Additive effect of lipid lowering drug (simvastatin) in combination with antidiabetic drug (glibenclamide) on alloxan induced diabetic rats with long term dyslipidemia.
High blood glucose level, elevated level of liver enzyme, necrosis and shrinkage of islets of Langerhans has been implicated in the pathogenesis of type 2 diabetes. High blood glucose cause oxidative stress, production of free radical as well as elevated SGPT and SGOT level. Both glibenclamide and simvastatin in fixed dose used as antihyperglycemic antidyslipidemic and antioxidative agents for type 2 diabetes treatment. This study therefore aimed to evaluate the antihyperglycemic, antidyslipidemic and antioxidative effect of fixed dose combination of glibenclamide (0.6 mg/70 kg body weight) and simvastatin (5 mg/70 kg body weight) on long term alloxan induced diabetic rats with cardiovascular disease using various diagnostic kits as a parameter of phamacotherapeutic and pharmacological effect. The study was carried out using 96 Swiss Albino male rats weighing about 200-220 g. Combination therapy induced a significant decrease in blood glucose level in alloxan induced diabetic rats, from 33.75 ± 1.65 to 5.80 ± 0.07 mmol/l 2 h after last dose administration, after 4 weeks treatment. In case of dyslipidemic effect, combination therapy reduced total cholesterol (45 %), triglyceride (36 %) and low density lipoprotein-cholesterol (32 %) levels significantly and increased high density lipoprotein-cholesterol level (57 %) in comparison with their respective diabetic control groups. Results of this study showed that combination therapy effectively decreased SGPT (ALAT) (55 %) and SGOT (ASAT) (51 %) in comparison with diabetic control group. It was also observed that catalase and superoxide dismutase enzyme activity was increased by 58 and 91 % respectively in comparison with diabetic control group after 4 weeks treatment with combination of both drugs. In conclusion, these findings of combination therapy (glibenclamide and simvastatin) on alloxan induced diabetes in rats are significantly better than monotherapy using single drug. The results of the present study suggest that, combination of the fixed dose of glibenclamide and simvastatin might be efficacious in patients with diabetic dyslipidemia and increased oxidative stress. Furthermore, this combination therapy offer dosage convenience to the patients and by virtue of its dual mode of action might be a useful addition to the therapeutic armamentarium for patients with diabetic dyslipidemia and oxidative stress.


Mixed neuroendocrine-non-neuroendocrine carcinoma (MiNEN) in gallbladder with liver metastasis of neuroendocrine carcinoma component: a case report.
Mixed neuroendocrine-non-neuroendocrine neoplasms of the gallbladder are rare with a lack of established standardized therapeutic strategies. We report a case of gallbladder mixed neuroendocrine-non-neuroendocrine neoplasm with liver metastasis of neuroendocrine carcinoma. A patient who underwent radical cholecystectomy for gallbladder adenocarcinoma was detected with increasing liver mass, and hepatectomy was performed. Pathological report revealed neuroendocrine carcinoma. To find primary origin, pathological review of the old specimen from previous cholecystectomy with a slightly different perspective was conducted, where the neuroendocrine component was positively dyed. In conclusion, though it might be impossible to review every pathological result in cases with ambiguous findings, reviewing the previous specimen can be a useful option in diagnosis.


Increased antibody affinity confers broad in vitro protection against escape mutants of severe acute respiratory syndrome coronavirus.
Even though the effect of antibody affinity on neutralization potency is well documented, surprisingly, its impact on neutralization breadth and escape has not been systematically determined. Here, random mutagenesis and DNA shuffling of the single-chain variable fragment of the neutralizing antibody 80R followed by bacterial display screening using anchored periplasmic expression (APEx) were used to generate a number of higher-affinity variants of the severe acute respiratory syndrome coronavirus (SARS-CoV)-neutralizing antibody 80R with equilibrium dissociation constants (K(D)) as low as 37 pM, a >270-fold improvement relative to that of the parental 80R single-chain variable fragment (scFv). As expected, antigen affinity was shown to correlate directly with neutralization potency toward the icUrbani strain of SARS-CoV. Additionally, the highest-affinity antibody fragment displayed 10-fold-increased broad neutralization in vitro and completely protected against several SARS-CoV strains containing substitutions associated with antibody escape. Importantly, higher affinity also led to the suppression of viral escape mutants in vitro. Escape from the highest-affinity variant required reduced selective pressure and multiple substitutions in the binding epitope. Collectively, these results support the hypothesis that engineered antibodies with picomolar dissociation constants for a neutralizing epitope can confer escape-resistant protection.


The role of behaviour in inequality in increments of dental caries among Finnish adults.
Evidence from cross-sectional studies implies that dental behaviours partially explain inequalities in oral health. To assess whether dental behaviours completely eliminate inequality in increments of dental caries in a sample of Finnish adults. The baseline data were collected from the Health 2000 survey, a nationally representative survey of 8,028 individuals aged 30 years or older living in mainland Finland. Four years later, 1,248 subjects were invited for oral re-examination, and 1,049 agreed to participate (84% response rate). At baseline, participants provided information on demographics, education and dental behaviours (dental attendance, tooth brushing with fluoride toothpaste, sugar consumption and daily smoking). Oral examinations at baseline and follow-up were identical. Adults with basic education had significantly greater increments of DMFT (incidence rate ratio 1.41, 95% CI 1.07-1.85) and DT (incidence rate ratio 2.23, 95% CI 1.27-3.90) than those with high education. Adjusting for single behaviours attenuated but did not eliminate education inequality in DMFT and DT increments, tooth brushing having the greatest impact on inequality. Simultaneous adjustment for all behaviours eliminated the significant relationship between education and caries increment. Accounting for important dental behaviours appears to explain all education inequality in dental caries in Finnish adults. The results should be interpreted with caution when applied to less egalitarian populations.


Theoretical modeling of the uranium 4f XPS for U(VI) and U(IV) oxides.
A rigorous study is presented of the physical processes related to X-Ray photoelectron spectroscopy, XPS, in the 4f level of U oxides, which, as well as being of physical interest in themselves, are representative of XPS in heavy metal oxides. In particular, we present compelling evidence for a new view of the screening of core-holes that extends prior understandings. Our analysis of the screening focuses on the covalent mixing of high lying U and O orbitals as opposed to the, more common, use of orbitals that are nominally pure U or pure O. It is shown that this covalent mixing is quite different for the initial and final, core-hole, configurations and that this difference is directly related to the XPS satellite intensity. Furthermore, we show that the high-lying U d orbitals as well as the U(5f) orbital may both contribute to the core-hole screening, in contrast with previous work that has only considered screening through the U(5f) shell. The role of modifying the U-O interaction by changing the U-O distance has been investigated and an unexpected correlation between U-O distance and XPS satellite intensity has been discovered. The role of flourite and octahedral crystal structures for U(IV) oxides has been examined and relationships established between XPS features and the covalent interactions in the different structures. The physical views of XPS satellites as arising from shake processes or as arising from ligand to metal charge transfers are contrasted; our analysis provides strong support that shake processes give a more fundamental physical understanding than charge transfer. Our theoretical studies are based on rigorous, strictly ab initio determinations of the electronic structure of embedded cluster models of U oxides with formal U(VI) and U(IV) oxidation states. Our results provide a foundation that makes it possible to establish quantitative relationships between features of the XPS spectra and materials properties.


Specific Enhancement of Catalytic Activity by a Dicopper Core: Selective Hydroxylation of Benzene to Phenol with Hydrogen Peroxide.
A dicopper(II) complex, stabilized by the bis(tpa) ligand 1,2-bis[2-[bis(2-pyridylmethyl)aminomethyl]-6-pyridyl]ethane (6-hpa), [Cu2 (μ-OH)(6-hpa)]3+ , was synthesized and structurally characterized. This complex catalyzed selective hydroxylation of benzene to phenol using H2 O2 , thus attaining large turnover numbers (TONs) and high H2 O2 efficiency. The TON after 40 hours for the phenol production exceeded 12000 in MeCN at 50 °C under N2 , the highest value reported for benzene hydroxylation with H2 O2 catalyzed by homogeneous complexes. At 22 % benzene conversion, phenol (95.2 %) and p-benzoquinone (4.8 %) were produced. The mechanism of H2 O2 activation and benzene hydroxylation is proposed.


Quantifying Carbon Emissions Generated by Monorail Transits: A Life Cycle Assessment Approach.
The use of rail transits results in the generation of a large amount of carbon emissions. Throughout the life cycle of a rail transit system, huge amounts of carbon are emitted, which contributes to the threat posed by carbon emission on the city ecosystem. Despite the many methods previously proposed to quantify carbon emissions from rail transit systems, a method that can be applied to measure carbon emissions of monorail systems is yet to be developed. We have used the life cycle assessment (LCA) method to propose a method that can be used to quantify carbon emissions from monorail transits. The life cycle of a monorail transit system was divided into four stages (production, construction, use, and end-of-life). A monorail transit line segment in Chongqing, China, was selected for a case study. The results show that the "use" stage of the monorail transit line system significantly increases (93.2%) carbon emissions, while the "end-of-life" stage does not contribute significantly to the total carbon emitted. The processes of generation of steal, concrete, and cement are the three leading processes that contribute to the emission of carbon dioxide. The percentages of carbon emitted during these processes are 32%, 29.6%, and 13.3%, respectively. Prestressed concrete activity accounts for the largest proportion (91.1%) of the total carbon emissions. The results presented herein can potentially help in realizing sustainable development and developing green transportation.


Has the 'Fast-Track' referral system affected the route of presentation and/or clinical outcomes in patients with colorectal cancer?
The aim of this study is to determine whether the 'Fast-Track' referral system has changed the route by which patients present with colorectal cancer (CRC) and whether the route of presentation has any effect on clinical outcome. A retrospective cohort study of patients diagnosed with CRC under the care of two consultant colorectal surgeons between April 2006 and December 2012. The route by which patients presented was categorised as Fast-Track (FT), non-Fast-Track (non-FT) or acute. Outcome variables were operative intent, disease stage and 2- and 5-year survival. A total of 558 patients were identified. One hundred ninety-seven patients (35.3 %) were referred as FT, 108 (19.4 %) presented acutely and 253 patients (45.3 %) presented via other routes (non-FT). Over the study period, the route of presentation did not change significantly (P = 0.135). There was no significant difference between FT and non-FT groups in terms of the proportion of patients undergoing potentially curative surgery (70.6 vs 74.3 %, P = 0.092) or with node-negative disease (48.2 vs 52.2 %, P = 0.796) nor was there any difference in 2-year or 5-year survival (74.1 vs 73.9 %, P = 0.837 and 52.3 vs 53.8 %, P = 0.889, respectively). Patients who presented acutely were less likely to undergo curative resection, had more advanced disease and had worse 2- and 5-year survival. The Fast-Track referral system has not affected the route by which patients present with CRC nor has it had any effect on clinical outcomes. Alternative strategies are required if the desired improvement in outcomes is to be achieved.


