An early life hypoxia event has a long-term impact on protein digestion and growth in juvenile European sea bass.
Ocean warming, eutrophication and the consequent decrease in oxygen lead to smaller average fish size. Although such responses are well known in an evolutionary context, involving multiple generations, this appears to be incompatible with current rapid environmental change. Instead, phenotypic plasticity could provide a means for marine fish to cope with rapid environmental changes. However, little is known about the mechanisms underlying plastic responses to environmental conditions that favour small phenotypes. Our aim was to investigate how and why European sea bass that had experienced a short episode of moderate hypoxia during their larval stage subsequently exhibited a growth depression at the juvenile stage compared with the control group. We examined whether energy was used to cover higher costs for maintenance, digestion or activity metabolisms, as a result of differing metabolic rate. The lower growth was not a consequence of lower food intake. We measured several respirometry parameters and we only found a higher specific dynamic action (SDA) duration and lower SDA amplitude in a fish phenotype with lower growth; this phenotype was also associated with a lower protein digestive capacity in the intestine. Our results contribute to the understanding of the observed decrease in growth in response to climate change. They demonstrate that the reduced growth of juvenile fishes as a consequence of an early life hypoxia event was not due to a change of fish aerobic scope but to a specific change in the efficiency of protein digestive functions. The question remains of whether this effect is epigenetic and could be reversible in the offspring.


Effect of exogenous ammonium gluconate on growth, ion flux and antioxidant enzymes of maize (Zea Mays L.) seedlings under NaCl stress.
Ammonium gluconate (AG) provides both an organic carbon source and a nitrogen source, which can positively improve soil fertility and delay soil degradation. We investigated the underlying mechanisms of both NH4 + - and C6 H11 O7 - -mediated resistance to high salt concentrations in maize (Zea mays L.), and how they relate to antioxidant cellular machinery, root system architecture, root activity and lignin content in roots. Seedlings treated with AG maintained lower Na+ content, higher chlorophyll content, higher CAT and POD activity, compared with those without AG and ammonium carbonate (AC). The total size of the root system, primary root length and number of lateral roots detected on the primary root treated with AG decreased compared with those not treated with AG at the same NaCl concentration. However, average root diameter and root activity when treated with AG were significantly higher than roots without AG at the same NaCl concentration. Furthermore, total size of the root system, primary root length and number of lateral roots detected on primary rootsof seedlings treated with AG were higher than those treated with AC at the same NaCl concentration. These results suggested that AG may be a good organic fertiliser under salt stress by decreasing Na+ content and increasing chlorophyll content, activity of antioxidant enzymes, root diameter and root activity in maize seedlings.


[Personnel and bed supplies for Occupational Diseases Centers in Russian Federation].
The author presents calculations of required quantities of beds and staffers for Occupational Diseases Centers. Those calculations are based on scientific norms concerning activities of doctors in the Centers and number of staffers exposed to work conditions that do not meet sanitary and hygienic regulations on Russian Federation territory. Evidence is that most territories face actual staffers and beds numbers much lower than quantities necessary for effective occupational medical care.


CD169 is a marker for highly pathogenic phagocytes in multiple sclerosis.
Phagocytes, such as macrophages and microglia, are key effector cells in the pathophysiology of multiple sclerosis (MS). It is widely accepted that they instigate and promote neuroinflammatory and neurodegenerative events in MS. An increasing amount of studies indicate that Siglec-1, also known CD169, is a marker for activated phagocytes in inflammatory disorders. In this study, we set out to define how CD169+ phagocytes contribute to neuroinflammation in MS. CD169-diphtheria toxin receptor (DTR) mice, which express human DTR under control of the CD169 promoter, were used to define the impact of CD169+ cells on neuroinflammation. Flow cytometry and immunohistochemistry were utilized to determine the expression and distribution of CD169. We show that CD169 is highly expressed by lesional and circulating phagocytes in MS and experimental autoimmune encephalomyelitis (EAE). Our data further indicate that CD169 represents a selective marker for early activated microglia in MS and EAE lesions. Depletion of CD169+ cells markedly reduced neuroinflammation and ameliorated disease symptoms in EAE-affected mice. Our findings indicate that CD169+ cells promote neuroinflammation. Furthermore, they suggest that CD169+ phagocytes play a key role in the pathophysiology of MS. Hence, targeting CD169+ phagocytes may hold therapeutic value for MS.


Post-traumatic bony impingement into vagina: a rare cause of urethrovaginal fistula.
A 22-year-old woman met with road traffic accident 6 months back following which she underwent exploratory laparotomy with intraperitoneal bladder rupture repair. She presented with urethrovaginal fistula due to a fragment of fractured pubic bone impinging into the anterior vaginal wall. The findings were confirmed on CT scan and cystoscopy. The patient was managed with removal of the bony spicule and transvaginal repair of urethrovaginal fistula with Martius fat pad interposition.


CYT387, a JAK-Specific Inhibitor Impedes Osteoclast Activity and Oophorectomy-Induced Osteoporosis via Modulating RANKL and ROS Signaling Pathways.
Osteoclasts are of hematopoietic lineage and have the ability to degrade mineralized bone tissues. Abnormalities in osteoclastic activity under certain pathological conditions are common in bone diseases such as osteoporosis, osteosclerosis, and arthritis. Although many kinds of drugs are currently used to treat osteoporosis, they have obvious adverse reactions and limitations. CYT387 is a new small-molecule Janus kinase (JAK) inhibitor involved in hematopoiesis, immune modulation, fertility, lactation, and embryonic development. However, it has remained unclear whether CYT387 functionally impacts osteoclast formation. Our study demonstrated through osteoclast formation assay in vitro, that the use of CYT387 is a potential drug candidate for treating osteoclast-associated bone disease. The effects of CYT387 on osteoclast formation, bone resorption, NFATc1 activation, and especially intracellular ROS levels were investigated in vitro. Further, we examined the preclinical prospects of CYT387 using an oophorectomy (OVX) mouse model of osteoporosis with its anti-osteoclast activity in vivo. On the whole, this study shows that CYT387 holds promise for treating osteoclast-related bone illnesses including osteoporosis.


CD154 is expressed during treatment with calcineurin inhibitors after organ transplantation.
CD154 (CD40 ligand) monoclonal antibody prevents allograft rejection in rodents and monkeys. Inasmuch as calcineurin inhibitors (CI) inhibit CD154 expression by pharmacologic agents in vitro, we investigated whether CD154 is also inhibited by CI in vivo and in vitro during allogeneic stimulation. CD154 expression was determined by immunohistochemistry and flow cytometry in human lymph nodes and spleen sections from rhesus monkeys with or without CI treatment. The effect of CI on induction of CD154 expression was studied by stimulating lymphocytes with phorbol 12-myristate 13-acetate (PMA) and ionomycin or with allogeneic monocyte-derived mature dendritic cells. Lymph nodes from patients with or without CI cyclosporine (CsA) or FK506 (FK) treatment showed comparable CD154 expression, which was present on the cell surface of T cells. CD154-expressing cells were also present in spleens from monkeys treated with CsA in comparable numbers to those in the nontreated group. Moreover, in several liver transplant rejection biopsies taken during CI therapy CD154-expressing cells were observed. In vitro, CsA and FK strongly inhibited induction of CD154 expression on peripheral blood mononuclear cells by pharmacologic stimuli. Maximum inhibition was found at 50 ng/ml CsA and 20 ng/ml FK. CD154 expression induced by dendritic cells in peripheral blood mononuclear cells or spleen cells was also almost completely inhibited by CsA. Although CI strongly suppressed pharmacologic and allogeneic induction of CD154 expression on T cells in vitro at concentrations at approximately clinical trough levels, CD154 is prominently expressed during CI therapy in lymphoid tissue and (sporadically) in liver allografts. This suggests that the CD154-CD40 pathway remains functional during CI therapy, which may contribute to allograft rejections in the clinical setting.


Highly preserved consensus gene modules in human papilloma virus 16 positive cervical cancer and head and neck cancers.
In this study, we investigated the consensus gene modules in head and neck cancer (HNC) and cervical cancer (CC). We used a publicly available gene expression dataset, GSE6791, which included 42 HNC, 14 normal head and neck, 20 CC and 8 normal cervical tissue samples. To exclude bias because of different human papilloma virus (HPV) types, we analyzed HPV16-positive samples only. We identified 3824 genes common to HNC and CC samples. Among these, 977 genes showed high connectivity and were used to construct consensus modules. We demonstrated eight consensus gene modules for HNC and CC using the dissimilarity measure and average linkage hierarchical clustering methods. These consensus modules included genes with significant biological functions, including ATP binding and extracellular exosome. Eigengen network analysis revealed the consensus modules were highly preserved with high connectivity. These findings demonstrate that HPV16-positive head and neck and cervical cancers share highly preserved consensus gene modules with common potentially therapeutic targets.


Therapeutic Potential of Date Palm Pollen for Testicular Dysfunction Induced by Thyroid Disorders in Male Rats.
Hyper- or hypothyroidism can impair testicular function leading to infertility. The present study was designed to examine the protective effect of date palm pollen (DPP) extract on thyroid disorder-induced testicular dysfunction. Rats were divided into six groups. Group I was normal control. Group II received oral DPP extract (150 mg kg(-1)), group III (hyperthyroid group) received intraperitoneal injection of L-thyroxine (L-T4, 300 μg kg(-1); i.p.), group IV received L-T4 plus DPP extract, group V (hypothyroid group) received propylthiouracil (PTU, 10 mg kg(-1); i.p.) and group VI received PTU plus DPP extract. All treatments were given every day for 56 days. L-T4 or PTU lowered genital sex organs weight, sperm count and motility, serum levels of luteinizing hormone (LH), follicle stimulating hormone (FSH) and testosterone (T), testicular function markers and activities of testicular 3β-hydroxysteroid dehydrogenase (3β-HSD) and 17β-hydroxysteroid dehydrogenase (17β-HSD). Moreover, L-T4 or PTU increased estradiol (E2) serum level, testicular oxidative stress, DNA damage and apoptotic markers. Morphometric and histopathologic studies backed these observations. Treatment with DPP extract prevented LT4- or PTU induced changes. In addition, supplementation of DPP extract to normal rats augmented sperm count and motility, serum levels of LH, T and E2 paralleled with increased activities of 3β-HSD and 17β-HSD as well as testicular antioxidant status. These results provide evidence that DPP extract may have potential protective effects on testicular dysfunction induced by altered thyroid hormones.


