Effect of farrowing pen size on pre-weaning performance of piglets.
Litter sizes in commercial pig production have increased substantially over recent years; however, farrowing pen sizes have generally not changed over the same time period. The objective of this study was to evaluate the effect of farrowing pen size on piglet pre-weaning growth and mortality. Differences in pen size were created by varying the width of pens of the same length, increasing the creep area available to the piglets. The study used a total of 1,786 litters in a randomized complete block design to compare two farrowing pen size treatments (FPS): Standard (pen width 1.52 m) and Increased (pen width 1.68 m). Litter sizes were equalized across treatments (12.9 ± 1.95 piglets) at 24 h after birth using cross-fostering. Litter weights were collected at birth and weaning (21.3 ± 2.08 d); pre-weaning mortality was recorded. The experimental unit was the litter; models for statistical analysis included FPS and replicate. Farrowing pen size had no effect (P > 0.05) on litter size at birth (12.8 and 13.0 for the Standard and Increased FPS, respectively), after cross-fostering (12.9 for both treatments), or at weaning (11.2 and 11.3, respectively). There was no effect (P > 0.05) of FPS on total litter or average piglet weight at birth, after cross-fostering, and at weaning. These results suggest no benefit in piglet performance from increasing the width of farrowing pens. As litter sizes continue to increase in commercial production, further research is warranted to re-evaluate the impact of farrowing pen size on pre-weaning mortality.


[Preconscious and conscious stimulation of erotic imagination].
The stimulation of erotic fantasies through the association of relaxation and erotic conscious or preconscious suggestions has been evaluated. This study was attempted following positive results in the stimulation of fantasmatic activity in alexithymic subjects with a similar procedure. Thirty female subjects, allocated into three groups practiced relaxation daily for two weeks including three sessions with psychological measures. During the second week, erotic suggestions, preconscious for one group and conscious for another one, were added. The third group (control) received only relaxation throughout. Results have shown an increase of sexual arousal and erotic imagery during the sessions with erotic suggestions. Sexual activities and desire increased in the two experimental groups. There was no difference between the effects of the preconscious and conscious suggestions. Possible clinical applications of such a procedure are discussed.


Towards Magnetic Field Gradient-Based Imaging and Control of In-Body Devices.
This papers reports a magnetic field gradient-based imaging system for in-body devices which takes inspiration from the localization principles of magnetic resonance imaging. By applying three orthogonal magnetic field gradients, the location of a device inside the body can be determined by measuring the magnetic fields in the device and transmitting this information to an external reader. The proposed system consists of one pair of Helmholtz coils and two pairs of saddle coils and is capable of generating the three orthogonal gradient fields. To emulate an implantable device, a miniature sensor module was designed using off-the-shelf components and semi-passive UHF RFID. The proposed localization system produces magnetic field gradients up to 187.4 G/m while consuming 1 A and achieves an average localization error of 80 μm.


Surgical management of hands in children with recessive dystrophic epidermolysis bullosa: use of allogeneic composite cultured skin grafts.
Recessive dystrophic epidermolysis bullosa (RDEB) is characterised by progressive childhood hand syndactyly and flexion contractures, which can be managed surgically but require split thickness autografts to facilitate satisfactory postoperative healing. We report on the partial substitution, for autografts, of improved composite cultured skin (CCS) allografts. The structure and preparation of these CCSs is outlined and their application in the course of 16 operations performed on 7 RDEB children with syndactyly and flexor contractures of fingers is described. Hand contractures were released and web spaces were covered with local flaps and split thickness autografts, while adjacent sides of the digits and other areas, as well as donor sites were generally grafted with CCS. Morphologic and functional results with CCS were judged to be good to excellent, the average time to recurrence was increased approximately 2-fold and smaller autografts needed to be used. In addition, healed CCS-treated donor sites could provide superior donor sites for further surgery.


Mechanical reinforcement of a supramolecular hydrogel comprising an artificial glyco-lipid through supramolecular copolymerization.
Supramolecular copolymer hydrogels were prepared by mixing 1 and the additives 2-8, and their rheological properties were evaluated. It was found that additive 3 reinforced the mechanical strength of the resultant hydrogel most efficiently, increasing the yield stress of SCH 1+3 about fourfold. The optimal mixing between the glyco-lipid hydrogelator 1 and the additive 3 sufficiently enhanced the mechanical strength of the resultant SCH, which improved the handling of the SH on the large scale. These results indicate that supramolecular copolymerization can provide the supramolecular hydrogel with desired properties and/or functions.


Terminal phase of bird schistosomiasis caused by Trichobilharzia regenti (Schistosomatidae) in ducks (Anas platyrhynchos f. domestica).
The terminal phase of the migration of Trichobilharzia regenti Horák, Kolárová et Dvorák, 1998 in the definitive host (Anas platyrhynchos f. domestica) was studied 12-27 days post infection (p.i.). Brain meninges were the last part of the nervous system where the worms were detected before their occurrence in the nasal cavity. In meninges, the parasites started to feed on red blood cells. Then the worms occurred in the nasal mucosa 14-25 days p.i. and the first immature eggs appeared 15 days p.i. The fully developed miracidia were recorded in the eggs from 17 days p.i. and freely in the nasal mucosa 19 days p.i. Infiltrates of lymphocytes, later also eosinophils and heterophils around the eggs and free miracidia, were observed from 15 and 19 days p.i., respectively. The haemorrhages occurring from 17 days p.i., and the granulomas with lymphocytes, eosinophils and heterophils forming around the eggs from 22 days p.i. were the most apparent pathological changes of nasal tissue.


Tracking sickness through social networks - the practical use of social network mapping in supporting the management of an E. coli O157 outbreak in a primary school in London.
This paper describes the practical use of social network diagrams in the management of an outbreak of Escherichia coli O157 (VTEC) in a primary school in London. The diagrams were created during the outbreak to establish the extent and nature of person-to-person transmission in the cases and their contacts. The diagrams supported a tailored public health action, and hence aided in the control of the outbreak. We conclude that for selected infectious diseases, social network diagrams can provide a valuable tool in the management of an outbreak.


Clinical and biochemical evaluation of HIV-related lipodystrophy in an ambulatory population from the Hospital Universitário Cassiano Antonio de Morais, Vitória, ES, Brazil.
We designed a retrospective cohort study to identify factors associated with HIV-1 related lipodystrophy at a tertiary HIV-care center in Vitória, ES, Brazil. Inclusion criteria were documented HIV diagnosis, anti-retroviral therapy and age above 17 years. Highly active antiretroviral therapy (HAART) was initially the exposure variable, but a second analysis was also performed, as a nested case-control, based on the presence or absence of lipodystrophy. Use of protease inhibitors (PI) was associated with an increase in serum triglycerides (243.7 +/- 189 mg/dL vs. 172.7 +/- 131 mg/dL, p = 0.015), but not of total cholesterol (TC) or HDL fraction levels. Non-nucleoside reverse transcriptase inhibitors (NNRTI) were associated with an increase in serum TC (180.6 +/- 46.8 mg/dL versus 162.4 +/- 41.4 mg/dL; p= 0.018) and an increase in HDL cholesterol (47.3 +/- 13.8 mg/dL versus 23.3 +/- 24.3 mg/dL; p < 0.001), with no significant effect on triglyceride levels. Lipodystrophy was diagnosed in 59.3% of the patients, but exposure to PI versus NNRTI did not affect the frequency of this disorder (43.4% versus 37.2%; p = 0.68). Serum TC, but not HDL cholesterol or triglyceride levels, was higher among the lipodystrophy cases (183.8 +/-47.5 mg/dL versus 162.1 +/-35.7; p=0.006). Among the controls (patients without lipodystrophy), HDL cholesterol (45.3 +/-14.4 mg/dL vs. 27.1 +/-26.3; p=0.001)and triglyceride levels (178.3 +/-146.3 mg/dL vs. 126.3 +/-126.9; p=0.013) also increased, but not TC. In conclusion, lipodystrophy was highly prevalent in our series. Lipid disorders were also frequent and apparently were related to lipodystrophy, except for triglyceride levels.


Endocrine responses and acute mTOR pathway phosphorylation to resistance exercise with leucine and whey.
Leucine ingestion reportedly activates the mTOR pathway in skeletal muscle, contributing to a hypertrophy response. The purpose of the study was to compare the post-resistance exercise effects of leucine and whey protein supplementation on endocrine responses and muscle mTOR pathway phosphorylation. On visit 1, subjects (X±SD; n=20; age=27.8±2.8yrs) provided baseline blood samples for analysis of cortisol, glucose and insulin; a muscle biopsy of the vastus lateralis muscle to assess mTOR signaling pathway phosphorylation; and were tested for maximum strength on the leg press and leg extension exercises. For visits 2 and 3, subjects were randomized in a double-blind crossover design to ingest either leucine and whey protein (10g+10g; supplement) or a non-caloric placebo. During these visits, 5 sets of 10 repetitions were performed on both exercises, immediately followed by ingestion of the supplement or placebo. Blood was sampled 30 min post-, and a muscle biopsy 45 min post-exercise. Western blots quantified total and phosphorylated proteins. Insulin increased (α<.05) with supplementation with no change in glucose compared to placebo. Relative phosphorylation of AKT and rpS6 were greater with leucine and whey supplementation compared to placebo. Supplementation of leucine and whey protein immediately after heavy resistance exercise increases anabolic signaling in human skeletal muscle.


Role of actin polymerization in monocyte phagocytosis of yeast cells effect of cytochalasin B.
The role of the cortical actomyosin-like contractile system in monocyte phagocytosis was studied by means of inhibition with cytochalasin B. Monocyte phagocytosis of yeast cells was assayed with a fluorescence extinction technique of surface-located phagocytosis which distinguishes between adherence and ingestion phases of total phagocytosis. Cytochalasin B, 10 micrograms/ml, inhibited monocyte phagocytosis by 20-30%. The cytochalasin inhibition was significant and restricted to the ingestion phase. The finding supported the hypothesis that the contractile structures of the cell have a contributory role in IgG-mediated monocyte phagocytosis on a surface. It is suggested that the cytochalasin effect reflected the role of chemotaxis in monocyte phagocytosis assayed by the present technique.


Comparison of 55% TFA/CH2Cl2 and 100% TFA for Boc group removal during solid-phase peptide synthesis.
Two parallel syntheses of 40 C-terminal amide peptides, ranging in length from 4 to 20 residues, have been carried out using simultaneous multiple peptide synthesis. All synthetic steps, other than the removal of the Boc group, were performed simultaneously under identical experimental conditions. The two sets of peptides were deprotected with either 55% TFA/DCM for 30 min or 100% TFA for 5 min. The purity of the peptides obtained when deprotecting with 55% TFA/DCM was, on average, 9% higher than with 100% TFA. The major impurity obtained during synthesis when 100% TFA was used for Boc removal corresponded to the omission of the second amino-acid residue added. Volumetric measurements of the swelling of the resin in the different deprotection solvents were carried out. These showed that the omission analogs generated are probably due to insufficient swelling of the resin, resulting in limited solvent transfer of 100% TFA into the resin and, in turn, incomplete Boc removal.