Corticoids and cultured human epidermal keratinocytes: specific intracellular binding and clinical efficacy.
Cytosol of cultured human epidermal keratinocytes contains macromolecules, that bind corticoids with high affinity. Binding constants were in the same range for cultured keratinocytes originating from different individuals and did not change during serial cell cultivation. At 0 degree C and using 3H-triamcinolone acetonide as ligand, we obtained the following values; apparent Bmax = 160- 250 fmoles/mg protein and Kdiss = 3.1-5.0 nM; with 3H-dexamethasone Bmax = 200-350 fmoles/mg protein, Kdiss = 6.0-11.1 nM, and with 3H-hydrocortisone Bmax = 140-220 fmoles/mg protein, Kdiss = 17-25 nM. There was an indication that the binding capacity of the receptor system is higher the younger the age of the skin donor. A number of steroids and corticoids commonly used in dermatological practice were tested with respect to displacement of 3H-triamcinolone acetonide, 3H-dexamethasone, and 3H-hydrocortisone from binding sites in cytosol. Good correlation between clinical efficacy and specific binding was observed for all 3 ligands. Other steroids such as 17-beta estradiol and nandrolone did not show any affinity for the corticoid binding system. Progesterone displace 3H-corticoids from their binding sites, but the IC50 was of one order of magnitude larger.


Two arthroderma benhamiae isolates showing mitochondrial DNA type of Trichophyton verrucosum.
Two Trichophyton mentagrophytes isolates from skin lesions on a girl and her rabbit, which were identified as Arthroderma benhamiae by mating tests, were studied by mtDNA (mitochondrial DNA) analysis and sequencing of ITS (internal transcribed spacer) regions of nuclear ribosomal RNA genes. The mtDNA-RFLP (restriction fragment length polymorphism) patterns showed the two isolates to be T. verrucosum rather than A. benhamiae. The ITS sequence showed the isolates to be closer to A. benhamiae Americano-European race than to T. verrucosum and closer to T. verrucosum than to their mating partner A. benhamiae African race. These results suggest that there are three genetic types of A. benhamiae - an Americano-European type, an African type and a T. verrucosum type - and that T. verrucosum is an anamorph of A. benhamiae.


Dermatomyositis post vaccine against SARS-COV2.
Dermatomyositis belongs to an infrequent group of diseases predominantly found in patients older than 40 years old and is characterized by dermal and muscular findings. This disease presents itself as proximal, ascending and symmetric weakness and typical dermatosis with findings such as elevated muscle enzymes, altered electromyography and typical changes in muscle biopsy; as of today, the etiology of the disease in unknown. The COVID-19 vaccine has been a fundamental tactic to achieve control of the coronavirus (SARS CoV2), and it's clear that the benefits of getting the vaccine overweight the risks that might come along with it. Although rare, all adverse effects should be reported, this could help us to understand the elusive pathophysiology of inflammatory idiopathic myopathy. In this text we will describe the case of a patient with dermatomyositis who was vaccinated against SARS CoV2 with BNT162b2 mRNA (Pfizer-BioNTech), showing a temporal relation between the vaccination and the beginning of her symptoms. We realized all the diagnostic approach to the suspected disease including electromyography, muscle biopsy and laboratory findings, corroborating the diagnosis. The patient received standard treatment for this disease (steroid therapy) and have a classic slow improvement. Although it´s not possible to confirm a direct correlation between the vaccine and the onset of the disease, we considered that there are enough data to suspect that this could be a trigger event and therefore should always be considered a possible cause for a case of inflammatory idiopathic myopathy.


RipetaScore: Measuring the Quality, Transparency, and Trustworthiness of a Scientific Work.
A wide array of existing metrics quantifies a scientific paper's prominence or the author's prestige. Many who use these metrics make assumptions that higher citation counts or more public attention must indicate more reliable, better quality science. While current metrics offer valuable insight into scientific publications, they are an inadequate proxy for measuring the quality, transparency, and trustworthiness of published research. Three essential elements to establishing trust in a work include: trust in the paper, trust in the author, and trust in the data. To address these elements in a systematic and automated way, we propose the ripetaScore as a direct measurement of a paper's research practices, professionalism, and reproducibility. Using a sample of our current corpus of academic papers, we demonstrate the ripetaScore's efficacy in determining the quality, transparency, and trustworthiness of an academic work. In this paper, we aim to provide a metric to evaluate scientific reporting quality in terms of transparency and trustworthiness of the research, professionalism, and reproducibility.


Cytokine-directed therapies in multiple sclerosis and experimental autoimmune encephalomyelitis.
Secreted and cell surface molecules that control the nature of immune responses or directly mediate tissue damage are important targets for therapeutic intervention of autoimmune inflammatory disorders. The precise aetiology of multiple sclerosis (MS), an inflammatory demyelinating disease of the central nervous system is unknown and therapeutic interventions for this disease are limited. However, as it is believed that MS is autoimmune in nature, it seems likely that targeting of the immune system, either to deviate it down a more benign pathway or to directly block tissue damaging effector mechanisms, may enable this disease to be controlled. In this overview we examine three alternative approaches to therapy of MS: cytokine-directed immune deviation, immunoregulation by type I interferons and blockade of TNF. Underlying rationales for the application of these approaches to the treatment of MS are based largely on studies in the disease model experimental autoimmune encephalomyelitis. These studies are reviewed.


Artificial intelligence in perioperative medicine: a narrative review.
Recent advancements in artificial intelligence (AI) techniques have enabled the development of accurate prediction models using clinical big data. AI models for perioperative risk stratification, intraoperative event prediction, biosignal analyses, and intensive care medicine have been developed in the field of perioperative medicine. Some of these models have been validated using external datasets and randomized controlled trials. Once these models are implemented in electronic health record systems or software medical devices, they could help anesthesiologists improve clinical outcomes by accurately predicting complications and suggesting optimal treatment strategies in real-time. This review provides an overview of the AI techniques used in perioperative medicine and a summary of the studies that have been published using these techniques. Understanding these techniques will aid in their appropriate application in clinical practice.


Image-guided sinus surgery: navigation without road maps.
Many otorhinolaryngologists have recognized the necessity of developing new methods to increase the safety of endoscopic sinus surgery and improve patient outcomes. Despite the rapid advances made in the field, serious iatrogenic complications still occur. To counteract these complications, one recent advancement has been the development of a computed tomographic image-guided surgery (IGS) system, which can enhance the ability to treat the crippling effects of sinus disease. These systems have gained a degree of accuracy, making them suitable for difficult surgical procedures, and they may soon become standard of care. The perioperative nurse must understand and be able to work with IGS.


Amorphous calcium carbonate precipitation by cellular biomineralization in mantle cell cultures of Pinctada fucata.
The growth of molluscan shell crystals is generally thought to be initiated from the extrapallial fluid by matrix proteins, however, the cellular mechanisms of shell formation pathway remain unknown. Here, we first report amorphous calcium carbonate (ACC) precipitation by cellular biomineralization in primary mantle cell cultures of Pinctada fucata. Through real-time PCR and western blot analyses, we demonstrate that mantle cells retain the ability to synthesize and secrete ACCBP, Pif80 and nacrein in vitro. In addition, the cells also maintained high levels of alkaline phosphatase and carbonic anhydrase activity, enzymes responsible for shell formation. On the basis of polarized light microscopy and scanning electron microscopy, we observed intracellular crystals production by mantle cells in vitro. Fourier transform infrared spectroscopy and X-ray diffraction analyses revealed the crystals to be ACC, and de novo biomineralization was confirmed by following the incorporation of Sr into calcium carbonate. Our results demonstrate the ability of mantle cells to perform fundamental biomineralization processes via amorphous calcium carbonate, and these cells may be directly involved in pearl oyster shell formation.


Functional Cryogel Microstructures Prepared by Light-Induced Cross-Linking of a Photoreactive Copolymer.
A novel, highly efficient method for the preparation of functional, microstructured and surface-attached cryogels is described. Photoinduced C,H-insertion reactions are used to generate cryogels in a single, rapid photo-cross-linking process. To this end, solutions containing both a photoreactive copolymer and the (bio)molecules to be immobilized are placed on a polymeric substrate followed by freezing and a short UV exposure. This strategy combines photolithography and cryogel formation allowing for a simultaneous generation and (bio)functionalization of cryogels in a single reaction step. To demonstrate the potential of the generated materials for bioanalytical applications, we successfully prepared DNA and protein cryogel microarrays.


[Relationship between cyclooxygenase (COX)-2 and malignant tumors].
Recently, epidemiologic studies and animal experiments have demonstrated that nonsteroidal anti-inflammatory drugs(NSAIDs) reduce the incidence of colorectal carcinoma. Cyclooxygenase(COX) is the principal target of NSAIDs. COX is the first oxidase in the process of prostaglandins(PGs) production from arachidonic acid(AA). PGs and COX enzyme may be involved in the initiation and/or the promotion of carcinogenesis because the major action of NSAIDs is the inhibition of COX. In this review, we demonstrated the expression of COX-2 in urological cancer(renal cell carcinoma, bladder tumor, prostate cancer, and testicular tumor) tissues as well as the effects of COX inhibitors.