Three-dimensional nasal morphology in cleft lip and palate operated adult patients.
Nasal morphology was assessed three-dimensionally in 18 cleft lip and palate operated patients aged 19 to 27 years, and in 161 sex- and age-matched control subjects. Comparisons were performed by Student t and Watson-Williams' tests. No differences were found in nasal volume or surface. Nasal width, alar base width, and inferior width of the nostrils were significantly larger in male patients than in the reference men. The nasal bridge was shorter. Similar differences were found in the female patients. In addition, the right nostril was larger and the nasal height shorter. In men, the nasolabial and the nasal tip angles were smaller in the patients than in the reference subjects, whereas the facial convexity angle was larger in the patients. In conclusion, the nose of adult operated cleft lip and palate patients differed from that of normal control subjects. Surgical corrections of the cleft lip and palate failed to provide a completely normal appearance. The methods might be used to indicate where additional procedures might be performed to approximate a reference population.


Synthesis and Self-Assembly of Chiral Cylindrical Molecular Complexes: Functional Heterogeneous Liquid-Solid Materials Formed by Helicene Oligomers.
Chiral cylindrical molecular complexes of homo- and hetero-double-helices derived from helicene oligomers self-assemble in solution, providing functional heterogeneous liquid-solid materials. Gels and liotropic liquid crystals are formed by fibril self-assembly in solution; molecular monolayers and fibril films are formed by self-assembly on solid surfaces; gels containing gold nanoparticles emit light; silica nanoparticles aggregate and adsorb double-helices. Notable dynamics appears during self-assembly, including multistep self-assembly, solid surface catalyzed double-helix formation, sigmoidal and stairwise kinetics, molecular recognition of nanoparticles, discontinuous self-assembly, materials clocking, chiral symmetry breaking and homogeneous-heterogeneous transitions. These phenomena are derived from strong intercomplex interactions of chiral cylindrical molecular complexes.


A new method for the classification of invasive cervical cancer screening histories.
To examine the ability of existing classification systems to provide screening histories for invasive cervical cancers which can be used in the evaluation of the NHS Cervical Screening Programme (NHSCSP), and to provide the diagnostic route data item required for the National Cancer Data Set (NCDS). The ability of existing classification systems to derive unique, consistent screening histories for a cohort of invasive cervical cancers diagnosed in the West Midlands region in the period 2000-03 was tested using two separate timelines for women on normal routine recall (usually 3 or 5 years) and those on early recall having had an inadequate, low-grade abnormal or negative smear. Neither of the existing classification systems was capable of adequately categorizing all invasive cervical cancers. An original classification system incorporating features from the existing systems was therefore developed. This system includes both a 'screening status' component that essentially describes the status of a woman's interaction with the NHSCSP at the time her cancer was diagnosed, and a 'screening history' component that describes the results of previous screening tests. National adoption of this new screening histories classification system would provide a detailed, consistent, nationally comparable screening history for all invasive cervical cancers which can be used in the national and regional evaluation of the NHSCSP and in local audit by clinical teams supplemented by histology and colposcopy data. The classification categories could be collapsed down to provide the diagnostic route data item required for the NCDS.


A deficiency in respiratory complex I in heart mitochondria from vitamin A-deficient rats is counteracted by an increase in coenzyme Q.
Defects of NADH:coenzyme Q oxidoreductase (complex I) of mitochondria have been described in many congenital and acquired diseases. Administration of coenzyme Q (CoQ, ubiquinone) has been shown to benefit patients with some of these diseases. However, the mechanisms by which CoQ exerts the therapeutic effects are not clearly understood. A reason could be the lack of saturation of CoQ, in kinetic terms, for complex I activity. However, this hypothesis has not been proved in vivo because of the difficulty to incorporate CoQ into the mitochondrial membranes. We have found a deficiency in respiratory complex I in heart mitochondria from vitamin A-deficient rats which was accompanied by high CoQ content. The defect in complex I activity was compensated by the increase in CoQ to maintain the mitochondrial electron transfer rate. This finding supports, for the first time in an in vivo experimental approach, the kinetic hypothesis to explain the short-term therapeutic effects of CoQ.


Correlation analysis of relationships between vitamin-K-dependent clotting factors and effective hepatic blood flow, albumin and other liver function tests.
Relationships between Normotest, prothrombin time, albumin, gamma-globulin, GPT, and the hepatic fractional clearance of 198Au-colloids as a measure of effective hepatic blood flow were studied by correlation analysis, in 50 patients with liver diseases, including chronic hepatitis or cirrhosis. Simple correlation coefficients were highly significant between Normotest, prothrombin time, albumin, and the hepatic fractional clearance; however, not between GPT or gamma-globulin and the other parameters. Further correlation analysis revealed a highly significant partial correlation coefficient between Normotest and albumin and the hepatic clearance; however, not between Normotest and albumin. As effective hepatic blood flow is considered to be proportional to the liver parenchymal volume, the above results indicate that vitamin-K-dependent clotting factors, as well as albumin, reflect the liver cell mass.


Risk of venous thromboembolism in abdominal versus minimally invasive hysterectomy for benign conditions.
We sought to describe the incidence of venous thromboembolism (VTE) following hysterectomy for benign conditions and to estimate if VTE incidence differs for abdominal and minimally invasive hysterectomy. Data for patients who underwent hysterectomy for benign conditions from 2010 through 2012 were abstracted from the American College of Surgeons National Surgical Quality Improvement Program database. Cases of VTE were compared to those without VTE. Minimally invasive hysterectomy was defined as both vaginal and laparoscopic hysterectomy. Pearson χ2 test, Student t test, and binary logistic regression were used for analysis. A total of 44,167 patients underwent hysterectomy; 12,733 (28.8%) underwent open hysterectomy, 22,559 (51.1%) underwent laparoscopic hysterectomy, and 8875 (20.1%) underwent vaginal hysterectomy. The incidence of VTE for open hysterectomy was higher (0.6%, 81/12,733) than minimally invasive hysterectomy (0.2% 73/31,434, P<.001). Open surgery (P<.001), body mass index (P=.006), race (P<.001), diabetes (P=.037), preoperative functional status (P<.001), American Society of Anesthesiologists class (P<.001), total operative time (P<.001), and time from surgery to discharge (P<.001) were each associated with VTE. Age, hypertension, current smoking, pack-year history, and year operation was performed were not associated with VTE. Using binary logistic regression, open surgery (P<.001), operative time (P<.001), and length of stay (P<.001) remained associated with VTE. The odds ratio for VTE after open hysterectomy compared with minimally invasive hysterectomy was 2.45 (95% confidence interval, 1.77-3.40). In this large quality database, a minimally invasive approach to hysterectomy was independently associated with a decreased incidence of VTE when compared with open hysterectomy.


Norepinephrine in Combination with Antibiotic Therapy Increases both the Bacterial Replication Rate and Bactericidal Activity.
We previously demonstrated that the rate and extent of an antimicrobial agent's bactericidal effects were coupled to the bacterial replication rate, the latter of which was modulated with the sodium chloride concentration. Herein, we describe the results from a 24-h one-compartment in vitro infection model study that was designed to demonstrate that an antimicrobial agent's bactericidal effects could be amplified when it is administered with a pharmaceutical agent that increases the bacterial replication rate. The antimicrobial and growth-promoting agents selected were levofloxacin and norepinephrine, respectively. The challenge isolate was Escherichia coli JMI 21711R (levofloxacin MIC, 8 mg/liter). Within the in vitro infection model, a human levofloxacin concentration-time profile (half-life, 7 h) was simulated and the challenge isolate was subjected to an ineffective monotherapy exposure (free-drug area under the concentration-time curve over 24 h divided by the MIC [AUC/MIC] ratio of 6) with and without norepinephrine as a continuous infusion (275 mg/liter). Samples were collected from the model during the course of the study for bacterial density determinations and drug concentration assay using liquid chromatography-tandem mass spectrometry (LC-MS/MS). As expected, the norepinephrine and no-treatment control arms failed immediately, followed by the levofloxacin monotherapy arm, which failed slowly over time. The levofloxacin-epinephrine regimen resulted in a 2-log10 CFU reduction in bacterial density over the first 6 to 8 h of the study, which was followed by regrowth of a highly levofloxacin-resistant subpopulation (MIC, 64 mg/liter). These data demonstrate that increasing the rate of bacterial replication with a pharmaceutical product in combination with antimicrobial therapy represents an opportunity to increase the rate and magnitude of bactericidal effect.


Training of affect recognition in schizophrenia patients with violent offences: behavioral treatment effects and electrophysiological correlates.
Violent offenders with schizophrenia have a particularly poor performance level in facial affect recognition. Nineteen male schizophrenia patients, who had been committed to psychiatric hospital detention because of violent offences and lack of criminal responsibility, were recruited to receive the Training of Affect Recognition (TAR). Performance in the Pictures of Facial Affect (PFA)-test and event-related potentials (ERPs) were registered in a pre-post-treatment design. TAR was feasible with a very high treatment effect (Cohen's d = 1.88), which persisted for 2 months post-treatment. ERPs remained unchanged post- vs. pre-treatment, while low resolution brain electromagnetic tomography (LORETA) revealed activation decreases in left-hemispheric parietal-temporal-occipital regions at 172 msec and activation increases in right dorsolateral prefrontal cortex and anterior cingulate at 250 msec. Possibly, violent offenders with schizophrenia are particularly amenable to TAR because of a high level of dysfunction at baseline. Post- vs. pre-treatment changes of neural activity (LORETA) may mirror a gain of efficiency in structural face decoding and a shift towards a more reflective mode of emotional face decoding, relying on increased frontal brain activity. Functional magnetic resonance imaging (BOLD-fMRI) -data from another study further supports this notion. TAR treatment might enable subjects with schizophrenia and a disposition to violence to reach a higher degree of deliberation of their reactive behavior to facial affect stimuli.


Role of Tranexamic Acid in the Clinical Setting.
Tranexamic acid (TXA) is labeled as an antifibrinolytic agent that decreases mortality, reduces blood loss after trauma or surgery, and lowers transfusion requirements in trauma patients with bleeding. This review of the literature is related to TXA use in a variety of settings, with a specific focus on trauma patients, to assess therapeutic efficacy and safety. As seen in large, randomized, placebo-controlled trials, TXA has been shown to decrease mortality over placebo in trauma patients, It is also noted to have good safety parameters upon administration and should be recommended for use in trauma patients with bleeding. Further studies are warranted for the use of TXA in gastrointestinal bleeding and pediatric trauma.


