The tap-tpg gene pair on the linear plasmid functions to maintain a linear topology of the chromosome in Streptomyces rochei.
Streptomyces rochei 7434AN4 carries three linear plasmids, pSLA2-L (211 kb), pSLA2-M (113 kb) and pSLA2-S (18 kb), their complete nucleotide sequences having been determined. Restriction and sequencing analysis revealed that the telomere sequences at both ends of the linear chromosome are identical to each other, are 98.5% identical to the right end sequences of pSLA2-L and pSLA2-M up to 3.1 kb from the ends and have homology to those of typical Streptomyces species. Mutant 2-39, which lost all the three linear plasmids, was found to carry a circularized chromosome. Sequence comparison of the fusion junction and both deletion ends revealed that chromosomal circularization occurred by terminal deletions followed by nonhomologous recombination. Curing of pSLA2-L from strain 51252, which carries only pSLA2-L, also resulted in terminal deletions in newly obtained mutants. The tap-tpg gene pair, which encodes a telomere-associated protein and a terminal protein for end patching, is located on pSLA2-L and pSLA2-M but has not hitherto been found on the chromosome. These results led us to the idea that the tap-tpg of pSLA2-L or pSLA2-M functions to maintain a linear chromosome in strain 7434AN4. This hypothesis was finally confirmed by complementation and curing experiments of the tap-tpg of pSLA2-M.


Effect of thyroxine and ethanol on cerebral nucleic acids during early postnatal period in rabbits.
In the view of the fact ethanol increases the blood-brain barrier permeability for thyroxine (T4) during a critical period of postnatal brain development in the rabbit, the influence of ethanol with or without T4 on cerebral RNA and DNA concentration has been investigated. Generally accepted measures of thyroid hormone action on developing neural tissue such as the changes in the nucleic acids, cell density and size and in protein level, dry matter and cholesterol have been used. Ethanol alone caused an increase in RNA concentration and the RNA/DNA ratio. In addition, it tended to alter the brain tissue composition in the same direction as T4 administration, i.e. characteristic for an accelerated development of CNS. The changes provoked by T4 with ethanol were more pronounced when compared to those after T4 only. It is concluded that the action of ethanol might be indirect and presumably results from a greater supply of thyroxine to the brain tissue due to increased permeability of blood-brain barrier for thyroxine.


Two's company, is three a crowd? Ethical cognition in decision making and the role of industry third parties in pediatric diabetes care.
Families of children with diabetes increasingly obtain health information from a variety of sources. Doctor-patient relationships have accordingly become more fluid and dynamic with input from other parties. These outside parties include representatives from the diabetes health care industry-industry third parties (ITPs). This review is an exploration of the ethical principles and cognitive processes involved when doctors and patients negotiate around health care practices and the role of ITPs in that dialogue. Ethical principles of conflicts of interest, beneficence (act in the best interests of the patient), non-maleficence (act so as to do no harm) and justice (act so as to allocate resources fairly or justly) are relevant considerations. Reflexive and analytic thinking and various cognitive biases also play a significant part in clinical decision making. A complex case example is analyzed to highlight a process of ethical cognition in decision making to ensure high-value care and optimal patient outcomes.


Dihydropyrimidine Dehydrogenase Deficiency: Metabolic Disease or Biochemical Phenotype?
Dihydropyrimidine dehydrogenase (DPD) deficiency is an autosomal recessive disorder of pyrimidine metabolism that impairs the first step of uracil und thymine degradation. The spectrum of clinical presentations in subjects with the full biochemical phenotype of DPD deficiency ranges from asymptomatic individuals to severely affected patients suffering from seizures, microcephaly, muscular hypotonia, developmental delay and eye abnormalities.We report on a boy with intellectual disability, significant impairment of speech development, highly active epileptiform discharges on EEG, microcephaly and impaired gross-motor development. This clinical presentation triggered metabolic workup that demonstrated the biochemical phenotype of DPD deficiency, which was confirmed by enzymatic and molecular genetic studies. The patient proved to be homozygous for a novel c.2059-22T>G mutation which resulted in an in-frame insertion of 21 base pairs (c.2059-21_c.2059-1) of intron 16 of DPYD. Family investigation showed that the asymptomatic father was also homozygous for the same mutation and enzymatic and biochemical findings were similar to his severely affected son. When the child deteriorated clinically, exome sequencing was initiated under the hypothesis that DPD deficiency did not explain the phenotype completely. A deletion of the maternal allele on chromosome 15q11.2-13-1 was identified allowing the diagnosis of Angelman syndrome (AS). This diagnosis explains the patient's clinical presentation sufficiently; the influence of DPD deficiency on the phenotype, however, remains uncertain.


Treatment of lower urinary tract symptoms/benign prostatic hyperplasia and erectile dysfunction.
This article summarizes years of challenging research on erectile dysfunction (ED), a condition that has an important social and cultural relevance. Preclinical and clinical research progress has led to new therapeutic approaches to ED in patients with different comorbidities and particularly in those with low urinary tract symptoms (LUTS)/benign prostatic hyperplasia (BPH). These goals were possible only by combined work of specialists and researchers of different and intertwined medical disciplines. Currently, tadalafil (5 mg/d) is the best choice; other phosphodiesterase-5 inhibitors (PDE5i) are not included among options, despite the growing evidence of therapeutic effects. Different regimens of tadalafil may be prescribed based on patient needs, severity of LUTS/BPH - ED profile, and clinical experience. An integrated approach is necessary to choose for a combined therapy with PDE5i and α-blockers following urological and cardiac counseling in terms of outcomes and adverse effects.


Cystatin C-based formula is superior to MDRD, Cockcroft-Gault and Nankivell formulae in estimating the glomerular filtration rate in renal allografts.
There are conflicting reports on the reliability of the various glomerular filtration rate formula in renal allografts, to assess the performance of various glomerular filtration rate formula in estimating renal function of renal allografts. Glomerular filtration rate was measured using an isotope Tc99m DTPA in 97 renal transplant patients and estimated using modification of diet in renal disease, Cockroft-Gault formula, Nankivell, and a cystatin C-based formula. The overall performance of these formula was evaluated by calculating bias, accuracy and precision. Mean age was 39.8 years (-/+ 12.7), body mass index was 26.9 (-/+ 6.3) and serum creatinine was 114.5 micromol/L (-/+ 39.3). The mean measured glomerular filtration rate was 58.1 mL/min (-/+ 25.6). The bias with modification of diet in renal disease was 7.7 (P = .03), with Cockroft-Gault formula it was 3.2 (P = .3), with Nankivell it was 10.3 (P = .0002), and with cystatin C it was 0.31 (P = .9) The precisions (r) for modification of diet in renal disease, Cockroft-Gault formula, Nankivell, and cystatin C were 0.26 (P = .01), 0.26 (P = .01), 0.42 (P = .0001), and 0.60 (P < .0001), respectively. We also investigated the impact of sex, age, body mass index, and glomerular filtration rate on the performance of these 4 formula. The best correlation, highest precision, accuracy, and least bias were seen when using cystatin C. The largest bias was seen when using Nankivell and modification of diet in renal disease formula.


Successful bronchotracheal reconstruction in esophageal bronchus: two case reports.
Esophageal bronchus is the most common congenital bronchopulmonary foregut malformation. Current surgical treatment is resection of anomalous pulmonary tissue, which is often hypoplastic and destroyed by infection. The authors report two cases of bronchotracheal reconstruction. The diagnosis was early, before 15 days of age. The anomalous pulmonary tissue had a pulmonary arterial supply and venous drainage as assessed by angiography and a good functional capacity on selective ventilation. Bronchotracheal anastomosis was successful in both cases: a right main bronchus at 25 days of age and a left main bronchus at 13 days of age. One child underwent reoperation 1 year later for bronchomalacia of the reimplanted bronchus. Both children are well with normal growth 3 and 7 years after surgery. Chest roentgenograms showed normal and symmetrical lung aeration. Tracheal reimplantation may be preferred to pulmonary resection when the anomalous pulmonary tissue is not destroyed. The pulmonary functional capacity is increased and the complications of pneumonectomy avoided.


Qishen Granule (QSG) Inhibits Monocytes Released From the Spleen and Protect Myocardial Function via the TLR4-MyD88-NF-κB p65 Pathway in Heart Failure Mice.
Preliminary clinical and basic researches have proved that Qishen granule (QSG) is an effective prescription for treating heart failure (HF) in China, with a characteristic of regulating the ratio of M1/M2 macrophage in the myocardium. However, the regulative mechanism of monocytes targeting the cardio-splenic axis has not been fully elucidated. This study aimed to investigate the effects and mechanism of QSG inhibiting the release of splenic monocytes and the recruitment of myocardial tissue both in vivo and in vitro. Experiments in mice with acute myocardial infarction (AMI)-induced HF demonstrated that QSG could exert anti-inflammatory effects by inhibiting splenic monocytes release and phenotypic changes. Moreover, in vitro experiments indicated QSG could inhibit LPS-stimulated macrophage-conditioned medium (CM)-induced H9C2 cardiomyocyte injury by upregulating the key proteins in TLR4-MyD88-NF-κB p65 pathway. In addition, knockdown or overexpression of TLR4 in H9C2 cells further confirmed that QSG could attenuate inflammatory injury in cardiomyocytes via the TLR4-MyD88-NF-κB p65 pathway. Overall, these data suggested that QSG could improve cardiac function and reduce the inflammatory response in AMI-induced HF by inhibiting splenic monocytes release, and protecting myocardial function via the TLR4-MyD88-NF-κB pathway in heart failure mice.


[Development and application of a method for molecular diagnosis of 21-hydroxylase deficiency].
To develop a method for elucidating genetic basis of 21-hydroxylase deficiency. Sanger sequencing of entire 21-hydroxylase coding gene CYP21A2 was carried out to detect point mutations, and multiplex ligation-dependent probe amplification (MLPA) and locus-specific PCR/enzyme restriction method were used to detect large deletions and conversion mutations. Nine children were analyzed. Point mutations of the CYP21A2 gene have been identified as: IVS2 13A/C>G (9 alleles), p.Arg356Trp (1 allele), Cluster E6 (1 allele), p.Gln318X (1 allele), and Prom conv (1 allele). While the former 4 mutations are pathogenic, the role of Prom conv mutation in the pathogenesis was uncertain. Three cases had entire CYP21A2 gene deletions (3 alleles), three had CYP21A1P/CYP21A2 chimeric mutations (3 alleles). The genotypes of all patients were determined. And all of the mutations were inherited from parents. A rational method for detecting point mutations and large deletions/conversions of CYP21A2 gene has been established.


