Photoprotective effect of a psoralen-UVA-induced tan.
To determine whether a tan produced by 8-MOP and UVA protects from subsequent solar light irradiation, volunteers were irradiated with unfiltered Xenon arc light before and 10 days after a 1 week's course of four 8-MOP-UVA treatments. Evaluation of the minimal erythema doses and of histological changes before and after 8-MOP-UVA treatment revealed that the 8-MOP-UVA induced tan protected against the erythemogenic and cell damaging effects of Xenon arc light. Unscheduled repair DNA synthesis, used as a measure for UVB-induced DNA damage and repair, was also investigated in skin irradiated with the Xenon arc before and after 8-MOP-UVA induced tanning. Both the number of grains per sparse labeled cell and the number of sparse labeled cells per 1000 cells, were found to be significantly lower in tanned skin; taking decreased unschedules repair DNA synthesis as a measure for decreased DNA-damage, these findings also demonstrate a photoprotective effect of the 8--MOP-UVA induced tan.


Interleukin-10 induces apoptosis in developing mast cells and macrophages.
Interleukin (IL)-10 is a potent immunoregulatory cytokine capable of inhibiting the inflammatory response. As mast cells and macrophages are central effectors of inflammation, we investigated the effects of IL-10 on mast cell and macrophage development from mouse bone marrow progenitors. Bone marrow cells were cultured in IL-3 + stem cell factor (SCF), giving rise to mixed populations of mast cells and macrophages. The addition of IL-10 greatly decreased the expansion of bone marrow progenitor cells through a mechanism requiring signal tranducer and activator of transcription-3 expression. The inhibitory effects were a result of the induction of apoptosis, which occurred with caspase-3 activation and reduced mitochondrial membrane potential. Supporting a role for the mitochondrion, bone marrow cells from p53-deficient or Bcl-2 transgenic mice were partly resistant to the effects of IL-10. Further, IL-10 decreased Kit receptor expression and inhibited survival signaling by SCF or IL-3. These data indicate that IL-10 induces an intrinsic, mitochondrial apoptosis cascade in developing mast cells and macrophages through mechanisms involving blockade of growth factor receptor function. The ability of IL-10 to inhibit survival could support immune homeostasis by dampening inflammatory responses and preventing chronic inflammation.


Indocyanine green fluorescent lymphography during open inguinal hernia repair in a patient who developed postoperative ultrasonic hydrocele: A case report.
To our knowledge, no reports of indocyanine green (ICG) fluorescent lymphography during inguinal hernia repair currently exist. We report the case of a patient who underwent ICG fluorescent lymphography during open inguinal hernia repair. A 63-year-old man was referred to our department for treatment of a right inguinal hernia, during which an ICG lymphography was performed. The patient had a history of robot-assisted radical prostatectomy for prostate cancer. Following induction of general anesthesia, 0.25 mg of ICG was injected into the right testicle and the scrotum was gently massaged, after which an open inguinal hernia repair was performed. During the operation, fluorescence from the ICG was observed in two lymphatic vessels in the spermatic cord. The ICG fluorescent vessels were resected due to the strong adhesion between the lymphatic vessels and the hernia sac. ICG leakage was observed in the resected vessels. An open tension-free technique was performed using an open mesh plug. The patient was discharged one day postoperatively. The histological diagnosis of the resected vessel was a lymphatic vessel. He had a slight postoperative hydrocele that was detected at the follow-up clinic 10 days postoperatively during ultrasonic examination (ultrasonic hydrocele). We report the use of ICG fluorescent lymphography during open inguinal hernia repair in a patient who developed postoperative ultrasonic hydrocele. This case may indicate a relationship between lymphatic vessel injury and hydrocele.


β-Lactam Exposure Triggers Reactive Oxygen Species Formation in Enterococcus faecalis via the Respiratory Chain Component DMK.
Whereas the primary actions of β-lactams are well characterized, their downstream effects are less well understood. Although their targets are extracellular, β-lactams stimulate respiration in Escherichia coli leading to increased intracellular accumulation of reactive oxygen species (ROS). Here, we show that β-lactams over a large concentration range trigger a strong increase in ROS production in Enterococcus faecalis under aerobic, but not anaerobic, conditions. Both amoxicillin, to which the bacterium is susceptible, and cefotaxime, to which E. faecalis is resistant, triggers this response. This stimulation of ROS formation depends mainly on demethylmenaquinone (DMK), a component of the E. faecalis respiratory chain, but in contrast to E. coli is observed only in the absence of respiration. Our results suggest that in E. faecalis, β-lactams increase electron flux through the respiratory chain, thereby stimulating the auto-oxidation of reduced DMK in the absence of respiration, which triggers increased extracellular ROS production.


Harrington rod distraction instrumentation: its effect on vertebral rotation and thoracic compensation.
The effects of Harrington rod distraction instrumentation on vertebral rotation and thoracic decompensation were investigated radiographically both pre- and post-operatively. A method for semiquantitatively evaluating thoracic decompensation is introduced to serve as an adjunct to the evaluation of spinal deformity. Although little derotation of the vertebrae occurs with lateral correction, thoracic decompensation should be significantly improved.


Dysgenesis of the corpus callosum and hypopituitarism.
A high resolution CT scan demonstrated the unexpected finding of dysgenesis of the corpus callosum in addition to the expected finding of pituitary hypoplasia in three children who presented with growth failure secondary to hypopituitarism. Several of the clinical features reported in association with dysgenesis of the corpus callosum may be ascribed to hypothalamo-pituitary dysfunction. These children emphasize the need to assess the endocrine function of patients with midline structural defects. It should not be assumed that the clinical manifestations are related solely to the anatomical abnormality.