[Three-dimensional motion of the radial artery and attributes of position, rhythm, shape and variance of pulse diagnosis].
In using the sophisticated colour Doppler image-forming technique, and analysis with the self-made cardioelectric phasic mark fixed point as well as the limb minus/plus pressure bathtub, 44 healthy youths were observed. (1) The superficial arteries in the limbs have their motion forms of radial expansion, axial extension and axis shifting. (2) These three motions, together with the pulsation present periodical changes. (3) Compared with the results on the survey of the topographical autopsy of a cadaver, the scope and forms of aforementioned artery motion were related to the anatomical positions of cadaver in which they were located. (4) The above-mentioned axial position shifting of the arteries constitute the whole body shifting or revolving of the blood vessels through plain observations on two dimensions and provide three-dimensional signals. (5) A systematic study was made between the relationship of the vascular motion pattern in human body and the form attributes of position, rhythm, shape and variance. It is significant to study the individuality of vascular activities as well as to elucidate the mechanism in forming the pulse conditions of TCM.


Supramolecular Organization and Functional Implications of K+ Channel Clusters in Membranes.
The segregation of cellular surfaces in heterogeneous patches is considered to be a common motif in bacteria and eukaryotes that is underpinned by the observation of clustering and cooperative gating of signaling membrane proteins such as receptors or channels. Such processes could represent an important cellular strategy to shape signaling activity. Hence, structural knowledge of the arrangement of channels or receptors in supramolecular assemblies represents a crucial step towards a better understanding of signaling across membranes. We herein report on the supramolecular organization of clusters of the K+ channel KcsA in bacterial membranes, which was analyzed by a combination of DNP-enhanced solid-state NMR experiments and MD simulations. We used solid-state NMR spectroscopy to determine the channel-channel interface and to demonstrate the strong correlation between channel function and clustering, which suggests a yet unknown mechanism of communication between K+ channels.


A new test for both neutrophil marrow reserves and intravascular survival.
Reinfusion of a patient's own blood through a hemodialysis coil causes neutrophilia, reaching a peak less than 1 hour after starting the blood reinfusion and returning to baseline count over the next few hours, resulting from a transient release of neutrophils from the bone marrow. This report gives data regarding the double clinical utility of so stimulating a patient's marrow. First, we found that the magnitude of this neutrophilia was a good measure of marrow neutrophil reserves, as determined by comparison with the marrow mature neutrophil cellularity. Second, the falloff from peak neutrophilia to baseline count was a good estimate of neutrophil intravascular survival, as determined by comparison with the standard, in vitro, diisopropylfluorophosphate (DF32P) survival procedure. Thus, this one test could detect abnormalities both of marrow neutrophil production (release) and of peripheral destruction. The coil test requires no radioactive isotope, utilizes commonly available equipment, is apparently harmless and acceptable to the patients, and can be greatly simplified by the development of a blood bag containing sterile cellophane. Even in its present form, it offers considerable clinical and economic advantages in the assessment of pathophysiology of neutropenia in individual patients.


Polarized THG microscopy identifies compositionally different lipid droplets in mammalian cells.
Cells store excess lipids as two major compounds, triacylglycerols (TAGs) and cholesteryl esters (CEs), inside lipid droplets (LDs). The degree of lipid ordering is considered to play a major role in the mobility and enzymatic processing of lipids in LDs. Here, we provide evidence that polarized third-harmonic generation (THG) microscopy distinguishes between native TAG- and CE-enriched LDs in cells due to the different ordering of the two lipid species. We first demonstrate that the responses from synthetic TAG- and CE-enriched LDs using THG microscopy with linear and circular polarizations differ according to their different intrinsic ordering. We then employ simulations to dissect how polarization effects influence the THG from an isotropic LD. Finally, we induce TAG- and CE-enriched LDs in murine macrophages and demonstrate that polarized THG responses increase in a nonlinear fashion with increasing CE/TAG ratio. This suggests that with an increasing CE content, there is a rather sharp transition toward increased LD ordering. Our results demonstrate that polarized THG microscopy enables label-free quantitative analysis of LD ordering and discriminates between compositionally different LDs in intact mammalian cells.


Salvianolic acid B promotes bone formation by increasing activity of alkaline phosphatase in a rat tibia fracture model: a pilot study.
Radix Salviae miltiorrhizae is a herb frequently used within traditional Chinese medicine for the treatment of cardiovascular- and trauma-related diseases. Danshen is the dried root of Salviae miltiorrhizae, from which the polyphenolic compound Salvianolic acid B (Sal B) can be obtained. Sal B is a key component of Danshen. The aim of this study was to determine the effect of Sal B on the healing of long bones following trauma in a rat tibia fracture model. Tibia fractures were created in 20 male Sprague Dawley rats. The animals were divided into two groups: (1) experimental group (n = 10); and (2) control group (n = 10). Rats in the experimental group were intraperitoneally administered with Sal B (40 mg/kg/d) for 3 weeks, while rats in the control group received an identical volume of physiological saline solution, administered in the same way. X-ray photographs were taken of all animals at the time points. Rats were euthanized at weeks 1, 3, 8 and 12 post-fracture. Fracture calluses were measured and callus sections were obtained and stained using hematoxylin and eosin (HE) and the calcium cobalt method. HE stained sections were observed and evaluated according to different grades of bone remodeling. Sections stained using the calcium cobalt method were analyzed with an imagine analysis system. Data showed that callus growth was significantly greater in the experimental group compared with the control group (P < 0.05). Furthermore, histological scores in the Sal B-treated group were statistically higher than in the saline treated group at weeks 1, 3 and 8 post-fracture (P < 0.05). Alkaline phosphatase (ALP) activity was enhanced in the experimental group at weeks 1 and 3 post-fracture (P < 0.05). Our results suggest that Sal B may accelerate early-stage fracture healing. Increased activity of ALP may be one factor which promotes the healing process. This pilot study provides brief insight into the effect of Sal B in fracture healing. These findings will contribute to the development of more and enhanced treatment options for trauma fracture patients.


Inflammatory stress promotes the development of obesity-related chronic kidney disease via CD36 in mice.
Ectopic fat located in the kidney has emerged as a novel cause of obesity-related chronic kidney disease (CKD). In this study, we aimed to investigate whether inflammatory stress promotes ectopic lipid deposition in the kidney and causes renal injury in obese mice and whether the pathological process is mediated by the fatty acid translocase, CD36. High-fat diet (HFD) feeding alone resulted in obesity, hyperlipidemia, and slight renal lipid accumulation in mice, which nevertheless had normal kidney function. HFD-fed mice with chronic inflammation had severe renal steatosis and obvious glomerular and tubular damage, which was accompanied by increased CD36 expression. Interestingly, CD36 deficiency in HFD-fed mice eliminated renal lipid accumulation and pathological changes induced by chronic inflammation. In both human mesangial cells (HMCs) and human kidney 2 (HK2) cells, inflammatory stress increased the efficiency of CD36 protein incorporation into membrane lipid rafts, promoting FFA uptake and intracellular lipid accumulation. Silencing of CD36 in vitro markedly attenuated FFA uptake, lipid accumulation, and cellular stress induced by inflammatory stress. We conclude that inflammatory stress aggravates renal injury by activation of the CD36 pathway, suggesting that this mechanism may operate in obese individuals with chronic inflammation, making them prone to CKD.


Mothers who silence themselves: a concept with clinical implications for women living with HIV/AIDS and their children.
The number of women newly infected with the human immunodeficiency virus (HIV) continues to rise. Women living with HIV or the acquired immunodeficiency syndrome (AIDS) are often mothers who deal with the unenviable task of balancing the stigma and physical needs of illness with the needs of their families and, in particular, their children (DeMarco, Johnsen, Fukuda, & Deffenbaugh, 2001). This article addresses both the communication style and subsequent concept identified in women living with HIV/AIDS called "silencing the self," and the clinical implications for pediatric nurses who support and offer family-centered care to their patients. Mothers living with HIV/AIDS, often view the needs of the children primary as they deal with the trajectory of their own illness. In doing this, they effectively "silence" their own needs and may actually put their own psychosocial and physical needs in abeyance. It is critical that nurses in pediatric practice consider how to tangibly assess, refer, and educate mothers who silence their own needs in the process of providing care for their children.


A method for the degradation of radioactive nicotinic acid.
A chemical degradation scheme is reported, which permits the measurement of the radioactivity of each carbon atom of nicotinic acid. Nicotinic acid is decarboxylated by heating with copper chromite to give carbon dioxide (C-7) and pyridine. The pyridine is converted into 4-nitropyridine 1-oxide, which is heated with aqueous calcium hypobromite to give tribromonitromethane. Combustion of the latter gives carbon dioxide derived from C-4 of the nicotinic acid. Nicotinic acid is also reduced to nipecotic acid, which is oxidized to succinic acid by acidic potassium permanganate. Stepwise degradation of the succinic acid by standard procedures gives two samples of carbon dioxide, which correspond to C-3, C-6 and C-4, C-5 of the nicotinic acid. Benzoylation of the nipecotic acid, followed by oxidation with permanganate at pH7, gives 5-amino-4-carboxyvaleric acid; this is converted into 2-methyleneglutaric acid by the action of nitrous acid. Hydrogenation of the 2-methyleneglutaric acid over rhodium in methanol gives 2-methylglutaric acid, which is oxidized with dilute chromic acid to acetic acid. Stepwise degradation of the acetic acid by standard procedures gives two samples of carbon dioxide, which correspond to C-2 and C-3 of the nicotinic acid. Thus the radioactivities of C-2, C-3, C-4 and C-7 are determined directly and those of C-5 and C-6 by difference. The method was shown to be isotopically valid for [2,3,7-(14)C]-, [4,6-(14)C(2)]- and [5-(14)C]-nicotinic acid.


Comorbid Illness, Bowel Preparation, and Logistical Constraints Are Key Reasons for Outpatient Colonoscopy Nonattendance.
Background. Colonoscopy nonattendance is a challenge for outpatient clinics globally. Absenteeism results in a potential delay in disease diagnosis and loss of hospital resources. This study aims to determine reasons for colonoscopy nonattendance from a Canadian perspective. Design. Demographic data, reasons for nonattendance, and patient suggestions for improving compliance were elicited from 49 out of 144 eligible study participants via telephone questionnaire. The 49 nonattenders were compared to age and sex matched controls for several potential contributing factors. Results. Nonattendance rates were significantly higher in winter months; the OR of nonattendance was 5.2 (95% CI, 1.6 to 17.0, p < 0.001) in winter versus other months. Being married was positively associated with attendance. There was no significant association between nonattendance and any of the other variables examined. The top 3 reasons for nonattendance were being too unwell to attend the procedure, being unable to complete bowel preparation, or experiencing logistical challenges. Conclusions. Colonoscopy attendance rates appear to vary significantly by season and it may be beneficial to book more colonoscopies in the summer or overbook in the winter. Targets for intervention include more tailored teaching sessions, reminders, taxi chits, and developing a hospital specific colonoscopy video regarding procedure and bowel preparation requirements.


