; 73.5% were considered observational in design. The varied representation of disability conditions, and differences across opioid use category and study design classification point to a complicated relationship between opioid use and disability. The present research portfolio would benefit from research matching informational needs of a specific disability area or opioid use category to provide the evidence necessary to advance current knowledge and promote inclusion in national agendas.


Gender incongruence and timing of puberty: a population-based cohort study.
To study whether the timing of puberty in adolescents who reported gender incongruence (incongruence between birth-assigned sex and self-identified gender) was different from those adolescents who reported gender congruence. Population-based cohort study using data from the Danish National Birth Cohort. Not applicable. Birth-assigned boys and girls born between 2000 and 2003, who self-reported gender incongruence at 11 years (N = 10,046) and their pubertal developmental stages from age 11 years to every 6 months throughout puberty were included. Not applicable. Mean age differences in months at reaching Tanner stages 2-5 for breast or genital development and pubic hair, voice break, first ejaculation, menarche, axillary hair, acne, and the average difference at attaining all pubertal milestones (primary outcome). In total, 549 (5.5% ) adolescents reported part or full gender incongruence at 11 years. Tendencies toward earlier timing of puberty were observed in adolescents who reported part gender incongruence (average difference, birth-assigned boys: -3.2 months [95% confidence interval {CI}: -6.7; 0.3]; birth-assigned girls: -2.0 months [95% CI: -3.9; -0.1]). Tendencies toward earlier timing of puberty were observed in adolescents who reported full gender incongruence (average difference, birth-assigned boys: -2.4 months [95% CI: -5.0; 0.4]; birth-assigned girls: -1.9 months [95% CI: -5.1; 1.2]). The results from this study indicated that birth-assigned boys and girls who reported either part or full gender incongruence tended to reach puberty slightly earlier than those adolescents who reported gender congruence at 11 years of age. Knowledge on the timing of puberty among adolescents who experience gender incongruence is essential to inform mutual decision-making in clinical settings.


Obtaining automated diagnostic information and pain relief.
The silent confluent flow of a conglomerate of sensory related signals is automatically delegated to the total specific distribution of a single spinal nerve. This silent confluent flow may be accessed, evaluated, and modified by using intradermal saline infiltration to stimulate the sensory receptors located in the skin overlying its nerve root. An unmistakable augmented burst of infiltration pain immediately followed by profound long lasting pain relief identifies a spinal nerve monitoring peripheral pathology. The identification of a monitoring spinal nerve tentatively confirms the presence of pathology confined to the specific peripheral distribution of that specific spinal nerve. The practically unknown visceral distribution proves to be specific and visceral pathology echoes through its collated spinal nerve without patent variation. Practically cost free and without side effects or contraindications dermatomal infiltration opens a whole new chapter in the field of diagnosis as it may be used to determine the presence of pathology, to locate that pathology to the specific distribution of a specific spinal nerve or nerves, and to produce unequalled pain relief.


Structure and stability analysis of cytotoxic complex of camel α-lactalbumin and unsaturated fatty acids produced at high temperature.
α-Lactalbumin α-La), together with oleic acid can be converted to a complex, which kills tumor cells selectively. Cytotoxic α-La -oleic acid and α-La -linoleic acid complexes were generated by adding fatty acid to camel holo α-La at 60 ° C (referred to as La-OA-60 and La-LA-60 state, respectively). Structural properties of these complexes were studied and compared to the camel α-La. The experimental results show that linoleic acid induces α-La partial unfolding but oleic acid does not change the protein structure significantly. Also the stability of La-OA-60 and La-LA-60 toward thermal denaturation was measured. The order of temperature at the transition midpoint is as follows: La-LA-60 < La-OA-60 < α-La. La-OA-60 complex inhibited tubulin polymerization in vitro. Although the structures of La-OA-60 and La-LA-60 were different, these two complexes had similar cytotoxic effect to DU145 human prostate cancer cells. Samples of La-OA-60 that have been renatured after denaturation lost the specific biological activity toward tumor cells.