Intra-operative error during Austin Moore hemiarthroplasty.
To examine the frequency of technical errors during implantation of the Austin Moore prosthesis in a public hospital. Radiographs and charts of 147 consecutive uncemented Austin Moore hemiarthoplasty patients were retrospectively reviewed with particular reference to intra-operative errors associated with early failure of the prosthesis. 48% of the patients had at least one error pertinent to implantation and 14% sustained intra-operative fractures. The error rates between relatively junior doctors and consultants were not significantly different. The uncemented Austin Moore prosthesis is a technically demanding prosthesis that is difficult to implant well. Greater selectivity should be exercised when considering its use for femoral neck fractures.


Coronary heart disease in the elderly: identifying established and subclinical disease with stress testing.
Although cardiovascular disease is a major cause of mortality, morbidity, and healthcare expense in the United States, diagnosis in elderly patients, especially those who are asymptomatic, can be challenging. Noninvasive testing offers an opportunity to identify these patients, but guidelines reflect uncertainty of the impact of diagnosis on long-term outcomes. We review the role of different forms of noninvasive testing in both symptomatic and asymptomatic patients, as well as patients under consideration for elective surgery.


Effect of ACE2 and angiotensin-(1-7) in a mouse model of early chronic kidney disease.
Angiotensin-converting enzyme 2 (ACE2) is expressed at high levels in the kidney and converts angiotensin II (ANG II) to ANG-(1-7). We studied the effects of ACE2 inhibition and ANG-(1-7) in the (5/6) nephrectomy ((5/6) Nx) mouse model of chronic kidney disease (CKD). Male FVB mice underwent sham surgery (Sham) or (5/6) Nx and were administered either vehicle, the ACE2 inhibitor MLN-4760 (MLN), the AT(1) receptor antagonist losartan, MLN plus losartan, or ANG-(1-7) for 4 wk. In (5/6) Nx mice with or without MLN, kidney cortical ACE2 protein expression was significantly decreased at 4 wk, compared with Sham. Inhibition of ACE2 caused a decrease in renal cortical ACE2 activity. Kidney cortical ACE expression and activity did not differ between groups of mice. In (5/6) Nx mice treated with MLN, kidney levels of ANG II were significantly increased, compared with Sham. (5/6) Nx induced a mild but insignificant increase in blood pressure (BP), a 50% reduction in FITC-inulin clearance, and a significant increase in urinary albumin excretion. ACE2 inhibition in (5/6) Nx mice did not affect BP or FITC-inulin clearance but significantly increased albuminuria compared with (5/6) Nx alone, an effect reversed by losartan. Treatment of (5/6) Nx mice with ANG-(1-7) increased kidney and plasma levels of ANG-(1-7) but did not alter BP, FITC-inulin clearance, or urinary albumin excretion, and it increased relative mesangial area. These data indicate that kidney ACE2 is downregulated in the early period after (5/6) Nx. Inhibition of ACE2 in (5/6) Nx mice increases albuminuria via an AT(1) receptor-dependent mechanism, independent of BP. In contrast, ANG-(1-7) does not affect albuminuria after (5/6) Nx. We propose that endogenous ACE2 is renoprotective in CKD.


Clonal hematopoiesis of indeterminate potential and clonal cytopenias of undetermined significance: 2023 update on clinical associations and management recommendations.
Clonal hematopoiesis (CH) refers to age-associated expansion of somatic variants in hematopoietic stem and progenitor cells (HSPC). CH of indeterminate potential (CHIP) is operationally defined as pathogenic variants in HSPCs at a variant allele frequency ≥2%. CH is associated with increased occurrence of several hematological conditions such as cytopenias (also called clonal cytopenia of undetermined significance), hematological (predominantly myeloid but also lymphoid) neoplasms, cytosis (including monocytosis), and non-hematological conditions such as atherosclerotic cardiovascular and cerebrovascular disease, ischemic congestive heart failure, venous thromboembolism, type 2 diabetes mellitus, chronic obstructive pulmonary disease, osteoporosis, gout, with a potential protective effect in Alzheimer's disease (AD). As of now, there is limited prospective data for CH testing; however, CH detection is becoming increasingly prevalent due to ubiquitous use of somatic and germline NGS testing. This in addition to data suggesting that therapy related myeloid neoplasm (tMN) in many cases is preceded by the detection of CH clones, has led to the establishment of CH clinics at several institutions. At our institution, on a research basis, we currently recommend testing for CH for individuals with persistent (≥4 months) unexplained cytopenias, in patients with malignancies prior to adjuvant cytotoxic chemotherapy and/or radiation or radionuclide therapy, screening prior to autologous hematopoietic stem cell transplantation and chimeric antigen receptor T cell (CAR-T) therapy and to assess as to whether or not, potential germline mosaic variants actually represent CH.


Repeated Cold Stress Reduces Cyclophosphamide-Induced Cystitis/Bladder Pain and Macrophage Activity in Mice.
We examined the effect of repeated cold (RC) stress on cyclophosphamide (CPA)-induced cystitis/bladder pain in mice, in relation to macrophage activity. CPA, given i.p. at 400 mg/kg, caused bladder pain symptoms accompanying cystitis in both unstressed and RC-stressed mice, which were prevented by the macrophage inhibitor minocycline. A low dose, that is, 200 mg/kg, of CPA still produced bladder pain symptoms in unstressed but not RC-stressed mice. Lipopolysaccharide-induced cytokine production in peritoneal macrophages from RC-stressed mice was less than that from unstressed mice. Thus, RC stress appears to reduce CPA-induced bladder pain in mice, which may be associated with the decreased macrophage activity.


Synthesis of N-alkylated chitosan and its interactions with blood.
When hydrophobically modified chitosan (HM-CHI) comes into contact with red blood cells (RBCs), it can cause agglomeration. This property leads HM-CHI to be a potential agent to form a rapid haemostatic plug to stop bleeding at wound sites. In this study, we investigated the properties of the HM-CHI biopolymer to act as an agent that rapidly clots blood. We have examined the synthesis and structural characteristics of HM-CHI - blood substances using X-ray diffraction, infrared spectroscopy and elemental analysis. To understand the rheological behaviour of RBCs within HM-CHI, we have studied the effects of HM-CHI on RBC aggregation and morphology using a rheometer and scanning electron microscopy (SEM), respectively. When mixed with sodium citrate, HM-CHI rapidly transformed human blood into an elastic gel. In contrast, un-modified chitosan (i.e. without hydrophobes) was unable to clot blood. The hydrophobias within HM-CHI entered into the RBC membranes and connected to the cells by a sample-spanning network, which subsequently led to the formation of an elastic gel. The gelling ability of HM-CHI is similar to that of fibrin-based sealants, but at a much lower cost and greater availability.


Evolution of gene order and chromosome number in Saccharomyces, Kluyveromyces and related fungi.
The extent to which the order of genes along chromosomes is conserved between Saccharomyces cerevisiae and related species was studied by analysing data from DNA sequence database. As expected, the extent of gene order conservation decreases with increasing evolutionary distance. About 59% of adjacent gene pairs in Kluyveromyces lactis or K. marxianus are also adjacent in S. cerevisiae, and a further 16% of Kluyveromyces neighbours can be explained in terms of the inferred ancestral gene order in Saccharomyces prior to the occurrence of an ancient whole-genome duplication. Only 13% of Candida albicans linkages, and no Schizosaccharomyces pombe linkages, are conserved. Analysis of gene order arrangements, chromosome numbers, and ribosomal RNA sequences suggests that genome duplication occurred before the divergence of the four species in Saccharomyces sensu stricto (all of which have 16 chromosomes), but after this lineage had diverged from Saccharomyces kluyveri and the Kluyveromyces lactislmarxianus species assemblage.


OpenTein: a database of digital whole-slide images of stem cell-derived teratomas.
Human stem cells are promising sources for regenerative therapy. To ensure safety of future therapeutic applications, the differentiation potency of stem cells has to be tested and be widely opened to the public. The potency is generally assessed by teratoma formation comprising differentiated cells from all three germ layers, and the teratomas can be inspected through high-quality digital images. The teratoma assay, however, lacks consistency in transplantation protocols and even in interpretation, which needs community-based efforts for improving the assay quality. Here, we have developed a novel database OpenTein (Open Teratoma Investigation, http://opentein.hgc.jp/) to archive and freely distribute high-resolution whole-slide images and relevant records. OpenTein has been designed as a searchable, zoomable and annotatable web-based repository system. We have deposited 468 images of teratomas derived by our transplantation of human stem cells, and users can freely access and process such digital teratoma images. Approximately, the current version of OpenTein responds within 11.2 min for processing 2.03 gigapixel teratoma images. Our system offers valuable tools and resources in the new era of stem cell biology.


Signaling Inclusivity in Undergraduate Biology Courses through Deliberate Framing of Genetics Topics Relevant to Gender Identity, Disability, and Race.
The study of genetics centers on how encoded information in DNA underlies similarities and differences between individuals and how traits are inherited. Genetics topics covered in a wide variety of undergraduate biology classrooms can relate to various identities held by students such as gender identity, disability, and race/ethnicity, among others. An instructor's sensitive approaches and deliberate language choices regarding these topics has the potential to make the critical difference between welcoming or alienating students and can set a tone that communicates to all students the importance of diversity. Separating the sperm/egg binary from gendered terms in coverage of inheritance patterns, along with inclusion of transgender people in pedigree charts, may make the classroom more welcoming for students of diverse gender identities. Choosing nonstigmatizing language and acknowledging disability identities in discussions of genetic conditions may help students with visible and invisible disabilities feel validated. Counteracting genetics-based pseudoscientific racism and the stereotype threat to which it contributes may be facilitated by more thorough integration of quantitative and population genetics topics. Instructors may thus potentially enhance retention of students of diverse backgrounds in biology through careful consideration and crafting of how human differences are described and connected with principles of genetics.


Dual-targeting for brain-specific drug delivery: synthesis and biological evaluation.
Ibuprofen is one of the most potent non-steroid anti-inflammatory drugs (NSAIDs) and plays an important role in the treatment of neurodegenerative diseases. However, its poor brain penetration and serious side effects at therapeutic doses, has hindered its further application. Thus, it is of great interest to develop a carrier-mediated transporter (CMT) system that is capable of more efficiently delivering ibuprofen into the brain at smaller doses to treat neurodegenerative diseases. In this study, a dual-mediated ibuprofen prodrug modified by glucose (Glu) and vitamin C (Vc) for central nervous system (CNS) drug delivery was designed and synthesized in order to effectively deliver ibuprofen to brain. Ibuprofen could be released from the prepared prodrugs when incubated with various buffers, mice plasma and brain homogenate. Also, the prodrug showed superior neuroprotective effect in vitro and in vivo than ibuprofen. Our results suggest that chemical modification of therapeutics with warheads of glucose and Vc represents a promising and efficient strategy for the development of brain-targeting prodrugs by utilizing the endogenous transportation mechanism of the warheads.