Electrospinning of Biodegradable, Monolithic Membrane with Distinct Bimodal Micron-Sized Fibers and Nanofibers for High Efficiency PMs Removal.
Atmospheric particulate matter (PMs) pollution has raised increasing public concerns, especially with the outbreak of COVID-19. The preparation of high-performance membranes for air filtration is of great significance. Herein, the biosynthetic polymer poly(3-hydroxybutyrate-co-3-hydroxyvalerate) (PHBV) was adopted to create a hierarchical structure and biodegradable nonwoven membrane for PMs filtration through a facile directly electrospinning method. The as-prepared membranes with hierarchical structure contain abundant nanowires (5-100 nm) and microfibers (2-5 μm) with different diameter (1000-5000 nm). We have achieved realization of formation mechanisms of such bimodal micro- and nanofibers, which stem from the branching of microfiber at early stage of electrospinning. The PHBV membranes exhibit a very high PM0.3 removal efficiency of 99.999% and PM2.5 removal efficiency of 100% with 0.077% standard atmospheric pressure in the air flow speed of 5.3 cm/s. More importantly, the PHBV membranes can be completely disintegrated within 1 week under composted conditions, indicating the great biodegradability of PHBV membranes. Our work provides insights for the development of biodegradable, high performance air filters for pollutants, molds, bacteria, and viruses.


Administration of Inulin-Supplemented Gluten-Free Diet Modified Calcium Absorption and Caecal Microbiota in Rats in a Calcium-Dependent Manner.
In coeliac disease (CD), the risk of adverse calcium balance and reduced bone density is induced mainly by the disease, but also by a gluten-free diet (GFD), the only accepted CD therapy. Prebiotics through the beneficial impact on intestinal microbiota may stimulate calcium (Ca) absorption. In the present study, we hypothesised that the dietary inulin in GFD would influence positively the intestinal microbiota, and by that will stimulate the absorption of calcium (Ca), especially in the conditions of Ca malnutrition. In a six-weeks nutritional experiment on growing a significant (p < 0.05) luminal acidification, decrease in ammonia concentration and stimulation of short chain fatty acids formation indicated inulin-mediated beneficial effects on the caecal microbiota. However, the effect of inulin on characteristics of intestinal microbiota and mineral utilization depended on the dietary Ca intake from GFDs. Inulin stimulated bifidobacteria, in particular B. animalis species, only if a recommended amount of Ca was provided. Most benefits to mineral utilization from inulin consumption were seen in rats fed Ca-restricted GFD where it increased the relative Ca absorption. Administration of inulin to a GFDs could be a promising dietary strategy for beneficial modulation of intestinal ecosystem and by that for the improvement the Ca absorption.


Regenerative Endodontic Therapy in the Management of Nonvital Immature Permanent Teeth: A Systematic Review-Outcome Evaluation and Meta-analysis.
Although the protocols in previously published studies appeared to be largely similar, there were inadequate evidence-based guidelines to support a single protocol. Using a meta-analysis, this systematic review aimed to summarize and quantitatively evaluate the outcomes for nonvital immature permanent teeth treated using the regenerative endodontic technique (RET) as well as critically appraise the level and quality of evidence of the existing publications. Risk of bias assessment and level of evidence grading were performed on all included studies. Meta-analyses using a random effects model were performed to combine the results of randomized controlled trials. The pooled success rate for each exposure was estimated for each outcome (event rates with 95% confidence intervals). The outcomes of all included studies were summarized. Success rates for tooth survival and resolution of periapical pathosis were excellent; however, results for apical closure and continued root development were inconsistent. There are few well-reported randomized prospective clinical studies. Reporting of long-term outcomes and late-stage effects was sparse. No study evaluated health economic outcomes and improvements to patients' quality of life. Many knowledge gaps still exist within the studies published. Current published evidence is unable to provide definitive conclusions on the predictability of RET outcomes.


DNA nanodevices.
The molecular recognition properties of DNA molecules combined with the distinct mechanical properties of single and double strands of DNA can be utilized for the construction of nanodevices, which can perform ever more tasks with possible applications ranging from nanoconstruction to intelligent drug delivery. With the help of DNA it is possible to construct machinelike devices that are capable of rotational motion, pulling and stretching, or even unidirectional motion. It is possible to devise autonomous nanodevices, to grab and release molecules, and also to perform simple information-processing tasks.


Alpha-Emitter Radium-223 Induces STING-Dependent Pyroptosis to Trigger Robust Antitumor Immunity.
Radium-223 (223 Ra) is the first-in-class alpha-emitter to mediate tumor eradication, which is commonly thought to kill tumor cells by directly cleaving double-strand DNA. However, the immunogenic characteristics and cell death modalities triggered by 223 Ra remain unclear. Here, it is reported that the 223 Ra irradiation induces the pro-inflammatory damage-associated molecular patterns including calreticulin, HMGB1, and HSP70, hallmarks of tumor immunogenicity. Moreover, therapeutic 223 Ra retards tumor progression by triggering pyroptosis, an immunogenic cell death. Mechanically, 223 Ra-induced DNA damage leads to the activation of stimulator of interferon genes (STING)-mediated DNA sensing pathway, which is critical for NLRP3 inflammasome-dependent pyroptosis and subsequent DCs maturation as well as T cell activation. These findings establish an essential role of STING in mediating alpha-emitter 223 Ra-induced antitumor immunity, which provides the basis for the development of novel cancer therapeutic strategies and combinatory therapy.


Water makes it hydrophobic: contraphilic wetting for polyurethanes with soft blocks having semifluorinated and 5,5-dimethylhydantoin side chains.
A series of polyurethanes with novel copolymer soft blocks display a new surface phenomenon, contraphilic wetting, in which the dry surface is hydrophilic and the wetted surface is hydrophobic. A precursor polymer was prepared with copolymer soft blocks containing semifluorinated (trifluoroethoxy, 3FOx, or pentafluoropropoxy, 5FOx) and bromomethyl functional pendant groups with 2:1, 1:1, and 1:2 semifluorinated/bromomethyl ratios. The hard block consists of isophorone diisocyanate (IPDI) and 1,4-butanediol (BD). 5,5-Dimethylhydantoin was introduced by the substitution of Br via reaction-on-polymer. The composition, structure, and percent of 5,5-dimethylhydantoin substitution for both the precursor and the 5,5-dimethylhydantoin-substituted polyurethanes were analyzed by 1H NMR. The difference between the advancing contact angle on the wetted surface and that on the dry surface (deltaC) is highest (38 degrees ) for the polyurethane with the highest ratio of semifluorinated/hydantoin soft block side chains. A model is proposed according to which contraphilic wetting is driven enthalpically by hydrogen bonding. For the dry surface, hydrogen bonding of 5,5-dimethylhydantoin amide carbonyl groups to methylene hydrogens of semifluorinated groups disrupts the normal surface concentration of semifluorinated groups, whereas the geometric arrangement of hydantoin N-H results in availability for hydrogen bonding with water. Upon exposure to water, amide groups switch from hydrogen bonding to -CH2CF2CF3 to stronger hydrogen bonding with water. As a result, semifluorinated groups are "released", and the surface becomes hydrophobic. Drying the coating (50 degrees C) reversibly restores hydrophilic character. Coatings stored at ambient temperature and humidity have deltaC values intermediate between dry and wet states.


Intermittent Administration of Parathyroid Hormone [1-34] Prevents Particle-Induced Periprosthetic Osteolysis in a Rat Model.
We examined whether intermittent administration of parathyroid hormone [1-34] (PTH[1-34]; 60 μg/kg/day) can prevent the negative effects of titanium (Ti) particles on implant fixation and periprosthetic osteolysis in a rat model. Eighteen adult male rats (12 weeks old, bones still growing) received intramedullary Ti implants in their bilateral femurs; 6 rats from the blank group received vehicle injections, and 12 rats from the control group and PTH treatment group received Ti particle injections at the time of operation and intra-articular injections 2 and 4 weeks postoperatively. Six of the rats that received Ti particles from the PTH group also received PTH[1-34] treatment. Six weeks postoperatively, all specimens were collected for assessment by X-ray, micro-CT, biomechanical, scanning electron microscopy (SEM), and dynamic histomorphometry. A lower BMD, BV/TV, Tb.N, maximal fixation strength, and mineral apposition rate were observed in the control group compared to the blank group, demonstrating that a periprosthetic osteolysis model had been successfully established. Administration of PTH[1-34] significantly increased the bone mineral density of the distal femur, BV/TV, Tb.N, Tb.Th, Tb.Sp, Con.D, SMI, and maximal fixation strength in the PTH group compared to that in the control group. SEM revealed higher bone-implant contact, thicker lamellar bone, and larger trabecular bone area in the PTH group than in the control group. A higher mineral apposition rate was observed in the PTH group compared to both the blank and control groups. These findings imply that intermittent administration of PTH[1-34] prevents periprosthetic osteolysis by promoting bone formation. The effects of PTH[1-34] were evaluated at a suprapharmacological dosage to the human equivalent in rats; therefore, additional studies are required to demonstrate its therapeutic potential in periprosthetic osteolysis.


Application of neural network model in assisting device fitting for low vision patients.
To explore the application of neural network models in artificial intelligence (AI)-aided devices fitting for low vision patients. The data of 836 visually impaired people were collected in southwestern Fujian from May 2014 to May 2017. After a full eye examination, 629 low vision patients were selected from this group. Based on the visual functions, rehabilitation needs, and living quality scores of the selected patients, the professionals chose assistive devices that were the best fit for the patients. The data of these three factors were then subjected to the quantitative analysis, and the results were digitized and labeled. The final datasets were used to train a fully connected deep neural networks to obtain an AI-aided model for assistive device fitting. In this study, the main causes of low vision in southwestern Fujian were congenital diseases, among which congenital cataract was the most common. During the low vision AI-aided devices fitting, we found that the intermediate distance magnifier was suitable for the largest number of patients. Through quantitative analysis of the research results, it was found that AI-aided devices fitting was closely related to visual function, rehabilitation needs and quality of life. If this complex relationship can be mapped into the neural network model, AI-aided device fitting can be realized. We built a fully connected neural network model for AI-aided device fitting. The input of the model was the characteristic data of low vision patients, and the output was the forecast of suitable devices. When the threshold of the model was 0.4, the accuracy was about 80% and the F1 value was about 0.31. This threshold can be used as the classification judgment threshold of the model. Low vision AI-aided device fitting is closely related to visual function, rehabilitation needs, and quality of life scores. The neural network model based on full connection can achieve high accuracy in AI-aided devices fitting. It has a great impact on clinical application.