Phase 3 trial of coronavir (favipiravir) in patients with mild to moderate COVID-19.
Favipiravir has demonstrated efficacy against the SARS-CoV-2 virus in several preliminary studies. This study aimed to evaluate the efficacy and safety of favipiravir for treatment of mild to moderate COVID-19 in outpatients and hospitalized patients. We conducted an open-label, randomized, active-controlled trial of a generic form of favipiravir in patients with COVID-19 confirmed by PCR-test. Eligible patients (18-60 years) after stratification were randomly assigned (in a 2:1 ratio) to receive either favipiravir (1800 mg BID on day 1, followed by 800 mg BID for up to 9 days), or standard of care (SOC) treatment (umifenovir + intranasal interferon alpha-2b, or hydroxychloroquine) for up to 10 days. The co-primary outcomes were the time to clinical improvement and the time to viral clearance. Among 190 patients assessed for eligibility 168 were randomized to favipiravir (n=112) or to SOC (n=56) group. The median time to clinical improvement was 6.0 days (IQR 4.0; 9.3) in the favipiravir group and 10.0 (IQR 5.0; 21.0) days in the SOC group; the median difference was 4 days (HR 1.63; 95% CI 1.14-2.34; P=0.007). The statistically significant difference in the median time to viral clearance was observed only for hospitalized patients: 3.0 (IQR 3.0; 3.0) days in the favipiravir group vs. 5.0 (IQR 4.5; 5.5) days in the SOC group (HR 2.11; 95% CI 1.04-4.31; P=0.038). The rate of viral elimination on Day 5 in the favipiravir group was significantly higher than in SOC group: 81.2% vs. 67.9% (RR 1.22; 05% CI 1.00-1.48; P=0.022). The rate of clinical improvement on Day 7 in the favipiravir group was 1.5-fold higher than in SOC group: 52.7% vs. 35.8% (RR 1.50; 95% CI 1.02-2.22; P=0.020). Favipiravir was well-tolerated and the most common adverse reactions were asymptomatic hyperuricemia, transient elevation of ALT & AST, and mild gastrointestinal disorders. Favipiravir was superior to the SOC in shortening the time to clinical improvement in patients with mild to moderate COVID-19.


An initiator-free and solvent-free in-situ self-catalyzed crosslinked polymer electrolyte for all-solid-state lithium-metal batteries.
Linear polymer (e.g. polyethylene oxide, PEO) based electrolytes have been widely studied due to their flexibility and relatively good contact against electrodes. However, the linear polymers are prone to crystallization at room temperature and melting at moderate temperature, restricting their application in lithium metal batteries. To address these problems, a self-catalyzed crosslinked polymer electrolyte (CPE) was designed and prepared by the reaction of poly (ethylene glycol diglycidyl ether) (PEGDGE) and polyoxypropylenediamine (PPO) with only the bistrifluoromethanesulfonimide lithium salt (LiTFSI) added and with no any initiators. LiTFSI catalyzed the reaction by reducing the activation energy to form a crosslinked network structure, which was identified by calculation, NMR and FTIR. The as-prepared CPE has high resilience and a low glass transition temperature (Tg = -60 °C). Meanwhile, the solvent-free in-situ polymerization technique has been adopted in the assembly of the CPE with electrodes to decrease the interfacial impedance greatly and improve the ionic conductivity to 2.05 × 10-5 S cm-1 and 2.55 × 10-4 S cm-1 at room temperature and 75 °C, respectively. As a result, the in-situ LiFeO4/CPE/Li battery exhibits outstanding thermal and electrochemical stability at 75 °C. Our work has proposed an initiator-free and solvent-free in-situ self-catalyzed strategy of preparing high performance crosslinked solid polymer electrolytes.


The impact of thyroid diseases starting from birth on reproductive function.
The aim of this review is to provide relevant information regarding the impact of thyroid disease, starting from birth and mainly concerning hyperthyroidism and hypothyroidism, on reproduction. Hyperthyroidism occurs much less commonly in children than hypothyroidism, with Graves' disease (GD) being the most common cause of thyrotoxicosis in children. Children born with neonatal GD have no defects in the reproductive system that could be related to hyperthyroidism. Current treatment options include antithyroid drugs (ATD), surgery, and radioactive iodine (RAI). In males, normal thyroid function seems important, at least in some parameters, for maintenance of semen quality via genomic or non-genomic mechanisms, either by locally acting on Sertoli cells, Leydig cells, or germ cells, or by affecting crosstalk between the HPT axis and the HPG axis. Sexual behavior may also be affected in thyroxic men, although many of these patients may have normal free testosterone levels. In women, menstrual irregularities are the most common reproduction-related symptoms in thyrotoxicosis, while this disorder is also associated with reduced fertility, although most women remain ovulatory. An increase in sex hormone-binding globulin (SHBG) and androgens, thyroid autoimmunity, and an impact on uterine oxidative stress are the main pathophysiological mechanisms which may influence female fertility. Thyroid hormones are responsible for normal growth and development during pre- and postnatal life, congenital hypothyroidism (CH) being the most common cause of neonatal thyroid disorders, affecting about one newborn infant in 3500. The reproductive tract appears to develop normally in cretins. Today, CH-screening programs allow for early identification and treatment, and, as a result, affected children now achieve normal or near-normal development. Hypothyroidism in males is associated with decreased libido or impotence. Although little is currently known about the effects of hypothyroidism on spermatogenesis and fertility, it has been established that sperm morphology and motility are mainly affected. In women of reproductive age, hypothyroidism results in changes in cycle length and amount of bleeding. Moreover, a negative effect on fertility and higher miscarriage rates has also been described.


