Metastatic basal cell carcinoma: report of two cases and literature review.
Metastatic basal cell carcinoma (MBCC) is defined as primary cutaneous basal cell carcinoma (BCC) that spreads to distant sites as histologically similar metastatic deposits of BCC. There are less than 300 reported cases of MBCC in the literature. This article examines two cases of MBCC and provides a literature review of risk factors inherent in epidemiology, patient demographics, and the clinicohistopathological characteristics of primary and metastatic BCC lesions. MBCC is a rare complication of BCC with high morbidity and mortality rates. Patients with MBCC often begin with long-standing primary BCC lesions that are either large or recurrent after treatment. Cases of MBCC have a higher incidence of the more aggressive histologic patterns (morpheic, infiltrating, metatypical, and basosquamous). Perineural space invasion may be an indicator of aggressive disease. Metastases often involve regional lymph nodes, lungs, bone, and skin. These case reports and review provide important diagnostic and management considerations for primary BCC and MBCC. Early intervention with aggressive treatment measures may improve the prognosis and survival of MBCC patients.


Genomic organization, structure and possible function of histidine-rich proteins of malaria parasites.
The current status of histidine-rich proteins in malaria parasites with regard to their genomic organization, protein structure and function is discussed, one of such protein present in an avian malaria parasite Plasmodium lophurae contains about 73% histidine and called as HRP (histidine-rich protein). Among human malaria parasites, in Plasmodium falciparum, only three such proteins have been described, namely knob protein also known as knob associated histidine-rich protein (KP or KAHRP), soluble histidine-alanine rich protein (soluble HARP or PfHRP II) and small histidine-alanine rich protein (SHARP) containing 8, 35 and 30% histidine contents respectively. With rapid emergence of powerful tools in molecular biology the genes of all these histidine-rich proteins have been cloned and sequenced within a short period of time. The genomic organizations of all these proteins are very much similar to each other, in each case the gene contains a signal peptide coding sequence (exon 1) followed by an intron. This intron is followed by the main coding region (exon 2) which has no further intervening sequences. In the main coding region of each gene, the histidine-rich sequences start after 25-30 amino acids from N-terminal end (75-90 nucleotides from 5' in exon 2). All the three histidine-rich proteins of P. falciparum share some homology with the HRP of P. lophurae; they all cross react with anti HRP and incorporate higher amount of exogenous histidine. The relationship between KP and HRP resides in the repeated polyhistidine sequences, (His) 6-9, from the core of the multiple tandem repeats of HRP, whereas, the peptide Ala-His-His is commonly shared by HRP and two other proteins of P. falciparum (soluble HARP and SHARP).(ABSTRACT TRUNCATED AT 250 WORDS)


Single-incision total laparoscopic hysterectomy with conventional laparoscopy ports.
To study the feasibility of performing single-incision total laparoscopic hysterectomy using conventional ports and instruments. Patients undergoing laparoscopic surgery at Galaxy Care Laparoscopic Institute, Pune, India, between January 2007 and December 2010 were selected for participation. All procedures were performed using conventional laparoscopic instruments and trocars. Operative data-including operative time (from incision to port closure), blood loss, additional ports used, energy sources used, and intraoperative complications-were recorded. Twenty-three procedures were performed during the study period. All procedures were completed via single incision only. Operative time, blood loss, and hospital stay were comparable with those associated with conventional laparoscopy. It is debatable whether laparoscopic surgery via a single incision would threaten the position of the current gold standard of conventional laparoscopic procedures. The present study showed that single-incision laparoscopic surgery using conventional instruments is feasible and effective.


Metabolic Mediators of the Effects of Family History and Genetic Risk Score on Coronary Heart Disease-Findings From the Malmö Diet and Cancer Study.
Family history of coronary heart disease (CHD) as well as genetic predisposition to CHD assessed by a genetic risk score (GRS) are predictors of CHD risk. It is, however, uncertain to what extent these risk predictors are mediated by major metabolic pathways. Total effects of self-reported family history and a 50-variant GRS (GRS50), as well as effects mediated by apolipoprotein B and A-I (apoB, apoA-I), blood pressure, and diabetes mellitus, on incidence of CHD were estimated in 23 595 participants of the Malmö Diet and Cancer study (a prospective, population-based study). During a median follow-up of 14.4 years, 2213 participants experienced a first CHD event. Family history of CHD and GRS50 (highest versus other quintiles) were associated with incident CHD, with hazard ratios of 1.52 (95% CI: 1.39-1.65) and 1.53 (95% CI: 1.39-1.68), respectively, after adjusting for age, sex, and smoking status. Small proportions of the family history effect were mediated by metabolic risk factors: 8.3% (95% CI: 5.8-11.7%) by the apoB pathway, 1.7% (95% CI: 0.2-3.4%) by apoA-I, 8.5% (95% CI: 5.9-12.0%) by blood pressure, and 1.5% (95% CI: -0.8% to 3.8%) by diabetes mellitus. Similarly, small proportions of GRS50 were mediated: 8.1% (95% CI: 5.5-11.8%) by apoB, 1.2% (95% CI: 0.5-3.0%) by apoA-I, 4.2% (95% CI: 1.3-7.5%) by blood pressure, and -0.9% (95% CI: -3.7% to 1.6%) by diabetes mellitus. A fraction of the CHD risk associated with family history or with GRS50 is mediated through elevated blood lipids and hypertension, but not through diabetes mellitus. However, a major part (≥80%) of the genetic effect operates independently of established metabolic risk factor pathways.


The visual system in subterranean African mole-rats (Rodentia, Bathyergidae): retina, subcortical visual nuclei and primary visual cortex.
We have studied the visual system of subterranean mole-rats of the rodent family Bathyergidae, for which light and vision seem of little importance. The eye diameter varies between 3.5mm in Bathyergus suillus and 1.3mm in Heterocephalus glaber. The small superficial eyes have features typical of sighted animals (clear optics, well-developed pupil and well-organized retina) and appear suited for proper image formation. The retinae are rod-dominated but possess rather high cone proportions of about 10%. The total number of retinal ganglion cells and optic nerve fibres ranges between 6000 in Bathyergus suillus and 2100 in Heliophobius argenteocinereus. Visual acuity (estimated from counts of peak ganglion cell density and axial length of the eye) is low, ranging between 0.3 and 0.5 cycles/degree. The retina projects to all the visual structures described in surface-dwelling sighted rodents. The suprachiasmatic nucleus is large and receives bilateral retinal input. All other visual nuclei are reduced in size and receive almost exclusively contralateral retinal projections of varying magnitude. The primary visual cortex is small and, in comparison to other rodents, displaced laterally. In conclusion, the African mole-rats possess relatively well-developed functional visual subsystems involved in photoperiodicity, form and brightness discrimination. In contrast, visual subsystems involved in coordination of visuomotor reflexes are severely reduced. This pattern suggests the retention of basic visual capabilities. Residual vision may enable subterranean mammals to localize breaches in the burrows that let in light thus providing a cue to enable mole-rats to reseal such entry points and to prevent entry of predators.


Selective isolation of multiple positively charged peptides for 2-DE-free quantitative proteomics.
A method for quantitative proteomic analysis based on the selective isolation of multiply charged peptides (RH peptides) containing arginine and histidine residues is described. Two pools of proteins are digested in tandem with lysyl-endopeptidase and trypsin and the primary amino groups of proteolytic peptides are separately labeled with d3- and d0-acetic anhydride. This reaction has a dual purpose: (i) to allow the relative protein quantification in two different conditions and (ii) to restrict the positive charges of peptides to the presence of arginine and histidine. The N-acylated peptides are separated by cation-exchange chromatography into two groups, neutral and singly charged peptides (R+H<or=1) that are neither retained nor analyzed, whereas the multiply charged peptides (R+H>1) are retained into the column and can be eluted in batch or further fractionated using a saline gradient before LC-MS/MS analysis. In silico analysis revealed that the selective isolation of RH peptides considerably simplifies the complex mixture of peptides (three RH peptides/protein) and at the same time they represent 84% of the whole proteomes. The selectivity, and recovery of the method were evaluated with model proteins and with a complex mixture of proteins extracted from Vibrio cholerae.


Plasma homovanillic acid and treatment response in a large group of schizophrenic patients.
Plasma levels of homovanillic acid (pHVA), a metabolite of dopamine, were measured in ninety-five Chinese schizophrenic patients free of neuroleptics for at least four weeks. These patients were treated with classical antipsychotics for six weeks. Pretreatment pHVA was positively correlated with the subsequent clinical response (r = 0.408, p < 0.0001). Good responders (BPRS improvement > or = 50%, n = 47) had higher pretreatment pHVA levels than poor responders (BPRS improvement < 50%, n = 48) (15.7 +/- 8.4 ng/ml versus 9.9 +/- 3.7 ng/ml, p < 0.0001). A higher than 15 ng/ml pretreatment pHVA level was associated with a more consistent clinical response to the subsequent treatment. Using a pHVA level of 12 ng/ml as a demarcation point, 72% of patients (34 of 47) who had pHVA > or = 12 responded whereas 65% (31 of 48) who had < 12 did not respond (chi-square = 13.02, p < 0.0001). These results suggest that higher pretreatment pHVA levels may predict a better clinical response to antipsychotics. Based upon the pHVA findings, two hypothetical subtypes of schizophrenia are proposed.


Pattern and pathways for mercury lifespan bioaccumulation in Carcinus maenas.
Carcinus maenas is an important and exploited natural resource in temperate estuaries, being consumed by local populations and also used as fish bait. Through bioaccumulation and bioamplification processes occurring in polluted estuarine ecosystems, this species may directly or indirectly represent a major pathway for Human contamination. No information is available on the overall lifespan bioaccumulation pattern of mercury for this species, which would be an invaluable tool for assessing the risks associated with C. maenas harvest in contaminated areas. Taking that in mind, the main objectives of this work were to clarify the lifespan bioaccumulation pattern of mercury for this species. A consistent lifespan accumulation pattern was found for this species, both for total and organic mercury, and coherent differences were found between genders, suggesting different physiological responses to contamination. From our results two scenarios emerge: (a) for low mercury contamination areas where the diet is the major pathway for metal uptake, with higher levels in muscle and hepatopancreas (twice as high as in gills) and higher organic mercury fractions (as high as 80-90% in muscle), crabs bioaccumulate with age and (b) on high contaminated areas, environmental exposure is predominant, with higher levels found in gills (reaching 0.8 mg kg(-1)), lower organic fractions and no mercury increment with age. Detoxification strategies, dietary differences and species mobility may account for these two accumulation patterns.