Inferring phenotypic properties from single-cell characteristics.
Flow cytometry provides multi-dimensional data at the single-cell level. Such data contain information about the cellular heterogeneity of bulk samples, making it possible to correlate single-cell features with phenotypic properties of bulk tissues. Predicting phenotypes from single-cell measurements is a difficult challenge that has not been extensively studied. The 6th Dialogue for Reverse Engineering Assessments and Methods (DREAM6) invited the research community to develop solutions to a computational challenge: classifying acute myeloid leukemia (AML) positive patients and healthy donors using flow cytometry data. DREAM6 provided flow cytometry data for 359 normal and AML samples, and the class labels for half of the samples. Researchers were asked to predict the class labels of the remaining half. This paper describes one solution that was constructed by combining three algorithms: spanning-tree progression analysis of density-normalized events (SPADE), earth mover's distance, and a nearest-neighbor classifier called Relief. This solution was among the top-performing methods that achieved 100% prediction accuracy.


The reductive acetyl coenzyme A pathway: sequence and heterologous expression of active methyltetrahydrofolate:corrinoid/iron-sulfur protein methyltransferase from Clostridium thermoaceticum.
The methyltransferase (MeTr) from Clostridium thermoaceticum transfers the N5-methyl group of (6S)-methyltetrahydrofolate to the cobalt center of a corrinoid/iron-sulfur protein in the acetyl coenzyme A pathway. MeTr was purified to homogeneity and shown to lack metals. The acsE gene encoding MeTr was sequenced and actively expressed in Escherichia coli at a level of 9% of cell protein. Regions in the sequence of MeTr and the E. coli cobalamin-dependent methionine synthase were found to share significant homology, suggesting that they may represent tetrahydrofolate-binding domains.


Five cases of new onset refractory status epilepticus (NORSE) syndrome: outcomes with early immunotherapy.
Cryptogenic new onset refractory status epilepticus (NORSE) syndrome has been described in both adults and children, and is often associated with poor outcome. A variety of terms have been used in the literature to refer to this syndrome. The condition may be triggered by as yet unidentified infections or an immunological mechanism. We present a series of 5 patients with NORSE syndrome treated at 2 neuroscience centres in the North of England, in whom early use of immunotherapy appears to be associated with good neurological outcomes. Case note review of the index case and four other patients was undertaken to obtain details of clinical presentation, imaging and CSF findings, infectious/inflammatory tests, management of seizures, immunotherapy and outcome. Case 1 was a 26 year old male with a prodrome of headache and vomiting. He developed refractory multifocal and generalised seizures, which required admission to intensive care unit and administration of general anaesthetic. Seizures recurred on withdrawal of barbiturate anaesthetic until day 29. MR imaging, CSF examination and serological tests for viral and autoimmune aetiologies were normal apart from positive anti-TPO antibodies: the patient had previously treated hyperthyroidism. He was initially treated with aciclovir and antibacterials. IV steroids were administered day 12 and IV immunoglobulin day 18. He made a good recovery being discharged home 2 months after admission. Seizures recurred on withdrawal of steroid therapy, and required longer term immunosuppressant treatment with azathioprine. Clinical features and investigations of the four other patients were similar. Two were given early immunotherapy with steroids and intravenous immunoglobulins and survived with few deficits. One patient who was not given immunotherapy died from complications associated with prolonged ICU stay. Outcome was not known for the fourth patient as she was repatriated to her home country in thiopentone coma. In our experience, early immunotherapy has been associated with good outcomes in NORSE. Multicentre collaboration is required to establish the diagnostic criteria and appropriate management of patients presenting with NORSE.


Manure contamination with Clostridium botulinum after avian botulism outbreaks: management and potential risk of dissemination.
Persistence of Clostridium botulinum in the environment is well known. Getting rid of it after animal botulism outbreaks is so tricky, especially as far as manure concerns. This study aimed at 1. describing manure management on 10 poultry farms affected by botulism and 2. assessing the persistence of C botulinum in poultry manure after the outbreak. Each farm was visited twice at two different manure storage times (two weeks after manure removal and two months later). Fifteen samples of manure were collected on each visit and C botulinum was detected using real-time PCR. Management of manure varied among poultry farms (classical storage, addition of quicklime, bacterial flora or incineration). C botulinum was detected in the manure of all 10 farms, 56.5per cent of samples being positive. C botulinum was detected significantly more frequently at the second visit (65.8per cent vs 49.7per cent, P<0.01) and on the surface of the pile (63.1per cent vs 50per cent, P=0.025). This study shows the persistence of C botulinum in poultry manure over time after a botulism outbreak and highlights manure management as a key health issue in preventing spore dissemination in the environment and recurrence of the disease.


Nonquenching of charge carriers by Fe3O4 core in Fe3O4/ZnO nanosheet photocatalyst.
Fe3O4-implanted ZnO and pristine ZnO nanosheets have been synthesized hydrothermally. High-resolution scanning electron microscopy, high-resolution transmission electron microscopy, energy dispersive X-ray spectroscopy, elemental mapping, selected area electron diffractometry, powder X-ray diffractometry, Raman spectroscopy, vibrating sample magnetometry, solid state impedance spectroscopy, UV-visible diffuse reflectance spectroscopy, and photoluminescence spectroscopy show implantation of Fe3O4 in ZnO nanosheets. Fe3O4 core with ZnO shell is of type I core/shell heterostructure which is to quench charge carriers and suppress photocatalysis. But the photocatalytic activity is not suppressed on implantation of Fe3O4 in ZnO nanosheets, and time controlled single photon counting lifetime spectroscopy shows that the photogenerated charge carriers are not quenched by the Fe3O4 core in the ZnO nanosheets. The composite nanosheets are photostable, reusable, and magnetically recoverable, revealing potential application in mineralization of organic pollutants.


Association of glycaemic index and glycaemic load with metabolic syndrome in an Iranian adult population: Isfahan Healthy Heart Program.
There is controversy around the clinical effects of the dietary glycaemic index (GI) and glycaemic load (GL) on cardiovascular diseases risk factors such as metabolic syndrome (MetS). So, the present study was performed to evaluate the relationship between GI or GL and metabolic syndrome in an Iranian adult population in 2007. The study was based on data from a sub-sample of the Isfahan Healthy Heart Program (IHHP), collected across three cities in central Iran, in the year 2007. This was a cross-sectional survey of 1618 randomly selected adults aged ≥19 years. Nutritional assessment was conducted by a single 24-hour recall questionnaire. Fasting serum lipids, anthropometric indicators and blood pressure were measured by standard methods. Analysis of covariance was used to compare metabolic syndrome components according to energy-adjusted GI and GL levels. To expose the effect of potential confounders, hierarchical logistic regression models were utilised to determine adjusted odds ratios (OR) and 95% CI. After adjustment for age, gender, body mass index and energy intake, high GI was found to be significantly associated with MetS (OR 95% CI) (1.46 (1.01-2.12)). This was attenuated marginally by excluding the confounding effects of dietary fibre intake (1.29 (1.01-1.74)). All hierarchical models illustrated no significant association between energy-adjusted GL and the risk of MetS adjusted for confounders. There is a positive relationship between dietary GI, but not GL, and the presence of MetS after adjustment for potential confounders. However, studies with long duration of follow up and experimental studies are still required to confirm this relationship.


Assessment of the probability of introduction of Thaumatotibia leucotreta into the European Union with import of cut roses.
Following a request from the European Commission, the EFSA Panel on Plant Health performed a quantitative pest risk assessment to assess whether the import of cut roses provides a pathway for the introduction of Thaumatotibia leucotreta (Lepidoptera: Tortricidae) into the EU. The assessment was limited to the entry and establishment steps. A pathway model was used to assess how many T. leucotreta individuals would survive and emerge as adults from commercial or household wastes in an EU NUTS2 region climatically suitable in a specific season. This pathway model for entry consisted of three components: a cut roses distribution model, a T. leucotreta developmental model and a waste model. Four scenarios of timing from initial disposal of the cut roses until waste treatment (3, 7, 14 and 28 days) were considered. The estimated median number of adults escaping per year from imported cut roses in all the climatically suitable NUTS2 regions of the EU varied from 49,867 (90% uncertainty between 5,298 and 234,393) up to 143,689 (90% uncertainty between 21,126 and 401,458) for the 3- and 28-day scenarios. Assuming that, on average, a successful mating will happen for every 435 escaping moths, the estimated median number of T. leucotreta mated females per year from imported cut roses in all the climatically suitable NUTS2 regions of the EU would vary from 115 (90% uncertainty between 12 and 538) up to 330 (90% uncertainty between 49 and 923) for the 3- and 28-day scenarios. Due to the extreme polyphagia of T. leucotreta, host availability will not be a limiting factor for establishment. Climatic suitability assessment, using a physiologically based demographic modelling approach, identified the coastline extending from the northwest of the Iberian Peninsula through the Mediterranean as area suitable for establishment of T. leucotreta. This assessment indicates that cut roses provide a pathway for the introduction of T. leucotreta into the EU.


Estimating the health loss due to poor engagement with cardiac rehabilitation in Australia.
Cardiac rehabilitation (CR) programs are effective in reducing cardiovascular mortality and readmissions. However, most patients are denied the benefits of CR due to low referral rates. Of those patients referred, commencement rates vary from 28.4% to 60%. This paper quantifies the scale of health loss in Australia due to poor engagement with the program, and estimates how much public funding can be justifiably reallocated to address the problem. Economic decision modelling was undertaken to estimate the expected lifetime health loss and costs to Medicare. Key parameters were derived from Australian databases, CR registries and meta-analyses. Population health gains associated with uptake rates of 60%, and 85% were calculated. CR was associated with a 99.9% probability of being cost-effective, even at a cost-effectiveness threshold lower than conventionally applied. Importantly, an average of 0.52 years of life expectancy are lost due to national uptake being below 60% achieved in some best performing programs in Australia, equivalent to 0.28 quality adjusted life years. The analysis indicates that $12.9 million/year could be justifiably reallocated from public funds to achieve a national uptake rate of 60%, while maintaining cost-effectiveness of CR due to the large health gains that would be expected. CR is a cost-effective service for patients with coronary heart disease. In Australia, less than a third of patients commence CR, potentially resulting in avoidable patient harm. Additional investment in CR is vital and should be a national priority as the health gains for patients far outweigh the costs.