Mastication and acid secretion.
The gastric acid response and the buffer capacity of the stomach were measured in 30 control subjects and 22 duodenal ulcer patients in response to a masticatory (solid) and a non-masticatory (homogenized) meal having the same chemical composition. The peak acid output values were equal after a masticatory and after a non-masticatory diet in control subjects (masticatory 18.1 +/- 1.2, non-masticatory 15.7 +/- 1.3 mmol/hr) as well as in duodenal ulcer patients (masticatory 35.7 +/- 1.5, non-masticatory 33.7 +/- 1.1 mmol/hr). The buffer capacity of the stomach contents 1 hr after the meal was significantly greater after a masticatory diet than a non-masticatory diet in both controls (14.6 +/- 1.4 and 9.0 +/- 1.9 mmol) and in duodenal ulcer patients (9.5 +/- 1.5 and 7.5 +/- 1.2 mmol). Duodenal ulcer patients had a significantly lower buffer capacity compared with controls. Masticatory diets may play a part in protecting individuals from developing duodenal ulcer.


Extra-framework aluminium species in hydrated faujasite zeolite as investigated by two-dimensional solid-state NMR spectroscopy and theoretical calculations.
Extra-framework aluminium (EFAL) species in hydrated dealuminated HY zeolite were thoroughly investigated by various two-dimensional solid-state NMR techniques as well as density functional theoretical calculations. (27)Al MQ MAS NMR experiments demonstrated that five-coordinated and four-coordinated extra-framework aluminium subsequently disappeared with the increase of water loading, and the quadrupole interaction of each aluminium species decreased gradually during the hydration process. (1)H double quantum MAS NMR revealed that the EFAL species in the hydrated zeolite consisted of three components: a hydroxyl AlOH group, and two types of water molecule (rigid and mobile water). (1)H-(27)Al LG-CP HETCOR experiments indicated that both the extra-framework and the framework Al atoms were in close proximity to the rigid water in the fully rehydrated zeolite. The experimental results were further confirmed by DFT theoretical calculations. Moreover, theoretical calculation results further demonstrated that the EFAL species in the hydrated zeolite consisted of the three components and the calculated (1)H NMR chemical shift for each component agreed well with our NMR observations. It is the rigid water that connects the extra-framework aluminium with the four-coordinated framework aluminium through strong hydrogen bonds.


The Northland Regional-Rural program (Pūkawakawa): broadening medical undergraduate learning in New Zealand.
Medical schools in Australasia are using a range of initiatives to increase the number of graduates working outside major centres. This article describes the design, implementation and selected outcomes of the University of Auckland's regional-rural program, Pūkawakawa. The program is based on a 'hub and spoke' model located in Northland, New Zealand, an area of 150,000 people with a high proportion of Māori and relative social deprivation. A 27 week curriculum for 20 volunteer year 5 students was developed in collaboration with stakeholders. The curriculum had three main attachments: integrated care and general practice; women and children's health; and secondary care. These were designed to promote better continuity with patients and supervisors, and a greater likelihood of a rural career. Funding for Pūkawakawa came from existing government grants with a contribution from the Northland District Health Board. A mixed-methods evaluation of the first year was conducted. Staff and students reported high levels of satisfaction with the program and students performed at an academic level similar to their standard-program counterparts. Early reservations related to the experience of supervisors with assessment standards, and the resourcing required to maintain academic equivalence across sites. It is too soon to detect whether students' career aspirations are altered as a result of Pūkawakawa. Areas for future study include student preparedness for later stages of training, career destination, how students learn in this environment and the benefits to the Northland region more broadly.


Growth hormone effects on metabolism, body composition, muscle mass, and strength.
It is clear that the anthropometric ramifications, especially with respect to muscle mass, of the metabolic actions of GH and IGF-I treatment in intact and GH-deficient adults require further study. At present, it appears that daily GH or IGF-I treatment modestly increases nitrogen retention in most normal adults, probably by separate but permissive mechanisms, but only for a short period of time (approximately 1 month). During prolonged GH administration, resistance to the anabolic actions of GH seems to occur, and optimizing the anabolic effects of GH or IGF-I treatment will require a better understanding of the interactions among GH, GHBP, IGF-I production, IGFBPs, the GH dose regimen, and other unidentified regulatory factors. On the basis of the similar increases in muscle protein synthesis, muscle cross-sectional area, and muscle strength observed in placebo and GH-treated exercising young adults, it is doubtful that the nitrogen retention associated with daily GH treatment results in an increase in contractile protein, improved muscle function, strength and athletic performance. Even in catabolic or GH-deficient populations, GH treatment provides only modest increments in nitrogen retention, muscle size, strength, and exercise capacity. Further, the side effects of GH treatment (water retention, carpal tunnel compression, insulin resistance) would be a detriment, rather than an aid, to athletic performance. In addition, whether prolonged (> 6 months) GH treatment alone or in combination with other agents used by athletes (e.g., anabolic steroids, beta-agonists) is associated with other adverse side effects (e.g., cancer, diabetes) has not been evaluated. Therefore, health professionals should continue to discourage the use of GH by exercise enthusiasts.


Polariton-Assisted Singlet Fission in Acene Aggregates.
Singlet fission is an important candidate to increase energy conversion efficiency in organic photovoltaics by providing a pathway to increase the quantum yield of excitons per photon absorbed in select materials. We investigate the dependence of exciton quantum yield for acenes in the strong light-matter interaction (polariton) regime, where the materials are embedded in optical microcavities. Starting from an open-quantum-systems approach, we build a kinetic model for time-evolution of species of interest in the presence of singlet quenchers and show that polaritons can decrease or increase exciton quantum yields compared to the cavity-free case. In particular, we find that hexacene, under the conditions of our model, can feature a higher yield than cavity-free pentacene when assisted by polaritonic effects. Similarly, we show that pentacene yield can be increased when assisted by polariton states. Finally, we address how various relaxation processes between bright and dark states in lossy microcavities affect polariton photochemistry. Our results also provide insights on how to choose microcavities to enhance similarly related chemical processes.


Draft Genome Sequence of Pseudoalteromonas sp. Strain PLSV, an Ulvan-Degrading Bacterium.
We present the draft genome sequence of Pseudoalteromonas sp. strain PLSV, isolated from the feces of an Aplysia sea slug. The addition of the PLSV genome to the existing genomes of three other ulvan-degrading bacterial species will enhance our understanding of ulvan utilization.


[Research results on gamma-glutamyl-transferases and amino-peptidases in mycobacteria].
The activity of 68 mycobacteria strains belonging to 21 different species has been studied on 8 different chromogenic substrates utilized for determining the gamma-GT and various aminopeptidases. The assay was carried out using a simple method (bacterial suspension in solution M/10 of substrate and reading the result after 24 and 48h of incubation according to the color change) and interesting data were obtained about gamma-GT. This enzyme was present in all the strains of M.tuberculosis and in all the strains of the rapid growth species, absent in the other species. Thus, gamma-GT research is taxonomically and diagnostically useful in mycobacteria.


Prostate cancer risk assessment program. A model for the early detection of prostate cancer.
Prostate cancer is the most common form of cancer (except skin cancer) in men. Several factors have been associated with an increased risk for prostate cancer, including age, ethnicity, family history, lifestyle, and environmental exposures. Recognition of the importance of the interaction of these factors in prostate cancer has led to an interest in their evaluation as a model both for studying genetic susceptibility patterns and for studying and providing educational tools and preventive interventions. One such model has been developed at Fox Chase Cancer Center. Critical to the implementation of the model has been the establishment of the Prostate Cancer Risk Registry (PCRR) and Prostate Cancer Risk Assessment Program (PRAP). Together, they serve as a unique resource for investigating the interaction between environmental factors and genetic susceptibility patterns; exploring the early, premalignant biological markers of prostate cancer; and prospectively assessing the quality of life (QOL) of men at risk. In addition, PRAP facilitates the evaluation of models for prostate cancer risk counseling and screening in the community. This paper describes this model for early detection and risk reduction, along with preliminary data from its first two study aims. The program is particularly relevant in view of the wealth of genetic information emerging from the Human Genome Project.


Amiodarone-induced thyroid dysfunction: brand-name versus generic formulations.
Amiodarone is associated with dysfunction of the thyroid. Concerns have arisen regarding the potential for adverse effects with generic formulations of amiodarone. We evaluated and compared the risk of thyroid dysfunction between patients using brand-name versus generic formulations of amiodarone and identified risk factors for thyroid dysfunction. We conducted a retrospective cohort study of patients with atrial fibrillation aged 66 years and older. We used administrative databases that linked information on demographics and clinical characteristics, claims for prescription drugs and discharges from hospital. We estimated thyroid dysfunction using person-year incidence. Of the 60,220 patients in the cohort, 2804 (4.7%) used the brand-name formulation of amiodarone and 6278 (10.4%) used the generic formulation. Baseline characteristics between these two groups were comparable. The median maintenance dose of amiodarone was 200 mg/d for both groups. The total incidence rate for thyroid dysfunction was 14.1 per 100 person-years for both formulations. The mean time to clinical dysfunction of the thyroid was 4.32 years for the brand-name formulation and 4.09 years for the generic formulation. In a multivariate analysis, there was no significant difference in the incidence rates of thyroid dysfunction between the generic and brand formulations (hazard ratio 0.97, 95% confidence interval 0.87-1.08). Factors associated with an increased risk of thyroid dysfunction were being a woman, increasing age and having chronic obstructive pulmonary disease. In this population-based study, we saw no difference between brand-name and generic formulations of amiodarone in terms of incidence of thyroid dysfunction.