Reduced Recurrence Rate and Comparable Functionality in Wide Resection and Reverse Total Shoulder Arthroplasty with Allograft-Prosthetic Composite vs. Curettage for Proximal Humerus Giant Cell Tumor: A Multicenter Retrospective Study.
Giant cell tumors of bone (GCTB) are rare aggressive tumors and proximal humerus is a relatively rare location for GCTB as well, limited evidence exists on which surgical approaches and reconstruction techniques are optimal. Here, using the largest case series to date, we evaluated the recurrence rate of proximal humerus GCTBs and the functional outcomes of different resection and reconstruction options in this multicenter study. All 51 patients received initial surgical treatment for proximal humerus GCTBs from January 2007 to December 2020, with a minimum two-year follow-up. Local recurrence and functional outcomes were statistically analyzed in relation to demographic, clinical, and primary surgical variables. Functional outcomes were patient-reported and assessed by the Musculoskeletal Tumor Society (MSTS) score and the Disabilities of the Arm, Shoulder and Hand (QuickDASH) instrument. Mean follow-up was 81.5 months (range, 30-191 months), and overall recurrence rate was 17.6% (9/51). The majority of the recurrence (N=7) occurred in the first two years of follow-up. The intralesional curettage group (N=23) had a statistically significant difference in recurrence rate compared to en-bloc resection (N=28) (34.8% vs. 3.6%, p=0.007). Among patients receiving en-bloc resection, 16 shoulders were reconstructed with hemiarthroplasty, 8 with reverse total shoulder arthroplasty (rTSA) with allograft-prosthetic composite (APC) reconstruction, and 4 with arthrodesis. Based on intention-to-treat analysis, the mean functional MSTS scores of the curettage groups, rTSA with APC, hemiarthroplasty, or arthrodesis was 26.0±3.1 vs. 26.0±1.7 vs. 20.3±2.8 vs. 22.5±1.3 (p<0.001 [curettage vs. hemiarthroplasty, p<0.001; rTSA with APC vs. hemiarthroplasty, p=0.004]), respectively, while for QuickDASH, it was 14.0±11.0 vs. 11.6±4.5 vs. 33.1±11.8 vs. 21.6±4.7 (p<0.001 [curettage vs. hemiarthroplasty, p<0.001; rTSA with APC vs. hemiarthroplasty, p=0.003]), respectively. Based on our data, en-bloc resection followed by reverse shoulder arthroplasty showed a lower recurrence rate, and no significant difference in functional outcome scores for proximal humerus GCTBs compared with intralesional curettage. Therefore, we believe that rTSA with APC may be reasonable for initial treatment of proximal humerus GCTBs.


DNase I hypersensitive site II of the human growth hormone locus control region mediates an essential and distinct long-range enhancer function.
Locus control regions (LCRs) comprise sets of DNA elements capable of establishing autonomous chromatin domains that support robust and physiologically appropriate expression of target genes, often working over extensive distances. Human growth hormone (hGH-N) expression in the pituitary is under the regulation of a well characterized LCR containing four DNase I hypersensitive sites (HSs). The two pituitary-specific HS, HSI and HSII, are located 14.5 and 15.5 kb 5' to the hGH-N promoter. HSI is essential for activation of hGH-N during pituitary development and for sustaining robust activity in the adult. To determine whether the closely linked HSII has a role in hGH-N expression, it was deleted from a previously validated hGH/P1 transgene. Analysis of three independent hGH/P1(ΔHSII) transgenic mouse lines revealed that this deletion had no adverse effect on the formation of HSI, yet resulted in a substantial loss (70%) in hGH-N mRNA expression. This loss of expression was accompanied by a corresponding reduction in recruitment of the pituitary-specific transcription factor Pit-1 to the hGH-N promoter and a selective decrease in promoter occupancy of the elongation-linked isoform of RNA polymerase II. Sufficiency of HSI and HSII in LCR activity was explored by establishing two additional sets of mouse transgenic lines in which DNA segments containing these HS were positioned within the λ phage genome. In this "neutral" DNA context, HSII was required for the recruitment of HAT activity. These data establish HSII as a nonredundant component of the hGH LCR essential for establishment of robust levels of hGH-N gene expression.


Dissociative trance and spirit possession: Challenges for cultures in transition.
The cross-cultural validity of dissociative possession and trance disorders is a matter of some debate, limiting research and meaningful interpretation of prevalence data. Intimate to these concerns is the status of spirit possession categories studied in the social sciences, particularly anthropology. These two categories are phenomenologically related and display similar epidemiological associations. In India, dissociative and conversion disorders are fairly common in clinical settings. There is no doubt that there are true cultural variations in possession and trance disorders. A new framework may enable clinicians to better understand possession states and spirit possession.


Recycled and Nickel- or Cobalt-Doped Lead Materials from Lead Acid Battery: Voltammetric and Spectroscopic Studies.
The active mass of the plates of aspent car battery with higher wear after an efficient desulfatization can be used as sources of a new electrode. This paper proposes the recycling of spent electrodes from a lead acid battery and the incorporation of NiO or Co3O4 contents by the melt-quenching method in order to enrich the electrochemical properties. The analysis of X-ray diffractograms indicates the gradual decrease in the sulfated crystalline phases, respectively, 4PbO·PbSO4 and PbO·PbSO4 phases, until their disappearance for higher dopant concentrations. Infrared (IR) spectra show a decreasing trend in the intensity of the bands corresponding to the sulfate ions and a conversion of [PbO3] pyramidal units into [PbO4] tetrahedral units by doping with high dopant levels, yielding to the apparition of the PbO2 crystalline phase. The observed electron paramagnetic resonance (EPR) spectra confirm three signals located on the gyromagnetic factor, g~2, 2.2 and 8 assigned to the nickel ions in higher oxidation states as well as the metallic nickel nanoparticles. This compositional evolution can be explained by considering a process of the drastic reduction in nickel ions from the superior oxidation states to metallic nickel. The linewidth and the intensity of the resonance lines situated at about g~2, 2.17, 4.22 and 7.8 are attributed to the Co+2 ions from the EPR data. The best reversibility of the cyclic voltammograms was highlighted for the samples with x = 10 mol% of NiO and 15 mol% of Co3O4, which are recommended as suitable in applications as new electrodes for the lead acid battery.


Amino acid residues within conserved domain VI of the vesicular stomatitis virus large polymerase protein essential for mRNA cap methyltransferase activity.
During mRNA synthesis, the polymerase of vesicular stomatitis virus (VSV) copies the genomic RNA to produce five capped and polyadenylated mRNAs with the 5'-terminal structure 7mGpppA(m)pApCpApGpNpNpApUpCp. The 5' mRNA processing events are poorly understood but presumably require triphosphatase, guanylyltransferase, [guanine-N-7]- and [ribose-2'-O]-methyltransferase (MTase) activities. Consistent with a role in mRNA methylation, conserved domain VI of the 241-kDa large (L) polymerase protein shares sequence homology with a bacterial [ribose-2'-O]-MTase, FtsJ/RrmJ. In this report, we generated six L gene mutations to test this homology. Individual substitutions to the predicted MTase active-site residues K1651, D1762, K1795, and E1833 yielded viruses with pinpoint plaque morphologies and 10- to 1,000-fold replication defects in single-step growth assays. Consistent with these defects, viral RNA and protein synthesis was diminished. In contrast, alteration of residue G1674 predicted to bind the methyl donor S-adenosylmethionine did not significantly perturb viral growth and gene expression. Analysis of the mRNA cap structure revealed that alterations to the predicted active site residues decreased [guanine-N-7]- and [ribose-2'-O]-MTase activity below the limit of detection of our assay. In contrast, the alanine substitution at G1674 had no apparent consequence. These data show that the predicted MTase active-site residues K1651, D1762, K1795, and E1833 within domain VI of the VSV L protein are essential for mRNA cap methylation. A model of mRNA processing consistent with these data is presented.


Role of substantia innominata in cerebral blood flow autoregulation.
Ascending projections from the substantia innominata (SI) may have an important role in the regulation of cerebral blood flow (CBF). However, several reports have suggested that unilateral lesion of the SI does not affect CBF autoregulation. On the other hand, it is also reported that several cortical and subcortical functions may be regulated not only by ipsilateral SI, but also by contralateral SI. Thus, the objective of this study is to test the hypothesis that bilateral lesions of the SI affect CBF autoregulation. Experiments were performed on anesthetized male Sprague-Dawley rats. Ibotenic acid or physiological saline was microinjected into bilateral SI. Rats were classified into four groups as follows: bilateral SI lesion rats (ibotenic acid was injected bilaterally), left or right SI lesion rats (ibotenic acid was injected into the unilateral SI and saline into the contralateral SI), and control rats (saline was injected bilaterally). Ten days after injection, CBF in the left frontal cortex was measured by laser-Doppler flowmetry during stepwise controlled hemorrhagic hypotension. In bilateral SI lesion rats, CBF was started to decrease significantly at 80 mm Hg (p<0.01). In the other three groups, CBF was well maintained until 50 mm Hg. Changes in CBF through stepwise hypotension in bilateral SI lesion rats were significantly different from the other groups (p<0.01). These results suggest that bilateral SI regulates cortical vasodilator mechanisms during hemorrhagic hypotension. Under unilateral SI lesion, some compensatory effects from the contralateral SI may maintain CBF autoregulation.


Nociceptors lacking TRPV1 and TRPV2 have normal heat responses.
Vanilloid receptor 1 (TRPV1) has been proposed to be the principal heat-responsive channel for nociceptive neurons. The skin of both rat and mouse receives major projections from primary sensory afferents that bind the plant lectin isolectin B4 (IB4). The majority of IB4-positive neurons are known to be heat-responsive nociceptors. Previous studies suggested that, unlike rat, mouse IB4-positive cutaneous afferents did not express TRPV1 immunoreactivity. Here, multiple antisera were used to confirm that mouse and rat have different distributions of TRPV1 and that TRPV1 immunoreactivity is absent in heat-sensitive nociceptors. Intracellular recording in TRPV1(-/-) mice was then used to confirm that TRPV1 was not required for detecting noxious heat. TRPV1(-/-) mice had more heat-sensitive neurons, and these neurons had normal temperature thresholds and response properties. Moreover, in TRPV1(-/-) mice, 82% of heat-responsive neurons did not express immunoreactivity for TRPV2, another putative noxious heat channel.


Partial tarsal arthrodesis with closing wedge ostectomy for treatment of bilateral twisted leg deformity in a cat.
A 5-month-old male domestic shorthair cat was presented with severe bilateral hind-limb deformities that caused the cat to walk on the dorsal aspect of the metatarsals. Computed tomography (CT) images revealed that the calcaneus was externally rotated, and the distal end of the calcaneus was turned medially to the talus in both hind limbs. The cat was diagnosed with twisted leg deformity, a congenital tarsal hyperextension deformity (clubfoot). Based on CT images, closing wedge ostectomy was done at the level of the tarsometatarsal joint with the wider part facing laterally. Partial transection of the common calcaneal tendon was not performed. Nine weeks after surgery, the cat was able to walk and jump, with its paws correctly placed on the ground, despite the limited range of motion in the tarsal joints. Based on radiographs with maximum tarsal flexion, the angle of the partial tarsal arthrodesis limited the range of motion. This is apparently the first case report describing CT images and closing wedge ostectomy in a cat with twisted leg deformity. Key clinical message: This article reports the findings obtained from CT imaging of a cat with twisted leg deformity. The current case was successfully managed by closing wedge ostectomy without partial transection of the common calcaneal tendon.