White blood-cell count and the risk of impaired fasting glucose or Type II diabetes in middle-aged Japanese men.
To investigate the association between white blood-cell (WBC) count and the development of diabetes, independent of cigarette smoking. We examined 2953 Japanese men who were office workers and between 35 and 59 years of age and who did not have impaired fasting glucose (IFG) (a fasting glucose concentration of 6.1-6.9 mmol/l), Type II (non-insulin-dependent) diabetes mellitus (a fasting glucose concentration of > or =7.0 mmol/l or more or receipt of hypoglycaemic medication), medication for hypertension, and a history of cardiovascular disease. Fasting glucose concentrations were measured at annual health examinations from May 1994 through May 2000. After controlling for potential predictors of diabetes, the relative risk for IFG or Type II diabetes mellitus compared with a WBC count of less than 5.3-10(9) cells/l was 1.2 (95 %-CI, 0.6-2.3), 1.6 (CI, 0.8-3.1), and 2.5 (CI, 1.2-5.1) among non-smokers (p for trend = 0.009): and 1.0 (CI, 0.4-2.5), 2.3 (CI, 1.0-5.1), and 3.1 (CI, 1.4-7.1) among ex-smokers (p for trend = 0.001) with WBC counts of 5.3-6.1, 6.2-7.2, and 7.3-10(9) cells/l or more, respectively. Among current smokers, the respective multivariate-adjusted relative risks for IFG or Type II diabetes mellitus were 1.1 (CI, 0.6-2.1), 1.4 (CI, 0.8-2.4), and 1.2 (CI, 0.7-2.1) (p for trend = 0.460). Although the selection of a rigorously normoglycaemic cohort might have had an influence on these observations, higher WBC counts seem to predict the development of IFG or Type II diabetes mellitus, primarily in non-smokers.


The yeast two-hybrid system and its role in drug discovery.
The yeast two-hybrid system is the most widely used genetic assay to identify and characterize novel protein interactions. Over the past decade, the system has been adapted to cover an increasingly wide range of applications, including various tasks within the drug discovery and development process. We highlight the role of different two-hybrid systems within the drug discovery process, including target identification and validation and the selection of affinity reagents for protein targets, such as peptides and small molecules. We have focused on applications where the two-hybrid system has been used to great advantage and have sought to put a special emphasis on less conventional but promising approaches, such as the identification of agents which block therapeutically relevant protein interactions. The yeast two-hybrid system has evolved from a method mainly used in basic research to a collection of versatile screening systems with the potential to affect many different aspects of drug discovery today.


Differential effects of religiosity on sexual initiation among Nigerian in-school adolescents.
Sexual initiation in adolescence has significant health implications; identifying associated risk and protective factors is critical for context-specific evidence-based interventions. This study examined the influence of religiosity on sexual debut among in-school adolescents in Lagos State, Nigeria. Data was obtained from 1350 randomly selected in-school adolescents using a self-administered questionnaire. Internal and external religiosity, defined based on the extant literature, were the independent variables. The dependent variable was "ever had sex." The association between religiosity and the age of sexual debut was assessed using Cox regression and controlling for relevant covariates. The hazard ratio (HR) and 95% confidence interval (CI) were calculated. Of the participants, 19.8% of the females and 26.6% of the males have had sex (p<0.004). Internal religiosity was protective against sexual debut among females (HR=0.63, 95% CI=0.44-0.91), whereas external religiosity was protective among the males (HR=0.70, 95% CI=0.51-0.71). Age was positively associated with sexual debut among both male (HR=1.11, 95% CI=1.001-1.24) and female adolescents (HR=1.26, 95% CI=1.11-1.42). Early pubertal development (HR=1.11; 95% CI=1.001-1.24) was also a risk factor for male adolescent sexual initiation. In addition, knowledge of HIV/AIDS risk (HR=0.47; 95% CI=0.30-0.72) was a protective factor against sexual debut among adolescent females, whereas the positive perspective of friends' involvement in sex (HR=1.014; 95% CI=1.21-2.58) was a risk factor. The protective effect of internal and external religiosity with regards to sexual debut varied by gender among Nigerian in-school adolescents; the gender differences as well as other significant factors should be taken into account in evidence-based programming to address adolescent sexual health challenges in Nigeria.


Low hemorrhage-related mortality in trauma patients in a Level I trauma center employing transfusion packages and early thromboelastography-directed hemostatic resuscitation with plasma and platelets.
Hemorrhage accounts for most preventable trauma deaths, but still the optimal strategy for hemostatic resuscitation remains debated. This was a prospective study of adult trauma patients admitted to a Level I trauma center. Demography, Injury Severity Score (ISS), transfusion therapy, and mortality were registered. Hemostatic resuscitation was based on a massive transfusion protocol encompassing transfusion packages and thromboelastography (TEG)-guided therapy. A total of 182 patients were included (75% males, median age 43 years, ISS of 17, 92% with blunt trauma). Overall 28-day mortality was 12% with causes of death being exsanguinations (14%), traumatic brain injury (72%, two-thirds expiring within 24 hr), and other (14%). One-fourth, 16 and 15% of the patients, received red blood cells (RBCs), plasma, or platelets (PLTs) within 2 hours from admission and 68, 71, and 75%, respectively, of patients transfused within 24 hours received the respective blood products within the first 2 hours. In patients transfused within 24 hours, the median number of blood products at 2 hours was 5 units of RBCs, 5 units of plasma, and 2 units of PLT concentrates. Nonsurvivors had lower clot strength by kaolin-activated TEG and TEG functional fibrinogen and lower kaolin-tissue factor-activated TEG α-angle and lysis after 30 minutes compared to survivors. None of the TEG variables were independent predictors of massive transfusion or mortality. Three-fourths of the patients transfused with plasma or PLTs within 24 hours received these in the first 2 hours. Hemorrhage caused 14% of the deaths. We introduced transfusion packages and early TEG-directed hemostatic resuscitation at our hospital 10 years ago and this may have contributed to reducing hemorrhagic trauma deaths.