Vogt-Koyanagi-Harada associated with diabetes mellitus and celiac disease in a 3-year-old girl.
To present a case of Vogt-Koyanagi-Harada (VKH) associated with type I diabetes mellitus and celiac disease in a 3 year old female. We studied a three-year old female who presented with clinical manifestation of VKH and type I Diabetes mellitus and celiac disease. Patient was found to have hyperglycemia with type I diabetes mellitus. Duodenal mucosal biopsy specimen confirmed the diagnosis of celiac disease. Patient's ocular inflammation was treated by topical and systemic corticosteroid and immune-suppressive therapy. Her diabetes mellitus was controlled by insulin and her celiac disease was controlled by gluten-free diet. The association of VKH with two autoimmune diseases (celiac disease and type I diabetes mellitus) is rare. This case is, to our knowledge, the youngest patient reported with VKH.


[Argon laser trichiasis treatment: Technique, indications and results (report of 230 cases)].
Trichiasis is a common misdirection of the eyelashes, creating a sharp point responsible for decreased vision, blepharospasm and corneal irritation. It may cause neurotrophic corneal disease leading to blindness. The etiology of trichiasis remains largely undetermined in our patient base. Treatment is based on pragmatic methods that take into account the ciliary ecosystem and the static and dynamic examination of the eyelids. For this, several therapeutic modalities exist: mechanical epilation, cryotherapy, surgery and electrolysis. Each of these techniques has its indications, advantages, and complications. Destruction of the lash follicles with argon laser has many advantages: it is an outpatient procedure, rapid, reproducible, well tolerated, and above all, effective in the long term. The aim of our study is to examine the advantages, technique, indications and results of argon laser trichiasis treatment. This was a retrospective study including 201 patients (230 eyelids) treated in our ophthalmology department over a period of 9years (from January 2011 to March 2020), all of whom were seen for various lash-related symptoms and treated with argon laser electrolysis. Results were considered satisfactory when no lash regrowth occurred within six months of the last laser session. Eighty-two percent of our patients (n=188) showed a good therapeutic response after the first session, 9% (n=21) needed an additional session, and only 6% of the patients (n=14) required a 3rd and/or 4th session, without resorting to surgery. The indications for this treatment should be limited to trichiasis of fewer than or equal to 7 per eyelid, without associated lid malposition (entropion), the treatment of which should be surgical and entirely different. Treatment of trichiasis with argon laser can be an alternative or complement to surgery. Results are excellent but require rigorous adherence to the technique and indications.


Reliability of manual and semi-automated measurements of nuchal translucency by experienced operators.
To compare intra-/inter-operator reliability of manual and semi-automated NT measurement by experienced operators. Images of 103 fetuses at 11 to 13+6weeks were selected. Two operators performed NT measurement independently 3 times each using both manual and semi-automated methods. Intraoperator reliability of the methods was evaluated using ICCs; interoperator reliability was assessed via correlation between the means of the 3 measurements of each operator. Agreement between the 2 methods was evaluated via Bland-Altman plot. ICCs for the manual method were 0.80 (95% CI, 0.73-0.85) for operator 1 and 0.82 (95% CI, 0.76-0.87) for operator 2; ICCs for the semi-automated method were 0.80 (95% CI, 0.74-0.85) for operator 1 and 0.82 (95% CI, 0.76-0.86) for operator 2. Interoperator reliability for both methods was high: correlation coefficients 0.91 (95% CI, 0.87-0.94) and 0.96 (95% CI, 0.94-0.97) for manual and semi-automated methods, respectively. Mean NT measured by manual and semi-automated methods was 1.15mm and 1.28mm, respectively (P<0.001). Agreement between the methods was good. The reliability of semi-automated NT measurements was comparable to that of the manual method. The new method was reproducible and may be used instead of the manual method in the normal range of NT.


The longer-term impact of the COVID-19 pandemic on wellbeing and subjective cognitive functioning of older adults in Belgium.
In earlier survey research, we observed a severe impact of the first peak of the COVID-19 pandemic on the subjective wellbeing, sleep and activity of adults aged 65 years or older in Flanders, Belgium. The impact on subjective cognitive functioning, however, was limited. Since then, periods of lockdown and periods with less strict regulations alternated, but social distancing remained, especially for older adults. To study the longer-term impact of the pandemic on wellbeing and subjective cognitive functioning, we re-assessed the older adults from the first measurement moment (May-June 2020) in a second (June-July 2020) and third (December 2020) wave of the survey (n = 371, M = 72 years old, range 65-97 years old). Results indicated that wellbeing fluctuated with the severity of the pandemic. Results for self-reported cognitive functioning were mixed. While participants indicated a slightly better general subjective cognitive functioning at the end of the study, experienced problems with most cognitive subdomains significantly increased over time. The presence of depressive and anxiety symptoms were related to the longer-term impact of the pandemic on wellbeing and subjective cognitive functioning. Our study shows the long-lasting impact of the pandemic on the wellbeing and subjective cognitive functioning of older adults, without full recovery from the first wave.


Prevalence and incidence of neuromuscular conditions in the UK between 2000 and 2019: A retrospective study using primary care data.
In the UK, large-scale electronic primary care datasets can provide up-to-date, accurate epidemiological information on rarer diseases, where specialist diagnoses from hospital discharges and clinic letters are generally well recorded and electronically searchable. Current estimates of the number of people living with neuromuscular disease (NMD) have largely been based on secondary care data sources and lacked direct denominators. To estimate trends in the recording of neuromuscular disease in UK primary care between 2000-2019. The Clinical Practice Research Datalink (CPRD) database was searched electronically to estimate incidence and prevalence rates (per 100,000) for a range of NMDs in each year. To compare trends over time, rates were age standardised to the most recent CPRD population (2019). Approximately 13 million patients were actively registered in each year. By 2019, 28,230 active patients had ever received a NMD diagnosis (223.6), which was higher among males (239.0) than females (208.3). The most common classifications were Guillain-Barre syndrome (40.1), myasthenia gravis (33.7), muscular dystrophy (29.5), Charcot-Marie-Tooth (29.5) and inflammatory myopathies (25.0). Since 2000, overall prevalence grew by 63%, with the largest increases seen at older ages (≥65-years). However, overall incidence remained constant, though myasthenia gravis incidence has risen steadily since 2008, while new cases of muscular dystrophy fell over the same period. Lifetime recording of many NMDs on primary care records exceed current estimates of people living with these conditions; these are important data for health service and care planning. Temporal trends suggest this number is steadily increasing, and while this may partially be due to better recording, it cannot be simply explained by new cases, as incidence remained constant. The increase in prevalence among older ages suggests increases in life expectancy among those living with NMDs may have occurred.


[Study of the liver by computerised tomography. Assessment of one years experience involving 1,480 investigations (author's transl)].
During a period of one year, and in two departments with identical equipment, 1,480 underwent examination of the liver by computerised tomography (C. T.). A critical analysis of the method is made, based upon the diagnostic results obtained as well as the errors and gaps noted. After describing the normal liver, the authors give the "C. T. appearances" of the main hepatic conditions, based upon correlation with macroscopic pathological findings.


A truncated FAK lacking the FERM domain displays high catalytic activity but retains responsiveness to adhesion-mediated signals.
In order to determine the role of the FERM domain in the regulation of FAK phosphorylation at Tyr-397, the major autophosphorylation site, we generated a truncated FAK lacking a region of the N-terminus corresponding to amino acids 1-384 (FAKDelta384). FAKDelta384 showed a striking increase in phosphorylation, as compared with wild type FAK, in lysates of either HEK 293 or FAK-/- cells. Interestingly, the truncated form of FAK lacking the N-terminal domain retains responsiveness to integrin-mediated signals, as judged by its dephosphorylation by holding cells in suspension and by the recovery of the phosphorylation when replating the cells on fibronectin. We propose a model in which removal of FERM-mediated auto-inhibition is important to increase FAK catalytic activity but the translocation and clustering of this enzyme at the focal adhesions is required for maximal phosphorylation at Tyr-397.


Leading Others Toward Excellence.
This essay puts forth the proposition that academic program excellence does not arise by accident. Effective leadership is required. To support this proposition, the essay discusses the characteristics common to effective leaders. It then proceeds to use the example of a successful academic oral-maxillofacial surgery department and characteristics of its leader to provide evidence that excellence derives from effective leadership.


An efficient new method of ytterbium(III) triflate catalysis approach to the synthesis of substituted pyrroles: DFT, ADMET, and molecular docking investigations.
In this study, the one-pot synthetic methodology for the preparation of substituted pyrroles with diethyl acetylene-dicarboxylate is reported for the various pyrrole derivatives via the Trifimow synthesis process from oximes. This method also offers the literature as a cyclization pathway using a ytterbium triflate catalyst. Another importance of this study is the use of pyrrole derivatives in pharmaceuticals, biological processes, and agrochemicals. From this point of view, the development of a new catalyst in synthetic organic chemistry and the difference in the method is also important. The syntheses of the target substituted pyrroles are accomplished in high yields. Also, all synthesized structures were confirmed by 1H NMR, 13C NMR, and IR spectra. The DFT computations were leveraged for structural and spectroscopic validation of the compounds. Then, FMO and NBO analyses were subsequently employed to elucidate the reactivity characteristics and intramolecular interactions within these compounds. Also, ADMET indices were ascertained to assess potential pharmacokinetic properties, drug-like qualities, and possible adverse effects of these compounds. Last, optimized molecules were analyzed by molecular docking methods against crystal structures of Bovine Serum Albumin and Leukemia Inhibitory Factor, and their binding affinities, interaction details, and inhibition constants were determined.


Effective detection and quantification of chemical adulterants in model fat-filled milk powders using NIRS and hierarchical modelling strategies.
Skimmed milk powder can be blended with indigenous vegetable oils to formulate fat-filled milk powder (FMP) to satisfy the growing demand of low-income consumers for dairy proteins in the developing countries where food control systems may be fragmented. Unscrupulous manufacturers may adulterate FMP with melamine or urea to give the false impression that it contains sufficient protein. This study investigated, for the first time, the efficacy of near infrared spectroscopy to detect and quantify melamine and urea (0.01-16.00%) in FMP formulated with 4 different vegetable oils (i.e., coconut, palm, soya-bean and sunflower). Multilevel analyses were able to detect, confirm and differentiate the adulterations with an efficiency ranging from 89.8 to 100.0%. The partial least square regression models yielded satisfactory predictions (R2p ≥0.96, RSR ≤0.19) at adulteration levels ≥1.00%. This study provides appropriate guidelines for cost-efficient screening of FMP products for adulterants to protect public health.