Candida species and yeasts in mouths of infants from a special care unit of a maternity hospital.
A group of 99 babies born in hospital and subsequently transferred to the special care unit were examined for the presence of candidas orally. The rate of isolation rose from 6% neonatally to 53% on day 14 of life. Among infants who did not harbour the organisms when discharged from hospital, colonization rapidly took place so that 79% did so at 4 weeks of age, after which the rate fell to 50% at one year of age. The low incidence of clinical candidosis suggests that in these babies as in other groups C. albicans is normally a harmless commensal.


Glucose transport into rat skeletal muscle: interaction between exercise and insulin.
This study was done to evaluate the effect of insulin on sugar transport into skeletal muscle after exercise. The permeability of rat epitrochlearis muscle to 3-O-methylglucose (3-MG) was measured after exposure to a range of insulin concentrations 30, 60, and 180 min after a bout of exercise. Thirty and 60 min after exercise, the effects of exercise and insulin on 3-MG transport were additive over a wide range of insulin concentrations, with no increase in sensitivity or responsiveness to insulin. After 180 min, when approximately 66% of the exercise-induced increase in sugar transport had worn off, both the responsiveness and sensitivity of the glucose transport process to insulin were increased. These findings appear compatible with the hypothesis that the actions of exercise and insulin result in activation and/or translocation into the plasma membrane of two separate pools of glucose transporters in mammalian skeletal muscle.


Lateral diffusion of lipids in membranes by pulse saturation recovery electron spin resonance.
Short-pulse saturation recovery electron spin resonance methods have been used to measure lateral diffusion of nitroxide-labeled lipids in multilamellar liposomal dispersions. Nitroxides with 14N and 15N isotopes introduced both separately and together were used. Differential equations have been written and solved for complex saturation recovery signals involving several superimposed exponentials. The time constants contain various combinations of the spin-lattice relaxation time (T1e) for both isotopes, Heisenberg exchange rates, and nuclear spin-lattice relaxation times (T1n). Signals of high quality were fitted by Monte Carlo variation of the amplitudes and time constants. The reliability of the approach was tested extensively by verifying that (i) the predicted number of exponentials agreed with the experimental number, (ii) relaxation parameters that were determined were independent of the observed hyperfine transition, (iii) the time constants were independent of saturating pulse length, (iv) T1e and T1n do not change when Heisenberg exchange is changed by varying the concentration, and (v) Heisenberg exchange is indeed proportional to the concentration. It has been established that bimolecular collision rates over a wide range of conditions can be reliably measured using the methodology described here. The methods depend on the favorable match of bimolecular collision rates at micromolar concentrations to nitroxide spin-lattice relaxation probabilities.


Association between microbiota-dependent metabolite trimethylamine-N-oxide and type 2 diabetes.
Background: The association of trimethylamine-N-oxide (TMAO), a microbiota-dependent metabolite from dietary choline and carnitine, with type 2 diabetes was inconsistent.Objective: We evaluated the association of plasma TMAO with newly diagnosed type 2 diabetes and the potential modification of TMAO-generating enzyme flavin monooxygenase 3 (FMO3) polymorphisms.Design: This was an age- and sex-matched case-control study of 2694 participants: 1346 newly diagnosed cases of type 2 diabetes and 1348 controls. Concentrations of plasma TMAO were measured, and FMO3 E158K polymorphisms (rs2266782) were genotyped.Results: Medians (IQRs) of plasma TMAO concentration were 1.47 μmol/L (0.81-2.20 μmol/L) for controls and 1.77 μmol/L (1.09-2.80 μmol/L) for type 2 diabetes cases. From the lowest to the highest quartiles of plasma TMAO, the multivariable adjusted ORs of type 2 diabetes were 1.00 (reference), 1.38 (95% CI: 1.08, 1.77), 1.64 (95% CI: 1.28, 2.09), and 2.55 (95% CI: 1.99, 3.28) (P-trend < 0.001); each SD of ln-transformed plasma TMAO was associated with a 38% (95% CI: 26%, 51%) increment in ORs of type 2 diabetes. The FMO3 rs2266782 polymorphism was not associated with type 2 diabetes. The positive association between plasma TMAO and type 2 diabetes was consistent in each rs2266782 genotype group, and no significant interaction was observed (P = 0.093).Conclusions: Our results suggested that higher plasma TMAO was associated with increased odds of newly diagnosed type 2 diabetes and that this association was not modified by the FMO3 rs2266782 polymorphism. This study was registered at clinicaltrials.gov as NCT03130894.


Clinical evaluation of the AutoPulse automated chest compression device for out-of-hospital cardiac arrest in the northern district of Shanghai, China.
Whether the AutoPulse automated chest compression device is worthy of clinical use for out-of-hospital cardiac arrest (OHCA) remains controversial. A prospective controlled study was conducted to evaluate the effect of AutoPulse versus manual chest compression for cardiopulmonary resuscitation (CPR) of OHCA patients in the northern district of Shanghai, China. A total of 133 patients with OHCA who were treated at the Emergency Medical Center of the Tenth People's Hospital Affiliated with Tongji University between March 2011 and March 2012 were included. The patients were randomly assigned to the Manual CPR (n = 64) and AutoPulse CPR groups (n = 69) in accordance with the approach of chest compression received. The primary outcome measure was return of spontaneous circulation (ROSC), and the secondary outcome measures included 24-h survival rate, hospital discharge rate, and neurological prognosis at hospital discharge. The ROSC rate of patients with OHCA was significantly higher in the AutoPulse CPR group than in the Manual CPR group (44.9% vs. 23.4%; p = 0.009). The 24-h survival rate of OHCA patients was significantly higher in the AutoPulse CPR group than in the Manual CPR group (39.1% vs. 21.9%; p = 0.03). The hospital discharge rate of the patients with OHCA was significantly higher in the AutoPulse CPR group than in the Manual CPR group (18.8% vs. 6.3%; p = 0.03). The proportion of patients with OHCA and a cerebral performance category score of 1 or 2 points at hospital discharge was higher in the AutoPulse CPR group than in the Manual CPR group, but the difference was not statistically significant (16.2% vs. 13.4%, p = 1.00). Use of the AutoPulse increases CPR success and survival rates in patients with OHCA, but its ability to improve cerebral performance requires further evaluation.


Clinical characteristics, radiologic findings, risk factors and outcomes of serum galactomannan-negative invasive pulmonary aspergillosis.
The sensitivity of galactomannan (GM) assay is suboptimal for detecting invasive pulmonary aspergillosis (IPA) in serum samples. However, the clinical characteristics, radiologic findings, and outcomes in patients with GM-negative IPA have not been fully elucidated. Over a 7-year period, adult patients with proven or probable IPA by the EORTC/MSG definition were retrospectively enrolled. Patients with negative GM results and positive Aspergillus spp. cultures from sputum or bronchoalveolar lavage were classified into GM-negative IPA group. GM-positive and culture-negative IPA cases were selected at a 1:2 ratio. Thirty-four patients with GM-negative IPA were compared to 68 randomly selected patients from 158 patients with GM-positive and culture-negative IPA. Patients with diabetes mellitus, chronic kidney disease, and steroid use were more common but those with hematologic malignancy, prior receipt of mold-active antifungal drugs, and neutropenia were less common in GM-negative IPA than in GM-positive IPA. Regarding radiologic findings, angioinvasive aspergillosis was less common in GM-negative IPA than in GM-positive IPA. The median number of days from diagnosis to appropriate antifungal therapy was higher in GM-negative IPA than in GM-positive IPA. Multivariate analysis indicated that neutropenia (adjusted odds ratio [aOR], 0.10) and prior receipt of mold-active antifungal drugs (aOR, 0.12) were inversely associated with GM-negative IPA. The 30-day and 90-day mortality were similar between the two groups. Neutropenia and prior receipt of mold-active antifungal drugs before GM assay were independently associated with GM positivity among patients with proven/probable IPA. Angioinvasive aspergillosis was less common in GM-negative IPA than in GM-positive IPA.


Liver Metastatic Colorectal Tumor Cells Change Their Phenotype During Consecutive Passages on Chick Embryo Chorioallantoic Membrane: Lessons from the Lab to the Clinic.
Colon cancer liver metastases with desmoplastic growth pattern (dGP) have a highly heterogeneous therapy response. The aim of the study was to evaluate the dGP liver metastasis molecular profile from a chemo-naive patient by mimicking metastatic process on an experimental chick embryo chorioallantoic membrane (CAM) model. Three successive CAM passages of dGP human colorectal liver metastases were immunophenotyped for keratin (K) 8, and 20, CLIC1, VEGF, EGFR, CD34, podoplanin, Ki67, E-cadherin and vimentin. Metastatic cells gradually lost K20 while K8, E-cadherin and vimentin heterogeneously increased during passages. VEGF, CLIC 1, EGFR expression increased in metastatic cells especially at the tumor graft periphery. Scattered proliferating and non-proliferating podoplanin-positive tumor cells, lymphatic and blood vessels were heterogeneously detected in tumor xenografts depending on passage stage. By mimicking repetitive metastatic processes we proved that metastatic cells change their phenotype. This may explain why not all metastases have a similar response to therapy.


A microglial cell model for acyl-CoA oxidase 1 deficiency.
Acyl-CoA oxidase 1 (ACOX1) deficiency is a rare and severe peroxisomal leukodystrophy associated with a very long-chain fatty acid (VLCFA) β-oxidation defect. This neurodegenerative disease lacks relevant cell models to further decipher the pathomechanisms in order to identify novel therapeutic targets. Since peroxisomal defects in microglia appear to be a key component of peroxisomal leukodystrophies, we targeted the Acox1 gene in the murine microglial BV-2 cell line. Using CRISPR/Cas9 gene editing, we generated an Acox1-deficient cell line and validated the allelic mutations, which lead to the absence of ACOX1 protein and enzymatic activity. The activity of catalase, the enzyme degrading H2O2, was increased, likely in response to the alteration of redox homeostasis. The mutant cell line grew more slowly than control cells without obvious morphological changes. However, ultrastructural analysis revealed an increased number of peroxisomes and mitochondria associated with size reduction of mitochondria. Changes in the distribution of lipid droplets containing neutral lipids have been observed in mutant cells; lipid analysis revealed the accumulation of saturated and monounsaturated VLCFA. Besides, expression levels of genes encoding interleukin-1 beta and 6 (IL-1β and IL-6), as well as triggering receptor expressed on myeloid cells 2 (Trem2) were found modified in the mutant cells suggesting modification of microglial polarization and phagocytosis ability. In summary, this Acox1-deficient cell line presents the main biochemical characteristics of the human disease and will serve as a promising model to further investigate the consequences of a specific microglial peroxisomal β-oxidation defect on oxidative stress, inflammation and cellular functions.