Single-dose pharmacokinetics of lomefloxacin in patients with normal and impaired renal function.
The quinolone antibiotic lomefloxacin was administered as a 400 mg single oral dose to 12 subjects with renal impairment (creatinine clearance 5-65 mL/min/1.73 m2) and to 13 healthy subjects (creatinine clearance 80-135 mL/min/1.73 m2). The concentrations of lomefloxacin in plasma and urine were determined by high-pressure liquid chromatography up to 48 hours post-administration. Linear correlations were found between lomefloxacin plasma and renal clearances and creatinine clearance. The mean nonrenal clearance of lomefloxacin (approximately 32 mL/min/1.72 m2) was not influenced by renal function. The mean plasma clearances of lomefloxacin in healthy subjects and in a subgroup of patients with severe renal impairment (creatinine clearance 5-15 mL/min/1.73 m2) were 209 and 43 mL/min/1.73 m2, respectively. The decrease in plasma clearance of lomefloxacin was explained fully by the decrease in renal clearance. The elimination half-life of lomefloxacin increased significantly with the degree of renal impairment, from 7.5 hours in normal subjects to 26.9 hours in subjects with severe renal impairment. The maximum serum concentration and the time to maximum serum concentration were not significantly affected by renal function. The pharmacokinetics of lomefloxacin are dependent on renal function, and appropriate dosage adjustment is necessary when creatinine clearance is less than 30 mL/min/1.73 m2.


Metal-free visible-induced C(sp2)-C(sp2) coupling of quinoxalin-2(H)-ones via oxidative cleavage of the C-N bond.
A C(sp2)-C(sp2) reaction between aromatic hydrazines and quinoxalines has been developed through a photocatalytic system. The protocol is established for C(sp2)-N bond cleavage and direct C(sp2)-H functionalization for the coupling of C(sp2)-C(sp2) via photocatalysis under mild and ideal air conditions without the presence of a strong base and metal. The mechanistic studies reveal that the generation of a benzene radical via the oxidative cleavage of aromatic hydrazines for the cross-coupling of C(sp2)-C(sp2) with the assistance of a photocatalyst is essential. The process exhibits excellent compatibility with functional groups and provides convenient access to various 3-arylquinoxalin-2(1H)-ones in good to excellent yields.


[The 2009 pandemic influenza A (H1N1) virus infection: experience of a paediatric service at a third-level hospital in Lisbon, Portugal].
The 2009 pandemic influenza A (H1N1) (i.e., Pandemic Influenza) is an acute, infectious illness caused by the influenza A (H1N1) 2009 virus. This disease involves respiratory, gastrointestinal and systemic symptoms along with a high incidence occurring at a paediatric age. To study the epidemiology, approach and complications of Pandemic Influenza in the paediatric population of a third-level hospital in Lisbon, Portugal, between September and December 2009. A retrospective study of children who had received the influenza A (H1N1) 2009 virus test by real time reverse transcriptase-polymerase chain reaction (RT-PCR) were included. The following parameters were analysed: number of tests, days of illness, sex, outcome, age, symptoms, hospitalisation and reason for testing. The distribution and test results were compared with the Pandemic Influenza activity in Portugal. Moreover, among the confirmed cases of infection, the need for hospitalisation, risk factors, severity, chest radiography, treatment and complications were also examined. A total of 351 tests were performed, on average, 2.6 days after initial symptoms, which included 71.8% outpatients and 30% children younger than three years of age. Overall, 54.4% of the tests were positive for the influenza A (H1N1) 2009 virus and the main comorbidities were respiratory and cardiovascular in nature. One hundred ninety-one cases were confirmed by laboratory studies, and 13.6% required hospitalisation, which lasted an average of 2.7 days. In 82.2% of the cases, the severity was mild, with fever and cough as the most frequent symptoms at 91.9% and 93.7%, respectively. Therapy with the antiviral drug, oseltamivir, was implemented in 35.6% of the cases. Additionally, oseltamivir was used in twelve infants younger than one year in age, including a one-month-old infant with no observed side effects. The epidemiological data obtained are consistent with the published national and international studies. The scientific information available and the recommendations of the irectorate-General for Health contributed to the uniformity of the approaches and the successful outcome.


Gut disease in systemic sclerosis - new approaches to common problems.
The goal of this manuscript is to discuss the new diagnostic and potential treatment options for gut disease in systemic sclerosis (SSc). The concepts of quantification of gut perfusion and motility is reviewed. The risks of empiric therapeutics and challenges of studying the microbiome in SSc is discussed. There are diagnostics that can provide information on gut perfusion and function that are of value in SSc. Easily implemented diagnostic tests are critical to avoid complications of empiric therapy. The role of the microbiome and drugs that target dysmotility are areas of active research. SSc-related gastrointestinal tract involvement can be heterogeneous in clinical presentation and disease course. Noninvasive gastrointestinal measurement techniques that quantify neural communications with microvasculature in SSc can potentially guide the proper addition and discontinuation of therapeutics. The role of the microbiome and the role of nitric oxide on gut function are important areas of research for understanding gut dysfunction in SSc.