Differential responses of choroidal melanocytes and uveal melanoma cells to low oxygen conditions.
Tissue culture is traditionally performed at atmospheric oxygen concentration (21%), which induces hyperoxic stress, as endogenous physiologic oxygen tension found in tissues varies between 2% and 9%. This discrepancy may lead to misinterpretation of results and may explain why effects observed in vitro cannot always be reproduced in vivo and vice versa. Only a few studies have been conducted in low physiologic oxygen conditions to understand the development and differentiation of cells from the eye. The aim of this study was to investigate the growth and gene expression profile of melanocytes from the choroid permanently exposed to 21% (hyperoxic) or 3% (physiologic) oxygen with proliferation assays and DNA microarray. The cellular behavior of the melanocytes was then compared to that of cancer cells. The gross morphology and melanin content of choroidal melanocytes changed slightly when they were exposed to 3% O2, and the doubling time was statistically significantly faster. There was an increase in the percentage of choroidal melanocytes in the active phases of the cell cycle as observed by using the proliferation marker Ki67. The caveolin-1 senescence marker was not increased in choroidal melanocytes or uveal melanoma cells grown in hyperoxia. In comparison, the morphology of the uveal melanoma cells was similar between the two oxygen levels, and the doubling time was slower at 3% O2. Surprisingly, gene expression profiling of the choroidal melanocytes did not reveal a large list of transcripts considerably dysregulated between the two oxygen concentrations; only the lactate transporter monocarboxylate transporter (MCT4) was statistically significantly upregulated at 3% O2. This study showed that the oxygen concentration must be tightly controlled in experimental settings, because it influences the subsequent cellular behavior of human choroidal melanocytes.


[Diagnostic value of different detection methods for Mycobacterium tuberculosis in bronchoalveolar lavage fluid from pulmonary tuberculosis patients].
To investigate the diagnostic value of different detection methods for Mycobacterium tuberculosis in bronchoalveolar lavage fluid (BALF) from patients with pulmonary tuberculosis. Methods: BALF from100 patients in Changsha Central Hospital from January 2013 to December 2015 was collected. Among 100 patients, 65 cases were clinically diagnosed as tuberculosis, and 35 cases served as control. BALF smear method, polymerase chain reaction (PCR) and membrane reverse dot blot (RDB) were used for synchronous detection of Mycobacterium tuberculosis. Results: The positive rates by BALF smear method, PCR and RDB were 43.08%, 73.84% and 92.31%, respectively (P<0.05). Sensitivity, specificity, accuracy, and negative predictive value for BALF smear were 43.08%, 88.57%, 59.00%, and 45.59%, respectively; for PCR were 73.85%, 100%, 83.00%, and 67.31%, respectively; for RDB were 92.31%, 100.00%, 95.00%, and 87.50%, respectively. Conclusion: The technique of membrane RDB can not only accurately diagnose Mycobacterium tuberculosis, but also can rapidly and easily identify the resistance of Mycobacterium tuberculosis to streptomycin (SM), rifampicin (RFP) and isoniazid (INH) genotypes. It possesses high clinical value.


Invasive alien species water hyacinth Eichhornia crassipes as abode for macroinvertebrates in hypertrophic Ramsar Site, Lake Xochimilco, Mexico.
This paper presents information on the density, diversity and functional feeding groups of macroinvertebrate assemblages associated with water hyacinth in Antiguo Canal Cuemanco, part of Lake Xochimilco in Mexico City. Rare (low frequency and density) and dominant (high frequency and density) taxa prevailed in the assemblages, with the most predominant being Hyalella azteca, Chironomus plumosus and Ischnura denticollis. Nonmetric Multidimensional Scaling confirmed two climatic seasons: warm-rainy and cold-dry; the former with the highest diversity and density of taxa. Canonical Correspondence Analysis showed that conductivity, nitrates and turbidity explained the density variations of taxa. Antiguo Canal Cuemanco waters are spatially homogeneous with the characteristics of hypertrophic shallow lakes, inhabited by scrapers and gathering-collectors. The species found were tolerant to organic pollution.


Impact of clinically significant portal hypertension on surgical outcomes for hepatocellular carcinoma in patients with compensated liver cirrhosis: a propensity score matching analysis.
The roles of portal hypertension (PHT) on the postoperative course after hepatectomy are still debated. The aim of this study was to evaluate surgical outcomes of hepatectomy in patients with PHT. Data from 152 cirrhotic patients who underwent hepatectomy for hepatocellular carcinoma (HCC) were collected retrospectively. Patients were divided into two groups according to the preoperative presence of PHT as follows: 44 patients with PHT and 108 without PHT. Propensity score matching (PSM) analysis was used to overcome selection biases. There were no significant differences in morbidity (56.8% vs. 51.9%, p=0.578) and 90-days mortality (4.5% vs. 4.6%, p=0.982) between the two groups. Post-hepatectomy liver failure (PHLF) was not significantly different between the two groups (43.2% vs. 35.2%, p=0.356). Patients without PHT had a better 5-year disease-free survival than those with PHT, although the difference did not reach statistical significance (30.9% vs. 17.2%, p=0.081). Five-year overall survivals were not significantly different between the two groups (46.6% vs. 54.9%, p=0.724). Repeat analyses after PSM showed similar rates of morbidity (p=0.819), mortality (p=0.305), PHLF (p=0.648), disease-free survival (p=0.241), and overall survival (p=0.619). The presence of PHT was not associated with either short-term or long-term poor surgical outcomes. Child-Pugh A and B patients with PHT have surgical outcomes similar to those without PHT. Hepatectomy can be safely performed and can also be considered as a potentially curative treatment in HCC patients with PHT.


A Versatile and Efficient Method to Isolate DNA-Polymer Conjugates.
We present a facile and adaptable method to purify and isolate DNA-polymer conjugates from different uncharged homo, random, or block copolymer families. Anion exchange chromatography is used to separate the reaction solution and retrieve the excess unreacted polymer and oligonucleotide. The stationary phase has a high efficiency (25 nmol of DNA per run), facilitating the purification of large batches without compromising the peak shape and resolution. To demonstrate the versatility of this method, different types of polymers, including acrylates, methacrylates, and acrylamides containing hydrophilic and hydrophobic blocks, were purified with high yields. Additionally, DNA-polymer conjugates with various DNA block lengths were also successfully purified, further highlighting the broad applicability of this method.


Phospholipase C gamma 1 (PLCG1) R707Q mutation is counterselected under targeted therapy in a patient with hepatic angiosarcoma.
Hepatic angiosarcoma is a rare and aggressive vascular neoplasm. Pathogenic driver mutations are largely unknown. We present the case of a patient with recurrent hepatic angiosarcoma, who initially showed good response to sunitinib, followed by progression. Using comprehensive molecular techniques, we explored the potential mechanisms of resistance. By low-read-depth whole-genome sequencing, the comparison of copy number aberrations (CNAs) of the primary tumor to the skin metastatic lesion that developed after progression on sunitinib, revealed high-level amplification of the 4q11-q13.1 region (containing KIT, PDGFRA and VEGFR2 genes) that was sustained in both lesions. Whole exome sequencing on the germline, primary and metastatic tumor DNAs, resulted in 27 confirmed mutations, 19 of which (including TP53 mutation) presented in both primary and metastatic lesions. One mutation, ZNF331 frameshift deletion, was detected only in the primary tumor. In contrast, seven other mutations, including phospholipase C-gamma1 (PLCG1) R707Q mutation, were found only in the metastatic tumor, indicating selection of cells with the resistant genotype under sunitinib pressure. Our study supports the notion that PLCG1-R707Q mutation may confer VEGFR2-independent signaling and may thus cause resistance against VEGF(R)-directed therapies. This case illustrates also the advantages of using next-generation technologies in identifying individualized targeted therapy.


Immediate maxillofacial prosthodontic rehabilitation after radical mid-face tumor resection.
Mid-facial surgical defects can adversely affect a patient's esthetics and psychological well-being. Fabrication of a definitive mid-facial prosthesis can be a time-consuming procedure. It is crucial to minimize the time between the tumor resection and initial prosthetic rehabilitation. This article describes a method for rapid fabrication of a transitional facial prosthesis for mid-facial defects.


Maternal-to-fetal allopurinol transfer and xanthine oxidase suppression in the late gestation pregnant rat.
Fetal brain hypoxic injury remains a concern in high-risk delivery. There is significant clinical interest in agents that may diminish neuronal damage during birth asphyxia, such as in allopurinol, an inhibitor of the prooxidant enzyme xanthine oxidase. Here, we established in a rodent model the capacity of allopurinol to be taken up by the mother, cross the placenta, rise to therapeutic levels, and suppress xanthine oxidase activity in the fetus. On day 20 of pregnancy, Wistar dams were given 30 or 100 mg kg(-1) allopurinol orally. Maternal and fetal plasma allopurinol and oxypurinol concentrations were measured, and xanthine oxidase activity in the placenta and maternal and fetal tissues determined. There were significant strong positive correlations between maternal and fetal plasma allopurinol (r = 0.97, P < 0.05) and oxypurinol (r = 0.88, P < 0.05) levels. Under baseline conditions, maternal heart (2.18 ± 0.62 mU mg(-1)), maternal liver (0.29 ± 0.08 mU mg(-1)), placenta (1.36 ± 0.42 mU mg(-1)), fetal heart (1.64 ± 0.59 mU mg(-1)), and fetal liver (0.14 ± 0.08 mU mg(-1)) samples all showed significant xanthine oxidase activity. This activity was suppressed in all tissues 2 h after allopurinol administration and remained suppressed 24 h later (P < 0.05), despite allopurinol and oxypurinol levels returning toward baseline. The data establish a mammalian model of xanthine oxidase inhibition in the mother, placenta, and fetus, allowing investigation of the role of xanthine oxidase-derived reactive oxygen species in the maternal, placental, and fetal physiology during healthy and complicated pregnancy.