An integrated network pharmacology and cell metabolomics approach to reveal the role of rhein, a novel PPARα agonist, against renal fibrosis by activating the PPARα-CPT1A axis.
Rhein, an anthraquinone compound, displays extensive antifibrotic effects; however, its potential mechanisms are not fully understood. In this study, we explored the underlying molecular mechanism of action of rhein. An integrated network pharmacology and cell metabolomics approach was developed based on network pharmacology and bioinformatics method, and then successfully applied to speculate the potential targets of rhein and construct a rhein-target-metabolic enzyme-metabolite network. Thereafter, the antifibrotic mechanism of rhein was validated in TGF-β- and oleic acid- induced HK-2 and NRK-52E cells in vitro as well as a unilateral ischemia-reperfusion injury Sprague-Dawley rat model. Based on the construction of the rhein-target-metabolic enzyme-metabolite network, we found that rhein played an antifibrotic role through the PPAR-α-CPT1A-l-palmitoyl-carnitine axis. In vitro experiments demonstrated that rhein effectively activated the expression of PPARα and its downstream proteins (CPT1A and ACOX1) to alleviate lipid accumulation and fibrosis development. In vivo experiments indicated that rhein attenuated renal fibrosis mainly by activating the fatty acid oxidation pathway and improving lipid metabolism. Taken together, our findings reveal that rhein is a novel agonist of PPARα, which contributes to its renoprotection through the regulation of the PPARα-CPT1A axis. Moreover, our study provides a novel insight into an integrated network pharmacology-metabolomics strategy for uncovering the pharmacological mechanisms of drugs from the system perspective.


Cytogenetic analysis of a human population occupationally exposed to pesticides.
A great deal of the flower cultivation in Italy is carried out in the western part of the Region of Liguria. The extensive use of pesticides professionally exposes floriculturists operating in this area to a complex mixture of compounds. The frequency of micronuclei in peripheral lymphocytes has been evaluated in 71 floriculturists and in a control group of 75 healthy blood donors living in the area. No correlation between age and micronucleus frequency was found in peripheral lymphocytes of the controls while an increase in this parameter was observed in the elderly of the exposed group. Our data suggest a sex-related effect in the induction of micronuclei. The frequencies of micronucleated lymphocytes were significantly higher in females than in males in both exposed and control groups (RR = 1.45, 95% C.I. 1.25-1.67). The main result of this study, however, is the observation of a significant increase in micronucleated lymphocyte frequency in people occupationally exposed to pesticides. The micronucleus frequency was 8.57/1000 for exposed persons and 6.67/1000 for controls (p < 0.05). A dose-response relationship with duration of exposure was apparent with a maximum increment of 71% in the frequency of micronuclei in subjects exposed for over 30 years.


Morphogenesis in Volvox: analysis of critical variables.
Inversion, the process by which Volvox embryos turn inside out, was analyzed by a combination of geometrical and experimental techniques. It was shown that simple geometric figures are adequate to represent cell shapes during inversion and that cell volumes remain constant as cell shapes change and the embryo inverts. The first stage of inversion, phialopore opening, results from the release of compressive forces as the embryo withdraws from its surrounding vesicle during a two-stage contraction of each cell around its radial axis. Premature phialopore opening occurs when withdrawal of the embryo from the vesicle is elicited artificially by exposure to either calcium ionophore or hypertonic solutions. The major event of inversion, generation of negative curvature, requires both microtubule-driven elongation of cells (to produce a classical "flask" shape) and cytochalasin-sensitive active migration of cytoplasmic bridges to the outermost ends of flask cells. Colchicine, cyclic GMP and isobutyl methyl xanthine (individually) block both normal elongation and bridge migration; cytochalasin D blocks bridge migration selectively. Flask cell formation and bridge migration are adequate to account for the negative curvature observed. An asymmetric bending of flask cell stalks along the ring of maximum curvature accounts for the fact that the embryo is not constricted in a "purse-string" fashion as negative curvature is generated. Inversion of the posterior hemisphere involves an elastic snap-through resulting from a combination of compressive stresses generated by inversion of the anterior hemisphere and the circumferential restraint imposed by cells at the equator. We conclude that the observed changes in cell shape and the migration of cytoplasmic bridges are the result of an ordered process of membrane-cytoskeletal interactions, and both necessary and sufficient to account for the morphogenetic process of inversion in Volvox.


Increasing the chemical space of proteins in living cells via genetic code expansion.
In recent years it has become possible to genetically encode an expanded set of designer amino acids with tailored chemical and physical properties (dubbed unnatural amino acids, UAAs) into proteins in living cells by expanding the genetic code. Together with developments in chemistries that are amenable to and selective within physiological settings, these strategies have started to have a big impact on biological studies, as they enable exciting in cellulo applications. Here we highlight recent advances to covalently stabilize transient protein-protein interactions and capture enzyme substrate-complexes in living cells using proximity-triggered and residue-selective photo-induced crosslinking approaches. Furthermore, we describe recent efforts in controlling enzyme activity with photocaged UAAs and in extending their application to a variety of enzymatic scaffolds. In addition, we discuss the site-specific incorporation of UAAs mimicking post-translational modifications (PTMs) and approaches to generate natively-linked ubiquitin-protein conjugates to probe the role of PTMs in modulating complex cellular networks.


Usefulness of acid and gastric juice secretion decreasing action of cimetidine in anaesthesia for the prevention of aspiration.
The effect of Histodil injection on the amount and pH of the gastric juice has been examined in women undergoing caesarean section under intratracheal anaesthesis. According to the results cimetidine decreases the volume and acidity of gastric secretion to a significantly higher extent than the pretreatment with atropine as a single agent. Maximum effect may be expected within 60-90 minutes. With Cimetidine pretreatment the risk of aspiration and pneumonitis may be prevented.


Determination of heparin in aqueous solutions.
To develop a volumetric method for assaying heparin in aqueous media. Heparin is precipitated out with an aqueous solution of an organic amine by titration and the end-point is based on the measurement of the medium dielectric permittivity. We studied the titration of a 500 IU/ml heparin solution with a 0.08 M cetylpyridinium chloride solution at pH 6.8. Then, we assayed sulphate groups selectively at pH 2. The results were compared against a classical method of SO2 determination. The sensitivity and reproducibility of the volumetric method were evaluated at pH 6.8 and compared with the characteristics of a chromogenic method, usually used for the assay of heparin in biological fluids. A linear relationship between anticoagulant activity and sulphate and carboxyl group concentration was observed. The method was less sensitive but more reproducible than the chromogenic method. The proposed method can be used for aqueous solutions and is easy to carry out. It can be fully automated and applied to formulation studies.


Switching from natalizumab to fingolimod: an observational study.
Multiple sclerosis patients who discontinue using natalizumab are at risk of a rebound in disease activity. However, the optimal alternative therapy is not currently known. We report on clinical and MRI data and patient safety in a group of relapsing-remitting multiple sclerosis patients who tested seropositive for the JC virus and who have switched from natalizumab to fingolimod because of concerns regarding PML risks. The test for JC virus antibodies was performed in 18 relapsing-remitting multiple sclerosis patients who were being treated with natalizumab for more than 1 year. Eight seropositive patients switched to fingolimod while the seronegative patients continued with natalizumab. After switching to fingolimod, five of eight patients (63%) experienced clinical relapses, and MRI activity was detected in six of eight patients (75%). Neither clinical relapses nor MRI activity was observed in the patients who continued with natalizumab. No serious adverse effects were detected. Natalizumab is an effective treatment for relapsing-remitting multiple sclerosis, but its discontinuation continues to be a complex problem. All of the therapies tried thus far, including fingolimod, have been unable to control the reactivation of the disease. Further studies addressing alternative therapies after natalizumab discontinuation are necessary.


High ratio of resting energy expenditure to body mass in childhood and adolescence: a mechanistic model.
Children have lower resting energy expenditure (REE) but higher ratio of resting energy expenditure to body mass (REE/BM) than do adults. This well-known observation has never been quantitatively explained. The aim of the present study is to understand the high REE/BM in childhood and adolescence. A mechanistic REE/BM model is proposed. Literature data on REE, BM and the masses of four high metabolic rate organs (i.e., liver, brain, heart and kidneys) of 1-18 y boys and girls were used to evaluate the proposed REE/BM model. Specifically, we tested the hypothesis that the magnitude and variation of the REE/BM can be predicted by a combination of four variables, including relative cellularity, growth energy expenditure for constructing new cells, fraction of body mass as individual organs/tissues, and their specific resting energy expenditure. The REE/BM provided by the literature is 54 kcal/kg per day at 1 year, decreasing to 26.0 kcal/kg per day at 18 years. Model-predicted REE/BM can account for 97.0% and 100.7% of the literature-reported REE/BM in males and females, respectively. The average differences between literature-reported and model-predicted REE/BM are 1.1 kcal/kg per day in boys and -0.3 kcal/kg per day in girls. The high REE/BM ratio in childhood results from two model variables: the high fraction of body mass as liver, brain, heart, and kidneys, and their high specific resting metabolic rates. The proposed REE/BM model promotes understanding of the REE, and allows a rational establishment of energy requirements for children and adolescents.


[Helicobacter pylori infection and relationship with endoscopic findings in patients treated at a referral endoscopic center in Panama].
Helycobacter pylori (HP) infection is a public health problem in Latin America with a prevalence of infection of up to 70%. There are endoscopic findings associated with the presence of infection, however we do not know the current prevalence in Panama and if the endoscopic findings are related to HP infection. To assess the frequency of HP infection in patients who underwent upper gastrointestinal endoscopy and its association with HP infection. An observational, cross-sectional and analytical study was carried out from January 1, 2019 to December 31, 2019 in the Gastroenterology service of Hospital Santo Tomás, Panama city. The frequency of HP infection in patients who underwent upper gastrointestinal endoscopy and the association of endoscopic findings with HP infection was evaluated. In total, 1,281 digestive endoscopies were performed. 21.4% of the patients included in the study confirmed HP infection. In endoscopic findings, the presence of nodular gastritis has an association OR 4.32 (2.74-6.80) with the presence of HP infection. The presence of duodenal ulcer and gastric ulcer were also significantly associated with the presence of HP infection, OR 3.71 (1.21-11.35) and OR: 2.59 (1.36-5.16). This is the first study in Panama to evaluate the association of endoscopic findings and the prevalence in a cohort of patients with an indication for upper endoscopy with the probability of Helicobacterpylori infection in the last decade. We conclude that certain endoscopic findings in an appropriate clinical context could increase the diagnostic probability of HP infection in patients seen in Panama.