INTRAMITOCHONDRIAL FIBERS WITH DNA CHARACTERISTICS. II. ENZYMATIC AND OTHER HYDROLYTIC TREATMENTS.
The effects of proteolytic enzymes, ribonuclease, and deoxyribonuclease upon a fibrous component of chick embryo mitochondria, which was previously shown to have many fixation and staining properties characteristic of the bacterial nucleoplasm, are reported. Pepsin digestion of formaldehyde-fixed tissues removed the membranes and matrices of mitochondria, but a pepsin-resistant fibrous material remained which was heavily stained by uranyl and lead ions. Experiments on a DNA "model system" showed that DNA treated with osmium tetroxide can be depolymerized by deoxyribonuclease. Zinc ions strongly inhibited the depolymerization of DNA. Digestion of osmium tetroxide-fixed tissues (fixed only briefly) with deoxyribonuclease for 1 hour greatly reduced the Feulgen staining of the nuclei, and after 4 hours the Feulgen reaction was completely abolished. The reduction and the disappearance of the Feulgen reaction in nuclei was paralleled by partial to complete digestion of the mitochondrial fibers in the regions studied (after 1 and 4 hours, respectively), without any other obvious changes in cellular structures. When deoxyribonuclease was inhibited by the addition of zinc ions, the nuclear Feulgen reaction was not diminished, nor were the mitochondrial fibers removed. Buffer control incubations for deoxyribonuclease and ribonuclease did not alter the structure or staining properties of the mitochondrial fibers, nor did incubation with ribonuclease. The latter reaction digested the cytoplasmic and nucleolar ribosomes after a 4-hour incubation period, in parallel with the abolishment of toluidine blue staining. The results contribute further evidence that these mitochondria contain deoxyribonucleic acid.


Distinct mechanism of oxidative trifluoromethylation with a well-defined Cu(II) fluoride promoter: hidden catalysis.
The fluoride [(bpy)CuF2(H2O)]·2H2O (1) reacts with CF3SiMe3 and PhB(OH)2 in DMF at rt to give PhCF3 in >95% yield within 15 min. Although 1 is a Cu(II) complex, this reaction occurs only in air; no Ph-CF3 coupling takes place under anaerobic conditions. A distinct mechanism is operational in this transformation. First, 1 is trifluoromethylated with TMSCF3 to give "[(bpy)Cu(CF3)2]" that spontaneously disproportionates to two Cu(III) ([Cu(CF3)4](-) and [(bpy)Cu(CF3)3]) and two Cu(I) ([(bpy)Cu(CF3)] and [Cu(CF3)2](-)) complexes. In contrast with the Chan-Evans-Lam reaction, where the Cu(III) products of the Cu(II) disproprotionation effect the coupling, those formed in the 1-TMSCF3 system, [Cu(CF3)4](-) and [(bpy)Cu(CF3)3], are stable and unreactive, remaining dead-end spectators throughout the coupling process. Consequently, the trifluoromethylation of PhB(OH)2 with 1-CF3SiMe3 does not and cannot occur in the absence of O2. Only by air oxidation of the Cu(I) disproportionation product, [(bpy)Cu(CF3)] in equilibrium with [Cu(CF3)2](-), is the reactive species generated, serving as a catalyst for the Ph-CF3 bond formation even if 1 is used in stoichiometric quantities.


Does fibroids surgery by endoscopy or laparotomy represent a malignancy threat?
The aim of this study was to 1) estimate the incidence of unsuspected uterine sarcoma in patients after myomectomies and hysterectomies for benign uterine fibroids; 2) to assess the incidence of uterine sarcomas among patient who had uterine fibroids or a suspicion of uterine sarcoma before undergoing the surgical procedures. Retrospective study in single center university hospital. Patient's records with uterine fibroids and uterine sarcoma from 2003 to 2015 collected. Data presented as mean and standard deviation for continuous variable and percentage for categorical variables. The exact Clopper-Pearson interval was used to calculate 95% confidence interval. The total number of women with uterine fibroids was 2269 and uterine sarcomas 7. Of these seven, four were uterine leiomyosarcomas (ULMS), one endometrial sarcoma (ESS), one high-grade undifferentiated uterine sarcoma (HGUS) and one embryonal rhabdomyosarcoma (ERMS). Six of these patients underwent direct open conventional cancer treatment. The mean age of the patients with ULMS was 73.7±3.9 years. Immunohistochemistry results indicated SMA(+), CD 10(+), desmin(+) and h-caldesmon(+). The two patients with HGUS and ERMS were also preoperatively diagnosed with suspected malignancy and operated upon according. However, only one woman 48 years old primarily diagnosed with benign uterine fibroids underwent a laparoscopic subtotal hysterectomy (LSH) procedure; however, the histological results detected an ESS. Immunohistochemistry showed CD10(+), desmin(+), smooth muscle actin (SMA)(-), Aktin(-) and 5% Ki67(+).Two weeks after the initial surgery, an open cervical stump resection with bilateral sapping-oophorectomy and an omentectomy was performed. The frequency of unsuspected ESS was 1/2269 among the women who underwent myomectomies and hysterectomies for the treatment of benign uterine fibroids. The total incidence of uterine sarcoma was 7/2275 among the patients who had presumed uterine fibroids or a suspicion of uterine sarcoma prior to undergoing the surgical procedures.


Comparative Studies on the Effect of Adjuvants with Urea to Reduce the Overwintering Inoculum of Venturia inaequalis.
A 2-year study on the use of organic and conventional adjuvants alone, or mixed with urea, was conducted for management of overwintering inoculum of the apple scab pathogen, Venturia inaequalis. Select adjuvants (LI 700, Bond Max, Latron B-1956, and Organic Wet Betty [OWB]) have the potential to hasten urea-driven leaf litter decomposition and reduce V. inaequalis overwintering inoculum comparable to urea, and that one organic surfactant could perform the same level of leaf decomposition as urea. Combinations of adjuvants with urea significantly improved leaf litter degradation compared with urea alone, concomitant with reducing the number of pseudothecia present and pseudothecium fertility. We demonstrate that the combination of urea with Bond Max or OWB reduced pseudothecia fertility and ascospore production to less than 5% in the remaining pseudothecia, a significantly greater reduction than with urea alone. These results suggest that conventional growers combine urea with Bond Max or OWB to more effectively reduce overwintering inoculum, and that the adjuvant OWB can provide organic growers with comparable performance to urea used in conventional orchards for improved sanitation.


Recent advances in managing and understanding uveitis.
Uveitis is a sight-threatening disease entity with intraocular inflammation that arises from various causes. It mainly affects working-age individuals and may lead to irreversible visual loss if not treated properly in a timely manner. This article reviews recent advances in the management and understanding of uveitis since 2014, including treatment with new immunosuppressive therapies that use biological agents, local therapy with steroid implants, and imaging studies for the evaluation of uveitis.


Synthesis of anti-HIV lithospermic acid by two diverse strategies.
An efficient and convergent route for the synthesis of the natural product (+)-lithospermic acid, which possesses anti-HIV activity, was accomplished. The (±)-trans-dihydrobenzo[b]furan core therein was prepared by two different strategies. The first strategy involved the use of a palladium-catalyzed annulation to generate an appropriately substituted benzo[b]furan ester followed by a stereoselective reduction of a carbon-carbon double bond with Mg-HgCl(2)-MeOH. The second strategy relied on an aldol condensation between a suitably substituted methyl arylacetate and 3,4-dimethoxybenzaldehyde, followed by cyclization. Finally, a total synthesis of (+)-lithospermic acid was completed via coupling of a trans-dihydrobenzo[b]furan cinnamic acid with an enantiomerically pure methyl lactate.


Clonal diversity of New Delhi metallobetalactamase-1 producing Enterobacteriaceae in a tertiary care centre.
New Delhi metallobetalactamase-1 (NDM-1) production is a major mechanism of resistance to carbapenems among the Enterobacteriaceae and is a cause for concern in the field of microbial drug resistance. This study was performed to detect NDM-1 in Enterobacteriaceae and to determine the clonal relatedness of NDM-1 producing Escherichia coli and Klebsiella pneumoniae isolated from patients admitted in a tertiary care centre. A total of 111 clinically significant Enterobacteriaceae isolates, resistant to cephalosporin subclass III were screened for carbapenemase production by the modified Hodge test. Minimum inhibitory concentration to imipenem and meropenem was determined and interpreted according to Clinical Laboratory Standards Institute 2011 criteria. Presence of bla NDM-1 was detected by polymerase chain reaction. To ascertain clonal relatedness, random amplification of polymorphic deoxyribonucleic acid (RAPD) was carried out for representative NDM-1 producers. bla NDM-1 was detected in 64 study isolates, of which 27 were susceptible to carbapenems. RAPD revealed a high degree of clonal diversity among NDM-1 producers except for a small clustering of isolates in the neonatal intensive care unit. There is extensive clonal diversity among the NDM-1 producing E. coli and K. pneumoniae. Hence, antibiotic selection pressure rather than horizontal transfer is probably an important operating factor for the emergence of NDM-1. This calls for increased vigilance, continuous surveillance and strict enforcement of antibiotic policy with restricted use of inducer drugs.


High Expression Levels of the SOCS3 Gene Are Associated with Acute Myocardial Infarction.
Aims: The present study was designed to evaluate whether the expression of the suppressor of cytokine signaling 3 (SOCS3) gene could serve as a biomarker to predict the risk of acute myocardial infarction (AMI). Basic Methods: Peripheral white blood cells were collected from 113 patients with AMI and 92 patients with stable coronary artery disease (SCAD). SOCS3 mRNA expression levels in peripheral blood cells were determined by a real-time quantitative polymerase chain reaction, and levels of the SOCS3 protein were determined by Western blotting. Results: The mRNA expression levels of the SOCS3 gene in AMI patients was 1.33-fold higher than that in the SCAD patients, and the level of the SOCS3 protein was 1.25-fold higher (p < 0.05 for both). Bivariate logistic regression analysis documented that elevated expression of the SOCS3 gene was an independent risk factor for AMI. A regression analysis demonstrated a lack of correlation between elevated expression levels of SOCS3 and the levels of fasting blood glucose high- and low-density lipoprotein, and cardiac troponin. Conclusions: Elevated expression of the SOCS3 gene results most likely from enhanced inflammatory responses and is an independent risk factor for AMI.