Translational medicine: an engine of change for bringing new technology to community health.
Bringing a new medical technology from the lab to the clinic is a daunting prospect, but making sure that same innovation is available to the average patient has proven to be even more challenging. Translational medicine is a movement intended to help bench researchers and bedside clinicians learn from each other for the benefit of patients. This goal can best be accomplished if a patient-centered focus is incorporated throughout the R&D continuum and changes are made so that biomedical innovation serves the broadest needs within the shortest period of time. All sectors of the biomedical enterprise must be engaged and committed for these changes to occur. If actions are taken in concert, we should see real change in one generation.


On how to be unpredictable: evidence from the voluntary task-switching paradigm.
The voluntary task-switching paradigm requires subjects to select randomly between tasks and promises to provide a window into executive task selection independent of exogenous influences present in standard task-switching situations. We show here that the degree to which subjects perseverate on tasks across trials captures unique individual differences variance, but also that the switch rate is under strong stimulus-driven control: "Voluntary" switches are much more frequent when the stimulus changes than when it repeats. Most important, we show that individuals whose no-switch trials are selectively slowed exhibit less perseveration and stimulus-driven effects (and thus more voluntary selection) than individuals whose no-switch trials do not show this slowing. We suggest that selective slowing indicates a strategy of treating trials as discrete events--possibly through inhibition of the preceding task set. These results not only demonstrate massive nonvoluntary influences on voluntary selection that are largely untapped by standard task-switching measures, but also show how such influences can be counteracted through strategic adaptations.


Expeditious preparation of β-sec-alkyl vicinal amino alcohols used for chiral ligand synthesis.
An economical route providing quick access to chiral β-amino alcohols bearing one β-sec-alkyl group was developed. This protocol starts with commercially available and cheap chiral sources such as derivatives of L-serine and L-threonine. A series of vicinal amino alcohols with high optical purity were prepared in good yields through 4 or 6 operationally simple steps. Two different strategies (three routes) were designed for the synthesis of amino alcohols bearing β-sec-alkyl groups with various steric hindrance.


A disadvantaged advantage in walkability: findings from socioeconomic and geographical analysis of national built environment data in the United States.
Urban form-the structure of the built environment-can influence physical activity, yet little is known about how walkable design differs according to neighborhood sociodemographic composition. We studied how walkable urban form varies by neighborhood sociodemographic composition, region, and urbanicity across the United States. Using linear regression models and 2000-2001 US Census data, we investigated the relationship between 5 neighborhood census characteristics (income, education, racial/ethnic composition, age distribution, and sex) and 5 walkability indicators in almost 65,000 census tracts in 48 states and the District of Columbia. Data on the built environment were obtained from the RAND Corporation's (Santa Monica, California) Center for Population Health and Health Disparities (median block length, street segment, and node density) and the US Geological Survey's National Land Cover Database (proportion open space and proportion highly developed). Disadvantaged neighborhoods and those with more educated residents were more walkable (i.e., shorter block length, greater street node density, more developed land use, and higher density of street segments). However, tracts with a higher proportion of children and older adults were less walkable (fewer street nodes and lower density of street segments), after adjustment for region and level of urbanicity. Research and policy on the walkability-health link should give nuanced attention to the gap between persons living in walkable areas and those for whom walkability has the most to offer.


Nutritional status of children under five in three state foster care institutions in Sri Lanka.
This study evaluated the prevalence of protein energy malnutrition (PEM) in children under five years (n = 52), in three randomly selected, State operated foster care institutions in Sri Lanka. The prevalence of PEM, was (51.9%), underweight (63.5%) and wasting (25.0%) was found to be considerably higher than the national prevalence (13.5%, 29.4%, 14.0%, respectively). Based on this preliminary evidence, it is recommended that a study representative of all institutionalised children in both State and private facilities be conducted to identify deficiencies and recommend improvements to institutional care in Sri Lanka.


Disruptions in asymmetric centrosome inheritance and WDR62-Aurora kinase B interactions in primary microcephaly.
Recessive mutations in WD repeat domain 62 (WDR62) cause microcephaly and a wide spectrum of severe brain malformations. Disruption of the mouse ortholog results in microcephaly underlain by reduced proliferation of neocortical progenitors during late neurogenesis, abnormalities in asymmetric centrosome inheritance leading to neuronal migration delays, and altered neuronal differentiation. Spindle pole localization of WDR62 and mitotic progression are defective in patient-derived fibroblasts, which, similar to mouse neocortical progenitors, transiently arrest at prometaphase. Expression of WDR62 is closely correlated with components of the chromosome passenger complex (CPC), a key regulator of mitosis. Wild type WDR62, but not disease-associated mutant forms, interacts with the CPC core enzyme Aurora kinase B and staining of CPC components at centromeres is altered in patient-derived fibroblasts. Our findings demonstrate critical and diverse functions of WDR62 in neocortical development and provide insight into the mechanisms by which its disruption leads to a plethora of structural abnormalities.


Inhibition by levorphanol and related drugs of amino acid transport by isolated membrane vesicles from Escherichia coli.
Levorphanol inhibits the transport of the amino acids proline and lysine by cytoplasmic membrane vesicles derived from Escherichia coli. The degree of inhibition increases with increasing levorphanol concentration and ranges from 26% at 10(-6) M levorphanol to 92% at 10(-3) M levorphanol. The effect is independent of the energy source, since levorphanol inhibits proline uptake to the same extent in the presence of 20 mM d-lactate or 20 mM succinate and in the absence of an exogenous energy source. Levorphanol does not irreversibly alter the ability of membrane vesicles to transport proline, since incubation of membrane vesicles for 15 min in the presence of 0.25 mM levorphanol, a concentration which inhibits proline transport by more than 75%, has no effect on the rate of proline transport by these vesicles once the drug is removed. Both the maximum velocity and the K(m) of proline transport are modified by levorphanol, hence, the type of inhibition produced by levorphanol is mixed. The inhibitor constant (K(i)) for levorphanol inhibition of proline transport is approximately 3 x 10(-4) M. Membrane vesicles incubated in the presence of levorphanol accumulate much less proline at the steady state than do control vesicles. Furthermore, the addition of levorphanol to membrane vesicles preloaded to the steady state with proline produces a marked net efflux of proline. Levorphanol does not block either temperature-induced efflux or exchange of external proline with [(14)C]proline present in the intravesicular pool. Dextrorphan, the enantiomorph of levorphanol, and levallorphan, the N-allyl analogue of levorphanol, inhibit proline and lysine transport in a similar manner. Possible mechanisms of the effects of these drugs on cell membranes are discussed.


Effect of pulp vitality on periodontal reattachment following free autogenous gingival graft in dogs.
The aim of the present study was to examine the effects of pulp vitality on the periodontal reattachment following the free autogenous gingival graft. Maxillary bilateral premolars in each of 4 dogs were used. Denuded root surfaces were prepared after the labial alveolar osteotomies on the experimental region. 4 weeks later, the pulp in the right teeth was exstirpated and the root canals either were filled with gutta percha points and root canal sealer or were left open (infected teeth). The left teeth were kept in the vital pulp as a control. The graft was placed over the denuded root after 4 weeks. The animals were sacrificed 4 and 12 weeks postoperatively and a serial section of the premolars with surrounding tissues was prepared for a light microscopic examination. The clinical and histopathological findings showed that the gingival recession was more found in the infected teeth than the vital teeth and the former produced less periodontal reattachment as compared with the latter, and the interface between the donor and the recipient bed was characterized by the increased number and size of blood vessels.


The chemodiversity of purine as a constituent of natural products.
In this review, I describe various natural manifestations of purine systems, i.e., methylated, higher-alkylated, and glycosylated forms. These comprise the purine alkaloids, cytokines, as well as the purine nucleoside antibiotics. In part, the compounds described herein were isolated from natural sources already long ago. However, some have been reported only during the last few years. The biological activities of most of the purine derivatives are briefly described, and, in some cases, syntheses are formulated. In particular, this article introduces the main synthetic principles for the generation of the purine ring system. The last chapter describes modern preparative routes for C-alkylation and C-arylation of purines.


Multi-material linearization beam hardening correction for computed tomography.
Since beam hardening causes cupping and streaking artifacts in computed tomographic images, the presence of such artifacts can impair both qualitative and quantitative analysis of the reconstructed data. When the scanned object is composed of a single material, it is possible to correct beam hardening artifacts using the linearization method. However, for multi-material objects, an iterative segmentation-based correction algorithm is needed, which is not only computationally expensive, but may also fail if the initial segmentation result is poor. In this study, a new multi-material linearization beam hardening correction method was proposed and evaluated. The new method is fast and implemented in the same manner as a mono-material linearization. The correction takes approximately 0.02 seconds per projection. Although facing a potential disadvantage of requiring attenuation measurements of one of the object's constituent materials, applying the new method has demonstrated its capability for a multi-material workpiece with substantial reduction in both cupping and streaking artifacts. For example, the study showed that the absolute cupping artefacts in steel, titanium and aluminum spheres were reduced from 22%, 20% and 20% to 5%, 1% and 0%, respectively.


Costs of epilepsy in an intermediate care facility for persons with mental retardation.
Epilepsy is a significant comorbid condition in institutionalized persons with developmental disabilities and may contribute significant additional costs. This study was conducted to provide an estimate of the costs of epilepsy from the institutional perspective. Costs were measured retrospectively for 50 persons with epilepsy and 50 persons without epilepsy matched by severity of developmental disability. A time and motion study was employed to assign opportunity costs to documented nursing and physician activities. Two separate methods of attribution were used and incremental costs attributable to epilepsy were found to be approximately $825 and $918 per person over a 6-month period. The following categories accounted for costs: personnel (47.0%), drug (39.6%), hospitalization (9.4%), and laboratories/procedures (4.0%). Results are useful for describing the economic burden of epilepsy.


The value-driven revenue cycle.
Conversations on improving the value of health care often focus on clinical performance improvement efforts. Yet during Phase 2 of HFMA's Value Project research, CFOs time and again identified the revenue cycle as the place where their hospital's performance improvement efforts have begun.