Male-specific cell migration into the developing gonad.
The gene Sry acts as a developmental switch, initiating a pathway of gene activity that leads to the differentiation of testis rather than ovary from the indifferent gonad (genital ridge) in mammalian embryos. The early events following Sry expression include rapid changes in the topographical organization of cells in the XY gonad. To investigate the contribution of mesonephric cells to this process, gonads from wild-type mice (CD1), and mesonephroi from a transgenic strain ubiquitously expressing beta-galactosidase (ROSA26), were grafted together in vitro. After culture, organs were fixed and stained for beta-galactosidase activity to identify cells contributed from the mesonephros to the male or female gonad. Migration of mesonephric cells occurred into XY but not XX gonads from 11.5-16.5 days post coitum (dpc). Somatic cells contributed from the mesonephros were distinguished by their histological location and by available cell-specific markers. Some of the migrating cells were endothelial; a second population occupied positions circumscribing areas of condensing Sertoli cells; and a third population lay in close apposition to endothelial cells. OFFgration from the mesonephros to the gonad is male specific at this stage of development and depends on an active signal that requires the presence of a Y chromosome in the gonad. The signals that trigger migration operate over considerable distances and behave as chemoattractants. We suggest that migration of cells into the bipotential gonad may have a critical role in initiating the divergence of development towards the testis pathway.


A reciprocating magnetic field assisted on-line solid-phase extraction coupled with liquid chromatography-tandem mass spectrometry determination of trace tetracyclines in water.
A reciprocating magnetic-field-assisted on-line solid-phase extraction (RMF-SPE) method coupled with liquid chromatography-tandem mass spectrometry (LC-MS/MS) has been developed for continuous enrichment of trace chemicals in water samples. Under the assist of the reciprocating magnetic field, carboxyl-modified magnetic nanoparticles (CMNPs) were applied to prepare microcolumn with even dispersion by periodical motion, instead of traditional compaction as extraction sorbents. When water sample passed through the extraction region, dynamic sorbents generates an advantage of countless contacts between sorbents and targets without blocking for high efficient extraction. In this study, the on-line RMF-SPE method was established and evaluated by determination of tetracyclines (TCs) from water samples as analysis models, including oxytetracycline, tetracycline, demeclocycline, metacycline, chlortetracycline, and doxycycline. Experimental conditions have been investigated such as flow rate, reciprocating speed, elution time, and so on. The method showed high relative recovery (95.4-111.1%) and good repeatability with RSD from 2.9 to 11.8% for the 200 mL water sample. The linearity range, limits of detection (LODs), and limits of quantification (LOQs) were 0.5-200 μg L-1 (chlortetracycline) and 0.1-200 μg L-1 (other TCs), 12.0-74.1 ng L-1, and 40.1-247 ng L-1, respectively. More importantly, the high enrichment factors in a range of 204 (chlortetracycline) to 276 (demeclocycline) indicate that a small amount of dynamic sorbents (only 10 mg) give full play to extraction attributing to the reciprocating movement, especially for trace analysis and continuous extraction, which is significant for water samples from sea, river and domestic waste.


Facilitating pharmacometric workflow with the metrumrg package for R.
metrumrg is an R package that facilitates workflow for the discipline of pharmacometrics. Support is provided for data preparation, modeling, simulation, diagnostics, and reporting. Existing tools and techniques are emphasized where available; original solutions are provided for otherwise unmet needs. In particular, metrumrg implements an R interface for the NONMEM(®) modeling software, optionally run in a distributed computing environment. The paradigm allows start-to-finish analyses in a single scripting language. Emphasis on text-based formats promotes traceability of results.