Negative BOLD-fMRI signals in large cerebral veins.
Reductions in blood oxygenation level dependent (BOLD)-functional magnetic resonance imaging (fMRI) signals below baseline levels have been observed under several conditions as negative activation in task-activation studies or anticorrelation in resting-state experiments. Converging evidence suggests that negative BOLD signals (NBSs) can generally be explained by local reductions in neural activity. Here, we report on NBSs that accompany hemodynamic changes in regions devoid of neural tissue. The NBSs were investigated with high-resolution studies of the visual cortex (VC) at 7 T. Task-activation studies were performed to localize a task-positive area in the VC. During rest, robust negative correlation with the task-positive region was observed in focal regions near the ventricles and dispersed throughout the VC. Both positive and NBSs were dependent on behavioral condition. Comparison with high-resolution structural images showed that negatively correlated regions overlapped with larger pial and ependymal veins near sulcal and ventricular cerebrospinal fluid (CSF). Results from multiecho fMRI showed that NBSs were consistent with increases in local blood volume. These findings confirm theoretical predictions that tie neural activity to blood volume increases, which tend to counteract positive fMRI signal changes associated with increased blood oxygenation. This effect may be more salient in high-resolution studies, in which positive and NBS may be more often spatially distinct.


Competing Heterogeneities in Vaccine Effectiveness Estimation.
Understanding the waning of vaccine-induced protection is important for both immunology and public health. Population heterogeneities in underlying (pre-vaccination) susceptibility and vaccine response can cause measured vaccine effectiveness (mVE) to change over time, even in the absence of pathogen evolution and any actual waning of immune responses. We use multi-scale agent-based models parameterized using epidemiological and immunological data, to investigate the effect of these heterogeneities on mVE as measured by the hazard ratio. Based on our previous work, we consider the waning of antibodies according to a power law and link it to protection in two ways: (1) motivated by correlates of risk data and (2) using a within-host model of stochastic viral extinction. The effect of the heterogeneities is given by concise and understandable formulas, one of which is essentially a generalization of Fisher's fundamental theorem of natural selection to include higher derivatives. Heterogeneity in underlying susceptibility accelerates apparent waning, whereas heterogeneity in vaccine response slows down apparent waning. Our models suggest that heterogeneity in underlying susceptibility is likely to dominate. However, heterogeneity in vaccine response offsets <10% to >100% (median of 29%) of this effect in our simulations. Our study suggests heterogeneity is more likely to 'bias' mVE downwards towards the faster waning of immunity but a subtle bias in the opposite direction is also plausible.


Early therapeutic intervention in females with Fabry disease?
Anderson-Fabry disease is an X-linked lysosomal storage disorder resulting from deficiency of alpha-galactosidase A. The subsequent accumulation of globotriaosylceramide (Gb3) in cells and tissues of the body has multisystemic effects and significantly impacts upon quality of life and survival of individuals with this condition. In general, Anderson-Fabry disease is more severe in male patients; however, despite X-linkage, females may develop severe signs and symptoms of the disease, although there is considerable phenotypic heterogeneity, which correlates most closely with age. Histological analyses of biopsies have shown evidence of Gb3 storage in the kidney and heart in female patients. Gb3 levels are also elevated in the urine of females, although plasma Gb3 levels are not reliably elevated. The efficacy of enzyme replacement therapy (ERT) with recombinant human alpha-galactosidase A has been demonstrated in females in a clinical trial and in observational studies, including those using data from outcome surveys. Benefits include a reduction in left ventricular mass, stabilization of renal function and improvements in pain and quality of life. If early intervention with ERT in females is to be advocated, it is necessary to demonstrate not only that females with Anderson-Fabry disease have clinical and biochemical features of alpha-galactosidase A deficiency and respond to ERT, but also that early intervention prevents the onset of the later manifestations of the disorder. Any strategy for early therapy should also balance future advantages against any impact on quality of life.


Multilayered textile coating based on a β-cyclodextrin polyelectrolyte for the controlled release of drugs.
The aim of this work was to develop the formation of multilayered coating incorporating a cyclodextrin polyelectrolyte onto a non-woven polyethylene terephthalate (PET) textile support in order to obtain reservoir and sustained release properties towards bioactive molecules. We optimized the multilayer assembly immobilization onto the PET surface according to the layer-by-layer (LbL) deposition process. After a pre-treatment of the textile support aiming to offer a sufficient ionic character to the surface, it was alternatively immersed into two polyelectrolytes aqueous solutions consisting of chitosan (CHT) as polycation on the one hand, and a β-cyclodextrin polymer (polyCTR-βCD) as polyanion on the other hand. In a second approach, a TBBA/polyCTR-βCD complex (4-tert-butylbenzoic acid, TBBA) was used in order to load the system with a drug model whose kinetics of release was assessed. Gravimetry, microscopy, OWLS, colorimetric titration, infrared and zetametry were used as characterization techniques. An effective deposition on the textile surface due to ionic interactions with alternation of up to 10 layers of each of both polyelectrolytes was clearly evidenced. However, we observed that layer formation occurred to a lesser extent when TBBA/polyCTR-βCD complex was applied instead of polyCTR-βCD alone. The release study showed that drug reservoir properties and release kinetics could be controlled by the number of layers in the system and that TBBA release was faster than the multilayered coating degradation.


Influence of medium composition on the production of cephamycins by S. griseus and S. lactamdurans and the characterization of their growth.
The process of cephamycin biosynthesis by S. griseus and S. lactamdurans strains was investigated. The antibiotic activities of both strains in thirteen media elaborated in our laboratory were compared with those in nine media described in the literature. The best medium was that one which contained 20 g/dcm3 of glucose and 30 g/dcm3 of corn steep liquor. In this medium after a two stage shaken culture fermentation both strains showed specific growth rate from 0.027 to 0.034 h-1 and biomass yield about 5 g of dry weight per 1 dcm3. Under these conditions the highest activity was achieved after 96 hours of the fermentation.


Silver staining of unconcentrated cerebrospinal fluid in agarose gel (Panagel) electrophoresis.
We subjected cerebrospinal fluid (CSF) from 20 patients with multiple sclerosis and 20 patients with other neurological diseases to agarose gel ( Panagel ) electrophoresis followed by staining with silver. Ten microliters of unconcentrated CSF from multiple sclerosis patients containing 0.4 to 0.8 microgram of immunoglobulin G was found to be optimum for detection of oligoclonal IgG bands, so identified by immunofixation. The band patterns for unconcentrated CSF stained with silver were almost identical to those for the same CSF concentrated 40-fold and stained with Coomassie Brilliant Blue. Silver staining thus enables the clinical laboratory to electrophorese unconcentrated CSF on commercially prepared ( Panagel ) plates.


Synthesis and Biological Evaluation of Five-Atom-Linker-Based Arylpiperazine Derivatives with an Atypical Antipsychotic Profile.
Herein we describe a focused set of new arylpiperazine derivatives as potential broad-spectrum antipsychotics. The general structure contains a quinolinone-like moiety, an arylpiperazine moiety, and a five-atom linker. Among them, 7-(5-(4-(benzo[d]isothiazol-4-yl)piperazin-1-yl)pentyl)quinolin-2(1H)-one (S6) shows a promising preclinical profile. Compound S6, characterized by partial D2 R agonism, 5-HT1A R agonism, 5-HT2A R antagonism, and blockade of SERT activities, was found to decrease psychosis- and depressive-like symptoms in rodents. The polypharmacological profile of S6 could provide opportunities for the treatment of various other central nervous system disorders such as anxiety, depression, and psychoses associated with dementia. Furthermore, S6 demonstrated acceptable safety, toxicology, and pharmacokinetic profiles, and has been selected as a preclinical candidate for further evaluation in schizophrenia.


Synthesis and biological evaluation of 1,2-disubstituted carbonucleosides of 2-amino-6-substituted purine and 8-azapurine.
One, two-disubstituted carbocyclic nucleoside analogues bearing a 2-amino-6-substituted (chloro, hydroxy or amino) purine or 8-azapurine base were prepared by constructing the base about (+/-)-2-aminocyclopentane methanol, and their activities against a selection of viruses and tumor cells were determined in vitro.


Expression of epidermal growth factor receptor proto-oncogene mRNA in regenerating rat liver.
The expression of EGF receptor mRNAs in regenerating rat liver was measured using two nonoverlapping cDNA probes for the human gene from a highly conserved region. These probes (pE7 and pE62) both hybridized to RNA species of 10 and 6 kb. The 10 and 6 kb RNA species were shown to decrease in the first 12 hours after partial hepatectomy. However, significant increases above control levels were noted at 24h and 72h. The level of alpha-actin mRNA increased as has been previously reported. These results suggest that a transcriptional and/or a posttranscriptional regulatory mechanism exists in regenerating rat liver with respect to EGF receptor gene expression.


Hodgkin's disease and infectious mononucleosis.
Sequential sero-positive infectious mononucleosis is described in 3 sibs, 2 of whom subsequently developed Hodgkin's disease. EB virus antibodies were present in the serum of both cases.


Differently sized rDNA repeating units of Xenopus laevis are arranged as internally homogeneous clusters along the nucleolar organizer.
The organization of differently sized genes coding for rRNA in Xenophus laevis has been investigated by partial EcoRI or HindIII digestion. The electrophoretic patterns obtained revealed that most adjacent repeating units are equally sized. This conclusion is in agreement with a previous suggestion that the nucleolar organizer is made up of internally homogeneous blocks of rRNA genes.


Tektin interactions and a model for molecular functions.
Tektins from echinoderm flagella were analyzed for microheterogeneity, self-associations and association with tubulin, resulting in a general model of tektin filament structure and function applicable to most eukaryotic cilia and flagella. Using a new antibody to tektin consensus peptide RPNVELCRD, well-characterized chain-specific antibodies and quantitative gel densitometry, tektins A, B and C were found to be present in equimolar amounts in Sarkosyl-urea-stable filaments. In addition, two isoforms of tektin A are present in half-molar ratios to tektins B and C. Cross-linking of AB filaments indicates in situ nearest neighbor associations of tektin A1B and A2B heterodimers, -trimers, -tetramers and higher oligomers. Soluble purified tektin C is cross-linked as homodimers, trimers and tetramers, but not higher oligomers. Tektin filaments associate with both loosely bound and tightly bound tubulin, and with the latter in a 1:1 molar ratio, implying a specific, periodic association of tightly bound tubulin along the tektin axis. Similarly, in tektin-containing Sarkosyl-stable protofilament ribbons, two polypeptides ( approximately 67/73 kDa, homologues of rib72, efhc1 and efhc2) are present in equimolar ratios to each other and to individual tektins, co-fractionating with loosely bound tubulin. These results suggest a super-coiled arrangement of tektin filaments, the organization of which has important implications for the evolution, assembly and functions of cilia and flagella.