Relationship of glycosylated hemoglobin, fetal macrosomia, and birthweight macrosomia.
Previous studies have shown that glycosylated hemoglobin (Hb A1C) once elevated correlated with fetal malformations, poor perinatal outcome, and macrosomia. To determine whether Hb A1C was related to fetal diabetic complications such as polyhydramnois, fetal macrosomia, and fat line detected on ultrasonographic evaluation, 66 diabetic patient, types I, II, and III, were followed longitudinally. These ultrasound markers were further assessed regarding the reliability of predicting birthweight macrosomia. Fetal macrosomia and birthweight macrosomia were defined by weight greater than the 90th percentile for gestational age based on the Williams growth curve. The Hb A1C values were compared to women with and without fetal diabetic complications. Fetal diabetic complications occurred in 13 (20%) of the cases and birthweight macrosomia occurred in 19 (29%) of the cases. Of those 13 women with fetal diabetic complications, 11 (85%) had Hb A1C greater than 6.3%. This level was significantly different in women with the ultrasound markers vs those without. Ultrasound-determined macrosomia in predicting birthweight macrosomia has a sensitivity, specificity, positive and negative predictive values of 53%, 94%, 77%, and 83%, respectively. There is a critical level of Hb A1C at which ultrasound fetal diabetic markers were observed; this level is greater than 6.3%. We conclude that there is a target level of glycemic control that one must avoid to prevent birthweight macrosomia.


Adult learners: are they really different?
Some knowledge of adult learning is essential in establishing a meaningful learning/teaching experience that will meet the needs of our students, employees, and patients. Specific learning characteristics that pertain directly to the adult, such as fluid and crystallized intelligence, problem-solving ability, the role of experience, and physiologic changes, strongly indicate a uniqueness in the way adults learn.


Oral Drug Delivery Systems Applied to Launched Products: Value for the Patients and Industrial Considerations.
Drug delivery systems (DDS) control the amount, rate, and site of administration of drug substances in the body as well as their release and ADME (absorption, distribution, metabolism, excretion). Among the various types of DDS, amount-controlled DDS for solubilization and absorption increase the bioavailability. Time- and amount-controlled DDS are controlled release formulations classified as (1) membrane-type, (2) matrix-type, (3) osmotic-type, and (4) ion-exchange type. Timed-release formulations also control the time and amount of release and the absorption of drugs. Site- and amount-controlled DDS are characterized by colonic delivery and intestinal lymph-targeting to improve release and ADME of drug substances. Finally, site-, time-, and amount-controlled DDS are gastroretentive formulations and local delivery in the oral cavity to improve site retention, release, and ADME of drugs. DDS can enhance efficacy, reduce adverse effects, and optimize the dosing frequency of various drug products to increase patient value. This review focuses on patient value and industrial considerations of launched oral DDS. We provide a technological overview of candidate and marketed DDS, as well as the pros/cons of the technologies for industrialization with consideration to excipients, manufacturing, and storage stability. Moreover, to demonstrate the usefulness of the technology and support the selection and development of the best technologies for patients, we also describe patient value from clinical studies and analyses, particularly with regard to increased new medical options, higher efficacy, reduced adverse effects, reduced number of doses and clinic visits, easier administration, higher quality of life, greater adherence, and satisfaction.


[Institutional policy for developing nurses' clinical skills].
The development of clinical skills in nursing can be integrated into the institutional policy of any hospital. Such a project combines training, the optimal use of the skills developed and recognition from the institution.


MeV gold ion induced sputtered nanoparticles from gold nanostructures: dependence of incident flux and temperature.
The high-energy and heavy-ion induced sputtered particles from nanostructures under various conditions can result in variety of size distributions. 1.5 MeV Au2+ ions induced sputtering from isolated gold nanostructures deposited on silicon substrate have been studied as a function of incident ion flux (dose rate) and the sputter particle catcher at low temperature. At higher fluxes, a bimodal distribution of the sputtered particles has been observed. Cross-sectional transmission electron microscopy and Rutherford backscattering spectrometry measurements showed that the sputter particle size distribution depends on morphology at surface and interfaces. The results for the size distribution from a catcher at low temperature showed the less agglomeration of ejected clusters on the catcher grids, resulting in the lower-disperse size distribution.


Shoulder Tip Pain After Cesarean Section.
The aim of this study was to investigate the frequency of postoperative shoulder tip pain (STP) after cesarean section and compare spinal and general anaesthesia with respect to STP. Three hundred patients who underwent cesarean section were randomly assigned to either spinal anaesthesia group (Group SA, n=143) or general anaesthesia group (Group GA, n=157). Postoperative STP was assessed at 8 hours and 24 hours after operation by Visual Analogue Scale of Pain (VAS). There were no statistically significant difference between the groups in terms of demographic data, operative findings, and clinical outcomes. The overall incidence of STP in study population was 35.7%. The incidence of STP in group SA (26.6%) was lower than that in group GA (43.9%)(p=0.005). Moreover VAS scores for STP at 6 hours and 24 hours were significantly lower in Group SA (p=0.001 and p<0.001, respectively). Shoulder tip pain is a common complaint after cesarean section, which is more prevalent in general anaesthesia.


MALAT1 Modulates TGF-β1-Induced Endothelial-to-Mesenchymal Transition through Downregulation of miR-145.
Endothelial-to-mesenchymal transition (EndMT) plays significant roles under various pathological conditions including cardiovascular diseases, fibrosis, and cancer. EndMT of endothelial progenitor cells (EPCs) contributes to neointimal hyperplasia following cell therapy Metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) is a long non-coding RNA (lncRNA) that promotes metastasis and cancer. MicroRNA-145 (miR-145) is a tumor suppressor that has been reported to inhibit SMAD3-mediated epithelial-to-mesenchymal transition (EMT) of cancer cells. In the present study, we investigated the role of MALAT1 and miR-145 in EndMT of human circulating EPCs induced by transforming growth factor beta1 (TGF-β1). Human circulating EPCs were isolated and characterized by fluorescence-activated cell sorting (FACS). Expression levels of EndMT markers were assessed by qRT-PCR and western blotting. Alpha-smooth muscle actin (α-SMA) expression was measured by cell immunofluorescence staining. The regulatory relationship between MALAT1 and miR-145 and its target genes, TGFBR2 (TGFβ receptortype II) and SMAD3 (mothers against decapentaplegic homolog 3) was analyzed using the luciferase reporter assay. We found that EndMT of EPCs induced by TGF-β1 is accompanied by increased MALAT1 expression and decreased miR-145 expression, and MALAT1 and miR-145 directly bind and reciprocally repress each other in these cells. Dual-Luciferase Reporter assay indicated that miR-145 inhibits TGF-β1-induced EndMT by directly targeting TGFBR2 and SMAD3. MALAT1 modulates TGF-β1-induced EndMT of EPCs through regulation of TGFBR2 and SMAD3 via miR-145. Thus, the MALAT1-miR-145-TGFBR2/SMAD3 signaling pathway plays a key role in TGF-β1-induced EndMT.


Serum soluble interleukin-2 receptor level at diagnosis predicts transformation in patients with follicular lymphoma.
We evaluated 121 patients with follicular lymphoma (FL) and analyzed the association between the soluble interleukin-2 receptor (sIL-2R) level at diagnosis and the cumulative incidence of transformation. By a receiver-operating characteristic analysis, we determined a cutoff value of sIL-2R for transformation at 4360 U/mL to classify patients into two groups. Patients in the high sIL-2R group showed a shorter progression-free survival (PFS) and shorter disease-specific survival (DSS) (p < 0.001 and p = 0.018). Furthermore, the cumulative incidence of transformation in the high sIL-2R group was higher than that in the low sIL-2R group (40.9% vs. 7.3% at 5 years, p < 0.001). In a multivariate analysis, high sIL-2R was an independent predictive risk factor for transformation (HR 7.42, 95% CI: 2.75-20.0, p < 0.001). This study showed that the sIL-2R level at diagnosis may be a prognostic factor for transformation, PFS, and DSS in patients with FL.


Gene signature associated with benign neurofibroma transformation to malignant peripheral nerve sheath tumors.
Benign neurofibromas, the main phenotypic manifestations of the rare neurological disorder neurofibromatosis type 1, degenerate to malignant tumors associated to poor prognosis in about 10% of patients. Despite efforts in the field of (epi)genomics, the lack of prognostic biomarkers with which to predict disease evolution frustrates the adoption of appropriate early therapeutic measures. To identify potential biomarkers of malignant neurofibroma transformation, we integrated four human experimental studies and one for mouse, using a gene score-based meta-analysis method, from which we obtained a score-ranked signature of 579 genes. Genes with the highest absolute scores were classified as promising disease biomarkers. By grouping genes with similar neurofibromatosis-related profiles, we derived panels of potential biomarkers. The addition of promoter methylation data to gene profiles indicated a panel of genes probably silenced by hypermethylation. To identify possible therapeutic treatments, we used the gene signature to query drug expression databases. Trichostatin A and other histone deacetylase inhibitors, as well as cantharidin and tamoxifen, were retrieved as putative therapeutic means to reverse the aberrant regulation that drives to malignant cell proliferation and metastasis. This in silico prediction corroborated reported experimental results that suggested the inclusion of these compounds in clinical trials. This experimental validation supported the suitability of the meta-analysis method used to integrate several sources of public genomic information, and the reliability of the gene signature associated to the malignant evolution of neurofibromas to generate working hypotheses for prognostic and drug-responsive biomarkers or therapeutic measures, thus showing the potential of this in silico approach for biomarker discovery.


Screening of dust grains in a weakly ionized gas: effects of charging by plasma currents.
Screening and charging of a grain in a weakly ionized plasma background are studied within the drift-diffusion approximation. The computations evidence that the account of grain charging results in a distinct qualitative change in the screened field as compared to the thermodynamically equilibrium case of a grain with a constant charge. The stationary grain charge as well as the field within the sheath around the grain are shown to be almost independent of the type of boundary conditions (for relatively low ionization rates and small grain sizes), whereas the asymptotical behavior of the effective field is rather sensitive to them.


Quality attributes and composition of meat from red deer (Cervus elaphus), fallow deer (Dama dama) and Aberdeen Angus and Holstein cattle (Bos taurus).
The consumption of venison from deer species has increased in recent years owing to presumably positive health effects. Therefore a comparison was made of the physical characteristics, chemical composition and sensory attributes of meat obtained from red deer, fallow deer and Aberdeen Angus and Holstein cattle raised under conditions typical for commercial farming practice and slaughtered at similar ages. Venison had one-quarter the crude fat content, lower total collagen and a higher proportion of heat-soluble collagen. It was darker and less yellow than beef. Deer species provided meat with higher polyunsaturated/saturated fatty acid ratio and lower atherogenic index. In addition, the venison of red deer contained five times as much n-3 polyunsaturated fatty acids as the beef. Steaks prepared from venison were scored higher than beef for flavour and aroma intensity; they were also tenderer and more easily chewable. Compared with beef, venison from two widely farmed deer species was superior in nutrient composition, thus offering potential benefits for human consumption, and it received higher scores for most of the sensory attributes examined.