Characterization and expression of two genes encoding isoforms of a putative Na, K-ATPase in the chytridiomycete Blastocladiella emersonii.
A P-type ATPase gene (BePAT1) from the aquatic fungus Blastocladiella emersonii, which surprisingly showed high similarity with the alpha-subunit of Na, K-ATPases from animal cells, has been reported recently [Biochim. Biophys. Acta 1383 (1998) 183]. In the present study, we describe the characterization of a second gene, denominated BePAT2, and show that these two genes have a different intron-exon structure but encode putative proteins with greater than 90% amino acid identity. Northern blot and multiplex reverse transcription and polymerase chain reaction (RT-PCR) assays have revealed that BePAT1 and BePAT2 genes have a non-coordinate, developmentally regulated expression during B. emersonii life cycle. Phosphoenzyme formation experiments using the immunopurified enzymes have indicated the presence of a Na, K-ATPase-like activity. Furthermore, immunofluorescence studies using B. emersonii zoospores localized the ATPases on the plasma membrane of these cells.


Crew time and workload in the EDEN ISS greenhouse in Antarctica.
The goal of the EDEN ISS project is to research technologies for future greenhouses as a substantial part of planetary surface habitats. In this paper, we investigate crew time and workload needed to operate the space analogue EDEN ISS greenhouse on-site and remotely from the Mission Control Center. Within the almost three years of operation in Antarctica, different vegetable crops were cultivated, which yielded an edible biomass of 646 kg during the experiment phase 2018 and 2019. Operating in such a remote environment, analogue to future planetary missions, both greenhouse systems and remote support capabilities must be carefully developed and assessed to guarantee a reliable and efficient workflow. The investigation of crew time and workload is crucial to optimize processes within the operation of the greenhouse. For the Antarctic winter seasons, 2019 and 2020, as well as the summer season 2019/2020, the workload of the EDEN ISS greenhouse operators was assessed using the NASA Task Load Index. In addition, crew time was measured for the winter season 2019. The participants consisted of on-site operators, who worked inside the EDEN ISS greenhouse in Antarctica and the DLR remote support team, who worked in the Mission Control Center at the DLR Institute of Space Systems in Bremen (Germany). The crew time results show that crew time for the whole experiment phase 2019 required by the on-site operator team 2019 is approximately four times higher than the crew time of the corresponding remote support team without considering planning activities for the next mission. The total crew time for the experiment phase 2019 amounts to 694.5 CM-h or 6.31 CM-h/kg. With the measurements of the experiment phase 2019 it was possible to develop a methodology for crew time categorization for the remote support activities, which facilitates the analysis and increases the comparability of crew time values. In addition, the development of weekly and monthly crew time demand over the experiment phase is presented. The workload investigations indicate that the highest workload is perceived by the remote support team 2019 + 2020, followed by the summer maintenance team 2019/2020. The on-site operator team 2019 and on-site operator team 2020 showed the lowest values. The values presented in this paper indicate the need to minimize crew time as well as workload demands of the operators involved in the operation of future planetary surface greenhouses.


Polymorphism in the C-reactive protein (CRP) gene affects CRP levels in plasma and one early marker of atherosclerosis in men: The Health 2000 Survey.
C-reactive protein (CRP) is an inflammatory protein that may play a role in the pathogenesis of cardiovascular disease (CVD). However, its status as a causal risk factor is still controversial. CRP gene single nucleotide polymorphisms (SNPs) have been shown to associate with CRP concentration, but not convincingly with early atherosclerotic changes. We assessed whether CRP genotypes or their haplotypes associate with plasma CRP levels or carotid artery intima-media thickness (IMT) or carotid artery elasticity (CAE) in a Finnish middle-aged study population. We genotyped CRP gene polymorphisms -717A>G (rs2794521), -286C>T>A (rs3091244), +1059G>C (rs1800947), +1444C>T (rs1130864) and +1846G>A (rs1205) and measured CRP concentration in a sub-population (N=1332, mean age 58.2 ± 8.0, women n=727 and men n=605) of a large Finnish cross-sectional health examination survey, The Health 2000 Study, carried out in 2000-2001. Results. Significant association (both sexes p<0.0001, women p=0.015 and men p=0.029) was found between CRP rs1800947 genotype and CRP concentration. Multivariate analysis showed an independent effect of the genotype on CRP concentration after adjustment for risk factors (women p=0.036 and men p=0.009). Similar associations were seen at the haplotype level in haplotype ACCCA where +1059 C-carriers had lower median CRP values than non-carriers (p=0.008). One CRP genotype (rs1130864) was associated with one CAE parameter in men but no association was observed between CRP genotypes and carotid artery IMT. CRP gene allelic variation is associated with CRP levels in both sexes and with one CAE parameter (SI) in men in a population-based Finnish cohort of middle-aged subjects.