Fundoplication and pediatric esophageal manometry: actuarial analysis over 7 years.
Sixty-one children and infants who had significant gastroesophageal reflux and associated complications underwent 73 surgical procedures to control the reflux. In order to evaluate the procedure, several esophageal manograms were obtained from each patient, before, during, and after the operation. Delayed follow-up reports were also obtained from follow-up visits, letter and telephone contact, in order to assess how the patient had progressed. The results were evaluated by actuarial analytic methods. Ninety-four percent of the patients remained alive over the 7-year follow-up period. At the completion of the seventh year, 62% of these patients (actuarially calculated) remained event free. All events occurred within 18 months of surgery. One patient could not be traced at long-term follow-up, which was therefore 92% complete. The 7-year actuarial probability of failure of the fundoplication at this institution is 24% when performed using this technique in these patients. These findings support that manometric calibration of the antireflux procedure tends to give uniform results in pediatric patients, but, compared with other published series has not proved to be superior to procedures that employ only a rubber bougie in the esophagus as an obdurator to prevent a repair that will be too tight.


Juvenile rhegmatogenous retinal detachment.
Between Jan 1, 1966, and June 30, 1974, 179 children, birth through 16 years of age with rhegmatogenous retinal detachments, underwent scleralbuckling procedures at Wills Eye Hospital. The detachments were associated most frequently with trauma (44%), myopia (15%), aphakia (10%), and retinopathy of prematurity (8%). Successful reattachment was achieved in 80% of the cases. Vision of 20/100 or better was present in 22% preoperatively and 58% postoperatively.


Extracytoplasmic processes impaired by inactivation of trxA (thioredoxin gene) in Bacillus subtilis.
The trxA gene is regarded as essential in Bacillus subtilis, but the roles of the TrxA protein in this gram-positive bacterium are largely unknown. Inactivation of trxA results in deoxyribonucleoside and cysteine or methionine auxotrophy. This phenotype is expected if the TrxA protein is important for the activity of the class Ib ribonucleotide reductase and adenosine-5'-phosphosulfate/3'-phosphoadenosine-5'-phosphosulfate reductase. We demonstrate here that a TrxA deficiency in addition causes defects in endospore and cytochrome c synthesis. These effects were suppressed by BdbD deficiency, indicating that TrxA in the cytoplasm is the primary electron donor to several different thiol-disulfide oxidoreductases active on the outer side of the B. subtilis cytoplasmic membrane.


[Urethroplasty in long strictures of the anterior urethra].
Strictures of the male urethra are always very serious therapeutic problem, regardless of their localization. The presence of variety of surgical modalities for their treatment, impose the need for differentiated approach and clear criteria for their use. Particularly interesting for the clinicians and the researchers are the long strictures of the anterior urethra For period of 12 years (1992-2004) 56 patients with urethral strictures were diagnosed, operated and followed. Of them 38 (67.9%) have stricture of the anterior urethra and 18 (32.1%) strictures of posterior urethra. In patients with stricture of the anterior urethra in 16(42.1%) the length of the stricture was between 2 and 5 cm, in 13 (34.2%) over 5 cm, and in 9 (23.7%) had multiple strictures. In patients with length of the stricture over 5 cm three surgical modalities of urethroplasty were mainly applied: free buccal mucosa graft--7 (53.8%); pediculated preputial flap--4 (30.8%) and longitudinal ventral skin flap--2 (15.4). Late results of the treatment of patients with long strictures of the anterior urethra show that in 76.9% of cases there is good and lasting patency of the urethra. In 2 cases (15.4%) formation of pseudodiverticula was observed, in another 2 (15.4%)--restrictures in the site of anastomosis, and in 1 (7.7%)--formation of urethral fistula. The long strictures of the urethra are extremely serious therapeutic problem, which demands a precise choice of the surgical technique for their treatment. The introduction in practice of the buccal mucosa graft urethroplasty sharply improved the options for treatment of this disease.


Varicose vein stripping vs haemodynamic correction (CHIVA): a long term randomised trial.
To compare the long-term results of stripping vs. haemodynamic correction (Ambulatory Conservative Haemodynamic Management of Varicose Veins, CHIVA) in the treatment of superficial venous incompetence resulting in chronic venous disease (CVD). Randomised comparative trial. 150 patients affected by CVD, CEAP clinical class 2-6, were randomised to saphenous stripping or to CHIVA. The clinical outcome was assessed by an independent observer who recorded the Hobbs clinical score for treated limbs. A subjective report of the outcome was provided by the patients. Recurrence of varices was assessed by both clinical examination and duplex ultrasonography. The mean follow-up was 10 years, 26 patients were lost to follow-up. The Hobbs score similar in the stripping and CHIVA groups. However recurrence of varicose veins was significantly higher in the stripping group (CHIVA 18%; stripping 35%, P<0.04 Fisher's exact test), without significant differences in the rate of recurrences from the sapheno-femoral junction. The associated risk of recurrence at ten years was doubled in the stripping group (OR 2.2, 95% CI 1-5, P=0.04). Recurrent varices occurred more frequently following saphenous stripping than after CHIVA treatment. The deliberate preservation of the saphenous trunk as a route of venous drainage in the CHIVA group may have been a factor reducing the recurrence rate.