Complexes of gastrin with In3+, Ru3+ or Ga3+ ions are not recognised by the cholecystokinin 2 receptor.
The peptide hormone gastrin (Gamide) binds trivalent metal ions, including indium (In), ruthenium (Ru) and gallium (Ga), with high affinity. Complexes of gastrin with chelated isotopes of In and Ga have previously been used for the location of tumours expressing the cholecystokinin 2 receptor (CCK2R). The aim of the present study was to purify the complexes of Gamide with radioactive isotopes of In, Ru or Ga and to investigate their ability to bind to the CCK2R. The radioactive Gamide complexes were purified on Sep-Pak C18 cartridges or by anion exchange HPLC. Binding to the CCK2R was assessed with a stably transfected clone of the gastric carcinoma cell line AGS. The 106Ru-Gamide complex could be eluted from the C18 cartridge; the 111In-Gamide and 68Ga-Gamide complexes bound irreversibly. All three complexes were successfully purified by anion exchange HPLC. The failure to detect binding of the 111In-Gamide, 106Ru-Gamide and 68Ga-Gamide complexes to the CCK2R suggests that formation of these complexes will not be useful for the detection of tumours expressing this receptor, but may instead provide alternative ways to block the actions of Gamide as a growth factor or a stimulant of gastric acid secretion. The complexes between the hormone gastrin and radioactive 111In, 106Ru or 68Ga ions were purified by anion exchange HPLC using a NaCl gradient. The failure to detect binding of the complexes to the cholecystokinin 2 receptor suggests that metal ion treatment may provide novel approaches to block the biological actions of gastrin.


The effects of bone therapy on tibial bone loss in young women with anorexia nervosa.
Osteoporosis is recognized as a common medical complication of anorexia nervosa (AN). The purpose of the current study was to investigate the recovery mechanism of osteoporosis in AN and the effect of medical treatment on the skeletal system. We conducted a randomized placebo-controlled study of the effects of etidronate and calcium and vitamin D on bone loss in 41 outpatients with the restricting type of AN (AN-R). We measured the tibial speed of sound (SOS) before and after 3 months of treatment. The bone mineral density (BMD) of the tibial SOS change in both the etidronate group and the calcium and vitamin D Group was significantly greater (p < .001) than in the control group. Urine-N-telopeptide cross-links of type I collagen (NTx) before and after treatment decreased significantly (p < .01) in the etidronate group. These findings suggest that both etidronate and calcium and vitamin D are equally efficacious for reversing the degree of osteoporosis in patients with AN.


Fetal pulmonary artery diameters and their association with lung hypoplasia and postnatal outcome in congenital diaphragmatic hernia.
We hypothesized that fetal branch pulmonary artery (PA) diameters indirectly reflect lung mass and are associated with postnatal outcome in cases of isolated congenital diaphragmatic hernia (CDH). We retrospectively reviewed echocardiograms of fetuses with CDH, measuring branch PA diameters and other echocardiographic parameters. Antenatal parameters were correlated with postmortem lung weights in 5 fetuses after pregnancy termination. Fetal echocardiographic measures were correlated with outcome variables in 29 live-born infants with CDH to identify antenatal indices associated with postnatal death and respiratory morbidity. Antenatal branch PA size correlated with postmortem lung weights from 5 terminated fetuses (r = 0.87). In 26 cases of left CDH in which the fetus continued to term, the ipsilateral branch PA diameter was significantly smaller than the contralateral branch PA diameter at presentation (P <.001). In these fetuses, a larger contralateral PA diameter was associated with worse postnatal survival (P =.049). Among survivors with left CDH, the main PA z score and the discrepancy between right and left PA diameters correlated positively with duration of supplemental oxygen requirement (P =.019 and P =.022, respectively) and ventilation (P =.036 and P =.012, respectively). Serial antenatal studies in 8 of 10 cases revealed progressive ipsilateral PA hypoplasia. Antenatal branch PA size correlates with postmortem lung weight. A larger contralateral PA, and significant branch PA discrepancy and larger main PA diameter, best correlate with postnatal death and respiratory morbidity, respectively. Progressive ipsilateral PA hypoplasia suggests progressive in utero lung hypoplasia in cases of CDH.


Novel mutation in boy with cartilage-hair hypoplasia.
Cartilage-hair hypoplasia (MIM 250250) is an autosomal recessive disease with diverse clinical manifestations. The clinical phenotypes include variable degrees of bone and hair dysplasia, deficient cellular and/or humoral immunity, and a predisposition to malignancy. We performed genetic studies of a patient with disproportionate short stature and brittle scalp hair. Genetic studies were also carried out in the patient's parents. A novel maternal mutation that consisted of a duplication of 14 nucleotides at position -13 of the RNA component of the RNA component of mitochondrial RNA processing endoribonuclease gene (RMRP; g. -26 to -13 dupTACTACTCTGTGAA, promoter region) and a paternal mutation base substitution of C to T at nucleotide + 230 (designated as + 1 in the transcription initiation site) in the coding sequence of RMRP were detected in this patient. A novel maternal RMRP mutation was found in a Chinese boy with typical cartilage-hair hypoplasia.


Single transluminal gateway transcystic multiple drainage for extensive walled-off pancreatic necrosis - a single-centre experience.
In last three decades we have observed development in minimally invasive techniques in the treatment of walled-off pancreatic necrosis (WOPN). Endoscopic treatment of the consequences of acute necrotising pancreatitis is a accepted and common minimally invasive method. Evaluation of the efficiency and safety of the innovative endoscopic treatment method (single transluminal gateway transcystic multiple drainage - SGTMD) in patients with extensive walled-off pancreatic necrosis. The retrospective analysis of 114 consecutive patients with symptomatic WOPN, who were treated endoscopically in our medical centre between 2011 and 2016. Single transluminal gateway transcystic multiple drainage was performed in 21/114 (18.42%) patients. Endoscopic necrosectomy under fluoroscopic guidance was performed in 12/21 (57.14%) patients. Complications of treatment appeared in 7/21 (33.33%) patients. The most common of complication was upper gastrointestinal bleeding treated conservatively with packed red blood cells transfusions. There were no deaths. Therapeutic success was reached in 20/21 (95.24%) patients. No patient required surgery. The medium time of follow-up was 22 months (16-47). During the observation the recurrence of pancreatic fluid collection was noticed in 1/21 (4.76%) patients. Long-term success of endoscopic treatment was achieved in 19/21 (90.47%) patients. Single transluminal gateway transcystic multiple drainage is an effective method of endoscopic treatment for extensive walled-off pancreatic necrosis with an acceptable amount of complications. However, the method of interventional treatment of pancreatic necrosis should depend not only on the location of necrosis, but also on the experience of the medical centre.


Tocainide analogues binding to human serum albumin: a HPLAC and circular dichroism study.
A series of synthesised tocainide analogues were characterized for their human serum albumin (HSA) binding, using high-performance liquid affinity chromatography (HPLAC) and circular dichroism (CD). The synthesis and physico-chemical characterization of compounds 7a-7d is reported here. For the HPLAC investigation HSA was covalently immobilized to the silica matrix of the HPLC column, using an anchoring procedure, which allows the binding properties of the protein to be maintained. The HSA-based column was used for getting information on the high affinity binding sites of the tocainide analogues to HSA. According to the displacement chromatography approach, the retentions of the analytes were determined in the absence and in the presence of increasing concentrations of competitors known to bind to specific binding sites on the protein. The same system, drug/protein, was investigated in solution by CD. The analysed compounds, proved active as sodium channel blockers, showed a much higher affinity to the serum carrier with respect to the parent compound, tocainide. Further, a non-cooperative interaction at sites I and II, and an almost independent binding at the bilirubin binding site on HSA were hypothesised on the bases of the competition experiments.


Magnetic Synthetic Receptors for Selective Clean-Up in Protein Biomarker Quantification.
Biomarker analysis by mass spectrometry (MS) can allow for the rapid quantification of low abundant biomarkers. However, the complexity of human serum is a limiting factor in MS-based bioanalysis; therefore, novel biomarker enrichment strategies are of interest, particularly if the enrichment strategies are of low cost and are easy to use. One such strategy involves the use of molecularly imprinted polymers (MIPs) as synthetic receptors for biomarker enrichment. In the present study, a magnetic solid-phase extraction (mSPE) platform, based on magnetic MIP (mMIP) sorbents, is disclosed, for use in the MS-based quantification of proteins by the bottom-up approach. Progastrin releasing peptide (ProGRP), a low abundant and clinically sensitive biomarker for small cell lung cancer (SCLC), was used to exemplify the mSPE platform. Four different mMIPs were synthesized, and an mSPE method was developed and optimized for the extraction of low concentrations of tryptic peptides from human serum. The mSPE method enabled the selective extraction of the ProGRP signature peptide, the nonapeptide NLLGLIEAK, prior to quantification of the target via LC-MS/MS. Overall, the mSPE method demonstrated its potential as a low cost, rapid, and straightforward sample preparation method, with demonstrably strong binding, acceptable recoveries, and good compatibility with MS. mMIPs are a potential low-cost alternative to current clinical methods for biomarker analysis.


Prolongation of allograft survival in mice by administration of anti-Thy 1 serum. I. Mediation by in vivo activation of regulatory T cells.
A single 0.5-ml dose of anti-Thy 1.2 serum raised in AKR (H-2k, Thy 1.1) mice by immunization with C3H (H-2k, Thy 1.2) thymocytes prolonged mean graft survival (MGS) of C57BL/L (H-2b, Thy 1.2) skin on BALB/c (H-2d, Thy, 1.2) mice from 9.2 to 13.0 days (p less than 0.01). Absorption of anti-Thy 1.2 serum with C3H but not AKR brain removed this activity. MGS was prolonged by anti-Thy 1.2 serum given as long as 2 weeks before grafting. Four separately raised anti-Thy 1.2 preparations prolonged MGS, one to a dilution of 1:128. Anti-Thy 1.1 serum prolonged MGS on AKR mice but not on BALB/c mice. Thymectomy 3 weeks or more before graft placement or treatment of BALB/c mice with anti-lymphocyte serum (ALS) diminished the effectiveness of anti-Thy 1.2 serum. Furthermore, infusion of 25 times 10(6) spleen cells from BALB/c mice given anti-Thy 1.2 serum prolonged MGS on syngeneic recipients to 15.6 days whereas spleen cells from mice given no treatment or ALS had no effect. Thymocytes from anti-Thy 1.2 serum treated donors were ineffective in prolonging MGS on transfer. Transfer or serum from anti-Thy 1.2 serum-treated mice also had no effect. The transfer of graft prolongation with lymphoid cells from anti-Thy 1 serum treated mice suggests anti-Thy 1 serum may prolong MGS by activating suppressor T cells.