The role of metal and bone cement fixation in the management of malignant lesions of the vertebral column.
Fifteen patients with malignant spinal metastases underwent fixation of the spine using metallic implants and bone cement. The operation provided considerable relief of pain in all 15 cases and a significant improvement in mobility in 12 cases. These results compared favourably with 77 patients with fatal metastatic cancer of the spine who were treated without spinal surgery. The technique seems to be best indicated for use in patients with breast and thyroid cancer with a relatively prolonged terminal course.


A national survey of screening and management of hypogammaglobulinemia in Canadian transplantation centers.
Infection remains one of the most common transplant-related causes of death in patients undergoing transplantation. Secondary hypogammaglobulinemia (HGG) as a component of immune suppression and deficiency is associated with both solid organ transplantation (SOT) and hematopoietic cell transplantation (HCT). Available data and clinical experience for the supplementation of immunoglobulin (Ig) in these patients is conflicting, and differing clinical opinion accounts for non-uniform practice in the use of Ig treatment. We aimed to survey lead transplant practitioners for current practice around polyvalent Ig use in post-transplant recipients across Canada. We performed a survey study using short questionnaires to estimate rate of screening of HGG, use of polyvalent Ig, and physician's opinion on Ig treatment and infection prevention. Directors of 24 SOT and 23 HCT centers across Canada were invited to participate in the survey via an electronic mail. Overall response rate was 63.8%. Twenty percent of SOT programs routinely measured Ig levels pre-transplant compared to 33% of allogeneic (allo-) and 21% of autologous (auto-) HCT programs. Post-transplant Ig levels were measured in 13%, 75%, and 29% in SOT, allo-HCT, and auto-HCT, respectively. The SOT and auto-HCT groups indicated that they do not prescribe Ig therapy (100% and 86%), contrary to the allo-HCT group (42%). Of the respondents in the SOT, allo-HCT, and auto-HCT groups, 60%, 67%, and 36%, respectively, thought infections could be prevented with intravenous immunoglobulins (IVIg). A majority of respondents indicated they would be interested in participating in a randomized controlled trial evaluating the use of IVIg in the SOT and in both HCT groups (100%, 83%, and 57%, respectively). Our study shows significant variation in practice between SOT and HCT centers with respect to screening and management of HGG. There is willingness to participate in a randomized controlled trial to address whether Ig treatment reduces infection in post-transplant recipients.


Plasticity of the mitochondrial genome in Podospora. Polymorphism for 15 optional sequences: group-I, group-II introns, intronic ORFs and an intergenic region.
The mitochondrial chromosome of 15 Podospora anserina and one Podospora comata wild-type strains have been extensively examined for the presence of optional elements and for sequence divergence. Among the P. anserina strains, nine optional sequences were found. By comparing P. anserina with the closely related and weakly interfertile P. comata species, six additional optional sequences were detected. These optional elements correspond to mitochondrial introns belonging to different groups and subgroups (11 cases), intronic open reading frames (two cases), a complex insert and an intergenic region. Although difficult to explain, the distribution of optional mitochondrial sequences among the 15 wild-type isolates of P. anserina is far from random.