Increasing proportion of herpes simplex virus type 1 as a cause of genital herpes infection in college students.
A retrospective review of genital herpes simplex virus (HSV) isolates collected in a university student health service over a 9-year period showed that an increasing proportion of isolates were HSV-1 rather than HSV-2. HSV-1 accounted for 78% of all genital isolates in this population by 2001, compared with 31% of isolates in 1993. Herpes simplex virus (HSV) type 1 is usually thought to cause less than 30% of genital herpes infections in the United States, but the proportion of infections resulting from HSV-1 is increasing in some populations. The goal was to review the relative proportion of HSV-1 and HSV-2 as the cause of newly diagnosed genital herpes infections in a population of U.S. college students and to assess trends in the change of this proportion over time. Genital HSV isolates collected at a university student health service from 1993 to 2001 (n = 499) were reviewed retrospectively. Analyses included comparisons of isolates by HSV type, age group, and sex. The proportion of newly diagnosed genital herpes infections resulting from HSV-1 increased from 31% in 1993 to 78% in 2001 (P <0.001, linear trend P <0.001). HSV-1 was more common in females than males, but increases were noted for both sexes. HSV-1 was more common in persons aged 16 to 21 than in persons aged 22 or older. HSV-1 has become the most common cause of newly diagnosed genital herpes infections in this population of college students and reflects a reversal of the usual HSV-1/HSV-2 ratio.


Risk factors for low birth-weight in areas with varying malaria transmission in Korogwe, Tanzania: implications for malaria control.
Low birth weight (LBW) is a risk factor for infant mortality, morbidity, growth retardation, poor cognitive development, and chronic diseases. Maternal exposure to diseases such as malaria, HIV, and syphilis has been shown to have a significant impact on birth weight (BW). This study was aimed at determining whether there was a difference in rates of LBW in areas of varying malaria transmission intensity in Korogwe, Tanzania. Retrospective data for one year (June 2004-May 2005) in three maternal and child health (MCH) clinics in the district were analysed. Villages were stratified into three strata: lowlands-semi urban (average altitude of 320m), lowlands-rural (below 600m) and highlands (> or =600m). There was a significant decreasing trend of rate of LBW from rural lowlands to highlands (chi2trend = 7.335, P=0.007). Adjusting for covariates, women in parity-two were at reduced risk of delivering LBW babies compared to first parity women (OR=0.44, 95% CI 0.19-0.98, P=0.045). Similarly, the risk of LBW was higher in women who had delayed MCH gestational booking and in women who conceived during high malaria transmission seasons. There was high degree of preference of digits ending with 0/5 in reporting BW in the studied MCHs. In conclusion, a rate of LWB was high in rural lowlands where malaria is also endemic, and was associated with high malaria transmission seasons.


Folliculocystic and Collagen Hamartoma: A Distinct Hamartoma Associated With Tuberous Sclerosis Complex.
Tuberous sclerosis complex (TSC) is a neurocutaneous disease characterized by cutaneous and extracutaneous hamartomas. Dermatologic evaluation is critical for early diagnosis because mucocutaneous manifestations account for 4 of 11 major and 3 of 6 minor diagnostic criteria. Folliculocystic and collagen hamartoma (FCCH) is a recently described entity associated with TSC. We herein describe the case of a 28-year-old woman with a history of TSC who presented with a scalp lesion present since childhood. Physical examination revealed a solitary, well-circumscribed exophytic tumor over the occipital scalp measuring 9 × 8 cm and covered with comedones and cyst-like structures. Biopsy of the lesion demonstrated thickening of the collagen bundles throughout the dermis, concentric perifollicular and perivascular fibrosis, an increased number of dilated vessels, and keratin-filled cysts lined by the infundibular epithelium. Clinicopathologic correlation was diagnostic for FCCH. The patient was referred for surgical excision. In addition, we review 11 other cases of FCCH previously reported in the literature.


Effect of tobacco smoking and smoking cessation on plasma lipoproteins and associated major cardiovascular risk factors: a narrative review.
Cigarette smoking, active or passive, kills about 6 million people each year worldwide. Cardiovascular disease (CVD) is responsible for 40% of all smoking-related deaths, lung cancer accounts for 20% of all smoking-related deaths, and chronic obstructive pulmonary disease is related to another 20% of deaths. In this narrative review we consider the relationship between cigarette smoking and CVD. We discuss disease states and/or CVD risk factors related to smoking, such as dyslipidaemia, vascular inflammation, endothelial dysfunction, arterial stiffness, insulin resistance, type 2 diabetes mellitus (T2DM), chronic kidney disease (CKD), and non-alcoholic fatty liver disease (NAFLD) as well as their complex interrelations. Smoking cessation can correct abnormalities related to smoking; however, success rates are relatively low. In cases of inability to quit, measures to minimize the adverse effects of smoking specifically related to CVD should be taken. Smokers should receive best practice treatment, according to guidelines, as for non-smokers.


Sweat conductivity diagnostic accuracy for cystic fibrosis: a systematic review and meta-analysis.
We conducted a systematic review and meta-analysis of diagnostic test accuracy studies to summarise the properties of sweat conductivity (SC) to rule in/out cystic fibrosis (CF). We searched PubMed, Embase, Web of Science, Google Scholar, SciELO and LILACS up to 13 March 2023. We selected prospective and retrospective diagnostic test accuracy studies which compared SC, measured through two well-established and commercially available devices, that is, Nanoduct or Sweat-Chek Analyser, to quantitative measurement of sweat chloride. Pooled sensitivity, specificity, positive likelihood ratio (+LR) and negative likelihood ratio (-LR), and their corresponding 95% CIs. The Preferred Reporting Items for a Systematic Review and Meta-analysis of Diagnostic Test Accuracy Studies guidelines were followed. Data were extracted by one reviewer and checked by another. The hierarchical summary receiver operating characteristics model was used to estimate diagnostic test accuracy. Ten studies involving 8286 participants were included. The pooled estimates of sensitivity, specificity, +LR and -LR were 0.97 (95% CI 0.94 to 0.98), 0.99 (95% CI 0.98 to 0.99), 171 (95% CI 58 to 500) and 0.02 (95% CI 0.01 to 0.05), respectively. Sensitivity analyses did not reveal a substantial impact of study-level factors on the results, such as study quality, cut-off values for a positive test, study sample size and participant age group. The quality of evidence was considered moderate. SC demonstrated excellent diagnostic performance. In addition, its accuracy parameters suggest its role as an alternative to the sweat test for CF diagnosis. CRD42022284504.


Spontaneous baroreflex sensitivity: toward an ideal index of cardiovascular risk in hypertension?
Estimating the risk entailed by classical risk factors like blood pressure (BP) or serum cholesterol may be difficult because of their variability and the often unknown duration of exposure. Having variables integrating the impact of those classical risk factors on the cardiovascular system would probably aid the prediction of cardiovascular events. The present study aimed at determining whether cardiac baroreflex sensitivity (BRS), correlates with several risk factors and thus is a good candidate for being such an integrative variable. As a comparison, left ventricular mass (LVM), pulse wave velocity (PWV), and creatinine were also tested for association with risk factors. A total of 302 subjects referred for hypertension, were considered. They had a 24-h BP recording and a determination of BRS by two different methods (sequence and alpha coefficient), in two different positions (lying and standing). They were also tested for the presence of left ventricular hypertrophy (LVH) (by echocardiography and electrocardiogram) and had a PWV measurement. Biological testing included serum lipids, blood glucose, creatinine, proteinuria and urinary excretion of microalbumin. There was a strong correlation between the two methods of BRS measurement in each position (P < 0.001). BRS determined by the sequence method in the lying position was correlated significantly and independently with age, 24-h systolic BP, heart rate, and serum cholesterol with P values < 0.001, < 0.001, < 0.01, and < 0.05, respectively. In an univariate analysis, BRS was also correlated with echocardiographic LVM index (r = -0.21, P < 0.05) and PWV (r = -0.27, P < 0.001), which possibly reflects its dependence on both vascular and cardiac damages. The present study supports the hypothesis that BRS could encompass the impact over time of several risk factors on the cardiovascular system. Thus, it may constitute a valuable parameter in assessing more precisely the risk of cardiovascular events.


CT assessment of operability in carcinoma of the oesophagogastric junction.
25 patients with adenocarcinoma of the oesophagogastric junction were evaluated preoperatively with thoracoabdominal computed tomography (CT). Despite limitations mainly in differentiating intramural from early extramural tumour growth and in predicting peritoneal carcinomatosis, CT was useful in determining local and distant spread of the malignancy and in assessing surgical resectability. CT may identify candidates for palliative procedures such as oesophageal intubation, radiation therapy or chemotherapy by demonstrating inoperability thus avoiding unnecessary surgery. CT should be performed routinely in all patients with carcinoma of the oesophagogastric junction.


Health funders' dissemination and implementation practices: results from a survey of the Ensuring Value in Research (EViR) Funders' Forum.
A significant gap persists between evidence from research and its use in practice. Research funders, important actors in the health research system, can help reduce this gap by initiating dissemination and implementation (D&I) activities. The specific types of D&I activities funders currently lead have not been explored thoroughly. The Ensuring Value in Research (EViR) Funders' Forum-an international collaboration of health-related research funders-was established in 2017 to address research waste issues and increase the value of research. The Forum surveyed funders to learn about their D&I practices and challenges. We distributed a five-item exploratory survey to participating funders in August 2018. The results informed the development of a survey instrument, distributed in June 2019. The survey instrument contained 15 items prompting respondents to categorize and describe their level of effort in six practice areas: release of findings, dissemination, knowledge exchange/partnering, implementation, building capacity, and implementation research. In addition, funders were asked to describe examples of their practices in detail. Thirty-one funders completed the survey instrument, a 58% response rate. Most funders regard D&I as a high priority, but funders vary in levels of activity per practice area. Over half of respondents reported that they have at least some activity in all D&I practice areas surveyed, with the exception of implementation research. The vast majority indicated some or significant activity in release of findings (97%) and dissemination (87%). Nearly one-fifth of funders (19%) indicated that implementation is outside their remit, and 26% indicated that implementation research is outside their remit. Survey respondents shared a broad range of examples of activities in each practice area. Lack of evidence for successful approaches and measuring impact were named frequently as challenges and as potential areas for collaboration. Although models of dissemination and implementation vary across organizations, the majority of funders indicated that D&I of research findings is a priority. Funders indicated a need for evidence on effectiveness of various approaches to D&I. Increased collaboration between funders, including sharing good practices, will increase our collective learning and knowledge development.