Sodium selenite alters microtubule assembly and induces apoptosis in vitro and in vivo.
Previous studies demonstrated that selenite induced cancer-cell apoptosis through multiple mechanisms; however, effects of selenite on microtubules in leukemic cells have not been demonstrated. The toxic effect of selenite on leukemic HL60 cells was performed with cell counting kit 8. Selenite effects on cell cycle distribution and apoptosis induction were determined by flow cytometry. The contents of cyclin B1, Mcl-1, AIF, cytochrome C, insoluble and soluble tubulins were detected with western blotting. Microtubules were visualized with indirect immunofluorescence microscopy. The interaction between CDK1 and Mcl-1 was assessed with immunoprecipitation. Decreasing Mcl-1 and cyclin B1 expression were carried out through siRNA interference. The alterations of Mcl-1 and cyclin B1 in animal model were detected with either immunohistochemical staining or western blotting. In situ detection of apoptotic ratio was performed with TUNEL assay. Our current results showed that selenite inhibited the growth of HL60 cells and induced mitochondrial-related apoptosis. Furthermore, we found that microtubule assembly in HL60 cells was altered, those cells were arrested at G2/M phase, and Cyclin B1 was up-regulated and interacted with CDK1, which led to down-regulation of the anti-apoptotic protein Mcl-1. Finally, in vivo experiments confirmed the in vitro microtubule disruption effect and alterations in Cyclin B1 and Mcl-1 levels by selenite. Taken together, the results from our study indicate that microtubules are novel targets of selenite in leukemic HL60 cells.


Dynamics of small unilamellar vesicles.
In this paper, we investigate the dynamics of small unilamellar vesicles with the aid of neutron spin-echo spectroscopy. The purpose of this investigation is twofold. On the one hand, we investigate the influence of solubilised cosurfactant on the dynamics of the vesicle's surfactant bilayer. On the other hand, the small unilamellar vesicles used here have a size between larger vesicles, with dynamics being well described by the Zilman-Granek model and smaller microemulsion droplets which can be described by the Milner-Safran model. Therefore, we want to elucidate the question, which model is more suitable for the description of the membrane dynamics of small vesicles, where the finite curvature of the bilayer is felt by the contained amphiphilic molecules. This question is of substantial relevance for our understanding of membranes and how their dynamics is affected by curvature, a problem that is also of key importance in a number of biological questions. Our results indicate the even down to vesicle radii of 20 nm the Zilman-Granek model appears to be the more suitable one.


Rapid Preparation of a Plasma Membrane Fraction: Western Blot Detection of Translocated Glucose Transporter 4 from Plasma Membrane of Muscle and Adipose Cells and Tissues.
Membrane proteins account for 70% to 80% of all pharmaceutical targets, indicating their clinical relevance and underscoring the importance of identifying differentially expressed membrane proteins that reflect distinct disease properties. The translocation of proteins from the bulk of the cytosol to the plasma membrane is a critical step in the transfer of information from membrane-embedded receptors or transporters to the cell interior. To understand how membrane proteins work, it is important to separate the membrane fraction of cells. This unit provides a protocol for rapidly obtaining plasma membrane fractions for western blot analysis. © 2016 by John Wiley & Sons, Inc.


New Systolic Array Algorithms and VLSI Architectures for 1-D MDST.
In this paper, we present two systolic array algorithms for efficient Very-Large-Scale Integration (VLSI) implementations of the 1-D Modified Discrete Sine Transform (MDST) using the systolic array architectural paradigm. The new algorithms decompose the computation of the MDST into modular and regular computational structures called pseudo-circular correlation and pseudo-cycle convolution. The two computational structures for pseudo-circular correlation and pseudo-cycle convolution both have the same form. This feature can be exploited to significantly reduce the hardware complexity since the two computational structures can be computed on the same linear systolic array. Moreover, the second algorithm can be used to further reduce the hardware complexity by replacing the general multipliers from the first one with multipliers with a constant that have a significantly reduced complexity. The resulting VLSI architectures have all the advantages of a cycle convolution and circular correlation based systolic implementations, such as high-speed using concurrency, an efficient use of the VLSI technology due to its local and regular interconnection topology, and low I/O cost. Moreover, in both architectures, a cost-effective application of an obfuscation technique can be achieved with low overheads.


Functional evolution of SARS-CoV-2 spike protein: Maintaining wide host spectrum and enhancing infectivity via surface charge of spike protein.
The SARS-CoV-2 virus, which causes the COVID-19, is rapidly accumulating mutations to adapt to the hosts. We collected SARS-CoV-2 sequence data from the end of 2019 to January 2023 to analyze for their evolutionary features during the pandemic. We found that most of the SARS-CoV-2 genes are undergoing negative purifying selection, while the spike protein gene (S-gene) is undergoing rapid positive selection. From the original strain to the alpha, delta and omicron variant types, the Ka/Ks of the S-gene increases, while the Ka/Ks within one variant type decreases over time. During the evolution, the codon usage did not evolve towards optimal translation and protein expression. In contrast, only S-gene mutations showed a remarkable trend on accumulating more positive charges. This facilitates the infection via binding human ACE2 for cell entry and binding furin for cleavage. Such a functional evolution emphasizes the survival strategy of SARS-CoV-2, and indicated new druggable target to contain the viral infection. The nearly fully positively-charged interaction surfaces indicated that the infectivity of SARS-CoV-2 virus may approach a limit.


High Plasma Oxalate Levels Early After Kidney Transplantation Are Associated With Impaired Long-Term Outcomes.
Background: Elevated levels of oxalate are common in renal failure patients and non-hyperoxaluria disease, and may cause damage after transplantation. We examined outcomes after 15 years for 167 kidney transplant recipients who had plasma oxalate measured early after transplantation. Analyses included plasma oxalate, recipient age, donor age, live donor, HLA-DR mismatch, mGFR, and smoking. Results: Median age was 52 years (range 18-81), 63% were male and 38% had live donors. Median plasma oxalate concentration 10 weeks after transplantation was 9.0 μmol/L (range 2.7-53.0), one third above the upper reference limit (11.0 μmol/L). Multivariable analysis revealed upper quartile plasma oxalate (>13.0 μmol/L, p = 0.008), recipient age (p < 0.001), deceased donor (p = 0.003), and current smoking (p < 0.001) as significant factors associated with patient survival. Upper quartile plasma oxalate (p = 0.021), recipient age (p = 0.001), deceased donor kidney (p = 0.001), HLA-DR mismatch (p = 0.015), and current smoking (p = 0.014) were also associated with graft loss. Factors associated with death censored graft losses were donor age (p = 0.012), deceased donor (p = 0.032), and HLA-DR mis-matched kidneys (p = 0.005) but plasma oxalate was not (p = 0.188). Conclusions: Plasma oxalate in the upper quartile early after transplantation was significantly associated with impaired long-term patient survival and graft losses, but not when censored for death.


Prolactin-independent induction of alpha-lactalbumin gene expression in mammary gland explants from pregnant Balb/c mice.
A four-fold increment of alpha-lactalbumin mRNA was induced in mammary gland explants from mid-pregnant Balb/c mice cultured for 24h in media containing insulin, cortisol and T3, and this response was enhanced by 40% with the addition of prolactin. In contrast, elevated beta-casein gene expression was evident only in explants cultured in media with insulin, cortisol, T3 and prolactin. These results suggest that the induction of the alpha-lactalbumin gene was prolactin-independent and did not result from retention of endogenous prolactin, or its effects, by the mammary explants.


Genetic screening by DNA technology: a systematic review of health economic evidence.
The Human Genome Project has led to a multitude of new potential screening targets on the level of human DNA. The aim of this systematic review is to critically summarize the evidence from health economic evaluations of genetic screening in the literature. Based on an extensive explorative search, an appropriate algorithm for a systematic database search was developed. Twenty-one health economic evaluations were identified and appraised using published quality criteria. Genetic screening for eight conditions has been found to be investigated by health economic evaluation: hereditary breast and ovarian cancer, familial adenomatous polyposis (FAP) colorectal cancer, hereditary nonpolyposis colorectal carcinoma (HNPCC), retinoblastoma, familial hypercholesterolemia, hereditary hemochromatosis, insulin-dependent diabetes mellitus, and cystic fibrosis. Results range from dominated to cost-saving. Population-wide genetic screening may be considered cost-effective with limited quality of evidence only for three conditions. The methodology of the studies was of varying quality. Cost-effectiveness was primarily influenced by mutation prevalence, genetic test costs, mortality risk, effectiveness of treatment, age at screening, and discount rate. Health economic evidence on genetic screening is limited: Only few conditions have properly been evaluated. Based on the existing evidence, healthcare decision makers should consider the introduction of selective genetic screening for FAP and HNPCC. As genetic test costs are declining, the existing evaluations may warrant updating. Especially in the case of hereditary hemochromatosis, genetic population screening may be about to turn from a dominated to a cost-effective or even cost-saving intervention.


Effects of a long-term volunteer surgical program in a developing country: the case in Vietnam from 1993 to 2003.
This study evaluates the activities of the Japanese Cleft Palate Foundation from 1993 to 2003 in southern Vietnam. We assessed trends associated with patient age at first operation for primary lip repair and palate repair by using medical records of the patients. This study consisted of 790 patients with nonsyndromic cleft lip and/or palate (CL/P). The median patient age for lip repair was reduced from 14.0 years in 1993 to 1.3 years by 2003. For palate repair, the median age was reduced from 13.5 years in 1993 to 5.0 years in 1999 through 2003. The age distributions of both lip and palate repair in the later years became smaller than the age distributions in 1993. The number of adult patients declined throughout the period. The Japanese Cleft Palate Foundation contributed to lowering the age at first operation for CL/P and to reducing the number of adult patients in Ben Tre province, southern Vietnam. However, appropriate supports will be necessary to maintain CL/P treatment and to improve locally supported health care for patients with CL/P.


Expression of basic fibroblast growth factor mRNA after transient focal ischemia: comparison with expression of c-fos, c-jun, and hsp 70 mRNA.
We have reported that basic fibroblast growth factor (bFGF) prevents retrograde degeneration of thalamic neurons after middle cerebral artery (MCA) occlusion. To identify the protective mechanism of bFGF, we examined bFGF mRNA expression in a model of transient focal ischemia with in situ hybridization. Compared to c-fos, c-jun, and hsp 70 mRNA expression, upregulation of the bFGF mRNA expression was delayed until 6 h after reperfusion. By 12 h, bFGF mRNA was markedly induced in the peri-infarcted cortex, cingulate cortex, and peri-infarcted white matter. At 24 h and 2 days the induction of bFGF mRNA in these regions persisted, and disappeared by 5 day. The quantitative assessment of bFGF mRNA expression revealed that optical density ratios of the cingulate gyrus and the caudoputamen were significantly higher at 12 h, 24 h, and 2 d after reperfusion than those in sham controls. Microscopic observation indicated bFGF mRNA signals were present in several types of cortical cells, including neurons and nonneuronal cells. Since intrinsic bFGF, released from the damaged tissue, can influence the healing response through receptors upregulated by injury, it is reasonable that this pattern of bFGF mRNA expression parallels the bFGFR mRNA expression previously reported.