To click or not to click: learning to teach to the microwave generation.
Teachers in higher education are faced with unique challenges associated with contemporary learners. Students entering college today have enjoyed a technology rich environment that has socialized them towards expectations of rapid information exchange, instant gratification, and a tendency towards reduced or non-textbook reading. Furthermore, the No Child Left Behind Act of 2001 in the USA has imprinted the notion that education should be directed towards teaching to the examination. Advances in technology have also provided educators with a host of gadgets to augment instruction. However, the majority of nursing faculty members are from a generation that may be resistant to welcoming newfangled electronic tools. The purpose of this article is to discuss the pedagogical method of using clicker technology in theory courses to achieve desired learning outcomes. A paradigm case and narrative are included to describe a resulting effect on teaching.


Contracting in crisis intervention.
The use of contracts in the social services is an important area that needs to be looked at. This paper is concerned specifically with the use of contracts in one particular part of social services: crisis intervention. Contracts that define the working relationship between the client and mental health counselor can be beneficial for both when they attempt to solve the problems that contributed to the crisis situation. There are five benefits to be gained from the use of contracts in crisis intervention and they are briefly discussed.


Regulation of erythropoietin production.
The hormone erythropoietin (Epo) maintains red blood cell mass by promoting the survival, proliferation and differentiation of erythrocytic progenitors. Circulating Epo originates mainly from fibroblasts in the renal cortex. Epo production is controlled at the transcriptional level. Hypoxia attenuates the inhibition of the Epo promoter by GATA-2. More importantly, hypoxia promotes the availability of heterodimeric (α/β) hypoxia-inducible transcription factors (predominantly HIF-2) which stimulate the Epo enhancer. The HIFs are inactivated in normoxia by enzymatic hydroxylation of their α-subunits. Three HIF-α prolyl hydroxylases (PHD-1, -2 and -3) initiate proteasomal degradation of HIF-α, while an asparaginyl hydroxylase ('factor inhibiting HIF-1', FIH-1) inhibits the transactivation potential. The HIF-α hydroxylases contain Fe(2+) and require 2-oxoglutarate as co-factor. The in vivo response is dynamic, i.e. the concentration of circulating Epo increases initially greatly following an anaemic or hypoxaemic stimulus and then declines despite continued hypoxia. Epo and angiotensin II collaborate in the maintenance of the blood volume. Whether extra-renal sites (brain, skin) modulate renal Epo production is a matter of debate. Epo overproduction results in erythrocytosis. Epo deficiency is the primary cause of the anaemia in chronic kidney disease and a contributing factor in the anaemias of chronic inflammation and cancer. Here, recombinant analogues can substitute for the hormone.


Leukotriene D4 potentiates fibronectin-induced migration of human lung fibroblasts.
Fibroblasts play an important role in the repair and remodeling processes following injury. Leukotriene D4 (LTD4) is a potent mediator in inflammatory processes, but the direct effect of cysteinyl leukotrienes on fibroblast migration remains unelucidated. In this study, the effect of the LTD4 on normal human lung fibroblasts (NHLF) chemotaxis induced by human plasma fibronectin (HFn) was investigated using the modified Boyden's chamber technique. LTD4 potentiated NHLF chemotaxis to HFn in concentration-dependent manner. A specific cysteinyl leukotriene receptor type 1 antagonist, pranlukast inhibited this effect, indicating that LTD4 affected cell migration via its specific receptor. The potentiating effect of LTD4 on fibroblast chemotaxis was completely abolished by pertussis toxin (PTX), suggesting that LTD4-induced effect was dependent on PTX-sensitive Gi/o signaling. These findings suggest that LTD4 has a potential to augment fibroblast chemotaxis, and to contribute to regulation of the wound healing and following remodeling in fibrotic processes of the lung.