The Role of Lipid and Lipoprotein Metabolism in Non-Alcoholic Fatty Liver Disease.
Due to the epidemic of obesity across the world, nonalcoholic fatty liver disease (NAFLD) has become one of the most prevalent chronic liver disorders in children and adolescents. NAFLD comprises a spectrum of fat-associated liver conditions that can result in end-stage liver disease and the need for liver transplantation. Simple steatosis, or fatty liver, occurs early in NAFLD and may progress to nonalcoholic steatohepatitis, fibrosis and cirrhosis with increased risk of hepatocellular carcinoma. The mechanism of the liver injury in NAFLD is currently thought to be a "multiple-hit process" where the first "hit" is an increase in liver fat, followed by multiple additional factors that trigger the inflammatory activity. At the onset of disease, NAFLD is characterized by hepatic triglyceride accumulation and insulin resistance. Liver fat accumulation is associated with increased lipotoxicity from high levels of free fatty acids, free cholesterol and other lipid metabolites. As a consequence, mitochondrial dysfunction with oxidative stress and production of reactive oxygen species and endoplasmic reticulum stress-associated mechanisms, are activated. The present review focuses on the relationship between intra-cellular lipid accumulation and insulin resistance, as well as on lipid and lipoprotein metabolism in NAFLD.


Insight into novel inhibitors from Sterculia urens against Cholera via pharmacoinformatics and molecular dynamics simulation approaches.
The underdeveloped countries with large populations are facing a grave global threat in the form of cholera. Vibrio cholerae, the etiologic agent of Cholera has drawn attention recently due to antimicrobial resistance and resulting outbreaks that necessitates establishment of novel medications to counteract virulence and viability of the pathogen. Sterculia urens Roxb. (Malvaceae) is an ethnomedicinally important tree, which harbors a good number of bioactive phytocompounds. In the present study, 53 phytocompounds of S. urens were screened against the promising target ToxT of V. cholerae employing structure-based drug design approach that revealed three lead compounds, viz., 4,4,5,8-Tetramethylchroman-2-ol (-8.2 kcal/mol), Beta-Bisabolol (-8.2 kcal/mol) and Ledol (-8.7 kcal/mol) with satisfactory ADMET properties. Molecular dynamics simulation for 150 ns unveiled notable compactness and structural stability for the lead compounds considering RMSD, RMSF, Rg, MolSA, PSA and protein-ligand contacts parameters. Molecular mechanics-based MM/GBSA binding energy calculation revealed Beta-Bisabolol (-66.74 kcal/mol) to have better scores than 4,4,5,8-Tetramethylchroman-2-ol (-47.42 kcal/mol) and Ledol (-65.79 kcal/mol). Enzymes were mostly found as drug target class, and Nabilone was found as a structurally similar analog for 4,4,5,8-Tetramethylchroman-2-ol. These discoveries could aid in revealing new antibacterial medications targeting ToxT to combat Cholera.Communicated by Ramaswamy H. Sarma.


Prospective analytical study of assessment of off loading by Total Contact Cast in treatment of non healing plantar ulcers in anaesthetic foot.
Chronic planter ulcer, also known as trophic ulcer, shows no tendency towards healing. It is usually seen in sensory deficient foot. The clinical result of a sensory, motor or autonomic loss of a nerve function is frequently the same--ulceration, although the exact cause may vary. The treatment principle involves dressing and avoiding pressure on the ulcerated site called 'offloading' and patient education for prevention. To determine the outcome of non-healing planter ulcers in an anaesthetic foot treated with offloading, total contact casting (TCC), in terms of rate and duration of healing and percentage of ulcers healed based on improvement of Wagner's grading with respect to the clinical profile of the patient. Detailed examination of the patients was done, and neuropathic foot confirmed. Surgical debridement of the ulcer was done to take off all the necrotic tissues, periwound callus, and infected material down to viable tissues. Once the ulcer became clean, a total contact cast was applied with a walking iron for ambulation. TCC was renewed every 2 weeks and rate of healing was assessed. 80% of the cases healed within 8 weeks, healing defined by complete re-epithelisation of wound. Average duration of healing of an ulcer was 6.73 ±1.92 weeks. Small sample size and the lack of control subjects for comparison. Offloading with total contact casts is believed to be the gold standard method with better and faster healing rates.


Emergent behavioural phenotypes of swarming models revealed by mimicking a frustrated anti-ferromagnet.
Self-propelled particle (SPP) models are often compared with animal swarms. However, the collective animal behaviour observed in experiments often leaves considerable unconstrained freedom in the structure of a proposed model. Essentially, multiple models can describe the observed behaviour of animal swarms in simple environments. To tackle this degeneracy, we study swarms of SPPs in non-trivial environments as a new approach to distinguish between candidate models. We restrict swarms of SPPs to circular (periodic) channels where they polarize in one of two directions (like spins) and permit information to pass through windows between neighbouring channels. Co-alignment between particles then couples the channels (anti-ferromagnetically) so that they tend to counter-rotate. We study channels arranged to mimic a geometrically frustrated anti-ferromagnet and show how the effects of this frustration allow us to better distinguish between SPP models. Similar experiments could therefore improve our understanding of collective motion in animals. Finally, we discuss how the spin analogy can be exploited to construct universal logic gates, and therefore swarming systems that can function as Turing machines.


Electrodermal activity as a predictor of social functioning in female schizophrenics.
Twenty-nine female schizophrenics and 20 female controls were presented with a series of moderately intense tones in a standard orienting habituation paradigm while skin conductance was monitored. Premorbid adjustment and symptoms were also rated, and the schizophrenics were observed 2 years later. The total schizophrenic group was divided into a good-outcome group and a poor-outcome group. Good social functioning outcome required both self-supporting ability in the job market and at least a minimal social life. The poor-outcome group had a significantly higher skin-conductance level and frequency of spontaneous skin-conductance fluctuations than the control group, whereas the few patients with good outcome did not differ from controls. These results are contrary to previous findings with a group of schizophrenic men in which poor social functioning was associated with low electrodermal activity. This discrepancy is discussed in terms of sex differences in schizophrenic disorder.


Fetal cardiac sectional schemas - Normal and abnormal. Part 1: Upper abdominal and thoracic sections.
A representational illustrated cardiac schema is useful for understanding and interpreting normal and abnormal fetal echocardiographic findings. Normal and abnormal fetal echocardiographic images can be better appreciated with the support of sectional schemas. An attempt is made to include normal and abnormal variations in both grayscale and color images for easy understanding with the help of the schemas. The fetal cardiac sectional schemas are drawn by the author, using Microsoft Office Word drawing canvas. It is based on the best grayscale, color Doppler, power-angio, 3-dimensional, and high definition flow ultrasound images, supported by embryological and anatomic specimens in literature. Different sections are drawn in accordance with the planes suggested by Society for Maternal-Fetal Medicine, Society of Radiologists in Ultrasound, American College of Obstetricians and Gynecologists, American Institute of Ultrasound in Medicine, American College of Radiology, and American Society of Echocardiography. Every effort has been meticulously pursued to match with the best ultrasound images with minor modifications for better clarity, understanding, and reproducibility. The drawings include normal and most of the common cardiac anomalies depicting different sectional views starting from the abdomen and upward. Each drawing complies with the ultrasound images. Users with basic computer knowledge can easily modify these images using them as templates for reference, reporting, and publications. An attempt is made to represent the fetal echocardiographic images by simplified memorable sectional schemas. These schemas will facilitate a better understanding and interpretation of various normal and abnormal fetal echocardiographic images. Being electronically transmittable, these schemas can be used as templates for further modifications.


Spinal navigation in tumor surgery of the thoracic spine: first clinical results.
In this clinical study, the accuracy of computed tomography-based and computer-guided decompression and insertion of pedicle screws in patients who have had tumor-related posterior surgery of the thoracic spine was evaluated. Eight patients with advanced metastatic disease were treated surgically using a posterior approach with the assistance of an optoelectronic navigation system. Postoperative computed tomography scans were obtained for all patients and provided information regarding decompression and transpedicle implant localization. In all eight patients accurate decompression of the spinal canal was seen. Using the navigation system, 22 of 26 scheduled transpedicle screws were inserted using computer guidance. Eighty-six percent (19 of 22) of the navigated pedicle screws were positioned centrally in the bone. Initial results indicate that computer-aided frameless navigation in tumor surgery of the thoracic spine is a safe system to improve surgical performance during posterior decompression and transpedicle stabilization. Although computed tomography-based computer-assisted spinal navigation is important, the system is not 100% accurate. Therefore, application of the navigation system should be restricted to experienced surgeons who can continue the operation using a conventional approach. Finally, detailed knowledge of the principles of the tracking systems is necessary to prevent possible misinterpretation of information provided by the computer.


The preferred nucleotide contexts of the AID/APOBEC cytidine deaminases have differential effects when mutating retrotransposon and virus sequences compared to host genes.
The AID / APOBEC genes are a family of cytidine deaminases that have evolved in vertebrates, and particularly mammals, to mutate RNA and DNA at distinct preferred nucleotide contexts (or "hotspots") on foreign genomes such as viruses and retrotransposons. These enzymes play a pivotal role in intrinsic immunity defense mechanisms, often deleteriously mutating invading retroviruses or retrotransposons and, in the case of AID, changing antibody sequences to drive affinity maturation. We investigate the strength of various hotspots on their known biological targets by evaluating the potential impact of mutations on the DNA coding sequences of these targets, and compare these results to hypothetical hotspots that did not evolve. We find that the existing AID / APOBEC hotspots have a large impact on retrotransposons and non-mammalian viruses while having a much smaller effect on vital mammalian genes, suggesting co-evolution with AID / APOBECs may have had an impact on the genomes of the viruses we analyzed. We determine that GC content appears to be a significant, but not sole, factor in resistance to deaminase activity. We discuss possible mechanisms AID and APOBEC viral targets have adopted to escape the impacts of deamination activity, including changing the GC content of the genome.


Nice guys finish last: When and why agreeableness is associated with economic hardship.
Recent research suggests that agreeable individuals experience greater financial hardship than their less agreeable peers. We explore the psychological mechanisms underlying this relationship and provide evidence that it is driven by agreeable individuals considering money to be less important, but not (as previously suggested) by agreeable individuals pursuing more cooperative negotiating styles. Taking an interactionist perspective, we further hypothesize that placing little importance on money-a risk factor for money mismanagement-is more detrimental to the financial health of those agreeable individuals who lack the economic means to compensate for their predisposition. Supporting this proposition, we show that agreeableness is more strongly (and sometimes exclusively) related to financial hardship among low-income individuals. We present evidence from diverse data sources, including 2 online panels (n1 = 636, n2 = 3,155), a nationally representative survey (n3 = 4,170), objective bank account data (n4 = 549), a longitudinal cohort study (n5 = 2,429), and geographically aggregated insolvency and personality measures (n6 = 332,951, n7 = 2,468,897). (PsycINFO Database Record (c) 2020 APA, all rights reserved).