Effects of early prenatal exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) on postnatal reproduction in the laying hen (Gallus gallus).
This study demonstrates the long-term effects of very early embryonic exposure to a single dose of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) (0, 10 and 20 ng/egg), administered before the beginning of embryonic development, on growth and reproductive performance in laying hens. Hatchability and body weight gain from 11 weeks onwards were significantly depressed in 20 ng treated hens. All hens started laying egg at around the same age and the laying performance of TCDD-treated hens was normal. No disturbances in the age-related pattern and concentrations of oestradiol, LH or FSH in plasma could be found but mean progesterone concentrations were significantly lower in 20 ng treated hens. Moreover, follicular distribution was changed with less small white follicles and smaller yellow follicles, which probably resulted in the lower egg weight of the 20 ng treated hens. At 43 weeks of age, hens treated in ovo with TCDD showed a retained right oviduct, mostly filled with clear fluid. From these results, it seems that in ovo exposure to TCDD interferes in the right oviduct regression during embryonic development and induces some changes in follicular distribution but without impairment of reproductive performance in the adult laying hen.


"Just not all ice users do that": investigating perceptions and potential harms of Australia's Ice Destroys Lives campaign in two studies.
In 2015, the Australian government launched the media campaign Ice Destroys Lives targeting crystal methamphetamine use. Previous research indicates mass media campaigns may have harmful effects for people engaged in drug use. This study investigated perceptions and harms of Ice Destroys Lives among adults with a history of injecting drugs and young people. This analysis includes data from two studies: an online questionnaire with young people and in-depth interviews with adults who use crystal methamphetamine. Young people from Victoria, Australia, were recruited through Facebook. We collected data on drug use, campaign recognition and behaviours. Participants who recognised the campaign indicated whether they agreed with five statements related to Ice Destroys Lives. We compared campaign perceptions between young people who reported ever using crystal methamphetamine and those who did not. Adults who use crystal methamphetamine were sampled from the Melbourne injecting drug user cohort study. We asked participants if they recognised the campaign and whether it represented their experiences. One thousand twenty-nine young people completed the questionnaire; 71% were female, 4% had used crystal methamphetamine and 69% recognised Ice Destroys Lives. Three quarters agreed the campaign made them not want to use ice. Ever using crystal methamphetamine was associated with disagreeing with three statements including this campaign makes you not want to use ice (adjusted odds ratio (AOR) = 4.3, confidence interval (CI) = 1.8-10.0), this campaign accurately portrays the risks of ice use (AOR = 3.2, CI = 1.4-7.6) and this campaign makes you think that people who use ice are dangerous (AOR = 6.6, CI = 2.2-19.8). We interviewed 14 people who used crystal methamphetamine; most were male, aged 29-39 years, and most recognised the campaign. Participants believed Ice Destroys Lives misrepresented their experiences and exaggerated "the nasty side" of drug use. Participants felt the campaign exacerbated negative labels and portrayed people who use crystal methamphetamine as "violent" and "crazy". In our study, Ice Destroys Lives was widely recognised and delivered a prevention message to young people. However, for people with a history of crystal methamphetamine use, the campaign also reinforced negative stereotypes and did not encourage help seeking. Alternative evidence-based strategies are required to reduce crystal methamphetamine-related harms.


[Structure-activity relationships applied to quinoxaline-1,4-dioxides].
Studies on structure-activity relationships applied to quinoxaline 1,4-dioxides were performed on the basis of Hansch analysis. It could be demonstrated that correlations exist between MIC values (Escherichia coli) and physicochemical parameters. On the other hand, correlations were also found between nutritive effects determined on chicken and structural parameters. The results obtained could be confirmed by means of Free-Wilson analysis.


Novel p-wave superfluids of fermionic polar molecules.
Recently suggested subwavelength lattices offer remarkable prospects for the observation of novel superfluids of fermionic polar molecules. It becomes realistic to obtain a topological p-wave superfluid of microwave-dressed polar molecules in 2D lattices at temperatures of the order of tens of nanokelvins, which is promising for topologically protected quantum information processing. Another foreseen novel phase is an interlayer p-wave superfluid of polar molecules in a bilayer geometry.


Novel fluoranthene structure for deep-blue organic light-emitting diodes.
As a new fluoranthene derivative, a synthesis of benzo[k]fluoranthene was suggested, so new blue emitting materials, 7,12-diphenylbenzo[k]fluoranthene [DPBF] and 7,8,10-triphenylfluoranthene [TPF] were synthesized. PLmax values of both compounds showed the wavelengths of 458 nm (TPF) and 434 nm, 453 nm (DPBF) that are in blue region. ELmax wavelength of the device using DPBF as an emitting layer was 436 and 454 nm in the deep-blue region, which are similar values with PL. The device that used DPBF as an emitting layer showed high efficiency of 2.11 cd/A and the excellent color coordinate value of (0.161, 0.131) in deep-blue region.


Tautomerization in naphthalenediimines: a keto-enamine Schiff base macrocycle.
[reaction: see text] A new [3 + 3] Schiff base macrocycle incorporating naphthalene groups has been prepared. By examination of its properties, X-ray crystallography of model compounds, and calculations, it has been determined that the macrocycle exists predominantly as the keto-enamine tautomer. This unexpected tautomerization presents an unusual hexaketo interior in the macrocycle.


Association of SNP of neuropeptide Y, leptin, and IGF-1 genes with residual feed intake in confinement and under grazing condition in Angus cattle.
In this study we quantify and compare the phenotypic variation in residual feed intake (RFI) in 2 groups of Angus female calves: one carrying simultaneously putative favorable allelic variants (SNP) of neuropeptide Y, leptin, and IGF-1 genes (VAL group) and another devoid of such alleles (CON group). We performed 2 sequential trials: under confinement feeding a high-concentrate diet and under grazing condition. In confinement, 38 purebred Angus female calves [mean age and BW of 247 d (SD = 15) and 186 kg (SD = 33.2), respectively] were offered a total mixed ration diet (60:40 concentrate: alfalfa hay, as fed) ad libitum during 57 d. Dry matter intake was estimated from the difference between offered and refused feed; BW was recorded every 2 wk. Under grazing, 12 heifers from each group were ranked by BW and RFI and randomly assigned to 4 pasture paddocks. Heifers were continuously stocked at high-quality, high-herbage-mass mixed pasture. Herbage DMI was determined using the n-alkane technique. Different models were used to determine RFI: models that use phenotypic data [RFI as described by Koch et al. (1963; RFIK) and RFI as described by ME (RFIME)] and models that use standards feeding data [RFI estimated by Fan et al. (1995; RFIF) and RFI in which the expected DMI was derived from equations in Standing Committee on Agriculture (1990; RFISCA)]. Least squares mean values (SE) of DMI (kg/d), metabolizable energy intake (MEI; Mcal/d), ADG (kg), RFIK (kg DM/d), and feed conversion ratio (FCR; kg DMI/kg ADG) for VAL and CON genotype groups were 6.65 and 6.89 (0.49), 16.7 and 17.4 (1.44), 1.24 and 1.24 (0.03), -0.11 and 0.11 (0.09), and 5.8 and 5.8 (0.14), respectively, in the confinement trial. In the grazing trial least squares mean values (SE) of herbage DMI (kg/d), ADG (kg), MEI (Mcal/d), RFIK, and FCR of VAL and CON groups were 8.76 and 10.93 (0.71), 1.4 and 1.37 (0.05), 25.5 and 31.7 (2.09), -1.02 and 1.02 (0.42), and 6.41 and 6.96 (0.46), respectively. Genotyped groups tended to differ in DMI (P = 0.10), in MEI (P = 0.06), and in RFIK (P = 0.10), differed in RFIF (P = 0.010), and did not differ in ADG or FCR during confinement. During grazing, genotyped groups differed in DMI (P = 0.005), in MEI (P = 0.006), and in RFIK (P = 0.002) but did not differ in ADG and FCR. Our results demonstrate a strong association between these 3 SNP and RFI when animals were grazing on a high-quality, high-availability pasture, whereas a weak effect was observed under confinement.


Alpha-2 adrenoreceptors mediate clonidine-induced hypoinsulinaemia in sheep.
Insulin and glucose concentrations in the blood of sheep were measured before, and up to 7 h after, feeding. The patterns reported by other workers were confirmed, namely: an early insulin concentration peak and decline in glucose concentration and, later, more prolonged changes. Intravenous injection of clonidine (2 micrograms/kg or 5 micrograms/kg) just before offering food caused hypoinsulinaemia and hyperglycaemia, abolishing the normal patterns. Administration of idazoxan (0.1 mg kg-1), an alpha-2 adrenoreceptor antagonist, before a 2 micrograms/kg dose of clonidine, completely blocked the effects of clonidine. By contrast, with prior injection of prazosin (0.1 mg/kg), an alpha-1 adrenoreceptor antagonist, the hypoinsulinaemia in response to clonidine still occurred and the hyperglycaemia appeared to be enhanced. The antagonists injected alone had only slight effects: idazoxan caused a slight hypoglycaemia and prazosin a slight hyperglycaemia. The results indicate that clonidine causes hypoinsulinaemia and hyperglycaemia by action on alpha-2 receptors. Possible mechanisms are discussed.


Effect of TGF-β/smad signaling pathway blocking on expression profiles of miR-335, miR-150, miR-194, miR-27a, and miR-199a of hepatic stellate cells (HSCs).
The aim of this study was to determine the effect of inhibition of TGF-β/smad signaling on the expression profiles of miR-335, miR-150, miR-194, miR-27a, miR-199a of hepatic stellate cells (HSCs). Liver fibrosis is excessive deposition of extracellular matrix proteins due to ongoing inflammation and HSC activation that occurs in most types of chronic liver diseases. Recent studies have shown the importance of microRNAs in the pathogenesis of chronic liver diseases. In this study, for inhibition of TGF-β smad-signaling pathway, expressing Smad4 shRNA plasmids were transfected into HSCs. Subsequently, using Real Time-PCR, we measured the expression levels of miR-335, miR-150, miR-194, miR-27a and miR-199a. Gene expression analysis showed that downregulation of Smad4 by vector Smad4shRNA significantly increased the expression levels of miR-335 (P<0.01) and miR-150 (P<0.001) and decreased the expression level of miR-27a (P<0.05). The results of this study suggest that blocking TGF-β smad-signaling can also differentially modulate microRNA expression in support of activation and fibrogenesis of HSCs.