Comparison of Subjective Responses of Low Back Pain Patients and Asymptomatic Controls to Use of Spinal Exoskeleton during Simple Load Lifting Tasks: A Pilot Study.
Spinal exoskeletons have been suggested as an approach for the prevention and rehabilitation of occupational low back pain (LBP). While the state-of-the-art exoskeletons were shown to substantially unload the back, user acceptance is still limited. Perceived discomfort and restriction of freedom of movement are commonly reported. In this pilot study, we explored the differences in subjective responses and user impressions to using passive spinal exoskeleton during a set of simple lifting tasks between LBP patients (n = 12) and asymptomatic individuals (n = 10). Visual analog scales (0-10) were used for all assessments. Overall, the results showed mostly similar responses or slightly more positive responses to the exoskeleton from LBP patients. Most notably, the LBP patients reported a statistically significant (p = 0.048) higher willingness to use the device daily (5.36 ± 4.05) compared to the control group (2.00 ± 1.85) and also gave the device a higher overall grade (6.58 ± 1.98 vs. 4.30 ± 2.26; p = 0.021). This study has demonstrated that individuals with current LBP responded more favorably to the use of the spinal exoskeleton for simple lifting tasks. This implies that current exoskeletons could be appropriate for LBP rehabilitation, but not preventions, as pain-free individuals are less willing to use such devices. Future studies should explore whether different exoskeleton designs could be more appropriate for people with no LBP issues.


Protection by pantethine, pantothenic acid and cystamine against carbon tetrachloride-induced hepatotoxicity in the rat.
The daily ip administration of pantethine (500 mg/kg), pantothenic acid (100 mg/kg) or cystamine (50 mg/kg) for 5 days conferred significant protection against the hepatotoxic and peroxidative actions of a 0.5 mL/kg ip dose of CCl4 in rats. All three treatments lessened the increases in serum ALT and liver TBARS values, and the reductions in serum triglyceride levels, and prevented the development of hepatic steatosis caused by the halocarbon. Pantethine was found to offer the greatest protection.


Palladium-catalyzed borylation of phenyl bromides and application in one-pot Suzuki-Miyaura biphenyl synthesis.
The coupling reaction of pinacolborane with various aryl bromides in the presence of a catalytic amount of Pd(OAc)(2) together with DPEphos as ligand and Et(3)N as base provided arylboronates. High yields were obtained in the case of electron-donor substituted aryl bromides. The direct preparation of arylboronates allowed the one-pot, two-step synthesis of unsymmetrical biaryls in high yields. [reaction: see text]


The SARS-COV-2 outbreak around the Amazon rainforest: The relevance of the airborne transmission.
At the beginning of the SARS-COV-2 outbreak in Brazil, there was a striking difference between the contamination rate in the Amazonian States and the South and the Southeast States. The regions near the Amazon rainforest presented much higher and faster contaminations. This paper attempts to explain this phenomenon through a global analysis of the COVID-19 epidemic in Brazil. It also investigates the relationship between climate conditions and airborne transmission with the evolution of contagion in the Amazonian states. The method of investigation of the spread of SARS-COV-2 in these different macro-environments was based on the analysis of three extensive daily official databases on the number of deaths, the percentage of adherence of the populations to the restriction policies, and the local climatic conditions. Besides, the social conditions in those States were also taken into account. Then, it was compared the epidemiologic results for States with very different climatic characteristics and that had adopted, almost simultaneously, similar social isolation measures. However, all these analyses were not able to explain the remarkable difference in the evolution of the pandemic among Brazilian regions. So, it was necessary to invoke airborne transmission, facilitated by the very high air humidity, as a decisive factor to explain the faster evolution of contagion in the rainforest region. Air humidity seems to be the most important climatic factor in viral spreading, while usual ambient temperatures do not have a strong influence. Another very important result of this analysis was the observation that the onset of collective immunity may have been achieved with a contamination rate of about 15% of the Amazonian population.