3D Bioprintable Hydrogel with Tunable Stiffness for Exploring Cells Encapsulated in Matrices of Differing Stiffnesses.
In vitro cell models have undergone a shift from 2D models on glass slides to 3D models that better reflect the native 3D microenvironment. 3D bioprinting promises to progress the field by allowing the high-throughput production of reproducible cell-laden structures with high fidelity. The current stiffness range of printable matrices surrounding the cells that mimic the extracellular matrix environment remains limited. The work presented herein aims to expand the range of stiffnesses by utilizing a four-armed polyethylene glycol with maleimide-functionalized arms. The complementary cross-linkers comprised a matrix metalloprotease-degradable peptide and a four-armed thiolated polymer which were adjusted in ratio to tune the stiffness. The modularity of this system allows for a simple method of controlling stiffness and the addition of biological motifs. The application of this system in drop-on-demand printing is validated using MCF-7 cells, which were monitored for viability and proliferation. This study shows the potential of this system for the high-throughput investigation of the effects of stiffness and biological motif compositions in relation to cell behaviors.


Dilated cardiomyopathy and successful cardiac transplantation in Becker's muscular distrophy. Follow-up after two years.
A 23 year-old man with x-linked Becker type muscular distrophy underwent cardiac transplantation because of dilated cardiomyopathy complicated by terminal heart failure. The muscular functional impairment was mild and slowly progressive, whereas the cardiac disease was severe and rapidly progressive. The ventricular cavities of the explanted heart were hugely dilated and the left ventricular wall thickness was moderately increased. Microscopically, a diffuse hypertrophy of the myocardial fibers and a widespread interstitial collagenous fibrosis were present. At a follow-up, two years after treatment, the patient is alive and fairly well; the degree of his muscular disability is substantially unchanged.


The rehabilitative effects on written language of a combined language and parietal dual-tDCS treatment in a stroke case.
In this paper we report the effect of a combined transcranial direct current stimulation (tDCS) and speech language therapy on linguistic deficits following left brain damage in a stroke case. We show that simultaneous electrical excitatory stimulation to the left and inhibitory stimulation to the right parietal regions (dual-tDCS) affected writing and reading rehabilitation, enhancing speech therapy outcomes. The results of a comparison with healthy controls showed that application of dual-tDCS could improve, in particular, sub-lexical transcoding and, specifically, the reading of non-words with increasing length and complexity. Positive repercussions on patient's quality of functional communication were also ascertained. Significant changes were also found in other language and cognitive tasks not directly treated (comprehension and constructive apraxia).


Novel Treatment Strategies for Secondary Prevention of Cardiovascular Disease: A Systematic Review of Cost-Effectiveness.
New pharmacological therapies for the treatment of cardiovascular disease (CVD) have emerged in recent years. The high rates of CVD and the need for long-term treatment to decrease risk factors makes cost-effectiveness crucial for their successful long-term implementation. This study assessed cost-effectiveness studies of novel pharmacological treatments (ezetimibe, proprotein convertase subtilisin/kexin type 9 [PCSK9] inhibitors, omega-3 polyunsaturated fatty acids [n-3 PUFAs], and the cardiovascular polypill) compared with standard care for the secondary prevention of CVD. We searched seven databases and the reference list of selected literature reviews for eligible cost-effective analyses (CEA) published between January 2009 and January 2020 that evaluated the above novel treatments versus standard care. Two independent reviewers performed the screening and evaluation in accordance with the Consolidated Health Economic Evaluation Reporting Standards statement. Cost results were adapted to 2018 US dollars (US$) to facilitate comparisons between studies. Consideration of cost-effectiveness was based on the original study criteria. Thirty-two studies were included in this review, most of them adopting a healthcare perspective. Studies evaluating ezetimibe, PCSK9 inhibitors and n-3 PUFAs assessed their addition to standard care compared with standard care alone, while studies analysing the polypill evaluated the replacement of multiple monotherapies for a fixed-dose combination. Ten studies reported on ezetimibe, fifteen evaluated PCSK9 inhibitors, five focused on n-3 PUFAs and seven on the polypill. From a healthcare perspective, ezetimibe was cost effective in 62.5% of the studies (incremental cost-effectiveness ratios [ICERs] ranged from US$27,195 to US$204,140), n-3 PUFAs in 60% (ICERs from US$57,128 to US$139,082) and the cardiovascular polypill in 100% (ICERs from dominant to US$30,731) compared with standard care. Conversely, only 10% of the studies considered PCSK9 inhibitors cost effective compared with standard care from a healthcare perspective (ICERs ranged from US$231,119 to US$1,223,831). Additionally, ezetimibe was cost effective in 50% of the studies, PCSK9 inhibitors in 33% and the polypill in 50% of the studies adopting a societal perspective. The key model-related parameters predicting cost-effectiveness included drug cost, time horizon, and the baseline risk of cardiovascular events. Based on current pricing and willingness-to-pay thresholds, most CEA studies considered ezetimibe, n-3 PUFAs and the polypill to be cost effective compared with standard care but not PCSK9 inhibitors for secondary prevention of CVD.


Public misperception that very low nicotine cigarettes are less carcinogenic.
The USA is considering a very low nicotine content (VLNC) cigarette standard. We sought to characterise the prevalence and correlates of the incorrect belief that VLNC cigarettes are less carcinogenic than current cigarettes, as this could reduce motivation to quit. Participants were a nationally representative sample of 650 adult smokers in the USA. In 2015-2016, before the VLNC proposal became public, these smokers took part in an online survey. We used multivariate weighted analyses to calculate ORs and percentages and a χ2 test to examine the association between variables. Overall, 47.1% of smokers believed that smoking VLNC cigarettes for 30 years would be less likely to cause cancer than smoking current cigarettes. This misperception was more common among smokers who were aged above 55 (56.6%) and black (57.4%). Additionally, 23.9% of smokers reported they would be less likely to quit if the USA adopted a VLNC standard. Thinking that VLNC cigarettes would be less carcinogenic was associated with smokers reporting they would be less likely to quit (P<0.01). Many smokers had the misperception that smoking VLNC cigarettes is less likely to cause cancer, and some stated that they would be less likely to quit. A VLNC standard may be more effective if accompanied by a communication campaign that emphasises the continued dangers of smoking VLNC cigarettes due to the many toxic chemicals in smoke.


Scientific Fluency as the Greatest Strength of Chemical Biologists.
Chemical biology has developed into an influential discipline in biological research, largely thanks to synergistic relationships that have arisen from the inclusion of students from diverse scientific backgrounds. We believe the greatest strengths of our field rely on active communication between fields and the fluency of chemical biologists in traversing them. In this special issue, besides cutting-edge chemical biology research articles, we will also highlight nonscientific topics about scientific training and mentorship to foster the training of next-generation chemical biologists.


[Salidroside improves pulmonary fibrosis by down-regulation of cathepsin B and NF-κBp65 in rats].
To investigate the mechanism of salidroside in improvement of pulmonary fibrosis in rats. Methods: SD rats were subjected to 6 groups: a blank group, a model group, a pirfenidone group, a high-dose salidroside group, a middle-dose salidroside group, and a low-dose salidroside group. The contents of ALB, ALP, LDH, PC-III and COL4, and the expression levels of cathepsin B (CB) and NF-κBp65 in the 6 groups were analyzed. Results: Lung coefficient and oxygen partial pressure in the blank group were lower than those in the model group (P<0.05). Compared with the model group, lung coefficients in the pirfenidone group, the high-dose salidroside group, the middle-dose salidroside group, and the low-dose salidroside group were decreased, while oxygen partial pressures were statistically increased (P<0.05). The contents of ALB, ALP and LDH in the model group were statistically increased (P<0.05) in a dose-dependent manner. Compared with the blank group, the contents of GSH, HYP, PC-III and COL4, and the expression levels of CB and NF-κBp65 in the model group were significantly increased (P<0.05), which were attenuated by alidroside in a dose-dependent manner (P<0.05). Conclusion: Salidroside can improve pulmonary fibrosis in rats, and the mechanism may be related to reduce the expression of CB and NF-κBp65.


Xenon-arc photocoagulation of medium-sized malignant melanomas.
Sixteen cases of medium-sized malignant melanomas were treated with xenon-arc photocoagulation. Early follow-up results are encouraging. Only minimal complications were encountered, and there was no evidence of metastasis. Meticulous follow-up of ocular malignant melanoma patients is strongly suggested, especially in cases in which the tumor is situated in the posterior pole.


Generation of the organo-rare gas dications HCCRg2+ (Rg = Ar and Kr) in the reaction of acetylene dications with rare gases.
Using doubly ionized acetylene as a superelectrophilic reagent, the new rare-gas compounds HCCAr2+ and HCCKr2+ have been prepared for the first time in hyperthermal collisions of mass-selected C2H2(2+) with neutral rare gases (Rg). However, electron transfer from the rare gas to the acetylene dication as well as proton transfer from C2H2(2+) to the rare gas efficiently compete with formation of HCCRg2+. The computational investigations show that the formation of HCCRg2+ from acetylene dication is endothermic with Rg = He, Ne, Ar and Kr and only weakly exothermic with Xe. These energetic factors, as well as the pronounced competition with the other reactive channels help to explain why HCCRg2+ is only observed with Rg = Ar and Kr.


Manifestations of Insomnia in Sleep Apnea: Implications for Screening and Treatment.
The aims of this study were to examine the presence, type, and severity of insomnia complaints in obstructive sleep apnea (OSA) patients and to assess the utility of the Sleep Symptom Checklist (SSC) for case identification in primary care. Participants were 88 OSA patients, 57 cognitive-behavioral therapy for insomnia (CBT-I) patients, and 14 healthy controls (Ctrl). Each completed a sleep questionnaire as well as the SSC, which includes insomnia, daytime functioning, psychological, and sleep disorder subscales. Results showed that OSA patients could be grouped according to 3 insomnia patterns: no insomnia (OSA), n = 21; insomnia (OSA-I), n = 30, with a subjective complaint and disrupted sleep; and noncomplaining poor sleepers (OSA-I-NC), n = 37. Comparisons among the OSA, CBT-I, and Ctrl groups demonstrate distinct profiles on the SSC subscales, indicating its potential utility for both case identification and treatment planning.


Cytolytic action of Vibrio vulnificus haemolysin on mast cells from rat peritoneal cavity.
The mode of action of Vibrio vulnificus haemolysin (VVH) on mast cells from the peritoneal cavity of the rat was examined. VVH induced histamine release, and damage to the mast cells, in a dose-dependent fashion. When 1 microgram of VVH was added to c. 10(5) mast cells at 37 degrees C, histamine release was observed after a lag period of 5-10 s, and was complete within 5 min. The action was temperature-dependent, and was not induced at 4 degrees C. Disodium cromoglycate, a membrane stabiliser for mast cells, inhibited the histamine release significantly, but the effect was not dose-dependent. Moreover, leakage of lactate dehydrogenase from VVH-treated mast cells was observed. These results suggest that VVH acts on the cell membrane of mast cells and is cytolytic.