Somatic and autonomic nerve function during the first year after diagnosis of type 1 (insulin-dependent) diabetes.
Somatic and autonomic nerve function was assessed by motor and sensory nerve conduction velocities (MNCV; SNCV), beat-to-beat variation at rest, speed of pupillary dilation, and pupillary latency time in 35 newly diagnosed type 1 diabetic patients aged 12-36 years. The nerve function tests were performed 18 +/- 2 (mean +/- SEM) days after the correction of initial ketosis and hyperglycaemia and again after 3 and 12 months of insulin therapy. Mean HbA1 levels of months 3 and 12 within the normal range less than 8.6% (mean: 7.2 +/- 0.2%) were observed in 24 patients (group 1) and greater than or equal to 8.6% (mean: 10.1 +/- 0.6%) in 11 patients (group 2). Group 1 showed no significant changes from baseline in the mean nerve conduction and autonomic functions after 3 and 12 months. In group 2 there was no change until three months, however, at 12 months there was a significant decrease in mean MNCV in the median, ulnar and peroneal nerves (p less than 0.05) and in mean SNCV in the median (p less than 0.05) and sural nerves (p less than 0.01), when compared to the baseline values. The autonomic function tests remained unchanged. No patient had symptoms of neuropathy during the period studied. These findings suggest that the deterioration of motor and sensory nerve conduction precedes that of cardiac and pupillary autonomic function in poorly controlled asymptomatic type 1 diabetic patients during the first year of the disease. Effective glycaemic control prevented progression of subclinical neuropathy, but did not reverse abnormalities which were present at diagnosis.


Reliable generation of induced pluripotent stem cells from human lymphoblastoid cell lines.
Patient-specific induced pluripotent stem cells (iPSCs) hold great promise for many applications, including disease modeling to elucidate mechanisms involved in disease pathogenesis, drug screening, and ultimately regenerative medicine therapies. A frequently used starting source of cells for reprogramming has been dermal fibroblasts isolated from skin biopsies. However, numerous repositories containing lymphoblastoid cell lines (LCLs) generated from a wide array of patients also exist in abundance. To date, this rich bioresource has been severely underused for iPSC generation. We first attempted to create iPSCs from LCLs using two existing methods but were unsuccessful. Here we report a new and more reliable method for LCL reprogramming using episomal plasmids expressing pluripotency factors and p53 shRNA in combination with small molecules. The LCL-derived iPSCs (LCL-iPSCs) exhibited identical characteristics to fibroblast-derived iPSCs (fib-iPSCs), wherein they retained their genotype, exhibited a normal pluripotency profile, and readily differentiated into all three germ-layer cell types. As expected, they also maintained rearrangement of the heavy chain immunoglobulin locus. Importantly, we also show efficient iPSC generation from LCLs of patients with spinal muscular atrophy and inflammatory bowel disease. These LCL-iPSCs retained the disease mutation and could differentiate into neurons, spinal motor neurons, and intestinal organoids, all of which were virtually indistinguishable from differentiated cells derived from fib-iPSCs. This method for reliably deriving iPSCs from patient LCLs paves the way for using invaluable worldwide LCL repositories to generate new human iPSC lines, thus providing an enormous bioresource for disease modeling, drug discovery, and regenerative medicine applications.


[Inflammatory glaucomas].
The prevalence of glaucoma in patients with intra- or extraocular inflammation is five to twenty percent. The etiopathogenesis is manifold, including classical secondary open and closed angle mechanisms as well as specific inflammatory elements. Diagnosis and follow-up studies of inflammatory glaucomas are often difficult. The therapeutic options are limited or are poorly evaluated. The development of a secondary glaucoma is a severe complication of intra- or extraocular inflammation and may even lead to blindness. Further investigations, especially with regard to the treatment of inflammatory glaucomas, are necessary to improve the prognosis.


Unequal death in T helper cell (Th)1 and Th2 effectors: Th1, but not Th2, effectors undergo rapid Fas/FasL-mediated apoptosis.
T helper cell (Th) 1, but not Th2, effectors undergo rapid Fas/Fas ligand (FasL)-mediated, activation-induced cell death upon restimulation with antigen. Unequal apoptosis is also observed without restimulation, after a longer lag period. Both effectors undergo delayed apoptosis induced by a non-Fas-mediated pathway. When Th1 and Th2 effectors are co-cultured, Th2 effectors survive preferentially, suggesting the responsible factor(s) is intrinsic to each population. Both Th1 and Th2 effectors express Fas and FasL, but only Th2 effectors express high levels of FAP-1, a Fas-associated phosphatase that may act to inhibit Fas signaling. The rapid death of Th1 effectors leading to selective Th2 survival provides a novel mechanism for differential regulation of the two subsets.


More than little fragments of matter: Electronic and molecular structures of clusters.
Small clusters have captured the imaginations of experimentalists and theorists alike for decades. In addition to providing insight into the evolution of properties between the atomic or molecular limits and the bulk, small clusters have revealed a myriad of fascinating properties that make them interesting in their own right. This perspective reviews how the application of anion photoelectron (PE) spectroscopy, typically coupled with supporting calculations, is particularly well-suited to probing the molecular and electronic structure of small clusters. Clusters provide a powerful platform for the study of the properties of local phenomena (e.g., dopants or defect sites in heterogeneous catalysts), the evolution of the band structure and the transition from semiconductor to metallic behavior in metal clusters, control of electronic structures of clusters through electron donating or withdrawing ligands, and the control of magnetic properties by interactions between the photoelectron and remnant neutral states, among other important topics of fundamental interest. This perspective revisits historical, groundbreaking anion PE spectroscopic finding and details more recent advances and insight gleaned from the PE spectra of small covalently or ionically bound clusters. The properties of the broad range of systems studied are uniquely small-cluster like in that incremental size differences are associated with striking changes in stability, electronic structures, and symmetry, but they can also be readily related to larger or bulk species in a broader range of materials and applications.


Implication of arginyl residues in mRNA binding to ribosomes.
Modification of Escherichia coli robosomes with phenylglyoxal and butanedione, protein reagents specific for arginyl residues, inactivates polypeptide polymerization, assayed as poly(U)-dependent polyphenylalanine synthesis, and the binding of poly(U). Inactivation is produced by modification of the 30-S subunit. Both the RNA and the protein moieties of 30-S subunits are modified by phenylglyoxal, and modification of either of them is accompanied by inactivation of polypeptide synthesis. Modification of only the split proteins released from 30-S subunits by prolonged dialysis against a low-ionic-strength buffer, which contain mainly protein S1, produces inhibition of poly(U) binding and inactivation of polypeptide synthesis. Amino acid analysis of the modified split proteins showed a significant modifications of arginyl residues. These results indicate that the arginyl residues of a few 30-S proteins might be important in the interaction between mRNA and the 30-S subunit, which agrees with the general role assigned to the arginyl residues of proteins as the positively charged recognition site for anionic ligands.


The novel protein ScrA acts through the SaeRS two-component system to regulate virulence gene expression in Staphylococcus aureus.
Staphylococcus aureus is a Gram-positive commensal that can also cause a variety of infections in humans. S. aureus virulence factor gene expression is under tight control by a complex regulatory network, which includes, sigma factors, sRNAs, and two-component systems (TCS). Previous work in our laboratory demonstrated that overexpression of the sRNA tsr37 leads to an increase in bacterial aggregation. Here, we demonstrate that the clumping phenotype is dependent on a previously unannotated 88 amino acid protein encoded within the tsr37 sRNA transcript (which we named ScrA for S. aureus clumping regulator A). To investigate the mechanism of action of ScrA we performed proteomics and transcriptomics in a ScrA overexpressing strain and show that a number of surface adhesins are upregulated, while secreted proteases are downregulated. Results also showed upregulation of the SaeRS TCS, suggesting that ScrA is influencing SaeRS activity. Overexpression of ScrA in a saeR mutant abrogates the clumping phenotype confirming that ScrA functions via the Sae system. Finally, we identified the ArlRS TCS as a positive regulator of scrA expression. Collectively, our results show that ScrA is an activator of the SaeRS system and suggests that ScrA may act as an intermediary between the ArlRS and SaeRS systems.


Clinical Challenges in Resection and Reconstruction of a Verrucous Carcinoma of the Right Calcaneus With a Medial Plantar Artery Perforator Flap: A Case Report.
A verrucous carcinoma is a rare, low-grade variant of a well-differentiated squamous cell carcinoma (SCC). It frequently occurs in Caucasian males aged 50 to 60. The tumour is locally destructive, grows into muscle, nerves and bones, but rarely metastasizes. Here we report a patient with verrucous carcinoma on the right calcaneus with the uncommon symptom of a haemorrhagic plaque at the centre and also an exophytic component. A 52-year-old man presented with a 10-year-old, progressive, painful, pruritic, exophytic growing, hyperkeratotic and haemorrhagic plaque of 5.2 x 3.5cm on the right calcaneus. The lesion emerged after extensive burns after blast trauma as a child. Excisional biopsy with 2mm margin in combination with clinical presentation favoured a verrucous carcinoma. The pathology report showed that the tumour was not excised radically; therefore, re-excision with 5mm margin was required and was performed two months later. The wound was closed with a medial plantar artery perforator (MPAP) flap. The donor site was closed with a full-thickness skin graft (FTSG) from the medial side of the right upper leg and was covered by a tie-over bandage. Verrucous carcinoma is a rare tumour and can be adequately surgically treated by excision with clear margins. In this case, the verrucous carcinoma of the right calcaneus was excised and reconstructed with an MPAP flap with decent results, despite a challenging postoperative course.


Using e-health in perioperative care: a survey study investigating shortcomings in current perioperative care and possible future solutions.
An e-health care program has previously shown to have a positive effect on return to work, quality of life and pain in patients who underwent gynaecological surgery. Plausibly, providing the care program to a population undergoing other types of surgery will be beneficial as well. The objectives of this study are to evaluate patients' opinions, needs and preferences regarding the information and guidance supplied to patients during the perioperative period, to investigate whether e-health may be of assistance and to explore if gender specific needs exist. A questionnaire was sent to all patients between 18 and 75 years (n = 362), who underwent various forms of abdominal surgery between August 2013 to September 2014 in a university hospital in the Netherlands. The questionnaire contained questions about the current situation in perioperative care and questions about patients' preferences in an e-health care program. Gender differences were evaluated. Two hundred seven participants (57.2%) completed the survey. The majority of the participants were relatively satisfied with the perioperative care they received (68.6%). Most reported shortcomings in perioperative care concerning the supply of information regarding the resumption of activities and guidance during the recovery course. An e-health care program was expected to be of added value in perioperative care by 78% of the participants; a website was reported as most useful. In particular practical functions on a website focusing on the preparation to surgery and monitoring after surgery were appraised to be highly valuable. Overall, women had slightly more needs for extra information and support during the perioperative course than men. In abdominal surgery, there is a need for an e-health care program, which should focus mainly on the supply of information about the resumption of activities as well as guidance in the postoperative course.