Trends in Etiologies, Demographics, and Neuroimaging in New-Onset Adult Strabismus at an Ophthalmic Emergency Department.
To evaluate new-onset strabismus in adults presenting to an ophthalmic emergency department, and to identify which patients require neuroimaging. This was a retrospective review of electronic medical records of patients 18 years and older who presented to an ophthalmic emergency department between January 1, 2019 and December 31, 2020 with new-onset strabismus. Data regarding demographics, causes, neuroimaging, and resolution were recorded and analyzed. Of the 557 patients in the current study, 54.8% were men and the mean age was 57.3 ± 16.7 years (range: 18 to 92 years). Most patients (72.4%) presented with diplopia. Esotropia was the most common ocular misalignment (43.6%) and was more common in women than men (51.6% vs 37.0%, respectively) (P = .001). The most common diagnoses were cranial nerve palsies (66.8%) for both sexes and all age groups, with the most common etiology being microvascular (48.1%) for patients 50 years and older and idiopathic (20.1%) for patients between 18 and 49 years old. The incidence of cranial nerve palsies was significantly higher in older patients (P < .001). Neuroimaging was performed in 58% of patients (n = 323), of whom 37.2% (n = 120) had abnormal findings. The most common abnormal neuroimaging finding was mass for all age groups and sexes (19.2%). Patients with cranial nerve palsy and microvascular etiology had a significantly lower proportion of abnormal neuroimaging findings (P < .001). Most cases of new-onset strabismus in adults presenting to the emergency department were due to cranial nerve palsy, particularly in older patients. Despite high rates of neuroimaging, patients with cranial nerve palsy had mostly normal findings. The current study supports the belief that neuroimaging may be deferred in patients older than 50 years with micro-vascular risk factors. [J Pediatr Ophthalmol Strabismus. 2022;59(4):269-273.].


Measurable Levels of Short-Chain Chlorinated Paraffins in Western Hudson Bay Fishes but Limited Biomagnification from Fish to Ringed Seals.
We investigated short-chain (C10-13 ) chlorinated paraffins (SCCP) in an Arctic marine food web. In zooplankton, fishes, and ringed seals from western Hudson Bay, Canada, SCCP concentrations ranged from 38.3 to 687 ng g-1 lipid weight. Monte Carlo-simulated trophic-adjusted biomagnification factors of individual SCCP congeners ranged from 0.07 to 0.55 for small pelagic fishes to seals. Despite relatively high concentrations in fishes, biomagnification of SCCPs within this food web appears limited. Environ Toxicol Chem 2021;40:2990-2999. © 2021 SETAC.


Initiating range of motion exercises within 24 hours following total knee arthroplasty affects the reduction of postoperative pain: A randomized controlled trial.
Postoperative limitations in the range of motion (ROM) after TKA may occur occasionally and restrict a patient's ADL. Although ROM exercise is a means of increasing the ROM after TKA, the optimal time of initiating ROM exercise is still unclear. The purpose of this study is to examine different initiation timings of postoperative ROM exercises after TKA and to compare the results in terms of postoperative pain, swelling, and ROM improvement to determine the optimal time of initiating ROM exercises following TKA. This was a prospective, single-center, single-blinded randomized controlled trial involving 109 patients scheduled for unilateral TKA. All patients underwent the physiotherapist assisted passive and active same rehabilitation program that only differed in the starting time of ROM exercise on postoperative day 1 or day 7. Postoperative assessment was performed with all attending personnel blinded to group assignment. Visual analog scale (VAS) of pain, ROM, thigh swelling, the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) score, and adverse outcomes were compared between groups on postoperative days within 2 years after surgery. VAS scores during the postoperative period from 18 to 72 h were significantly lower in the group with starting time of ROM exercise on postoperative day 1. The ROM, laboratory data, thigh girth, WOMAC and the incidence of complications did not differ between the two groups at any postoperative time-point. The results of this study suggested that ROM exercises beginning in the early postoperative stage are advantageous in reducing the postoperative pain after TKA.