Fibronectin-degrading activity in human crevicular fluid, gingival explants culture medium and bacterial plaques.
125I-fibronectin was incubated with extracts having presumably a proteolytic activity. Plaque from children without gingivitis, plaque from adults with chronic periodontitis, human gingival fluid and pooled culture media of human gingival explants were studied. Proteolysis was usually faster with plaque from patients with adult periodontitis than with plaque from children without gingivitis and the inhibition tests showed that several enzymes were implicated in the process. For the culture medium of gingival explants, the electrophoretic profile of the digestion products of fibronectin was different and showed a decreased activity. Nevertheless the gingival fluid gave a very similar degradation to bacterial plaque. The sulcular content was able to assume enzymatic activity capable of destroying fibronectin. These sulcular activities could be important for bacterial colonisation of sulcular surfaces and perhaps also for fibronectin destruction of periodontal tissues.


Validating a Computational Framework for Ionic Electrodiffusion with Cortical Spreading Depression as a Case Study.
Cortical spreading depression (CSD) is a wave of pronounced depolarization of brain tissue accompanied by substantial shifts in ionic concentrations and cellular swelling. Here, we validate a computational framework for modeling electrical potentials, ionic movement, and cellular swelling in brain tissue during CSD. We consider different model variations representing wild-type (WT) or knock-out/knock-down mice and systematically compare the numerical results with reports from a selection of experimental studies. We find that the data for several CSD hallmarks obtained computationally, including wave propagation speed, direct current shift duration, peak in extracellular K+ concentration as well as a pronounced shrinkage of extracellular space (ECS) are well in line with what has previously been observed experimentally. Further, we assess how key model parameters including cellular diffusivity, structural ratios, membrane water and/or K+ permeabilities affect the set of CSD characteristics.


Genome-wide identification, characterization and expression analyses of TLRs in Yesso scallop (Patinopecten yessoensis) provide insight into the disparity of responses to acidifying exposure in bivalves.
Toll-like receptors (TLRs) play a crucial role in innate immunity by recognizing specific pathogen-associated molecular patterns, including lipoproteins, lipopeptides, lipopolysaccharide, flagellin, dsRNA, ssRNA and CpG DNA motifs. Although significant effects of TLRs on immunity have been reported in most vertebrates and some invertebrates, the complete TLR superfamily has not been systematically characterized in scallops. In this study, 18 TLR genes were identified from Yesso scallop (Patinopecten yessoensis) using whole-genome scanning. Phylogenetic and protein structural analyses were performed to determine the identities and evolutionary relationships of the 18 genes. Extensive expansion of TLR genes from the Yesso scallop genome indicated gene duplication events. In addition, expression profiling of PyTLRs was performed at different acidifying exposure levels (pH = 6.50, 7.50) with different challenge durations (3, 6, 12 and 24 h) via in silico analysis using transcriptome and genome databases. Our results confirmed the inducible expression patterns of PyTLRs under acidifying exposure, and the responses to immune stress may have arisen through adaptive recruitment of tandem duplications of TLR genes. Collectively, this study provides novel insight into PyTLRs as well as the specific role and response of TLR signaling pathways in host immune responses against acidifying exposure in bivalves.


Methods for Biomechanical Testing of Posterior Malleolar Fractures in Ankle Fractures: A Scoping Review.
The treatment of posterior malleolar fractures (PMFs) is debated, including the need for surgery and method of fixation. Recent literature has suggested that fracture pattern, rather than fragment size, may be an important predictor for ankle biomechanics and functional outcome. Biomechanical studies have been conducted to provide evidence-based treatment on the effects of fracture and fixation on contact pressure and stability. The objective of this scoping review is to summarize the methodologies used in biomechanical studies on PMFs and assess whether they are sufficient to test the need for surgery and method of fixation. A scoping review of publications before January 2022 was performed. PubMed/Medline and Embase Ovid were searched for cadaver or finite element analysis (FEA) studies that created and tested the effects of PMFs in ankle fractures. Both cadaver and FEA studies were included. Data about fragment characteristics, mode of testing, and outcomes were charted by 2 persons from the study group. The data were synthesized when possible and compared. We included 25 biomechanical studies, including 19 cadaver studies, 5 FEA studies, and 1 cadaver and FEA study. Aside from the fragment size, few other fragment characteristics were reported. Mode of testing varied with different loads and foot positions. Strong conclusions on the effects of fracture and fixation on contact pressure and stability could not be made. Biomechanical studies on PMFs demonstrate wide variability in fragment characteristics and mode of testing, which makes it difficult to compare studies and draw conclusions on the need for surgery and method of fixation. Additionally, limited reporting of fragment measurements questions the applicability to clinical practice. The biomechanical literature on PMFs would benefit from the use of a standard classification and universal fragment measurements to match clinical injuries in future biomechanical studies. Based on this review, we recommend the Mason classification, which addresses the pathomechanism, and use of the following fragment measurements in all 3 anatomic planes when creating and describing PMFs: fragment length ratio, axial angle, sagittal angle or fragment height, and interfragmentary angle. The testing protocol needs to reflect the purpose of the study. This scoping review demonstrates wide methodological diversity of biomechanical studies. Consistency in methodology should enable comparison of study results, leading to stronger evidence-based recommendations to guide surgeons in decision making and offer PMF patients the best treatment.


Unilateral Ciliary Madarosis in a Child After Coronavirus Disease 2019 (COVID-19) Infection.
Coronavirus disease 2019 life-threatening signs have aroused a great deal of attention since the beginning of the pandemic. In the initial stages of the pandemic, the pediatric population was mostly protected, and the symptoms in affected children were mild. Here, the authors present a 7-year-old boy with left upper eyelid ciliary madarosis that developed 9 weeks after coronavirus disease 2019 infection. During comprehensive ophthalmologic examination, no conjunctival injection, chemosis, erythema, or crusts on the eyelids and no other meibomian gland disease findings were detected. Comprehensive laboratory workup was performed to exclude any other possible causes of ciliary madarosis. All laboratory parameters tested within normal limits. In addition to the patient's ocular surface and physical examination findings, laboratory results and the timing of the symptoms as well as spontaneous recovery at follow-up visits led the authors to conclude that telogen effluvium was to cause of the isolated, unilateral ciliary madarosis in this case.


Boundary effects in the stepwise structure of the Lyapunov spectra for quasi-one-dimensional systems.
Boundary effects in the stepwise structure of the Lyapunov spectra and corresponding wavelike structure of the Lyapunov vectors are discussed numerically in quasi-one-dimensional systems of many hard disks. Four different types of boundary conditions are constructed by combinations of periodic boundary conditions and hard-wall boundary conditions, and each leads to different stepwise structures of the Lyapunov spectra. We show that for some Lyapunov exponents in the step region, the spatial y component of the corresponding Lyapunov vector deltaq(yj), divided by the y component of momentum p(yj), exhibits a wavelike structure as a function of position q(xj) and time t. For the other Lyapunov exponents in the step region, the y component of the corresponding Lyapunov vector deltaq(yj) exhibits a time-independent wavelike structure as a function of q(xj). These two types of wavelike structure are used to categorize the type and sequence of steps in the Lyapunov spectra for each different type of boundary condition.


Effectiveness of co-treatment with traditional Chinese medicine and letrozole for polycystic ovary syndrome: a meta-analysis.
Polycystic ovary syndrome (PCOS) is an endocrine disease that affects gynecological health. Treatment of PCOS remains a big challenge for clinicians. This meta-analysis was developed to compare the efficacy of co-treatment with traditional Chinese medicine (TCM) and letrozole against letrozole monotherapy in the treatment of PCOS. Randomized controlled trials (RCTs) were electronically retrieved from PubMed, Cochrane Library, China Biomedical Literature Database, China National Knowledge Infrastructure and Wanfang Data; related papers that were not available electronically were manually checked. All papers were assessed according to the Cochrane Handbook for Systematic Reviews of Interventions and the valid data were analyzed using Revman software (The Cochrane Collaboration, Copenhagen, Denmark). We included RCTs that compared co-treatment with TCM and letrozole against letrozole monotherapy in women with PCOS, which was defined by anovulation, biochemical or clinical hyperandrogenemia and polycystic ovaries. We included trials from all sources. Two independent reviewers extracted data, and evaluated study quality according to the Cochrane Handbook for Systematic Reviews of Interventions criteria for RCT, including issues of patient randomization, blinding and bias. Eight RCTs, involving a total of 537 patients, were included in the present study. The meta-analysis showed that the cycle ovulation rate, the pregnancy rate and the total effective rate of symptom treatment were higher in treatments combining TCM with letrozole, compared with letrozole monotherapy. Although the rate of luteinizing hormone (LH)/follicle-stimulating hormone (FSH) and the body mass index of the group receiving combined therapy were lower than in letrozole monotherapy, no statistical difference was found in the LH and FSH level between the two groups. Available evidence showed that co-treatment with TCM and letrozole was more effective than letrozole monotherapy in the treatment of PCOS.


Involvement of palate and cheek in leprosy.
22 Cases of bacillary positive leprosy with no apparent lesion in the oral cavity, soft or hard palate were studied for any evidence of pathological involvement. Granulomata were present in 11 (65%) out of 17 cheek biopsies studied. M. leprae were identified in four specimens only. 9 specimens (64%) out of 14 palate biopsies showed definite granulomata. M. leprae were seen in six specimens.


[Behavior of the body weight in 2261 maturity-onset diabetics under conditions of ambulatory care].
Of 2,261 maturity-onset-diabetics (970 males, 1,691 females) body weight, size and Broca-index were established at the beginning of the treatment, one year after the beginning of the treatment and at the date of analysis (x=5.7 years after the manifestation of diabetes). 72% of the females and 49% of the males had a Broca-index of more than 10 at the beginning of the treatment. The average loss of weight of the diabetics of adult type with overweight with a Broca-index of more than 5 was in the first year 7.6 kg in males and 5.2 kg in females. In the first year after beginning of the disease in the diet group and in the buformin group was achieved an average reduction of weight in males of about 7 kg and in females of about 6 kg. After the first year of treatment in the groups mentioned the body weight remained or rose to one kg. The patients treated with sulfonylureas--compared with the diet-biguanide group--showed in the first year of treatment, indeed, a loss of weight which was about 50% smaller, however, also in the following years (x=4.7) a further continuous reduction of weight could be recognized. The initial results and the late results in the treatment of elderly diabetics with overweight show that, compared with former years, partial success is to be achieved with reduction cures performed in outpatient departments. The importance of the reduction of weight in elderly diabetics for the improvement of the carbohydrate tolerance and the fat metabolism is emphasized.