[Long-fragment DNA of blood plasma as one of the criteria of individual sensitivity to emotional stress and to cerebral ischemia].
Intravenous injection ofpolyethylenoxide WSR-301 reducing hydrodynamic blood resistance (Toms effect) improves gas exchange in the lungs and halved lethality of the animals with cerebral ischemia. The aim of the study was to establish whether free plasma DNA influences blood gases and lethality of the animals with brain ischemia. Common carotid arteries were ligated for 15 min in intact stressed and tested in the open field Wistar male rats, then some of the rats received intravenous solution of homologous long-fragment DNA (20x10(-6) g/ml of blood). Cerebral circulation, acid-base equilibrium, paO2, paCO2, asymptotic blood viscosity, plasmic concentration and length of DNA fragments in plasma, lethality and neurological status of the survivors were studied. It was found that long fragments of rat DNA show hydrodynamic Toms effect. In normal passive rats sensitive to cerebral ischemia part of plasm DNA is fragmented, gas composition and blood viscosity of blood is worse (p < 0.05) than in active animals. There is a direct correlation between the level of long-fragment DNA in plasm and paO2 (r = 0.55) and inverse--with paCO2 (r = -0.84). Intravenous injection of long-fragment DNA improved the course and reduced lethality of brain ischemia 2-3-fold. Thus, qualitative and quantitative characteristics of plasma circulating DNA are responsible for differences in blood gases in rats differently tolerable to cerebral ischemia and can serve as one of the criteria of individual sensitivity to it being essential in pathogenesis of ischemic stroke.


Entropy-driven triple point wetting in hard-rod mixtures.
We theoretically study binary mixtures of thin and thick hard rods with diameter ratio more extreme than 1:4. The bulk phase diagram of these systems exhibits a triple point, where an isotropic (I) phase coexists with two nematic phases ( N1 and N2) of different composition. Using density functional theory, we predict that the I-N2 interface is completely wet by N1 upon approach of the the I-N1-N2 triple point. This entropic triple point wetting should be experimentally observable in colloidal suspensions of rodlike particles.


Total quality management: achieving service excellence.
Total Quality Management (TQM) provides a philosophy and a method for organizational renewal and redesign. It is based on the principle that productive work is accomplished through processes. Improving these processes requires the office team to objectively measure performance, discover root causes of problems, take corrective action, determine the effect of these actions, and secure achievements. TQM is a technique that provides a series of steps and set of tools. Through staff involvement and a desire for quality improvement, organizations involved in total quality note the accompanying satisfaction in taking constructive action, improving patient relations, and achieving service excellence. In today's competitive delivery environment, implementation of TQM can result in more satisfied patients, higher staff morale, and a more effective office team.


Effects of arecoline in relaxing human umbilical vessels and inhibiting endothelial cell growth.
This study investigated the effects of arecoline, an active ingredient of the areca nut, on the tone of human umbilical arteries and veins and on the eNOS expression and cell proliferation of human umbilical vein endothelial cells (HUVECs). We found that arecoline relaxes the human umbilical artery and vein rings in a concentration-dependent manner; the higher the concentration of arecoline, the greater the relaxation of the rings. However, the relaxation decreases after the endothelium was removed or pretreated with L-NAME, a nitric oxide synthase inhibitor. Moreover, arecoline increases in a dose-dependent way the cGMP levels of human umbilical arteries and veins. In HUVECs, arecoline also increases the eNOS expression. Therefore, the relaxant effects of arecoline on the umbilical artery and vein rings were endothelium-dependent through the NO-cGMP systems. In addition, arecoline at higher doses (100-1000 microM) inhibits endothelial cell proliferation; the exposure toarecoline (100-1000 microM) for 24 and 48 h induces G2/M cell cycle arrest of HUVECs. Our results indicate that arecoline would decrease vascular tone, in part mediated by NO. Higher doses of arecoline inhibit endothelial cell growth, which suggest that long-term use or high doses of areca nut might induce endothelial dysfunction and associated diseases.


Perinatal development of laryngeal function.
The resistance of the upper airway is strongly influenced by the action of opposing sets of laryngeal muscles. Expiratory airflow may be retarded by active adduction of the arytenoid cartilages or by a reduction in the activity of abductor muscles. In developing sheep the adductor muscles appear to represent the principal means by which lung recoil is opposed. This mechanism, which is most pronounced during non-rapid-eye-movement sleep, is regulated by afferent traffic from the lungs. In fetal sheep the laryngeal muscles are also influenced by breathing movements and sleep states. The adductor muscles are normally tonically active during non-rapid-eye-movement sleep when rhythmical breathing movements are absent. It is possible that this activity is at least partially responsible for elevated tracheal pressures and depressed flow of tracheal fluid during fetal apnea. This hypothesis has been tested by observing the effects of fetal paralysis and recurrent laryngeal nerve section. These experiments suggest that in the fetus near term the larynx makes a major contribution to upper airway resistance and hence to the maintenance of pulmonary expansion which has been shown to influence lung development.


Activation of motility by sensing short-chain fatty acids via two steps in a flagellar gene regulatory cascade in enterohemorrhagic Escherichia coli.
The regulated expression of virulence genes is critical for successful infection by an intestinal pathogen. Bacteria rely on sensing environmental signals to find preferable niches and reach the infectious state. Orally ingested enterohemorrhagic Escherichia coli (EHEC) travels through the gastrointestinal tract and encounters a variety of environmental factors, some of which act as triggering signals for the induction of virulence genes. Butyrate, one of the main short-chain fatty acids (SCFAs), is such a signal, enhancing the expression of genes for intimate attachment and type III secretion. We further explored the role of SCFAs and found a positive effect of SCFAs on flagellar expression. Although EHEC did not produce flagella when grown in Dulbecco's modified Eagle's medium (DMEM), a tissue culture medium that enhances virulence gene expression, the addition of SCFAs to the medium induced the production of flagella, and the EHEC bacteria became motile. Among SCFAs, butyrate simultaneously activates both virulence and flagellar genes. Flagella did not affect initial adherence, and they were not expressed in adherent bacteria during microcolony formation. SCFAs activated flagellar genes via two regulatory steps. Butyrate activated the flhDC regulatory genes through leucine-responsive regulatory protein (Lrp), which is also a regulator of virulence genes. However, butyrate, acetate, and propionate also activated downstream genes independently of flhDC activation. Consequently, when encountering increased concentrations of SCFAs, which are abundant in acetate, in the intestine, EHEC first activates flagellar production and motility, followed by genes involved in adherence and type III secretion, which leads to efficient adherence in a preferable niche.


Diverse Redoxome Reactivity Profiles of Carbon Nucleophiles.
Targeted covalent inhibitors have emerged as a powerful approach in the drug discovery pipeline. Key to this process is the identification of signaling pathways (or receptors) specific to (or overexpressed in) disease cells. In this context, fragment-based ligand discovery (FBLD) has significantly expanded our view of the ligandable proteome and affords tool compounds for biological inquiry. To date, such covalent ligand discovery has almost exclusively employed cysteine-reactive small-molecule fragments. However, functional cysteine residues in proteins are often redox-sensitive and can undergo oxidation in cells. Such reactions are particularly relevant in diseases, like cancer, which are linked to excessive production of reactive oxygen species. Once oxidized, the sulfur atom of cysteine is much less reactive toward electrophilic groups used in the traditional FBLD paradigm. To address this limitation, we recently developed a novel library of diverse carbon-based nucleophile fragments that react selectively with cysteine sulfenic acid formed in proteins via oxidation or hydrolysis reactions. Here, we report analysis of sulfenic acid-reactive C-nucleophile fragments screened against a colon cancer cell proteome. Covalent ligands were identified for >1280 S-sulfenylated cysteines present in "druggable" proteins and orphan targets, revealing disparate reactivity profiles and target preferences. Among the unique ligand-protein interactions identified was that of a pyrrolidinedione nucleophile that reacted preferentially with protein tyrosine phosphatases. Fragment-based covalent ligand discovery with C-nucleophiles affords an expansive snapshot of the ligandable "redoxome" with significant implications for covalent inhibitor pharmacology and also affords new chemical tools to investigate redox-regulation of protein function.


Red blood cell phosphate concentration and osmotic resistance during dietary phosphate depletion in dairy cows.
Hypophosphatemia in early lactating dairy cows has been implicated as primary cause for postparturient hemoglobinuria in cattle. Decreased availability of phosphorus has been proposed to reduce adenosine triphosphate synthesis of erythrocytes and thereby reduce osmotic resistance of these cells. To study the effect of phosphorus depletion on the phosphate concentration ([Pi]) in plasma and erythrocytes and the osmotic resistance of erythrocytes and to determine the association between plasma [Pi] and erythrocyte [Pi]. Ten healthy midlactating dairy cows in their 3rd to 5th lactation. Prospective study. Dietary phosphorus depletion for 5 weeks followed by phosphorus supplementation. Plasma and erythrocyte [Pi] and erythrocyte osmotic resistance were measured. Four cows underwent continuous dextrose infusion at the end of phosphate depletion to exacerbate hypophosphatemia. Dietary P depletion resulted in a marked decline of the plasma [Pi] from 4.1 ± 1.0 mg/dL to a nadir of 1.7 ± 0,5 mg/dL, but did not alter erythrocyte [Pi] or osmotic resistance. Similarly, dextrose infusion induced a decline of the plasma [Pi] from 2.4 ± 0.5 mg/dL to 1.5 ± 0.5 mg/dL, but had no effect on erythrocyte [Pi] or osmotic resistance. In cattle, marked hypophosphatemia induced by dietary P depletion was neither associated with a decline in erythrocyte [Pi] nor with decreased osmotic resistance of erythrocytes. Phosphorus depletion alone is therefore unlikely to cause intravascular hemolysis and the plasma [Pi] is an unreliable index for the intracellular [Pi] of erythrocytes.


High efficient of females of B-type Bemisia tabaci as males in transmitting the whitefly-borne tomato yellow leaf curl virus to tomato plant with Q-PCR method confirmation.
It has been previously reported that TYLCV can be transmitted from viruliferous males to non-viruliferous females and from viruliferous females to non-viruliferous males, but not between insects of the same sex; female whiteflies transmit TYLCV-Is with higher efficiency than males through symptoms recognition and viral DNA identification in tomato test plants (one insect per plant, with 48 h AAP and 48 h IAP). However, it remains unclear whether non-infected female and male could obtain same virus from TYLCV-infected tomato plants, and whether TYLCV-infected female and male could transmit same virus to non-viruliferous tomato plants. To address this issue, quantitative real-time PCR were applied to detect TYLCV content in adults or tomato plant. The acquisition and transmission experiments showed that both female and male can acquire and transmit the virus and no acquisition capability difference was observed between newly emerged female and male, however, female demonstrated superior transmission capability than male. Moreover, gene expressions profilings of GroEL and Hamiltonella in non-viruliferous and viruliferous female was all higher than that in male. These results further indicated that sex is an important factor affecting TYLCV transmission efficiency in B. tabaci.