Changes in time to insulin initiation in type 2 diabetes patients: a retrospective database analysis in Germany and UK (2005-2010).
To study whether the time to insulin therapy in type 2 diabetic patients in primary care in Germany and UK has increased (2005-2010). Longitudinal data from general practices in Germany and UK (Disease Analyser) from 1995 to 2010 were analyzed. Patients who started their insulin treatment from 2005 to 2010 were analyzed regarding the time from the first diabetes diagnosis in the practices (index date) and the first insulin prescription, including 6368 patients (age: 68 (SD: 12) years) in Germany and 1998 patients (age: 64 (12) yrs) in UK. Median (interquartile range) time to insulin therapy in the practices increased from 943 (214-1994) days in 2005 to 1549 (957-2533) days in 2010 (p < 0.001). In UK, time to onset of insulin treatment increased from 1700 (649-2521) days in 2005 to 2061 (1309-2686) days in 2010 (p < 0.001). The last HbA1c values before insulin initiation were high and slightly increased during the study period (Germany: 2005: 8.2%, 2010: 8.4%; UK: 2005: 9.5%, 2010: 9.8%; both p < 0.001). This real world data shows that the time to insulin therapy has increased in type 2 diabetes patients from 2005 to 2010 (Germany, UK). The average HbA1c values before insulin therapy also slightly increased during this period.


A two-step enzymatic formation of a glucoprotein in potato tuber.
Evidence is presented on the occurrence of a two-step mechanism for the synthesis of protein bound glucan in a potato tuber particulate preparation. Experiments carried out with a differently labeled sugar donor for each step enabled the isolation of a double-labeled glucoprotein. Smith periodate degradation of the product confirmed this hypothesis.


A review on bisphenol A occurrences, health effects and treatment process via membrane technology for drinking water.
Massive utilization of bisphenol A (BPA) in the industrial production of polycarbonate plastics has led to the occurrence of this compound (at μg/L to ng/L level) in the water treatment plant. Nowadays, the presence of BPA in drinking water sources is a major concern among society because BPA is one of the endocrine disruption compounds (EDCs) that can cause hazard to human health even at extremely low concentration level. Parallel to these issues, membrane technology has emerged as the most feasible treatment process to eliminate this recalcitrant contaminant via physical separation mechanism. This paper reviews the occurrences and effects of BPA toward living organisms as well as the application of membrane technology for their removal in water treatment plant. The potential applications of using polymeric membranes for BPA removal are also discussed. Literature revealed that modifying membrane surface using blending approach is the simple yet effective method to improve membrane properties with respect to BPA removal without compromising water permeability. The regeneration process helps in maintaining the performances of membrane at desired level. The application of large-scale membrane process in treatment plant shows the feasibility of the technology for removing BPA and possible future prospect in water treatment process.


Vascular permeability to proteins and peptides in the mouse pineal gland.
The permeability of fenestrated capillaries in the mouse pineal gland to proteins and peptides was demonstrated by means of ultrastructural tracers. Horseradish peroxidase (HRP) and microperoxidase (MP) were injected intravenously and allowed to circulate for approximately 30 s, 1 min, 5 min, 1 or 2 h. The tissue was then fixed by vascular perfusion or by immersion with aldehydes. In all experiments a pronounced extravasation of HRP and MP occurred. Transendothelial vesicular transport seemed to have occurred across the fenestrated capillaries. The most pronounced tracer labeling of vesicles was found after 1 min of MP- or HRP-circulation. The vesicles were uncoated and more than 70% of the HRP- and MP-containing vesicles exhibited diameters between 50 and 110 nm. Furthermore, three other transcapillary pathways taken by the tracers are suggested: 1) via intercellular junctions, 2) through fenestrae and 3) via channels formed by fusion of vesicles with the luminal and abluminal cell membranes. Based on these results, it is assumed that the capillaries in the mouse pineal gland also permeable to peptides synthesized and secreted by the pineal gland.


Socioeconomic Deprivation Is Not Associated with Outcomes after Esophagectomy at a German High-Volume Center.
In Germany, socioeconomically deprived citizens more often develop esophageal carcinoma, since typical risk factors follow the social gradient. Therefore, we hypothesized that socioeconomic deprivation might also be associated with advanced tumor stages and comorbidities at the time of surgery. As a consequence, socioeconomic deprivation may be related to postoperative complications and reduced overall survival. Therefore, 310 patients who had undergone esophagectomy for cancer in curative intent between 2012 and 2020 at the University Medical Center Hamburg-Eppendorf (UKE) were included in this study. Socioeconomic status (SES) was estimated using the purchasing power of patients' postal codes as a surrogate parameter. No association was found between SES and tumor stage or comorbidities at the time of surgery. Moreover, SES was neither associated with postoperative complications nor overall survival. In conclusion, socioeconomic inequalities of patients treated at a high-volume center do not affect treatment outcomes.


Ofloxacin adsorptive interaction with rice husk ash: Parametric and exhausted adsorbent disposability study.
The present study investigates the adsorptive interaction of rice husk ash (RHA) with Ofloxacin (OFL) antibiotic. The OFL loaded RHA was studied for its disposability by solidification to find its possible use as a building material. Further, toxicity analysis of leachate from the solidified RHA was also studied for probable leaching of OFL. The effects of adsorption parameters such as initial pH, the dosage of RHA (m), initial OFL concentration (C0), and contact time (t) on the responses % OFL removal (X1) and adsorption capacity (mg/g) (X2) were evaluated using the central composite design (CCD) based on response surface method (RSM). Kinetic and thermodynamic studies were performed at optimized parameters, and adsorption equilibrium data were illustrated by using Langmuir, Redlich-Peterson (R-P), and Tempkin isotherm models. Optimum condition was found as m = 7.94 g/L, t = 430 min and pH = 6, and at this actual responses X1 and X2 were evaluated as 79.71% and 6.28 mg/g, respectively. Pseudo-first-order kinetic fitted best for the adsorption kinetic data. Toxicity analysis of leachate from solidified RHA indicated that most of the OFL was encapsulated inside the cement and the OFL present in leachate is not sufficient to eradicate the growth of E.coli and Bacillus subtilis.


Effects of progesterone and oestradiol-17 beta on 17 beta-ol-dehydrogenase activity in stromal cells of human endometrium under in-vitro conditions.
A 17 beta-ol-dehydrogenase activity could be demonstrated in fibroblast monolayer cell cultures of proliferative human endometrium. After 24 h incubation 100 nCi [6,7-3H]oestradiol-17 beta was completely oxidized to oestrone. Progesterone was not able to enhance the metabolizing velocity. In contrast, progesterone incubation revealed a decreasing oxidation rate with increasing molarity. Histological changes after transformation of the endometrium are discussed to explain in-vivo results showing an increased 17 beta-ol-dehydrogenase activity in the secretory phase of the cycle.


Highway to heaven: mammary gland development and differentiation.
In recent years, the mammary gland epithelium has been shown to be a mixture of differentiated cell populations in a hierarchical relationship with their stem and progenitor cells. However, the mechanisms that regulate their cellular differentiation processes are still unclear. The identification of genes that govern stem and progenitor cell expansion, or that determine daughter cell fate, will be of crucial interest for understanding breast cancer diversity and, ultimately, improving treatment. Two recent analyses have identified some of the key genes that regulate these processes, lighting up the highway to normal mammary gland development.


Sequence selectivity of DNA alkylation by adozelesin and carzelesin.
Adozelesin and carzelesin are synthetic analogues of the extremely potent antitumor antibiotic CC-1065, which alkylates N3 of adenine in a consensus sequence 5'-(A/T)(A/T)A* (A* is the site of alkylation). We have investigated the DNA sequence selectivity of adozelesin and carzelesin by thermally induced DNA strand cleavage assay using radiolabeled restriction DNA fragments. An analysis of alkylation patterns shows that the consensus sequences for carzelesin and adozelesin have been found to be 5'-(A/T)(A/T)A* and 5'-(A/T)(G/C)(A/T)A*. A new consensus sequence, 5'-(A/T)(A/T)CA*, has been observed to display an additional alkylation site for adozelesin but not for carzelesin. These results indicate that the pattern of sequence selectivity induced by carzelesin is similar but not identical to those induced by adozelesin.


Mortality and causes of death among people with convulsive epilepsy in northwestern China.
We analyzed mortality and causes of death among people with convulsive epilepsy in rural areas of northwestern China. We established a population-based prospective cohort of people with convulsive epilepsy in an epilepsy prevention and management program in rural northwestern China from January 2012 to December 2013. A uniform cause of death questionnaire was used to obtain detailed information on participants who died during the follow-up until December 2016. We calculated the standardized mortality ratios (SMRs) and proportional mortality rate for major causes of death. Cox proportional hazards regression analysis was used to investigate the risk factors associated with mortality. Among 4296 people with convulsive epilepsy, 216 died during a median follow-up of 59 months. The overall mortality rate was 10.9 per 1000 person-years, and the overall SMR was 2.0. Accidents (25.5%) ranked first in the cause of death, followed by status epilepticus (SE) (22.9%), probable sudden unexpected death in epilepsy (SUDEP) (22.7%), cerebrovascular disease (13.0%), and cardiovascular disease (6.5%). Drowning (10.6%), motor vehicle accidents (13.6%), and falls (4.6%) were the major causes of death by accidents. Female participants had a reduced risk of death from accidents with the hazard ratio (HR) of 0.3 (95% confidence interval (CI): 0.1-0.6). A high risk of death from cerebrovascular disease (HR: 7.2; 95% CI: 2.1-23.6) was found in participants with an onset age of epilepsy older than 16 years. The risk of death from convulsive epilepsy in rural northwestern China is twice that of the general population. Accidents, SE, and SUDEP are the leading putative causes of death. Educating people with epilepsy in different regions may help reduce death-related events.