PRDM14 promotes malignant phenotype and correlates with poor prognosis in colorectal cancer.
Emerging evidence suggests that stemness in cancer cells is a cause of drug resistance or metastasis and is an important therapeutic target. PR [positive regulatory domain I-binding factor 1 (PRDI-BF1) and retinoblastoma protein-interacting zinc finger gene (RIZ1)] domain containing 14 (PRDM14), that regulates pluripotency in primordial germ cell, has reported the overexpression and function of stemness in various malignancies, suggesting it as the possible therapeutic target. However, to our knowledge, there have been no reports on the expression and function of PRDM14 in colorectal cancer (CRC). Therefore, we investigated the expression and the role of PRDM14 in CRC. We performed immunohistochemistry evaluations and assessed PRDM14 expression on 414 primary CRC specimens. Colon cancer cell lines were subjected to functional and stemness assays in vitro and in vivo. We found that PRDM14 positive staining exhibited heterogeneity in the CRC primary tumor, especially at the tumor invasion front. The aberrant expression of PRDM14 at the invasion front was associated with lymph node metastasis and disease stage in patients with CRC. Furthermore, the multivariate analysis revealed high PRDM14 expression as an independent prognostic factor in the patients with Stage III CRC. Overexpression of PRDM14 enhanced the invasive, drug-resistant and stem-like properties in colon cancer cells in vitro and tumorigenicity in vivo. Our findings suggest that PRDM14 is involved in progression and chemoresistance of CRC, and is a potential prognostic biomarker and therapeutic target in the CRC patients.


Demonstration of an associated anisotropy decay by frequency-domain fluorometry.
We used frequency-domain fluorometry to demonstrate the presence of an associated decay of fluorescence anisotropy. In such systems the individual correlation times are associated with distinct emitting species, each with its own characteristic lifetime and rotational correlation times. We obtained an associated system using 1-anilino-8-naphthalenesulfonic acid (ANS) in the presence of increasing amounts of apomyoglobin. When both free and apomyoglobin-bound ANS contributed to the emission the differential polarized phase angles become negative at particular frequencies, even though the fundamental anisotropy (r0) is greater than zero. Additionally, the modulated anisotropy decreases at high frequencies. Both observations appear to be the unique consequence of an associated anisotropy decay, and are not possible for a multiexponential anisotropy decay of a single species.


Leucine improves growth performance of intrauterine growth retardation piglets by modifying gene and protein expression related to protein synthesis.
Leucine has been reported to alter the gene expression of proteins, the activation of signaling components, and the fractional rates of protein synthesis in multiple organs of piglets. The aim of this study was to investigate the effects of leucine on molecular mechanisms regulating protein synthesis and degradation in skeletal muscle and determine how these adaptations affect body weight gain in intrauterine growth retardation (IUGR) pigs. Thirty-two weaned piglets were randomly assigned to the following four experimental groups (n = 8 per group): normal birth weight, normal birth weight supplemented with leucine, IUGR, and IUGR supplemented with leucine. Piglets were fed from 14 to 35 d of age. Growth performance, major serum biochemical parameters, and enzyme activities were evaluated. The messenger RNA expression of muscle mammalian target of rapamycin (mTOR), muscle atrophy F-box (MAFbx), and muscle-specific ring finger-1 were investigated. Additionally, total and phosphorylated levels of mTOR and ribosomal protein S6 kinase 1 were measured in longissimus muscle. Average daily weight gain and average daily feed intake were increased by leucine in IUGR pigs. At the end of the experiment, IUGR pigs had lower liver and kidney weight compared with the normal piglets. However, IUGR supplemented with leucine decreased serum concentration of urea. Leucine supplementation affected the concentrations of isoleucine, valine, lysine, and phenylalanine in serum. There was no significant difference in the expression of mTOR and muscle-specific ring finger-1 in IUGR piglets, whereas muscle atrophy F-box was reduced only by IUGR dependent of leucine. Compared with the IC group, dietary supplementation with 0.35% l-leucine increased the phosphorylated levels of mTOR and ribosomal S6 kinase 1 in IUGR piglets. The present study identified a major role for leucine in the activation of the mTOR signaling pathway and reducing muscle atrophy in IUGR piglets, which contributed significantly to differences in body weight gain.


Prevalence and factors associated with severe depressive symptoms in older west African people living with HIV.
Depression is one of the most common psychiatric disorders in people living with HIV (PLHIV). Depression has a negative impact on both mental and physical health and is mainly associated with suboptimal HIV treatment outcomes. To encourage successful aging and the achievement of the 3 × 90 objectives in older PLHIV, the psychological domain must not be neglected. In this context and as data are scarce in West Africa, this study aimed to evaluate the prevalence and the factors associated with severe depressive symptoms in older PLHIV living in this region of the world. Data from PLHIV aged ≥50 years and on ART since ≥6 months were collected in three clinics (two in Côte d'Ivoire, one in Senegal) participating in the West Africa International epidemiological Databases to Evaluate AIDS (IeDEA) collaboration. The severity of depressive symptoms was measured using the Center for Epidemiological Studies Depression scale (CES-D), and associated factors were identified using logistic regressions. The median age of the 334 PLHIV included in the study was 56.7 (53.5-61.1), 57.8% were female, and 87.1% had an undetectable viral load. The prevalence of severe depressive symptoms was 17.9% [95% Confidence Interval (95% CI): 13.8-22.0]. PLHIV with severe depressive symptoms were more likely to be unemployed (adjusted Odd Ratio (aOR) = 2.8; 95% CI: 1.4-5.7), and to be current or former tobacco smokers (aOR = 2.6; 95% CI: 1.3-5.4) but were less likely to be overweight or obese (aOR = 0.4; 95% CI: 0.2-0.8). The prevalence of severe depressive symptoms is high among older PLHIV living in West Africa. Unemployed PLHIV and tobacco smokers should be seen as vulnerable and in need of additional support. Further studies are needed to describe in more details the reality of the aging experience for PLHIV living in SSA. The integration of screening and management of depression in the standard of care of PLHIV is crucial.