Application of Iron Oxide as a pH-dependent Indicator for Improving the Nutritional Quality.
Acid food indicators can be used as pH indicators for evaluating the quality and freshness of fermented products during the full course of distribution. Iron oxide particles are hardly suspended in water, but partially or completely agglomerated. The agglomeration degree of the iron oxide particles depends on the pH. The pH-dependent particle agglomeration or dispersion can be useful for monitoring the acidity of food. The zeta potential of iron oxide showed a decreasing trend as the pH increased from 2 to 8, while the point of zero charge (PZC) was observed around at pH 6.0-7.0. These results suggested that the size of the iron oxide particles was affected by the change in pH levels. As a result, the particle sizes of iron oxide were smaller at lower pH than at neutral pH. In addition, agglomeration of the iron oxide particles increased as the pH increased from 2 to 7. In the time-dependent aggregation test, the average particle size was 730.4 nm and 1,340.3 nm at pH 2 and 7, respectively. These properties of iron oxide particles can be used to develop an ideal acid indicator for food pH and to monitor food quality, besides a colorant or nutrient for nutrition enhancement and sensory promotion in food industry.


Pheromonal Control of Metamorphosis in the Pacific Sand Dollar, Dendraster excentricus.
Competent larvae are induced to undergo metamorphosis by sand from a sand dollar bed or an aqueous extract of the sand. Gel permeation chromatography and high-performance liquid chromatography of the extract yielded a 980-dalton peptide that will induce metamorphosis between 10(-6) and 10(-5) molar. Extracts of whole adults and gonads were also able to induce metamorphosis, and adults can condition substrates to induce metamorphosis. Therefore, the initiation of metamorphosis in Dendraster excentricus is controlled by a pheromone released by adult sand dollars.


Correlation of Surface Adsorption and Oxidation with a Floatability Difference of Galena and Pyrite in High-Alkaline Lime Systems.
When it comes to Pb-Zn ores with high amounts of pyrite, the major problem encountered is the low separation efficiency between galena and pyrite. By virtue of high dosage of lime and collector sodium diethyl dithiocarbamate (DDTC), pyrite and zinc minerals are depressed, allowing the galena to be floated. However, there have been significant conflicting reports on the flotation behavior of galena at high pH. In this context, correlation of the surface adsorption and oxidation with the floatability difference of galena and pyrite in high-alkaline lime systems would be a key issue for process optimization. Captive bubble contact angle measurements were performed on freshly polished mineral surfaces in situ exposed to lime solutions of varying pH as a function of immersion time. Furthermore, single mineral microflotation tests were conducted. Both tests indicated that the degree of hydrophobicity on the surfaces of galena and pyrite increased in the presence of DDTC at natural or mild pulp pH. While in a saturated lime solution, at pH 12.5, DDTC only worked for galena, but not for pyrite. Surface chemistry analysis by time-of-flight secondary ion mass spectrometry (Tof-SIMS) confirmed the preference of DDTC on the galena surface at pH 12.5, which contributed to a merit recovery. Further important evidence through measurements of Tof-SIMS, ion chromatography, and high-performance liquid chromatography indicated that in high-alkaline lime systems, the merit floatability of galena could exclude the insignificant contribution of elemental sulfur (S8) and was dominantly attributed by the strong adsorption of DDTC. In contrast, the poor flotation response of pyrite at high pH was due to the prevailing adsorption of CaOH+ species. This study provides an important surface chemistry evidence for a better understanding of the mechanism on the better selectivity in the galena-pyrite separation adopting high-alkaline lime systems.


Obstructive cholestasis induces TNF-alpha- and IL-1 -mediated periportal downregulation of Bsep and zonal regulation of Ntcp, Oatp1a4, and Oatp1b2.
Inverse acinar regulation of Mrp2 and 3 represents an adaptive response to hepatocellular cholestatic injury. We studied whether obstructive cholestasis (bile duct ligation) and LPS treatment affect the zonal expression of Bsep (Abcb11), Mrp4 (Abcc4), Ntcp (Slc10a1), and Oatp isoforms (Slco1a1, Slco1a4, and slco1b2) in rat liver, as analyzed by semiquantitative immunofluorescence. Contribution of TNF-alpha and IL-1beta to transporter zonation in obstructive cholestasis was studied by cytokine inactivation. In normal liver Bsep, Mrp4, Ntcp, and Oatp1a1 were homogeneously distributed in the acinus, whereas Oatp1a4 and Oatp1b2 expression increased from zone 1 to 3. Glutamine synthetase-positive pericentral hepatocytes exhibited markedly lower Oatp1a4 expression than the remaining zone 3 hepatocytes. In cholestatic liver Bsep and Ntcp immunofluorescence in periportal hepatocytes significantly decreased to 66 +/- 4% (P < 0.01) and 67 +/- 7% (P < 0.05), whereas it was not altered in pericentral hepatocytes. Oatp1a4 was significantly induced in hepatocytes with a primarily low expression, i.e., in periportal hepatocytes and in glutamine synthetase-positive pericentral hepatocytes. Likewise, Oatp1b2 was upregulated in periportal hepatocytes. Mrp4 zonal induction was homogeneous. Inactivation of TNF-alpha and IL-1beta prevented periportal downregulation of Bsep. Recruitment of neutrophils and polymorphonuclear cells mainly occurred in the periportal zone. Likewise, IL-1beta induction was largely found periportally. No significant transporter zonation was seen following LPS treatment. In conclusion, zonal downregulation of Bsep in obstructive cholestasis is associated with portal inflammation and is mediated by TNF-alpha and IL-1beta. Periportal downregulation of Ntcp and induction of Oatp1a4 and Oatp1b2 may represent adaptive mechanisms to reduce cholestatic injury in hepatocytes with profound downregulation of Bsep and Mrp2.


Catheter hemodynamic assessment of the univentricular circulation.
Children with very complex congenital heart disease not amenable to biventricular repair are increasingly being considered for a palliative univentricular care pathway. This involves a staged surgical approach culminating in the Fontan circulation with passive pulmonary blood flow and added resistances. The catheter based hemodynamic assessment at all three stages of this palliation is described in detail. Frequent pitfalls, inherent limitations and potential errors are discussed and clinical examples are illustrated.


Evaluation of rhamnolipid (RL) as a biosurfactant for the removal of chromium from aqueous solutions by precipitate flotation.
Rhamnolipid (RL) is a biosurfactant which is produced by the bacterial species Pseudomonas aeruginosa. Although applications of this material have been examined in various fields, its applications in the flotation of heavy metals remain to be explored. In this research, rhamnolipid was applied as a collector in the flotation of Cr(III) from aqueous solutions. FeSO4 was used for the precipitation of Cr(VI) to Cr(III) which was subsequently removed by flotation. A two level full factorial design (with center points) was used to evaluate the effects of pH, air flow rate, RL/Cr and Fe/Cr molar ratios on the performance of the flotation system. The results showed that the biosurfactant was highly effective in the removal of chromium, and all of the factors had significant effects on the flotation performance. The chromium removal efficiencies of greater than 95% were obtained with the initial chromium concentration of 40 ppm within 5 min. Kinetic studies showed that a first order kinetic model was appropriate to describe the precipitate flotation of Cr(III) using rhamnolipid as a collector. The interference of NaCl, CaCl2, CaSO4, and CaCO3 on the Cr removal was also investigated, and it was demonstrated that CaSO4 and CaCO3 as sparingly water soluble salts, and CaCl2 as a contributor to water hardness had significant negative impacts on Cr removal efficiency of rhamnolipid.


Volumetric and morphological analysis of intraductal papillary mucinous neoplasm of the pancreas using computed tomography and magnetic resonance imaging.
The purpose of this study was to predict the malignancy of intraductal papillary mucinous neoplasm (IPMN) based on data obtained by computed tomography and magnetic resonance imaging. Sixty-nine patients with IPMN underwent computed tomography, magnetic resonance imaging, and surgery. The tumors were classified pathologically as IPMN (adenoma), IPMN (in situ carcinoma), and invasive carcinoma derived from IPMN, and analyzed morphologically for the following characteristics: tumor size, main pancreatic duct (MPD) diameter, tumor area, MPD area, tumor volume, MPD volume, and intraductal volume (tumors volume + MPD volume). Main pancreatic duct diameter (P = 0.017) and intraductal volume (P = 0.0013) showed significant differences among IPMN (adenoma), IPMN (in situ carcinoma), and invasive carcinoma derived from IPMN. When IPMN (in situ carcinoma) and invasive carcinoma derived from IPMN were classified as malignant IPMN, an MPD diameter of 6 mm or more and an intraductal volume of 10 cm or more were set as cutoff levels predictive of malignancy using receiver operating characteristic curve analysis. On the basis of these criteria, the sensitivity and specificity for identifying malignancy in MPD were 83% and 59%, and those for intraductal volume were 70% and 73%, respectively. Intraductal volume (≥10 cm) determined by volumetric analysis is useful for diagnosis of malignant IPMN.


Vitiligo impact scale: an instrument to assess the psychosocial burden of vitiligo.
Vitiligo is a disease that significantly impairs quality of life. Previous studies have shown that vitiligo has an impact that may not correlate with the size and extent of depigmentation, indicating a need for an independent measure of the psychosocial burden. To develop a rating scale to assess the psychosocial impact of vitiligo. The study was undertaken in three broad phases: item generation, pre- and pilot testing, and test administration. Items were generated largely from a qualitative study using semi-structured interviews of patients. Face and content validity were assessed through pre- and pilot testing in 80 patients and the final version was administered to 100 patients who also received the Dermatology Life Quality Index (DLQI) and the Skindex-16. Each patient also underwent a physician global assessment (PGA) of the impact of vitiligo. Test-retest reliability was assessed in 20 patients. Of 72 items initially generated for the scale, 27 were retained in the final version. Subjects were able to comprehend the items and took about 5-7 min to complete the instrument. The scale was internally consistent (Cronbach's α = 0.85). Scores on the scale correlated moderately well with the DLQI and the Skindex (Spearman rank correlation: 0.51 and 0.65, respectively). The scale was able to discriminate between patients having mild and those having moderate and severe impact as assessed by PGA. The test-retest reliability coefficient (Spearman rank correlation) was 0.80. The Vitiligo Impact Scale appears to be a valid measure of the psychosocial impact of vitiligo and this instrument may be useful both in the clinic and in clinical trials.