Who should be first? How and when AI-human order influences procedural justice in a multistage decision-making process.
Artificial intelligence (AI) has fundamentally changed the way people live and has largely reshaped organizational decision-making processes. Particularly, AI decision making has become involved in almost every aspect of human resource management, including recruiting, selecting, motivating, and retaining employees. However, existing research only considers single-stage decision-making processes and overlooks more common multistage decision-making processes. Drawing upon person-environment fit theory and the algorithm reductionism perceptive, we explore how and when the order of decision makers (i.e., AI-human order vs. human-AI order) affects procedural justice in a multistage decision-making process involving AI and humans. We propose and found that individuals perceived a decision-making process arranged in human-AI order as having less AI ability-power fit (i.e., the fit between the abilities of AI and the power it is granted) than when the process was arranged in AI-human order, which led to less procedural justice. Furthermore, perceived AI ability buffered the indirect effect of the order of decision makers (i.e., AI-human order vs. human-AI order) on procedural justice via AI ability-power fit. Together, our findings suggest that the position of AI in collaborations with humans has profound impacts on individuals' justice perceptions regarding their decision making.


Plasmodium berghei: is nitric oxide involved in the pathogenesis of mouse cerebral malaria?
To analyze whether nitric oxide may be involved in the pathogenesis of the mouse cerebral malaria (CM), nitrate and nitrite were first measured in urines of Plasmodium species infected mice. The CM-susceptible CBA/J mice were infected with either Plasmodium berghei or Plasmodium chabaudi, and the CM-resistant BALB/c mice were infected with P. berghei. No increased levels of nitrate and nitrite were detected in urine of mice infected with Plasmodium whatever the time of monitoring. In contrast, the nitrite level was found to be increased in the urine of C3H/HeJ mice infected with Trypanosoma cruzi, used as a positive control for nitrate excretion in urine. Two analogs of L-arginine, the L-NG-monomethyl-arginine acetate hydrate (L-NMMA) and N omega-nitro-L-arginine, which inhibit the nitric oxide synthase were used. CBA/J mice infected with P. berghei and treated ip with the analogs developed full neurological symptoms. Even administered intracranially, L-NMMA did not reverse CM. The role of nitric oxide in the CM pathogenesis of the mouse model is discussed.


Genetics, Safety, Cost-Effectiveness, and Accessibility of Injectable Lipid-Lowering Agents: A Narrative Review.
Cardiovascular disease causes significant personal, financial, and societal burden and is a major cause of mortality and morbidity globally. Dyslipidemia has proven to be a major factor that contributes to its increased incidence; thus, since a long time, low-density lipoprotein cholesterol-lowering therapies have been employed to reduce coronary artery disease-associated mortality. The first-line therapy for hyperlipidemia and dyslipidemia is statins. Evidence showed that statins decrease the level of LDL-C resulting in a lower risk of CVD (20-25% for every decrease of 1 mmol/L). However, due to statin intolerance in some patients and despite using maximal doses, they have not been successful in lowering cardiovascular-associated mortality. Moreover, bococizumab was recently suspended due to its higher immunogenicity with time, resulting in less efficacy with long-term use. Alternatives to statins are PCSK9 inhibitors which are administered subcutaneously every two or four weeks. They are injectables with considerable lipid-lowering properties. This narrative review discusses their genetics, safety, tolerability, and cost-effectiveness. It also quantifies their benefit in certain subgroups by analyzing the findings from recent randomized clinical trials. Current data from phase 2 and 3 trials (ORION, ODYSSEY, and FOURIER) suggest a favorable profile for evolocumab, alirocumab, and inclisiran with minimal tolerable side effects and superior efficacy in statin-intolerant patients. Their cost-effectiveness has not yet been established clearly, but future outcomes seem promising.


[Epithelial ingrowth after LASIK--personal experience].
The current incidence of epithelial ingrowth after LASIK varies from 1% to 12%. After second procedure, it increases up to 32%. Known risk factors for this complication include epithelial defects at the time of surgery, or a history of recurrent corneal erosions, corneal basement membrane epithelial dystrophy, history of ingrowth in the other eye, hyperopic LASIK correction, flap instability, repeated LASIK surgeries. We performed 200 LASIK procedures. In 12 patients we found epithelial ingrowth. The follow up period was 2 years. We applied treatment: lifting and manual removal in 7 cases, phototherapeutic keratectomy in 3 cases. The rest of cases were under observation. Epithelial ingrowth is a relatively rare complication, following LASIK.


Antenatal diagnosis of tetrahydrobiopterin deficiency by quantification of pterins in amniotic fluid and enzyme activity in fetal and extrafetal tissue.
Prenatal diagnosis of tetrahydrobiopterin (BH4) deficiency was undertaken by evaluating the pterin patterns in amniotic fluid and the specific enzyme activities in fetal or extrafetal tissues. This allowed the prenatal diagnosis in 19 pregnancies at risk. In 8 families with a child already affected by dihydropteridine reductase deficiency 4 fetuses were diagnosed as homozygotes and 4 as heterozygotes for the defect. In 11 families with a child affected by 6-pyruvoyl tetrahydropterin synthase deficiency 4 fetuses were homozygous, 4 heterozygous and 3 normal. This study also advanced our knowledge of tetrahydrobiopterin metabolism during fetal development. The key enzymes involved in the biosynthesis of BH4 are expressed early and allow the fetus to be autotrophous for its cofactor requirement. In a twin pregnancy, both fetuses were diagnosed to be heterozygotes for dihydropteridine reductase deficiency and primapterin (7-biopterin) in amniotic fluid was increased. This indicates that pterin-4 alpha-carbinolamine dehydratase activity seems to be differently expressed during fetal life. As a consequence, pterins detected in amniotic fluid are of fetal origin and 6- and 7-substituted pterins can be present in amniotic fluid in higher proportions when compared with other body fluids.


Relationship between cytokines gene polymorphism and susceptibility to hepatitis B virus intrauterine infection.
The influences of genomic background are confirmed in more diseases. Immunologic tolerance after intrauterine infection of hepatitis B virus is considered to occur in T cells. Cytokines work effectively in eliminating virus by immune system after hepatitis B virus infection. To explore the relationship between cytokines (tumor necrosis factor-alpha, interferon-gamma, interleukin-4 and interleukin-10), which expressed abnormal quantity in the peripheral blood to intrauterine hepatitis B virus infectious children, gene single nucleotide polymorphism (SNP) and susceptibility to hepatitis B virus intrauterine infection. This is a cross sectional study of molecular clinical epidemiology. The subjects in this study were selected from outpatients of hepatitis B vaccine follow-up special clinics of our hospital in the period. According to intrant criteria, the high risk children of hepatitis B virus (HBV) intrauterine infection were divided into immune failure group (group I); and immune effective group (group II) and non high risk children belonged to the control group. Four gene SNP sites of TNF-alpha -238, IFN-gamma +874, IL-4 -590 and IL-10 -1082 were determined by real-time quantitative fluorescent polymerase chain reaction (PCR). The significant differences of TNF-alpha -238 A allele frequency were found between group I and group II (chi(2) = 6.797, P < 0.05) and between group I and the control group (chi(2) = 9.513, P < 0.05). No evident differences of TNF-alpha -238 A were found between group II and control group (chi(2) = 0.047, P > 0.05); the significant differences of IFN-gamma +874 A allele frequency were found between group I and group II (chi(2) = 7.238, P < 0.05), and between group I and the control group (chi(2) = 5.199, P < 0.05). No evident differences were found between group II and the control group (chi(2) = 0.602, P > 0.05); the significant differences of IL-4 -590 C/T allele frequency were not found between group I and group II (chi(2) = 0.632, P > 0.05), also group I and the control group (chi(2) = 0.584, P > 0.05), and the group II and the control group (chi(2) = 0.004, P > 0.05) respectively; The significant differences of IL-10 -1082 G allele frequency were found between group II and group I (chi(2) = 10.359, P < 0.001), and between group II and the controls (chi(2) = 35.418, P < 0.001), but the significant differences were not found between group I and the control group (chi(2) = 1.759, P > 0.05). This study suggested the possibility that the TNF-alpha -238 A allele and IFN-gamma +874 A allele were associated with HBV intrauterine infection. There was no evident relationship between IL-4 -590 C/T allele SNP and susceptibility to HBV intrauterine infection, but the IL-10 -1082 G allele was associated with preventive efficacy to HBV intrauterine infection.


Bile acids metabonomic study on the CCl4- and alpha-naphthylisothiocyanate-induced animal models: quantitative analysis of 22 bile acids by ultraperformance liquid chromatography-mass spectrometry.
Bile acids (BAs) are crucial for the diagnosis, follow-up, and prognostics of liver and intestinal disorders and other diseases affecting BA metabolism. A rapid, simple, and sensitive analytical method is needed to demonstrate the full metabolic profile and simultaneously determine the individual BAs in biological samples. In our present study, an ultraperformance liquid chromatography-mass spectrometry (UPLC-MS) method has been established and validated for simultaneous quantitation of 22 BAs and a metabonomic study was performed based on the chemometric analysis of the serum samples from carbon tetrachloride (CCl4)- and alpha-naphthylisothiocyanate (ANIT)-induced liver failure rats. The optimal chromatographic condition was effected by UPLC (Acquity UPLC BEH column, 1.7 microm, 2.1 mm x 100 mm) using a linear gradient elution system of methanol-5 mM ammonium acetate containing 0.01% acetic acid after a simple-step deproteinization by precipitation. The separation of the 22 BAs can be finished in less than 12 min, and the concentrations of these BAs in rat serums were simultaneously determined using a selective ions monitoring mode. The method was validated with respect to repeatability (relative standard deviation < 9.78%) and accuracy (relative errors from -13.55 to 9.58%). The range of each BA was found from not detected (nd) to 8301 ng mL(-1), respectively. Furthermore, the developed method was successfully applied to the metabonomics analysis of BAs in CCl4- and ANIT-induced liver failure rats, using principle component analysis and canonical discriminant analysis. The serum samples from the two types of rat liver injury could be distinguished from each other and from the untreated animals according to the varieties of BAs. It indicated that the level of BAs could be considered as a sensitive parameter of hepatotoxicity induced by different chemical toxins. This novel metabonomics study of BAs based on the UPLC-MS profile provides not only an accurate quantitative assay of the serum concentrations of biomarkers but also a promising methodology for evaluation of liver injury.