Development of auditory brainstem response to tone pip stimuli in the rat.
The course of development of the auditory brainstem response (ABR) in rat was examined. Pure tone pip stimuli of 3, 8 and 40 kHz at intensities up to 106 dB sound pressure level peak equivalent were presented to anesthetized rats on postnatal days (PND) 9, 10, 12, 14, 16, 20, 24, 36, 70 and 96. The peak-to-peak amplitude and the order of appearance of each wave was examined at each stimulus parameter. The first response to presentation of an auditory stimulus was observed on PND 12. This response was demonstrated to be of non-neural origin and presumed to be a summating potential representing hair cell function in the cochlea. The first neural responses, observed on PND 14, to 3- and 8-kHz tones only, appeared as two or more waves. High-frequency (40 kHz) tones did not elicit any substantive neural response on PND 14, but neural activity to this stimulus was observed consistently by PND 16. By PND 20, 4 waves were present consistently at all test frequencies, and by PND 36 the full adult complement of 5 vertex positive waves was recorded. The frequency-dependent sequential appearance of waves during development lends support to data charting the development of frequency mapping in the cochlea. The amplitude of waves I and II at 8 kHz decreased as the animal matured, while waves III-V generally showed an initial increase in amplitude at all test frequencies through PND 24 followed by a gradual amplitude decrease to adult levels. Possible sources for developmental changes in amplitude are discussed.


Selection and identification of streptomycin-specific single-stranded DNA aptamers and the application in the detection of streptomycin in honey.
Single-stranded DNA (ssDNA) aptamers specific to streptomycin were screened and identified from a random oligonucleotides library by affinity magnetic beads-based SELEX. After eight rounds of selection, 16 ssDNA with different sequences were identified. Then the dissociation constants (Kd) of these ssDNA were determined and an aptamer (STR1) with highest affinity for streptomycin was identified. Further study showed that aptamer STR1 exhibits very low affinity for other aminoglycoside antibiotics, indicating high specificity. With this aptamer, detection of streptomycin was achieved by using gold nanoparticles (AuNPs)-based colorimetric method. In the presence of streptomycin, the competitive binding of the target and the aptamer decreases the stability of AuNPs in NaCl solution, triggers the aggregation, and exhibits visible color change of AuNPs solution. Through UV-visible spectroscopic quantitative analysis, streptomycin can be detected in the range of 0.2-1.2 μM. The presence of other aminoglycoside antibiotics shows neglectable disturbance. Furthermore, the established method was utilized to detect streptomycin in honey, and the same low detection limit and linear detection range were achieved.


Interactions between CAP70 and actinfilin are important for integrity of actin cytoskeleton structures in neurons.
The integrity of dynamic actin structures is coupled to a variety of neurological processes. Actin-binding proteins play a critical role in regulating actin structure dynamics. A link between actin-binding proteins and receptor interacting scaffolding proteins may provide a conduit for transmitting signaling events to the cytoskeleton. Actinfilin is a brain-enriched actin-binding protein, though its functions are currently unknown. We report here that actinfilin interacts with the multi-PDZ domain protein CAP70. Recombinant expression of an actin-binding domain of actinfilin progressively causes marked changes of cellular morphology. The effect on cell morphology may be reduced by co-expression with CAP70. Mutation of actinfilin lacking the ability to interact with CAP70 abolished the effect by CAP70. The evidence suggests a role of actinfilin and possible regulation by scaffolding proteins.


Satellite Cell Heterogeneity in Skeletal Muscle Homeostasis.
The cellular turnover required for skeletal muscle maintenance and repair is mediated by resident stem cells, also termed satellite cells. Satellite cells normally reside in a quiescent state, intermittently entering the cell cycle to fuse with neighboring myofibers and replenish the stem cell pool. However, the mechanisms by which satellite cells maintain the precise balance between self-renewal and differentiation necessary for long-term homeostasis remain unclear. Recent work has supported a previously unappreciated heterogeneity in the satellite cell compartment that may underlie the observed variability in cell fate and function. In this review, we examine the work supporting this notion as well as the potential governing principles, developmental origins, and principal determinants of satellite cell heterogeneity.


Effects of successful intravenous reperfusion therapy on regional myocardial function and geometry in humans: a tomographic assessment using two-dimensional echocardiography.
This study tested the hypothesis that reperfusion therapy might provide benefit at two levels: 1) by arresting infarct migration at the endocardial level, such that partial or complete recovery of regional function occurs; and 2) if the former is not achieved, by preventing complete or near complete transmural migration and subsequent infarct expansion. To test this hypothesis, 24 patients who received intravenous streptokinase therapy within 4 h of chest pain were studied prospectively. All patients underwent two-dimensional echocardiography at the time of admission and 1, 2, 3 and 10 days later. The patients also underwent coronary angiography 2 h after completion of streptokinase therapy. Although 18 (75%) of the 24 patients had a patent infarct-related artery, only 8 (45%) of the 18 patients with this finding showed improvement in regional function. Improvement was not evident until 3 to 10 days after streptokinase therapy. In addition to the presence of an open infarct-related artery, the interval between chest pain and onset of streptokinase therapy (2.5 +/- 0.5 versus 3.2 +/- 0.7 h, p = 0.02) differed significantly between patients who did or did not show improved regional function. Of the 15 of 16 patients with no improvement in regional function, 4 showed infarct expansion, and all had a closed infarct-related artery compared with only 2 of the 11 not showing expansion (p = 0.01). In conclusion, intravenous streptokinase given within 4 h of chest pain results in improvement in regional function in about 33% of the patients, presumably by arresting the infarction within the endocardium.(ABSTRACT TRUNCATED AT 250 WORDS)


Computed tomography of the retroperitoneal space.
Computed body tomography is an easily accomplished method that precisely displays the normal and pathologic anatomy of the retroperitoneal space. Suspected retroperitoneal disorders, which are often clinically confusing or obscure, can now be detected or excluded with remarkable accuracy. Few innovations in radiology have more effectively fulfilled such a conspicuous need.


Topographic representation of periodicities in the forebrain of the mynah bird: one map for pitch and rhythm?
Coding of amplitude modulated acoustic stimuli was studied within isofrequency planes of the tonotopically organized field L, the avian analogue of the mammalian auditory cortex. The synchronization of unit responses to envelopes of sinusoidally amplitude modulated tones (AM) and repetitive noise bursts (RN) were determined as a function of envelope frequency (EF). From 249 synchronizing units, 66% were tuned to a best envelope frequency (BEF) using a synchronization criterion. BEFs varied from 0.3 to 380 Hz and showed an orderly representation within isofrequency planes orthogonal to the lamination of field L. The majority (68%) of these units had BEFs below 20 Hz down to 0.3 Hz. Thus, they were tuned to rhythms typical for animal communication sounds, speech, and music. Thirty-two % had BEFs between 20 Hz and 380 Hz and covered at least 4 of 5 octaves of the range of periodicity pitch sensation.


Intact Transition Epitope Mapping - Thermodynamic Weak-force Order (ITEM - TWO).
We have developed an electrospray mass spectrometry method which is capable to determine antibody affinity in a gas phase experiment. A solution with the immune complex is electrosprayed and multiply charged ions are translated into the gas phase. Then, the intact immune-complex ions are separated from unbound peptide ions. Increasing the voltage difference in a collision cell results in collision induced dissociation of the immune-complex by which bound peptide ions are released. When analyzing a peptide mixture, measuring the mass of the complex-released peptide ions identifies which of the peptides contains the epitope. A step-wise increase in the collision cell voltage difference changes the intensity ratios of the surviving immune complex ions, the released peptide ions, and the antibody ions. From all the ions´ normalized intensity ratios are deduced the thermodynamic quasi equilibrium dissociation constants (KDm0g#) from which are calculated the apparent gas phase Gibbs energies of activation over temperature (ΔGm0g#T). The order of the apparent gas phase dissociation constants of four antibody - epitope peptide pairs matched well with those obtained from in-solution measurements. The determined gas phase values for antibody affinities are independent from the source of the investigated peptides and from the applied instrument. Data are available via ProteomeXchange with identifier PXD016024. SIGNIFICANCE: ITEM - TWO enables rapid epitope mapping and determination of apparent dissociation energies of immune complexes with minimal in-solution handling. Mixing of antibody and antigen peptide solutions initiates immune complex formation in solution. Epitope binding strengths are determined in the gas phase after electrospraying the antibody / antigen peptide mixtures and mass spectrometric analysis of immune complexes under different collision induced dissociation conditions. Since the order of binding strengths in the gas phase is the same as that in solution, ITEM - TWO characterizes two most important antibody properties, specificity and affinity.


Evaluation of iron-deficiency anemia by an iron supplementation trial in children living at a 2,800-m altitude.
Hemoglobin, hematocrit, serum iron and total iron-binding capacity were measured in 38 apparently healthy children living in Quito (2:800 meters in altitude). One child was considered anemic according to the WHO reference adjusted to altitude (hemoglobin less than 12.3 g/dl) and 10 had transferrin saturation of less than 15%. Thirty children received orally 2 mg/kg per day of elemental iron for 3 mth. A significant increase in hemoglobin level, serum iron-concentration, and transferrin saturation, and a significant decrease in total iron-binding capacity were observed. Nine children increased their hemoglobin concentration by greater than 1 g/100 ml and could be considered as true anemics. At the end of the supplementation, only one child had a transferrin saturation coefficient of less than 15%. WHO references for hemoglobin adjusted to altitude seem to underestimate the prevalence of anemia for populations living at high altitudes.


Serum intercellular adhesion molecule (ICAM-1), a marker of renal scarring in infants with vesico-ureteric reflux.
To determine if serum intercellular adhesion molecule (ICAM-1) levels correlate with renal scarring in children with vesico-ureteric reflux (VUR). Serum ICAM-1 levels were measured in 81 children (29 boys and 52 girls, age range 2 months-13 years) with VUR using an enzyme-linked immunosorbent assay (ELISA) and compared with levels in a control group of 24 children (16 boys and eight girls, age range 2 days-13 years) with no urological abnormalities. The mean serum ICAM-1 level in the control group was 202 +/- 79 ng/mL (mean +/- 1 SD) compared with 347 +/- 96 ng/mL in children with VUR (P < 0.001). Fifteen of 26 children under 2 years of age demonstrated renal scarring while 18 of 44 children older than 2 years exhibited renal scarring. The mean serum ICAM-1 level in patients who were < 2 years of age and had renal scarring was 408 +/- ng/mL, significantly higher than in those who had no renal scarring (296 +/- 68 ng/mL, P < 0.01). In contrast, there was no difference in serum ICAM-1 levels in patients > 2 years of age with or with no renal scarring (353 +/- 87 and 325 +/- 91 ng/mL, respectively). Serum ICAM-1 levels are significantly higher in children with VUR and may represent a valuable marker of tubular damage in younger children with VUR.