[The scoring system for the risk-stratification in patients with the antiphospholipid syndrome].
Antiphospholipid syndrome (APS) is a clinical disorder characterized by thrombosis and/or pregnancy morbidity in the persistence of the pathogenic autoantibodies, the antiphospholipid antibodies (aPL). Recurernt thrombosis is often observed in patients with APS which requires persistent prophylaxis. However, an uniform prophylactic treatment for APS patients is inadequate and stratification of the thrombotic risks is important as aPL are prevalently observed in other various diseases or elderly population. It is previously known that the multiple positivity or high titre of aPL correlate to the thrombotic events. To progress the stratification of the thrombotic risks and to quantitatively analyze them, antiphospholipid score (aPL-S) and the Global Anti-Phospholipid Syndrome Score (GAPSS) were defined as the scoring-systems. Both of these scoring-systems were raised from the large patient cohort data and either aPL profile classified in detail (aPL-S) or simplified aPL profile with classical thrombotic risk factors (GAPSS) were put into scoring system. They have shown a degree of accuracy in identifying high-risk APS patients, especially those at a high risk of thrombosis. However, there are several areas requiring improvement, or at least that clinicians should be aware of, before these instruments are applied in clinical practice. One such issue is standardisation of the aPL tests, including general testing of phosphatidylserine dependent antiprothrombin antibodies (aPS/PT).


Degree of sympatry affects reinforcement in Drosophila.
In a recent paper, Yukilevich (2012) showed that asymmetries between Drosophila species in the strength of premating isolation tend to match asymmetries in the costs of hybridization (inferred from asymmetries in the strength of postzygotic isolation and range sizes). The results provide novel evidence that the outcome of reinforcement can depend on the strength and frequency of selection against hybridization. Here, I reanalyze the data to demonstrate that another (unconsidered) factor, namely the quantitative degree of sympatry between species, also predictably affects reinforcement. Specifically, premating isolation is strongest at intermediate degrees of sympatry. This result complements, rather than challenges, those of Yukilevich (2012). One possible explanation for this newly discovered pattern is that when the degree of sympatry is small, selection for avoidance of hybridization is rare, but when the degree of sympatry is large, homogenizing gene flow overcomes reinforcing selection. Thus, reinforcement may depend on the balance between selection and gene flow. However, the current work examined degree of sympatry, not gene flow itself. Thus, further data on gene flow levels in Drosophila is required to test this hypothesis, which emerged from the patterns reported here.


Numerical computation of diffraction catastrophes with codimension eight.
A computational strategy, aimed at evaluating diffraction catastrophes belonging to the X(9) family is presented. The approach proposed is based on the use of power series expansions, suitably derived for giving meaningful representation of the whole (0)X(9) subfamily, jointly with a powerful sequence transformation algorithm, the so-called Weniger transformation. The convergence features of the above series expansions are investigated, and several numerical experiments are carried out to assess the effectiveness of the retrieving action of the Weniger transformation, as well as the ease of implementation of the whole approach.


Transmigration: a new property of mature multinucleated osteoclasts.
Even though it is assumed that multinucleated osteoclasts are migrating cells on the bone surface to be resorbed, we show that they can also selectively transmigrate through layers of cells usually found in the bone microenvironment. This activity is associated with c-src and MMPs and can be stimulated by bone metastatic breast cancer cells, a process blocked by bisphosphonate treatment. Osteoclasts have an hematopoietic origin and are bone-resorbing cells. Monocytic precursors migrate to the bone surface where they fuse to form multinucleated osteoclasts able to migrate over the bone surface. We studied whether multinucleated osteoclasts were also able to transmigrate through tissues. Murine spleen-derived and green fluorescent protein (GFP)-Raw derived osteoclasts were seeded on osteoblasts and several other cell types. The cells were fixed for 20 minutes, 4 or 12 h after osteoclast seeding, and stained with phalloidin to visualize actin using confocal microscopy. Drugs such as PP2 and GM6001, inhibitors of c-src and matrix metalloproteinases (MMPs), respectively, and risedronate were used to determine osteoclast transmigration regulating factors. We observed by confocal microscopy that multinucleated osteoclasts specifically transmigrate through confluent layers of various cell types present in the bone microenvironment in vitro. This is an efficient process associated with c-src and MMPs but is independent of podosomes. Moreover, conditioned medium from bone metastatic breast cancer cells stimulates osteoclast transmigration in vitro, a process inhibited by bisphosphonate treatment. Our data describe a new property of mature multinucleated osteoclasts to transmigrate through various cell types. The ability to control this highly regulated osteoclast transmigration process may offer new therapeutic strategies for bone diseases associated with an imbalance in bone remodeling caused by excessive osteoclast resorption.


The amino acid sequence of mitogenic lectin-B from the roots of pokeweed (Phytolacca americana).
The complete amino acid sequence of pokeweed lectin-B (PL-B) has been analyzed by first sequencing seven lysylendopeptidase peptides derived from the reduced and S-pyridylethylated PL-B and then connecting them by analyzing the arginylendopeptidase peptides from the reduced and S-carboxymethylated PL-B. PL-B consists of 295 amino acid residues and two oligosaccharides linked to Asn96 and Asn139, and has a molecular mass of 34,493 Da. PL-B is composed of seven repetitive chitin-binding domains having 48-79% sequence homology with each other. Twelve amino acid residues including eight cysteine residues in these domains are absolutely conserved in all other chitin-binding domains of plant lectins and class I chitinases. Also, it was strongly suggested that the extremely high hemagglutinating and mitogenic activities of PL-B may be ascribed to its seven-domain structure.


Cervical and lumbar paraspinal calcinosis in systemic sclerosis.
Calcinosis is a well-recognized manifestation of systemic sclerosis. Paraspinal or intraspinal calcinosis is rare, with reports of calcinosis involving the cervical, thoracic and lumbar separately, but not together. We now report a case of limited cutaneous scleroderma with extensive paraspinal calcinosis of the cervical and lumbar spine.


Diagnosis of Chlamydia pneumoniae infection in patients with community-acquired pneumonia by polymerase chain reaction enzyme immunoassay.
We conducted a prospective study of 385 patients who had community-acquired pneumonia with use of a modified polymerase chain reaction (PCR) assay that detects amplified DNA by enzyme immunoassay (EIA). We used PCR-EIA to improve detection of Chlamydia pneumoniae infection and to differentiate C. pneumoniae infection from other chlamydial infections. Cultures of throat swab specimens from four patients yielded Chlamydia species (C. pneumoniae, one patient; Chlamydia species, two patients; and C. psittaci, one patient). C. pneumoniae was repeatedly detected by PCR-EIA for thirteen (3.4%) of these 385 patients. Six of these 13 patients were infected with the human immunodeficiency virus. Ten (76.9%) of the patients who were positive by PCR-EIA had IgG titers of > or = 1:16, and two (15.4%) of the 13 patients had IgG titers of < 1:16; no sera was available in one case. Other pathogens were recovered in eight (61.5%) of the 13 cases in which C. pneumoniae was detected by PCR-EIA. In addition, for 46 (11.9%) of the 385 patients the titers of antibody were considered diagnostic of C. pneumoniae infection; however, as 36 of the 46 patients were infected with the human immunodeficiency virus (which may have affected their serological response to C. pneumoniae), interpretation of these titers was problematic. As PCR-EIA was more sensitive than was culture for detecting C. pneumoniae infection in this study, this method may be a valuable tool for the prompt diagnosis of this infection.


Signals and players in the transcriptional regulation of root responses by local and systemic N signaling in Arabidopsis thaliana.
In natural environments, nitrogen (N) concentration in the soil fluctuates greatly and is often limiting for plant growth and development. The ability of plants to respond to changes in N availability is therefore essential for adaptation. The response of plants to N variations consists in particular of adjusting root N uptake systems and root architecture. To do so, plants integrate local sensing and signaling of external N availability with systemic sensing and signaling of their internal N status, in order to tune the functional and structural properties of the root system in accordance with the N demand for growth of the whole plant. Transcriptional regulation of gene expression is one of the most important processes plants use to adapt the properties of the root system in response to local and long-distance N pathways. This review focuses on the mechanisms that give rise to transcriptional responses in Arabidopsis roots under N fluctuations, with an emphasis on those associated with the regulation of nitrate uptake and transport systems. We discuss the putative long-distance signals triggering the gene expression responses, as well as the molecular players that locally induce transcriptional changes. We also highlight several observations revealing the importance of adopting an integrative approach in the regulation of N signaling.


Informed consent for gastrointestinal endoscopy: a view of endoscopists in Croatia.
There are many differences and deficiencies in the process of informed consent. The aim of this study was to get the view of gastrointestinal endoscopists in Croatia on obtaining patients' consent before endoscopic procedures. During the 2004 annual meeting of the Croatian Society of Gastroenterology, endoscopists were asked to answer a questionnaire according to common clinical practice in affiliated institutions. It included questions on endoscopists' experience and education in medical ethics, as well as on the nature and quality of information given to patients and their opinion on proposed measures for improvement of the informed consent process. The questionnaire was distributed to 96 endoscopists attending the meeting and the response rate was 54% (52/96). In only 50% of institutions was the obtained consent written and potential complications of endoscopic procedures are occasionally given to the patient. In the minority of cases the patient is provided with information about alternative diagnostic tests and/or treatment options, and the information about mortality rate was almost never discussed. In Croatia, the process of informed consent for endoscopy needs improvement and should be regarded against the background of education in medical ethics, regional burden in endoscopic practice and appropriateness of by-laws and local guidelines.