Indocyanine Green-Loaded Gold Nanoflowers@Two Layers of Silica Nanocomposites for Photothermal and Photodynamic Therapy of Oral Carcinoma.
Both photothermal therapy (PTT) and photodynamic therapy (PDT) are phototherapeutic approaches, which have been widely investigated for cancer therapy mediated by near infrared (NIR) light irradiation. Here, we successfully constructed a single-light triggered indocyanine green (ICG)-loaded gold nanocomposites which were composed of gold nanoflower core/two layers silica shell (AuNFs@SiO₂@mSiO₂-ICG) for enhanced PDT/PTT synergistic effect to oral carcinoma. The AuNFs@SiO₂@mSiO₂-ICG nanocomposites had no obviously cytotoxicity and could effectively arrest Cal27 cells in the G1 phase. Moreover, the conjugation of ICG caused significantly higher reactive oxygen species (ROS) productivity and apoptotic Cal27 cells compared to free ICG or free AuNFs@SiO₂@mSiO₂. In this study, compared with PTT or PDT alone, synchronous PTT and PDT produced by AuNFs@SiO₂@mSiO₂-ICG under NIR light irradiation induced enhanced Cal27 cells lethality in vitro and tumor growth inhibition in vivo, which might be a promising strategy for cancer treatment.


Evaluation of a complex intervention to improve primary care prescribing: a phase IV segmented regression interrupted time series analysis.
It is uncertain whether improvements in primary care high-risk prescribing seen in research trials can be realised in the real-world setting. To evaluate the impact of a 1-year system-wide phase IV prescribing safety improvement initiative, which included education, feedback, support to identify patients to review, and small financial incentives. An interrupted time series analysis of targeted high-risk prescribing in all 56 general practices in NHS Forth Valley, Scotland, was performed. In 2013-2014, this focused on high-risk non-steroidal anti-inflammatory drugs (NSAIDs) in older people and NSAIDs with oral anticoagulants; in 2014-2015, it focused on antipsychotics in older people. The primary analysis used segmented regression analysis to estimate impact at the end of the intervention, and 12 months later. The secondary analysis used difference-in-difference methods to compare Forth Valley changes with those in NHS Greater Glasgow and Clyde (GGC). In the primary analysis, downward trends for all three NSAID measures that were existent before the intervention statistically significantly steepened following implementation of the intervention. At the end of the intervention period, 1221 fewer patients than expected were prescribed a high-risk NSAID. In contrast, antipsychotic prescribing in older people increased slowly over time, with no intervention-associated change. In the secondary analysis, reductions at the end of the intervention period in all three NSAID measures were statistically significantly greater in NHS Forth Valley than in NHS GGC, but only significantly greater for two of these measures 12 months after the intervention finished. There were substantial and sustained reductions in the high-risk prescribing of NSAIDs, although with some waning of effect 12 months after the intervention ceased. The same intervention had no effect on antipsychotic prescribing in older people.


Reduction of subcutaneous mass, but not lean mass, in normal fetuses in Denver, Colorado.
To test the hypothesis that reduced birth weight in normal fetuses born at moderately high altitude (Denver), compared with the birth weight in normal fetuses born at sea level (Milan), is caused by a reduction in both lean mass and subcutaneous fat mass. Ninety-four normal singleton pregnancies (46 in Denver, 48 in Milan) had serial ultrasonographic axial images obtained to assess subcutaneous tissues of fetuses as a measure of body fat. The abdominal wall thickness and mid upper arm and mid thigh were examined. The equation was: Subcutaneous tissue equals total cross-sectional area minus bone and muscle area. Lean mass included the area of muscle and bone, head circumference, and femur length. Gestational age at delivery was similar between groups. Birth weight was less at Denver's altitude (2991 +/- 79 g versus 3247 +/- 96 g; P =.04). Abdominal wall thickness, mid upper arm, and mid thigh subcutaneous tissues measurements were significantly reduced at Denver's altitude and increased further in significance with advancing gestational age. Lean mass measurements were similar between groups. The reduced birth weight of the newborns in Denver was the result of a reduction in fetal subcutaneous fat tissue and not lean mass. Ultrasonography can be used to follow subcutaneous measurements longitudinally and to detect differences, and potentially disease processes, in study populations.


Fetal megacystis: Institutional experience and outcomes.
Fetal megacystis is a sonographic feature that may be indicative of several underlying pathologies. Despite advances in diagnosis and management, the overall prognosis of affected fetuses remains poor and about 50% of such pregnancies are terminated. To define the frequency, management, survival and renal outcomes of fetal megacystis over nine years at Wellington Hospital, New Zealand. A nine-year retrospective review of fetuses with an antenatal diagnosis of megacystis was undertaken. Sixteen cases were identified (nine live births, five terminations and two perinatal deaths). This gives an observed frequency of one per 940 fetuses scanned. Two-thirds of the live births have survived and been followed for a mean of 5.3 years. None have required renal dialysis or transplantation to date. The current series contributes to our knowledge of fetal megacystis and helps to inform antenatal counselling. Improved prognostic criteria are urgently required to accurately differentiate between fetuses with favourable versus poor outcomes.


Neurological complications in liver transplantation.
To define the incidence and type of neurological complications and associated factors, we reviewed 41 consecutive patients who had 45 procedures for liver transplantation. Encephalopathy occurred after 28 procedures (62%) with immediate onset and no significant recovery before death or re-transplantation in 11 (24%), slow recovery in eight (18%) and delayed onset (1-50 days, average 11) in six (13%). Intermittent confusion and agitation with full recovery followed three (6.6%), and focal and generalized seizures followed five (11%) procedures with multifocal myoclonus in two and status epilepticus in one; isolated focal seizures followed two and myoclonus or unclassified seizures, one each. All patients with seizures had encephalopathy. Three patients had neuropathy (2 generalised and 1 focal). Other complications included headache (2), tremors (2), fatigue (2), restlessness, nervousness, transient enuresis, intermittent dizziness, critical illness myopathy and detached retina. Brain imaging showed atrophy in three (6.6%) instances, intracerebral haemorrhage in two, multiple infarctions in one, and intracerebral and subarachnoid haemorrhage with infarction in one. Cerebrospinal fluid analysis showed increased protein in three, hemorrhage in one, and no abnormality in one patient. Of 12 patients (29%) who died before discharge, five in the first and three in the second week post-transplantation, 11 (92%) had encephalopathy post-operatively. Neurological complications after transplantation were associated with increased mortality. Post-operative hypomagnesaemia was associated with the development of nervous system complications. We did not identify any clear pre-operative predictors of development of post-operative neurological complications.


Dosage regimens for inhaled therapy in children should be reconsidered.
In current asthma guidelines, dosage regimens for inhalation therapy in children are based on adult doses and are generally titrated per kilogram of bodyweight or per square metre of body surface area. However, these recommendations do not correspond well with current knowledge of aerosol therapy in childhood. Lung deposition of the aerosolised drug is the key determinant for clinical efficacy and for systemic side effects of inhalation therapy. Lung deposition increases with age, whereas lung deposition expressed as a percentage per kilogram bodyweight is age-independent. This finding is explained by the self-regulating effect of age-dependent airway anatomy on lung deposition. Therefore, it is more likely that adult doses translate into paediatric doses only by virtue of the differences in self-limiting pulmonary deposition when using the same absolute nominal doses of the medication. Adapting the adult dose to a paediatric dose calculated on body size might be unnecessary and could lead to insufficient pulmonary deposition of medication. These findings suggest that dosage regimens for inhalation therapy for children may have to be reconsidered, and should be determined from dose-ranging studies rather than calculated from adult doses based on body size.


Syringomyelia associated with postmeningitic spinal arachnoiditis. Filling of the syrinx through a communication with the subarachnoid space.
A patient is described who became paraplegic because of postmeningitic spinal arachnoiditis. Twelve years later, upper limb signs appeared. Syringomyelia of an unusal communicating type was demonstrated by air myelography: Air, introduced by lumbar route, filled syrinx up to the level of the first cervical vertebra, through a communication with the subarachnoid space at the thoracic level.


The complete mitochondrial genome of the rayfish Raja porosa (Chondrichthyes, Rajidae).
We isolated mitochondrial DNA from the rayfish Raja porosa by long-polymerase chain reaction (Long-PCR) with conserved primers, and sequenced it by primer walking method using flanking sequences as sequencing primers. R. porosa mitochondrial DNA consists of 16,972 bp and its structural organization is conserved in comparison with other fishes and mammals. Based on the mitochondrial cytochrome b (cyt b) sequence, the phylogenetic position of R. porosa among cartilaginous fishes was inferred using different phylogenetic methods (ML-based quartet puzzling, Neighbor-joining (NJ) and Bayesian approaches). In this paper, we report the characteristics of the R. porosa mitochondrial genome including structural organization, base composition of rRNAs, tRNAs and protein-encoding genes and characteristics of mitochondrial tRNAs. These findings are applicable to comparative mitogenomics of R. porosa with other related taxa.


Hypophosphatemia.
Hypophosphatemia, defined as serum phosphate levels less than 2.5 mg%, is a relatively common disorder that can affect virtually every organ system. Phosphate deficiency can result from decreases in phosphate intake or absorption, increased loss from renal and nonrenal pathways, and transcellular phosphate shifts. Optimum therapy is directed at recognizing patients at greatest risk, correcting the underlying abnormality, and supplementing phosphate intake. Intravenous phosphate therapy is indicated for severe hypophosphatemia (serum phosphate less than 1 mg%) with close monitoring of serum phosphate, calcium, potassium, and magnesium levels. Indications for phosphate therapy and suggestions for empirical iv therapy in severe hypophosphatemia are presented.


[THE NATIONAL PROJECT "HEALTHCARE" AND ITS IMPACT ON THE EXPORT OF THERUSSIAN MEDICAL SERVICES].
The article reports on the main directions of the national project "Healthcare", providing for the formation of a medical sector with hospitals and polyclinics fitted with modern equipment, online services for the convenience of patients and medical personnel and staffed with highly qualified medical personnel. The author analyses the factors influencing the development of medical tourism in the Russian Federation. Preserving the best traditions of medical practice and developing together with global trends in the field of health preservation, Russian medicine is becoming innovative. In order to solve the tasks set to expand the scope of medical care to foreign citizens, the federal project "Development of the export of medical services" is being implemented within the framework of the national project "Healthcare", which has already united 71 regions of the country. The purpose of this work is to identify the factors influencing the development of the export of the Russian medical services within the framework of the implementation of the national project "Healthcare". In conclusion, it is reported that the implementation of the project contributes to the inflow of investment funds into the national healthcare system, the promotion of the Russian medical centers and the creation of a positive image of the country abroad.