Synaptically identified hippocampal slow potentials during behavior.
Averaged evoked slow-wave potentials (AEPs) were recorded from various locations within the dentate gyrus and CA1 field of the hippocampus of 16 rats during the performance of an operant tone discrimination task. Consistent time-locked tone averaged evoked potentials (AEPs) were recorded from the perforant path zone in the outer molecular layer of the dentate gyrus. Tone AEPs were never present in this region (1) prior to development of the discrimination, (2) during behavioral extinction, or (3) during the performance of other operant behaviors. Results are discussed in terms of the functions of the perforant path in neural and behavioral plasticity.


Everyday life after a hip fracture: what community-living older adults perceive as most beneficial for their recovery.
to gain insight into what older adults after hip fracture perceive as most beneficial to their recovery to everyday life. qualitative research approach. six skilled nursing facilities. 19 older community dwelling older adults (aged 65-94), who had recently received geriatric rehabilitation after hip fracture. semi-structured interviews were conducted with 19 older adults after hip fracture. Coding techniques based on constructivist grounded theory were applied. four categories were derived from the data: 'restrictions for everyday life', 'recovery process', 'resources for recovery' and 'performing everyday activities'. Physical and psychological restrictions are consequences of hip fracture that older adults have struggled to address during recovery. Three different resources were found to be beneficial for recovery; 'supporting and coaching', 'myself' and 'technological support'. These resources influenced the recovery process. Having successful experiences during recovery led to doing everyday activities in the same manner as before; unsuccessful experiences led to ceasing certain activities altogether. participants highlight their own role ('myself') as essential for recovery. Additionally, coaching provides emotional support, which boosts self-confidence in performing everyday activities. Furthermore, technology can encourage older adults to become more active and being engaged in the recovery process. The findings suggest that more attention should be paid to follow-up interventions after discharge from inpatient rehabilitation to support older adults in finding new routines in their everyday activities.A conceptual model is presented and provides an understanding of the participants' experiences and perspectives concerning their process of recovery after hip fracture to everyday life.


Cost-effectiveness of cognitive behaviour therapy in addition to mebeverine for irritable bowel syndrome.
Irritable bowel syndrome is often treated in primary-care settings, and it has a relatively large economic impact. Cognitive behaviour therapy (CBT) in addition to mebeverine has been shown to be effective in the short term, compared with treatment with mebeverine alone. This study assesses the impact that CBT in addition to mebeverine has on resource use, and its cost-effectiveness. Participants were recruited from general practices: those with ongoing symptoms were randomly allocated either to remain just on mebeverine or to receive CBT in addition to mebeverine. Service use and lost employment were measured at baseline and at the 3-month, 6-month and 12-month follow-ups. The net-benefit approach was used for combining the data on therapy costs and symptoms. The mean additional cost of CBT was pound 308. No significant impact of CBT on the use of other services or on lost employment was noted. The cost per clinically important reduction in symptoms was pound 220 by the end of treatment, pound 171 at the 3-month follow-up, pound 1027 at the 6-month follow-up and pound 3080 at the 12-month follow-up, for CBT in addition to mebeverine compared with mebeverine alone. CBT in addition to mebeverine seems to have reasonable cost-effectiveness in the short-term treatment of irritable bowel syndrome, but not beyond 3 months.


Topiramate enhances the risk of valproate-associated side effects in three children.
We present three children with severe therapy-refractory epilepsy who tolerated valproate (VPA) well in various combinations with other antiepileptic drugs (AEDs) but developed typical VPA side effects in combination with topiramate (TPM). The clinical symptoms began with apathy in all three children; two of them also had hypothermia. Furthermore all children had elevated blood ammonia levels, one child in combination with increased liver transaminases and one with thrombocytopenia. All children recovered completely after discontinuation of VPA or TPM. TPM seems likely to enhance the risk of side effects usually attributed to VPA and not described in TPM monotherapy. Our case reports suggest that possible adverse effects of VPA should be given particular attention when VPA is combined with TPM.


The measured effect of phenytoin withdrawal on gingival hyperplasia in children.
Gingival enlargement was studied and measured in ten patients before, and for 18 months after discontinuation of phenytoin therapy. A clinically evident decrease in gingival hyperplasia occurred after discontinuing phenytoin in all subjects; all subjects, however, had mild hyperplasia after 18 months. These results may encourage increased use of alternative antiseizure drugs.


Analysis of drug-endogenous human metabolite similarities in terms of their maximum common substructures.
In previous work, we have assessed the structural similarities between marketed drugs ('drugs') and endogenous natural human metabolites ('metabolites' or 'endogenites'), using 'fingerprint' methods in common use, and the Tanimoto and Tversky similarity metrics, finding that the fingerprint encoding used had a dramatic effect on the apparent similarities observed. By contrast, the maximal common substructure (MCS), when the means of determining it is fixed, is a means of determining similarities that is largely independent of the fingerprints, and also has a clear chemical meaning. We here explored the utility of the MCS and metrics derived therefrom. In many cases, a shared scaffold helps cluster drugs and endogenites, and gives insight into enzymes (in particular transporters) that they both share. Tanimoto and Tversky similarities based on the MCS tend to be smaller than those based on the MACCS fingerprint-type encoding, though the converse is also true for a significant fraction of the comparisons. While no single molecular descriptor can account for these differences, a machine learning-based analysis of the nature of the differences (MACCS_Tanimoto vs MCS_Tversky) shows that they are indeed deterministic, although the features that are used in the model to account for this vary greatly with each individual drug. The extent of its utility and interpretability vary with the drug of interest, implying that while MCS is neither 'better' nor 'worse' for every drug-endogenite comparison, it is sufficiently different to be of value. The overall conclusion is thus that the use of the MCS provides an additional and valuable strategy for understanding the structural basis for similarities between synthetic, marketed drugs and natural intermediary metabolites.