Evaluation of the Knowledge of Cow's Milk Allergy among Pediatricians.
The aim of this study was to determine the level of knowledge of pediatric residents and practicing pediatricians about cow's milk allergy (CMA) and to evaluate the effect of occupational education. Pediatric residents and pediatricians were included in the study. A survey about CMA was administered to the participants before and after occupational training. A total of 45 doctors were included in the study. Of the group, 31 were pediatric residents and 14 were practicing pediatricians. The pediatric resident group had a mean of 2.3 years professional experience, and the mean was 8.9 years in the pediatrician group. The mean number of correct answers of a possible score of 10 before the training was 8.32±1.37 in the resident group and 7.5±1.69 in the pediatrician group. There was no significant difference between the groups (p=0.09). The mean number of correct answers after training was 10 in the pediatric resident group, and 9.71±0.6 in the pediatrician group. The difference between the groups was statistically significant (p=0.01). Intragroup evaluation post training revealed significantly higher scores (p=0.001). The results of this study indicate that occupational education significantly increased the level of knowledge about CMA in both pediatric residents and practicing pediatricians.


Outcomes Among Patients Referred to Outpatient Rehabilitation Clinics After COVID-19 diagnosis - United States, January 2020-March 2021.
As of June 30, 2021, 33.5 million persons in the United States had received a diagnosis of COVID-19 (1). Although most patients infected with SARS-CoV-2, the virus that causes COVID-19, recover within a few weeks, some experience post-COVID-19 conditions. These range from new or returning to ongoing health problems that can continue beyond 4 weeks. Persons who were asymptomatic at the time of infection can also experience post-COVID-19 conditions. Data on post-COVID-19 conditions are emerging and information on rehabilitation needs among persons recovering from COVID-19 is limited. Using data acquired during January 2020-March 2021 from Select Medical* outpatient rehabilitation clinics, CDC compared patient-reported measures of health, physical endurance, and health care use between patients who had recovered from COVID-19 (post-COVID-19 patients) and patients needing rehabilitation because of a current or previous diagnosis of a neoplasm (cancer) who had not experienced COVID-19 (control patients). All patients had been referred to outpatient rehabilitation. Compared with control patients, post-COVID-19 patients had higher age- and sex-adjusted odds of reporting worse physical health (adjusted odds ratio [aOR] = 1.8), pain (aOR = 2.3), and difficulty with physical activities (aOR = 1.6). Post-COVID-19 patients also had worse physical endurance, measured by the 6-minute walk test† (6MWT) (p<0.001) compared with control patients. Among patients referred to outpatient rehabilitation, those recovering from COVID-19 had poorer physical health and functional status than those who had cancer, or were recovering from cancer but not COVID-19. Patients recovering from COVID-19 might need additional clinical support, including tailored physical and mental health rehabilitation services.


HR (Paroven, Venoruton; 0-(beta-hydroxyethyl)-rutosides) in venous hypertensive microangiopathy: a prospective, placebo-controlled, randomized trial.
The aim of this study was to demonstrate whether HR (Paroven-Venoruton; 0-(beta-hydroxyethyl)-rutosides), was effective in improving the microcirculation in venous hypertension and microangiopathy. Sixty patients with severe venous hypertension due to chronic venous insufficiency, ankle swelling, and lipodermatosclerosis were included. After informed consent, patients were randomized into a treatment group and a placebo group. Patients in the treatment group received oral HR (2 g/day for 8 weeks); those in the placebo group received a comparable placebo. The two groups were comparable for age and sex distribution. The mean age was 45 years (SD 9) in the treatment group (31 patients) and 45.5 (SD 10) in the placebo group (29 patients). There were no differences between the placebo and treatment groups at inclusion. There was no change between inclusion and measurements at 8 weeks in the placebo group. A significant decrease (P < 0.05) in flux at rest and rate of ankle swelling was observed in the treatment group. The decrease in capillary filtration was associated with improvement in signs and symptoms (P < 0.05). The difference in flux, sign and symptoms, and filtration was clinically important at 8 weeks in the treatment group when compared with the placebo group. No adverse effects were observed. Venous microangiopathy was improved by HR treatment.


Elasticity of two-dimensional crystals of polydisperse hard disks near close packing: surprising behavior of the Poisson's ratio.
The equation of state, elastic constants, and Poisson's ratio of a crystalline two-dimensional polydisperse hard disk system were determined in the close packing limit. Monte Carlo simulations in the NpT ensemble with variable shape of the periodic box reveal that the pressure and elastic constants grow with increasing polydispersity. The equation of state and the bulk modulus are well described by the free volume approximation. The latter approximation fails, however, for the shear modulus. The simulations also show that the introduction of any amount of size polydispersity in the hard disk systems causes a discontinuous "jump" of the Poisson's ratio in the close packing limit from the value ν(δ=0) = 0.1308(22), obtained for equidiameter hard disks, to ν(δ>0) ≈ 1, estimated for the polydisperse disks.


Interfacial Symmetry Control of Emergent Ferromagnetism at the Nanoscale.
The emergence of complex new ground states at interfaces has been identified as one of the most promising routes to highly tunable nanoscale materials. Despite recent progress, isolating and controlling the underlying mechanisms behind these emergent properties remains among the most challenging materials physics problems to date. In particular, generating ferromagnetism localized at the interface of two nonferromagnetic materials is of fundamental and technological interest. Moreover, the ability to turn the ferromagnetism on and off would shed light on the origin of such emergent phenomena and is promising for spintronic applications. We demonstrate that ferromagnetism confined within one unit cell at the interface of CaRuO3 and CaMnO3 can be switched on and off by changing the symmetry of the oxygen octahedra connectivity at the boundary. Interfaces that are symmetry-matched across the boundary exhibit interfacial CaMnO3 ferromagnetism while the ferromagnetism at symmetry-mismatched interfaces is suppressed. We attribute the suppression of ferromagnetic order to a reduction in charge transfer at symmetry-mismatched interfaces, where frustrated bonding weakens the orbital overlap. Thus, interfacial symmetry is a new route to control emergent ferromagnetism in materials such as CaMnO3 that exhibit antiferromagnetism in bulk form.


[Radioimmunoassay of carcinoembryonic antigen in the evaluation of the effectiveness of breast cancer treatment].
Changes in blood--CEA level in the course of tumor process were studied in 123 cases of breast cancer. In primary tumor patients, CEA concentration was found to be in correlation with tumor expansion. It depended upon the degree of involvement of regional lymphatics rather than on the size of primary tumor, since the involvement of lymph nodes was matched by an increase in CEA level. A persistent decline in CEA concentration during and after treatment served as an indication that the latter was adequate. A steady rise in CEA level despite treatment was prognostically unfavorable. It preceded clinical manifestations of metastases.


Molecular mechanism for genetic recombination.
Symmetry considerations of proteinnucleic acid interaction suggest the existence of an alternate branched configuration for DNA induced by binding specific structural proteins to symmetrically arranged polynucleotide base sequences. The concept that such sequences exist at the ends of genes or operons leads to a molecular model for genetic recombination in eukaryotic cells.


Influence of growth temperature and lipopolysaccharide on hemolytic activity of Serratia marcescens.
Log-phase cells of Serratia marcescens cultured at 30 degrees C were approximately 10-fold more hemolytic than those grown at 37 degrees C. By using a cloned gene fusion of the promoter-proximal part of the hemolysin gene (shlA) to the Escherichia coli alkaline phosphatase gene (phoA), hemolysin gene expression as a function of alkaline phosphatase activity was measured at 30 and 37 degrees C. No difference in alkaline phosphatase activity was observed as a function of growth temperature, although more hemolysin was detectable immunologically in whole-cell extracts of cells grown at 30 degrees C. The influence of temperature was, however, growth phase dependent, because the hemolytic activities of cells cultured to early log phase at 30 and 37 degrees C were comparable. Given the outer membrane location of the hemolysin, lipopolysaccharide (LPS) was examined as a candidate for mediating the temperature effect on hemolytic activity. Silver staining of LPS in polyacrylamide gels revealed a shift towards shorter O-antigen molecules at 37 degrees C relative to 30 degrees C. Moreover, there was less binding of O-antigen-specific bacteriophage to S. marcescens with increasing growth temperature, a finding consistent with temperature-mediated changes in LPS structure. Smooth strains of S. marcescens were 20- to 30-fold more hemolytic than rough derivatives, a result confirming that changes in LPS structure can influence hemolytic activity. The alkaline phosphatase activity of rough strains harboring the shlA-phoA fusion was threefold lower than that of smooth strains harboring the fusion plasmids, a result consistent with a decrease in hemolysin gene expression in rough strains. The absence of a similar effect of temperature on gene expression may be related to less-marked changes in LPS structure as a function of temperature compared with a smooth-to-rough mutational change.


Sonography in the diagnosis and management of pancreatic pseudocysts and effusions in childhood.
Blunt trauma to the abdomen is the main cause of pancreatic injury in childhood. One of the most common causes of injury is child abuse. Pancreatitis, pancreatic pseudocyst, and loculated peripancreatic effusion are sequellae of this trauma. The diagnosis of these lesions is aided by ultrasound. Pancreatic injury in children may require different methods of management than it does in adults. Persistently elevated serum amylase levels and increasing cyst size are indications for surgical intervention. However, the natural history of a pseudocyst in an otherwise normal child may lead to spontaneous resolution. In this report, three cases of pancreatic pseudocyst caused by child abuse are presented. In two of the patients, the cysts underwent spontaneous resolution.


Heart mitochondrial TTP synthesis and the compartmentalization of TMP.
The primary pathway of TTP synthesis in the heart requires thymidine salvage by mitochondrial thymidine kinase 2 (TK2). However, the compartmentalization of this pathway and the transport of thymidine nucleotides are not well understood. We investigated the metabolism of [(3)H]thymidine or [(3)H]TMP as precursors of [(3)H]TTP in isolated intact or broken mitochondria from the rat heart. The results demonstrated that [(3)H]thymidine was readily metabolized by the mitochondrial salvage enzymes to TTP in intact mitochondria. The equivalent addition of [(3)H]TMP produced far less [(3)H]TTP than the amount observed with [(3)H]thymidine as the precursor. Using zidovudine to inhibit TK2, the synthesis of [(3)H]TTP from [(3)H]TMP was effectively blocked, demonstrating that synthesis of [(3)H]TTP from [(3)H]TMP arose solely from the dephosphorysynthase pathway that includes deoxyuridine triphosphatelation of [(3)H]TMP to [(3)H]thymidine. To determine the role of the membrane in TMP metabolism, mitochondrial membranes were disrupted by freezing and thawing. In broken mitochondria, [(3)H]thymidine was readily converted to [(3)H]TMP, but further phosphorylation was prevented even though the energy charge was well maintained by addition of oligomycin A, phosphocreatine, and creatine phosphokinase. The failure to synthesize TTP in broken mitochondria was not related to a loss of membrane potential or inhibition of the electron transport chain, as confirmed by addition of carbonyl cyanide 4-(trifluoromethoxy) phenylhydrazone and potassium cyanide, respectively, in intact mitochondria. In summary, these data, taken together, suggest that the thymidine salvage pathway is compartmentalized so that TMP kinase prefers TMP synthesized by TK2 over medium TMP and that this is disrupted in broken mitochondria.