Retroperitoneal blue cell round tumor (Ewing sarcoma in a 35 years old male)- case report.
Ewing sarcoma is a highly aggressive tumor. It's common presentation is primary bone tumor, but very rarely as soft tissue sarcoma both of which are under the spectrum of Ewing sarcoma family of tumors (EFT). A 35 years old male who presented with advanced locally spreading tumor. He was diagnosed after presenting with epigastric pain and melena, CT abdomen revealed the retroperitoneal mass. CT guided core biopsy taken and was diagnosed as Ewing sarcoma. The patient presented with mass already grown so he was not a surgical candidate. Patient was managed symptomatically till he was sent for palliative care in a Sarcoma centre in Jordon and passed away on October 2021. Ewing Sarcoma family of tumors are group of small round blue cell tumors that are histogenetically related. The better known is Ewing 's sarcoma (EWS). It is a malignant small blue round cell tumor with variable degree of neuroectodermal differentiation. Retroperitoneal tumor are mostly malignant and accounts for one third of soft tissue sarcoma. They usually present as large masses at the time of the diagnosis. So they do not produce symptoms until they grow large enough to compress or invade contagious structures. ES-EWS is an aggressive tumor with high incidence of local recurrence and distant metastasis that's why is was given its poor prognosis characteristic. Multimodality treatment including surgical resection, chemotherapy and High dose radiotherapy will help in better survival rate.


Direct correlation between level of morphine and its biochemical effect on monoamine systems in mouse brain. Evidence for involvement of dopaminergic neurons in the pharmacological action of acute morphine.
The pharmacokinetics (uptake and elimination) and pharmacodynamics (biochemical effects on monoamine systems) of morphine in the CNS were investigated concurrently. ICR mice, weighing about 25 g, were injected intravenously with several doses (2.5-80 mg/kg) of morphine. The animals were killed by microwave irradiation (5 kW, 0.6 sec) at 10 and 30 min, and 1, 2, 4, 8 and 24 hr after the injection. The intracerebral levels of morphine and metabolically related substances consisting of monoamines [noradrenaline, dopamine (DA), 5-hydroxytryptamine (5-HT), 3, 4-dihydroxyphenylacetic acid (DOPAC), 3-methoxy-4-hydroxyphenylacetic acid [homovanillic acid (HVA)], 5-hydroxyindoleacetic acid (5-HIAA), tyrosine and tryptophan] were determined in identical samples by a combination of organic extraction and high-performance liquid chromatography with electrochemical detection. The intracerebral level of morphine was found to depend on the dose injected, and the biological half-life of the drug was estimated to be about 1 hr. The morphine injection (2.5-80 mg/kg) caused significant increases in monoamine metabolites although only slight changes occurred in the concns of parent transmitters. The intracerebral level of morphine was significantly correlated with the ratios DOPAC/DA and HVA/DA (r = 0.7033, P less than 0.0001; and r = 0.6455, P less than 0.0001, respectively). On the other hand, the correlation between the morphine level and 5-HIAA/5-HT was lower than those for DOPAC/DA and HVA/DA. These results suggest that monoamine systems, especially DA, are closely involved in the biochemical effects of morphine. Furthermore, the proposed procedure is demonstrated to be useful as a new approach in biochemical pharmacology, where the direct correlation between the distribution of a drug (pharmacokinetics) and the biochemical effects of the drug (pharmacodynamics) can be measured.


Update on Retinal Drug Toxicities.
This review aims to provide an update on the clinical presentations and diagnostic findings of drug-induced retinal toxicities. Several newly FDA-approved medications have been associated with acute retinal toxicities, including brolucizumab, MEK inhibitors, ulixertinib, and FGFR inhibitors. Additionally, as previously believed-to-be well-tolerated medications, such as pentosan sulfate sodium, anti-retroviral therapies, and certain intraoperative ocular medications, are used more frequently or for longer periods of time, associated toxic retinopathies and inflammatory reactions have been reported. Finally, advances in ocular imaging have revealed novel findings in hydroxychloroquine and tamoxifen maculopathies. Discovery of new medications, increased frequency of use, and longer-term use have led to increased reports of retinal toxicities. Advances in retinal imaging have allowed for earlier detection of subclinical changes associated with these medications, which may help prevent progression of disease. However, more research is needed to determine the point at which vision loss becomes irreversible. Risks and benefits must be assessed prior to discontinuation of the offending, but potentially lifesaving, therapy.


Antibiotic-impregnated calcium phosphate cement as part of a comprehensive treatment for patients with established orthopaedic infection.
The treatment of established orthopaedic infection is challenging. While the main focus of treatment is wide surgical debridement, systemic and local antibiotic administration are important adjuvant therapies. Several reports have described the clinical use of antibiotic-impregnated calcium phosphate cement (CPC) to provide local antibiotic therapy for bone infections. However, these were all individual case reports, and no case series have been reported. We report a case series treated by a single surgeon using antibiotic-impregnated CPC as part of a comprehensive treatment plan in patients with established orthopaedic infection. We enrolled 13 consecutive patients with osteomyelitis (n = 6) or infected non-union (n = 7). Implantation of antibiotic-impregnated CPC was performed to provide local antibiotic therapy as part of a comprehensive treatment plan that also included wide surgical debridement, systemic antibiotic therapy, and subsequent second-stage reconstruction surgery. We investigated the rate of successful infection eradication and systemic/local complications. The concentration of antibiotics in the surgical drainage fluids, blood, and recovered CPC (via elution into a phosphate-buffered saline bath) were measured. The mean follow-up period after surgery was 50.4 (range, 27-73) months. There were no cases of infection recurrence during follow-up. No systemic toxicity or local complications from the implantation of antibiotic-impregnated CPC were observed. The vancomycin concentration in the fluid from surgical drainage (n = 6) was 527.1 ± 363.9 μg/mL on postoperative day 1 and 224.5 ± 198.4 μg/mL on postoperative day 2. In patients who did not receive systemic vancomycin therapy (n = 3), the maximum serum vancomycin level was <0.8 μg/mL. In vitro vancomycin elution was observed from the CPC that was surgically retrieved (n = 2). Implantation of antibiotic-impregnated CPC is an option to provide local antibiotic therapy as part of a comprehensive treatment plan.


A device for determining the position of intraoral distractors for protracting the maxilla.
Distraction osteogenesis of the maxilla is indicated for jaw deformities in patients with extreme dysgnathia. First, extraoral appliances were introduced, and currently intraoral appliances are in vogue. These have significantly reduced the amount of physical and psychological stress placed on the patients. The direction of force vector may be varied according to the individual patient's requirements. This paper presents positioning devices for bilateral intraoral maxillary distraction plates, which have been developed to place maxillary distraction plates parallel to the direction of lengthening.


Cerebral infarction due to carotid occlusion and carbon monoxide exposure. II. Influence of preganglionic cervical sympathectomy.
Unilateral cerebral infarcts were produced in the rat by ligation of one common carotid artery and subsequent exposure to carbon monoxide. The incidence and extension of brain infarcts was increased in animals with additional ipsilateral cervical preganglionic sympathectomy. Sympathectomy did not affect markedly the respiration and systemic circulation. The effect of sympathectomy was attributed to a cutaneous vasodilation, leading to an extracranial steal phenomenon.


The life and death of the germinal center.
The formation, development and dissolution of germinal centers is a major part of immune system function. It is important to differentiate neoplastic processes from follicular hyperplasia and regressive follicular changes. Better understanding of germinal center development and dissolution also provides diagnostic clues to the underlying pathologic process. It is also important in identifying the immune basis of different pathologic entities as well as in immunotherapy decision making and follow up. In this study, we characterize the immunoarchitecture of lymphoid follicles with a focus on germinal center in one representative case, each of commonly encountered benign and malignant lymph node disorders, with morphologic and immunohistochemical alterations of germinal centers. The cases include reactive follicular hyperplasia (FH), florid follicular hyperplasia (FFH), follicular lymphoma (FL), angioimmunoblastic T-cell lymphoma (AITL), hyaline-vascular Castleman disease (HVCD), progressive transformation of germinal centers, nodular lymphocyte predominant Hodgkin lymphoma (NLPHL), lymphocyte-rich classic Hodgkin lymphoma (LR-CHL), human immunodeficiency virus (HIV)-associated follicular dissolution and chronic lymphocytic leukemia (CLL) with proliferation centers (PC). A panel of antibodies were used namely CD3, CD20, CD10, BCL2, BCL6, CD21, CD23, CD35, FOXP1, GCET1, HGAL/GCET2, LMO2, MUM1, IgD, Ki67, PD1 and PD-L1. We found that these entities show distinct immunoarchitectural patterns of germinal center formation, development and regression, particularly, the distribution of mantle zone B-cells, follicular helper T cells (Tfh) and FDC meshworks, confirming the influence of antigenic stimulation and status of immune system in these changes. This also confirms the interrelationship of underlying immunologic mechanisms in these disease processes.


[Automatic enzymatic determination of urea nitrogen].
Six BUN kits available on the market, applied on selective chemistry analyzer, shown acceptable accuracy, good stability and linearity, "borderline" within-day and among-day standard deviations. The cause is investigated, particularly in the dispenser of the analyzer for delivering samples and reagents.


Characteristics of temperature evolution from 1960 to 2015 in the Three Rivers' Headstream Region, Qinghai, China.
The cumulative anomaly analysis, the ensemble empirical mode decomposition (EEMD), the Bernaola Galvan heuristic segmentation algorithm (BGSA), the Le Page test, the moving t test at different sub-series scales, and the quasi-periodic oscillations (QPOs) were used to demonstrate the statistical characteristics of the temperature changes in the study area from 1960 to 2015. The results were as follows: the temperatures varied obviously among subregions and seasons and they generally increased; the climate tendency rates of autumn mean temperatures were higher than those of summer and spring; additionally, the temperatures in the three subregions of the Three Rivers' Headstream Region (THRHR) were relatively low in the 1960s, especially in the early 1960s, followed by those in the 1970s, and the annual mean temperature has been increasing since the mid-late 1980s, especially in the middle 1990s. The results of EEMD showed that the QPOs of the annual mean temperature series in the study area were mainly quasi-3 years, quasi-5-8 years, quasi-12-15 years, and quasi-35-38 years. The results of the annual mean temperature series mutational sites showed that a significant warming mutation began in approximately 1997; and the mutational sites of seasonal mean temperature series in the three subregions of the THRHR all began in the middle and late 1990s. The prediction result of the temperature series trend based on multiple methods showed that the warming persistence of annual and seasonal mean temperature series would be stronger, and their seasonal and regional differences were obvious.