Identification of QTL genes for BMD variation using both linkage and gene-based association approaches.
Low bone mineral density (BMD) is a risk factor for osteoporotic fracture with a high heritability. Previous large scale linkage study in Northern Chinese has identified four significant quantitative trait loci (QTL) for BMD variation on chromosome 2q24, 5q21, 7p21 and 13q21. We performed a replication study of these four QTL in 1,459 Southern Chinese from 306 pedigrees. Successful replication was observed on chromosome 5q21 for femoral neck BMD with a LOD score of 1.38 (nominal p value = 0.006). We have previously identified this locus in a genome scan meta-analysis of BMD variation in a white population. Subsequent QTL-wide gene-based association analysis in 800 subjects with extreme BMD identified CAST and ERAP1 as novel BMD candidate genes (empirical p value of 0.032 and 0.014, respectively). The associations were independently replicated in a Northern European population (empirical p value of 0.01 and 0.004 for CAST and ERAP1, respectively). These findings provide further evidence that 5q21 is a BMD QTL, and CAST and ERAP1 may be associated with femoral neck BMD variation.


[Research Scientific Centre of Military Medicine, Military-medical Techniques and Pharmacy of State Research Scientific Institute of Military Medicine of Ministry of Defence of RF celebrates 80 years].
The history of the 80-year activity of the Institute of Military Medicine, established in the Workers and Peasants, Red Army, Soviet Union. The Institute was founded in 1930 in Moscow and was originally called the Military Sanitary Institute. In a subsequent Institute repeatedly reformed, had different names, with the first years of its existence, has made and continues to contribute significantly to the development of means of medical services and other medical devices. The concrete results of operations and information about the staff are established.


Functional endoscopic transnasal dacryocystorhinostomy.
Endoscopic nasal surgical techniques are revolutionising the management of nasal and sinus disorders. Historically the surgical approach to the nasolacrimal sac and duct has been indirect by an external approach because of poor visualisation intranasally. The nasolacrimal apparatus is, however, intimately related to the lateral nasal wall and may readily be approached using an endoscopic technique which minimises functional interference with the physiological action of the lacrimal pump. This paper describes a technique of endoscopic intranasal dacryocystorhinostomy which has success rates comparable to those obtained by the more conventional external approach.


An ultrasensitive post chemiluminescence reaction of ammonium in NBS-dichlorofluorescein system and its application.
A strong post chemiluminescence (PCL) phenomenon was observed when ammonium was injected into the reaction mixture after the finish of CL reaction of N-bromosuccinimide (NBS) and dichlorofluorescein. Based on this, a sensitive flow injection PCL method was established for the determination of ammonium. The possible CL mechanism of the reaction was proposed based on a series of experiments. The PCL intensity responded linearly to the concentration of ammonium in the range 3.0 × 10(-11) -1.0 × 10(-7) g mL(-1) with a detection limit of 1 × 10(-11) g mL(-1). The relative standard deviation (R.S.D.) was 1.4% for 1.0 × 10(-9) g mL(-1) ammonium (n=11). This method had been applied to the determination of ammonium in samples of mineral water, tap water and river water.


Structural insights into WHAMM-mediated cytoskeletal coordination during membrane remodeling.
The microtubule (MT) and actin cytoskeletons drive many essential cellular processes, yet fairly little is known about how their functions are coordinated. One factor that mediates important cross talk between these two systems is WHAMM, a Golgi-associated protein that utilizes MT binding and actin nucleation activities to promote membrane tubulation during intracellular transport. Using cryoelectron microscopy and other biophysical and biochemical approaches, we unveil the underlying mechanisms for how these activities are coordinated. We find that WHAMM bound to the outer surface of MT protofilaments via a novel interaction between its central coiled-coil region and tubulin heterodimers. Upon the assembly of WHAMM onto MTs, its N-terminal membrane-binding domain was exposed at the MT periphery, where it can recruit vesicles and remodel them into tubular structures. In contrast, MT binding masked the C-terminal portion of WHAMM and prevented it from promoting actin nucleation. These results give rise to a model whereby distinct MT-bound and actin-nucleating populations of WHAMM collaborate during membrane tubulation.