Artificial intelligence for the vascular surgeon.
In recent years, artificial intelligence (AI) has permeated different aspects of vascular surgery to solve challenges in clinical practice. Although AI in vascular surgery is still in its early stages, there have been promising developments in its applications to vascular diagnosis, risk stratification, and outcome prediction. By establishing a baseline knowledge of AI, vascular surgeons are better equipped to use and interpret the data from these types of projects. This review aims to provide an overview of the fundamentals of AI and highlight its role in helping vascular surgeons overcome the challenges of clinical practice. In addition, we discuss the limitations of AI and how they affect AI applications.


MRI of atherosclerosis in clinical trials.
Magnetic resonance imaging (MRI) of the arterial wall has emerged as a viable technology for characterizing atherosclerotic lesions in vivo, especially within carotid arteries and other large vessels. This capability has facilitated the use of carotid MRI in clinical trials to evaluate therapeutic effects on atherosclerotic lesions themselves. MRI is specifically able to characterize three important aspects of the lesion: size, composition and biological activity. Lesion size, expressed as a total wall volume, may be more sensitive than maximal vessel narrowing (stenosis) as a measure of therapeutic effects, as it reflects changes along the entire length of the lesion and accounts for vessel remodeling. Lesion composition (e.g. lipid, fibrous and calcified content) may reflect therapeutic effects that do not alter lesion size or stenosis, but cause a transition from a vulnerable plaque composition to a more stable one. Biological activity, most notably inflammation, is an emerging target for imaging that is thought to destabilize plaque and which may be a systemic marker of vulnerability. The ability of MRI to characterize each of these features in carotid atherosclerotic lesions gives it the potential, under certain circumstances, to replace traditional trials involving large numbers of subjects and hard end-points--heart attacks and strokes--with smaller, shorter trials involving imaging end-points. In this review, the state of the art in MRI of atherosclerosis is presented in terms of hardware, image acquisition protocols and post-processing. Also, the results of validation studies for measuring lesion size, composition and inflammation will be summarized. Finally, the status of several clinical trials involving MRI of atherosclerosis will be reviewed.


How primary care providers might review evidence on hydration.
Primary care providers (PCPs) are increasing their use of evidence-based medicine (EBM) in the care they give patients. They evaluate the available evidence to determine if it applies to their patients and seek to complement their clinical experience with EBM to improve patient outcomes. In evidence-based practices, patient oriented data are valued more highly than disease oriented evidence. More than 8 million biomedical articles are published annually, but only an estimated 2% of those are relevant to improved patient outcomes (POEMs - patient oriented evidence that matters). This paper describes some of the tools used by PCPs to search for evidence and the decision-making process used to determine if they will change their practice. Understanding how PCPs evaluate research findings and other evidence can help hydration researchers frame their research questions and study reports.


[Teledermatology in Midi-Pyrenees].
Telemedicine has become commonplace since the creation of the European Center of Telemedicine, and dermatology was a pioneering discipline in this new technology. The Division of Dermatology is now involved at three different levels--The Midi-Pyrénées regional network, which allows doctors in the private and public sectors to seek expert advice, in real time, from university hospital specialists.--He Division of Dermatology pioneered telemedicine sessions devoted to file review, histological/clinical diagnosis, and information exchanges among subspecialists in dermatology. Both French and foreign specialists attend these sessions.--Teaching, particularly for students and private practitioners. Telemedicine has clear benefits for patients, doctors and society as a whole. The private and hospital community of the Midi-Pyrénées region is constantly seeking to improve its health services, and ensures that all new approaches are subject to strict quality controls.


When is it the right time to ask for a geriatrician?
Given an aging population coupled with a shortage of people to care for them, it is essential to understand the patient qualities for which geriatric expertise would be most beneficial. For the practicing physician attempting to understand the timing of geriatric-care provision, this article reviews the relevant literature, which suggests geriatric expertise should be considered for the patients who benefit most: any patient aged ≥ 85 years, or adults aged < 85 years with complex multimorbidity, frailty, or other geriatric conditions; disability or dementia; or need for palliative or end-of-life care.


What are postpartum women doing while the rest of the world is asleep?
Large individual differences characterize maternal postpartum sleep and adjustment. Our goal was to explore aspects of mothers' nocturnal environments and behaviours that may explain differences in postpartum adjustment. A total of 201 mothers of infants aged 0-6 months completed an online survey with demographics, number and duration of nocturnal awakenings, caretaking behaviours, environment and nocturnal activities during 'one typical night during the past week'. Mothers reported 2.9 [standard deviation (SD) ± 1.7] nocturnal awakenings, each lasting 33.9 (SD ± 22.5) min. Infant age was related inversely to duration but unrelated to number of awakenings. Falling asleep while feeding was less frequent among exclusively formula-feeders. Among the entire sample, mothers used a cellphone (59%), backlit tablet (25%), TV (20%) and computer (16%) during nocturnal awakenings. Watching TV and using a computer were each associated with longer nocturnal awakenings. Eighty-nine per cent of women used ≥1 extra light source during nocturnal awakenings: night light (35%), light from a cracked door (28%), desk lamp (25%), electronic device (19%) or room light (14%). Light source(s) was unrelated to number or duration of nocturnal awakenings. These data suggest that, although supplemental light sources were not associated with awakenings, TV and computer use accounted for longer awakenings. Feeding method and technology use may help to explain individual differences in postpartum adjustments and may be targets for more effective interventions.


Internal carotid artery disease.
Internal carotid artery disease is a challenge to the optometrist because of its full spectrum of manifestations. A detailed case history and a thorough evaluation of the ocular and visual signs and symptoms are invaluable in the appropriate management of the patient. The optometric practitioner must consider this disease in middle-aged or elderly patients who present with suggestive signs and/or symptoms. Appropriate diagnosis and management of the disease will, it is hoped, result in the continued visual health and longevity of these patients.


Structure of the Major G-Quadruplex in the Human EGFR Oncogene Promoter Adopts a Unique Folding Topology with a Distinctive Snap-Back Loop.
EGFR tyrosine kinase inhibitors have made remarkable success in targeted cancer therapy. However, therapeutic resistance inevitably occurred and EGFR-targeting therapy has been demonstrated to have limited efficacy or utility in glioblastoma, colorectal cancer, and hepatocellular carcinoma. Therefore, there is a high demand for the development of new targets to inhibit EGFR signaling. Herein, we found that the EGFR oncogene proximal promoter sequence forms a unique type of snap-back loop containing G-quadruplex (G4), which can be targeted by small molecules. For the first time, we determined the NMR solution structure of this snap-back EGFR-G4, a three-tetrad-core, parallel-stranded G4 with naturally occurring flanking residues at both the 5'-end and 3'-end. The snap-back loop located at the 3'-end region forms a stable capping structure through two stacked G-triads connected by multiple potential hydrogen bonds. Notably, the flanking residues are consistently absent in reported snap-back G4s, raising the question of whether such structures truly exist under in vivo conditions. The resolved EGFR-G4 structure has eliminated the doubt and showed distinct structural features that distinguish it from the previously reported snap-back G4s, which lack the flanking residues. Furthermore, we found that the snap-back EGFR-G4 structure is highly stable and can form on an elongated DNA template to inhibit DNA polymerase. The unprecedented high-resolution EGFR-G4 structure has thus contributed a promising molecular target for developing alternative EGFR signaling inhibitors in cancer therapeutics. Meanwhile, the two stacked triads may provide an attractive site for specific small-molecule targeting.


Depression alters maternal extended amygdala response and functional connectivity during distress signals in attachment relationship.
Maternal attachment-related parenting behaviors require mothers to regulate self-related and child-related distress. Emotion regulation is, in turn, influenced by maternal mood and personal developmental history. In the current study we examined how depressive mood may alter maternal limbic system function and functional connectivity underlying defensive and hedonic motivations. Twenty nine mothers were recruited to undergo a baby-cry task during a functional magnetic resonance imaging (fMRI) scan. Based on self-reported depression symptoms and clinical interview, the participants were grouped as healthy controls (n=15) and currently depressed (n=14). In the baby-cry task, 30s-long auditory stimuli of baby-cry sounds were presented to simulate four conditions: generic baby-cry (Just-Listen), baby-cry as if it were their own child's cry (Your-Baby), baby-cry as if it were themselves (Self), and matched control sounds (Noise). Depressed mothers, as compared to healthy controls, showed greater Self versus Just-Listen responses in left extended amygdala and decreased functional coupling between this left extended amygdala as the seed and nucleus accumbens (NAc) in self-oriented (Self versus Just-Listen) and child-oriented (Your-Baby versus Just-Listen) distress signals. Moreover, the extended amygdala's differential functional connectivity with dorsomedial prefrontal cortex (dmPFC) during the Your-Baby versus Self was increased for depressed mothers and decreased for healthy controls. Thus, depression may affect mothers by increasing baby-cry threat responses and dysregulating associations between threat and heathy child-oriented parenting motivations. These results are discussed in the context of attachment and self-psychology.


Acute invasive mucormycosis rhinosinusitis causing multigroup cranial nerve injury and meningitis-A case report.
This study reported a case of a Rhino-Orbital-Cerebral Mycosis (ROCM) patient with multiple groups of cranial nerve damage as the primary clinical manifestation, confirmed by histopathology and cerebrospinal fluid metagenomic next-generation sequencing (mNGS) technology. Relying on the MRI3D-SPACE technology, we observed the location and extent of the cranial nerve damage in the patient. The results suggested that fungal meningoencephalitis caused by mucor may enter the skull retrograde along the cranial nerve perineurium. The patient was admitted to the hospital with a preliminary diagnosis of mucormycosis infection after 1.5 days of mouth deviation. We treated the patient immediately with intravenous amphotericin B liposomes. After 21 days of hospitalization, the clinical symptoms of the patient did not improve significantly. The patient was discharged due to financial difficulties and antifungal treatment at home, and his disease had stabilized at the 6-month follow-up.