Design and synthesis of new potent 5-HT7 receptor ligands as a candidate for the treatment of central nervous system diseases.
Owing to their multifunctional pharmacological profiles (including dual 5-HT1A/5-HT7 action), arylpiperazine derivatives are widely used for treating central nervous system diseases including the depression or neuropathic pain. Herein we describe the design, synthesis and evaluation of biological activity of novel 5-HT7 ligands derived of 2,4,6-triamino-1,3,5-triazine. The studied compounds showed affinity and high selectively towards 5-HT7 receptor with the two most active compounds 34 (Ki = 61 nM), 22 (Ki = 109 nM) showing good metabolic stability and moderate affinity to CYP3A4 isoenzyme. Compound 22 had high hepatotoxicity at a concentration below 50 μM, while compound 34 showed low hepatotoxicity even at a concentration above 50 μM.


Gender differences in the impact of diabetes on mortality in patients with established coronary artery disease: a report from the eastern Taiwan integrated health care delivery system of Coronary Heart Disease (ET-CHD) registry, 1997-2006.
The effect of type 2 diabetes mellitus (DM) on mortality was more pronounced in women than men with coronary artery disease (CAD) in the pre-stent era before 1996. However this relationship is controversial in the post-stent era. We studied a cohort of 1073 patients with angiographically defined CAD from the Eastern Taiwan integrated health care delivery system of Coronary Heart Disease (ET-CHD) registry during 1997-2003 in Tzu-Chi General Hospital, Hualien, Taiwan. To evaluate gender-specific DM effect on mortality, the subjects were divided into 4 groups: diabetic women (n=147), non-diabetic women (n=127), diabetic men (n=239), and non-diabetic men (n=560). At a mean follow-up of 5.4 years, cardiac and all-cause mortality were the primary end points. Annual total mortality rates were 10.2%, 5.1%, 7.2%, and 4.8%; annual cardiac mortality rates were 8.2%, 3.0%, 4.3%, and 2.6% for diabetic women, non-diabetic women, diabetic men, and non-diabetic men, respectively. Multivariate Cox regression models, adjusted for possible confounders showed that gender-specific hazard ratios (HRs) of DM for total mortality were 2.02 (95% CI: 1.32-3.09), and 1.72 (95% CI: 1.32-2.25) for women and men, respectively. The HRs for total mortality associated with diabetes were not different between women and men (p=0.53). Similarly, adjusted gender-specific HRs of DM for cardiac mortality were 2.46 (95% CI: 1.45-4.19) for women, and 1.83 (95% CI: 1.28-2.62) for men, which were also not significantly different (p=0.36). Among patients with CAD, the impact of DM on mortality was consistently higher in women than in men, but the differences across sexes were not statistically significant after 1996 in Taiwan.


Glycerophosphorylcholine phosphocholine phosphodiesterase activity during the differentiation of glial progenitor cells.
O-2A progenitor cells were grown in medium containing either 1% or 10% fetal calf serum (FCS) for 4 weeks. The cells in 1% FCS were 75% oligodendrocytes by 3 weeks in culture. The cell population was so overgrown with astrocytes in the 10% medium that an accurate estimate of cell number could not be made. The activities of glycerophosphorylcholine phosphocholine phosphodiesterase (GPC-PC-PdE), p-nitrophenylphosphorylcholine phosphodiesterase (pNPPC-PC-PdE), and ceramide UDP galactose galactosyl transferase (CGalT) were barely detectable in the cells grown in 10% FCS. The activities of these 3 enzymes were low in the cells grown in 1% FCS for the first 2 weeks and then all 3 increased manyfold. These observations reinforce the evidence previously accrued showing that these two phosphodiesterase activities (GPC-PC-PdE and pNPPC-PC-PdE) are markers of oligodendroglial cells as well as myelin. In contrast, glycerophosphorylcholine choline phosphodiesterase (GPC-C-PdE) activities were present in cells grown in both 1% and 10% FCS.


Proteoglycans of bovine cementum: isolation and characterization.
The proteoglycans associated with the mineralized matrix of bovine cementum have been studied biochemically and their distribution within this tissue localized immunohistochemically. Both hyaluronate and proteoglycans were fractionated by DEAE-Sephacel ion-exchange chromatography. The proteoglycans eluted in three separate peaks of which two contained alkali labile protein associated with glycosaminoglycans, and one appeared as free glycosaminoglycan chains. Analysis of the glycosaminoglycans identified chondroitin sulfate as the predominant species, although minor quantities of dermatan sulfate and heparan sulfate were also identified. Agarose-acrylamide gel electrophoresis and Sepharose CL-6B molecular sieve chromatography of the proteoglycans indicated them to be smaller in size with respect to periodontal ligament and gingival proteoglycans, but similar to bone and dentine proteoglycans. Amino acid analyses indicated subtle differences between cementum and bone proteoglycans. Using a monoclonal antibody (9-A-2) which recognizes the unsaturated disaccharide of chondroitinase ACII-digested glycosaminoglycans, chondroitin sulfate was identified in the pericellular environment within the lacunae housing the cementoblasts as well as in the extracellular matrix of cementum.


Aryepiglottic fold width in patients with epiglottitis: where should measurements be obtained?
To determine the best site for measurement or assessment of the aryepiglottic folds and determine whether evaluation of the lower portion of the folds is useful. The lateral neck radiographs from 38 children with epiglottitis were retrospectively reviewed and compared with findings in 100 patients with croup and 100 control patients. In all patients, the fold thickness was measured at three levels: at the midpoint (site 1), just behind the epiglottis (site 2), and at the base, just above the false vocal cords (site 3). Full-thickness measurements obtained at sites 1 and 2 were statistically significant predictors of epiglottitis (sensitivity, 94.74%; specificity, at least 96.50%) in comparison with those obtained in patients with croup and control patients. The best site for width assessment is the upper half of the folds. Measurement at the base, where the folds overlie the arytenoid cartilage, is not nearly as accurate and should be avoided.


SPION-mediated soil DNA extraction and comparative analysis with conventional and commercial kit-based protocol.
Direct isolation of soil DNA comes as an emerging technology to understand the microbial diversity of a particular environment circumventing the dependency on culturable methods. Soil DNA isolation is tough due to the presence of various organic components present in soil which interfere in extraction procedure. Here, we report a novel direct soil DNA extraction protocol utilizing bare superparamagnetic iron oxide nanoparticles and its comparison with conventional and commercial kit-based soil DNA extraction methods. The quality, quantity and feasibility of the recovered DNA from all the three methods towards various molecular techniques were checked. Our magnetic nanoparticle-based soil DNA extraction successfully yields pure DNA without any RNA or protein contamination as revealed by the nanodrop spectrophotometer and agarose gel electrophoretic study. Different methods of soil DNA extraction were evaluated on the basis of PCR, denaturing gradient gel electrophoresis and real-time PCR. Soil DNA extracted using conventional method fails to carry out critical molecular biology techniques where as magnetic nanoparticle-based soil DNA extraction gave good results which is comparable to commercial kit. This comparative study suggests that protocol described in this report is novel, less time consuming, cost effective with fewer handling steps and yields high quantity, good quality DNA from soil.


Domino reactions consisting of heterocyclization and 1,2-migration-redox-neutral and oxidative transition-metal catalysis.
Two cats, two paths: two novel domino reactions starting from 6-hydroxy-2-alkyl-2-alkynylcyclohexanones have been discovered. While redox-neutral platinum catalysis gives rise to furans through a sequence of cyclization, 1,2-shift, and Grob fragmentation, oxidative copper catalysis provides an entry to bicyclic 2,3-dihydrofurans. Upon cyclization and oxidation, an unusual benzilic acid rearrangement can take place in this case.


Clinical Performance of the cobas Liat SARS-CoV-2 & Influenza A/B Assay in Nasal Samples.
Point-of-care type molecular diagnostic tests have been used for detecting SARS-CoV-2, although their clinical utility with nasal samples has yet to be established. This study evaluated the clinical performance of the cobas Liat SARS-CoV-2 & Influenza A/B (Liat) assay in nasal samples. Nasal and nasopharyngeal samples were collected and were tested using the Liat, the cobas 6800 system and the cobas SARS-CoV-2 & Influenza A/B (cobas), and a method developed by National Institute of Infectious Diseases, Japan (NIID). A total of 814 nasal samples were collected. The Liat assay was positive for SARS-CoV-2 in 113 (13.9%). The total, positive, and negative concordance rate between the Liat and cobas/NIID assays were 99.3%/98.4%, 99.1%/100%, and 99.3%/98.2%, respectively. Five samples were positive only using the Liat assay. Their Ct values ranged from 31.9 to 37.2. The Ct values of the Liat assay were significantly lower (p < 0.001) but were correlated (p < 0.001) with those of other molecular assays. In the participants who tested positive for SARS-CoV-2 on the Liat assay using nasopharyngeal samples, 88.2% of their nasal samples also tested positive using the Liat assay. The Liat assay showed high concordance with other molecular assays in nasal samples. Some discordance occurred in samples with Ct values > 30 on the Liat assay.


A retrospective analysis of azacitidine treatment for juvenile myelomonocytic leukemia.
Juvenile myelomonocytic leukemia (JMML) is a pediatric hematological malignancy with a poor prognosis. Although several case series have been published describing hematological and molecular responses to azacitidine (AZA) treatment in patients with JMML, the efficacy and safety profile of AZA is not well investigated, especially in Asian children and children undergoing hematopoietic stem cell transplantation (HSCT). We retrospectively analyzed 5 patients who received a total of 12 cycles (median 2 cycles) of AZA treatment in Japan. All five patients were boys and their ages at the time of treatment were 21, 23, 24, 26, and 46 months, respectively. All five patients tolerated AZA treatment, including four patients who received AZA after HSCT. Therapeutic toxicity with AZA was mostly limited to hematological toxicity. The only serious non-hematological adverse event was hyperbilirubinemia (grades III-IV) observed in a patient who received AZA after a second HSCT. Two out of five patients treated with AZA achieved a partial response (PR), while three patients treated for post-transplant relapse did not have an objective response. Future prospective studies should be conducted to develop combination therapies with AZA and other molecular targeted drugs for high-risk patients.


Slurry nebulization for the analysis of gypsum and cement by inductively coupled plasma spectrometry.
The usual form of presentation for a sample to be analyzed by an inductively coupled plasma-optical emission spectrometer is in the form of a liquid. For the analysis of solids, this involves a dissolution step and in the case of complex matrices this may be long and difficult. Should it be possible to analyse the sample without prior dissolution, then the problems associated with obtaining a solution would be resolved. A method for analyzing samples is to make use of slurry nebulization. Samples with complex matrices, such as cement and gypsum were selected and analysed as in the form of a slurry. Using different concentrations of a certified reference materials, calibration curves were obtained, from which the unknown samples could be determined directly. Use of aqueous solutions for calibration was also investigated. The method was evaluated using other reference materials or results obtained by an independent laboratory using different technique for the analysis. The slurry method was found to be accurate and precise.