Photochemical generation of C4'-oxidized abasic site containing oligodeoxynucleotide and its efficient amine modification.
[Structure: see text] We synthesized oligodeoxynucleotide (ODN, 3), which contains 4'-o-nitrobenzyloxythymidine (4) as a caged precursor of C4'-oxidized abasic site (1). Photoirradiation of 3 at 365 nm followed by amine treatment under neutral conditions afforded the lactam (2) efficiently. Duplexed ODN 3 was converted to 1 faster and more efficiently than single stranded 3, whereas amine treatment of 1 formed from single stranded 3 resulted in slightly faster lactam formation than with the duplex.


The minimally conscious state: defining the borders of consciousness.
There is no agreement as to where the limits of consciousness lie, or even if these putative borders exist. Problems inherent to the study of consciousness continue to confound efforts to establish a universally accepted theory of consciousness. Consequently, clinical definitions of consciousness and unconsciousness are unavoidably arbitrary. Recently, a condition of severely altered consciousness has been described, which characterizes the borderzone between the vegetative state and so-called "normal" consciousness. This condition, referred to as the minimally conscious state (MCS), is distinguished from the vegetative state by the presence of minimal but clearly discernible behavioral evidence of self or environmental awareness. This chapter reviews the diagnostic criteria, pathophysiology, prognostic relevance, neurobehavioral assessment procedures and treatment implications associated with MCS.


[Chemical Constituents from Periplaneta americana].
To study the chemical constituents in Periplaneta americana. The chemical constituents were separated and purified by chromatographic methods after solvent extraction and identified by spectroscopic analyses. Ten compounds were isolated from Periplaneta americana and identified as following: 8-hydroxy-3,4-dihydroquinolin-2 (1H)-one (1), cyclo-( L-Phe-L-Pro) (2), cyclo-(Pro-Ile) (3), cyclo-(L-Pro-D-Leu) (4), brevianamide F (5), cyclo-(Ile-Ala) (6), cyclo-( L-Val-L-Pro) (7), cyclo-(L-Pro-L-Tyr) (8), cyclo-(Trp-Val)-dipeptide (9), and (-)-(1S, 3S)-1-methyl-1,2,3,4-tetrahydro-β-carboline-3-carboxylic acid (10). Compounds 2 - 9 are isolated from Periplaneta americana for the first time.


Percutaneous obliteration of patent processus vaginalis: a rat model for future inguinal hernia repair in children.
Inguinal hernia repair is one of the most common procedures performed by pediatric surgeons. A percutaneous technique could be the next advance in inguinal hernia repair in children. We used a rat model to study the utility of percutaneous inguinal hernia repair (PHR) using 2-octyl-cyanoacrylate (OCT). Four-week-old Lewis male rats were randomly divided into three groups: bilateral PHR group (BH) (n=15), unilateral PHR group (UH) (n=12), and sham group (n=14). After inducing a pneumoperitoneum, a 24-gauge cannula was advanced into the patent processus vaginalis (PPV) once air was aspirated. The canal is then obliterated by injecting 0.2 ml of 2-octyl-cyanoacrylate. Mating and herniography were performed at postoperative weeks 2 and 6, respectively. All rats were sacrificed at week 12. Herniography revealed complete closure of PPV in (25/30) BH, (12/12) UH, and (0/28) of the sham group. All OCT-treated sides were found obliterated at the post-mortem gross examination. Histological analysis of the inguinal region revealed patent vase in all rats. However, mild to moderate foreign body reactions and fat necrosis were noticed at the injected sites. All rats demonstrated fertility at mating. Percutaneous obliteration of PPV was feasible and safe in rats and potentially less invasive than the current techniques used in children. However, demonstrating long-term effectiveness, the need for pneumoperitoneum and the risk of OCT intraperitoneal spillage remain as challenges to overcome.


We're working hard, but is it hardly working? Why process is critical in the delivery of worksite health promotion programs.
To evaluate the relationship between the process and outcomes of worksite wellness committees (WWCs) implementing worksite health promotion programs at PPG Industries, Inc. We developed two unique tools to understand how WWCs function and to assess their program implementation. We then analyzed survey data from 65 PPG worksites, measuring process and program implementation. Worksites that scored higher on the process indicator had more robust program implementation. The WWCs need increased attention from researchers and evaluators. Employers should consider administering worksite health promotion structural assessments to identify gaps in management support and program implementation that may influence program effectiveness.


Patients with a body surface area less than 1.7 m2 have a good outcome with the CardioWest Total Artificial Heart.
A body surface area (BSA) of 1.7 m2 was considered as the lower limit to implant a CardioWest Total Artificial Heart (TAH). We reviewed our experience with the TAH in patients with a BSA of less than 1.7 m2. From April 1986 to May 2003, among 149 patients implanted with a TAH in our institution, 30 had a BSA of less than 1.7 m2 (Group I). Results were compared with the remaining 119 patients (Group II). One patient in Group I experienced a fitting problem and was left with the chest open. Otherwise, in this group, the Day 1 cardiac index averaged 3.6 +/- 0.6 liter/min/m2, which was significantly higher than the 2.8 +/- 0.36 liter/min/m2 observed in Group II. Post-implantation central venous pressure and mean arterial pressure were similar in both groups: 14.7 +/- 3.8 mm Hg vs 14.5 +/- 4 mm Hg and 87 +/- 23 mm Hg vs 88 +/- 19 mm Hg, respectively. In Group I, survival on the device dramatically increased from 9% before 1992, to 36% between 1992 and 1997 and finally reached 75% after then. In the meantime, for the same time periods, global survival to hospital discharge increased from 9% to 36% and reached 50% after 1997. In Group II, global survival to hospital discharge was 25.5% before 1992, 34.6% between 1993 and 1997, and reached 52% thereafter. The CardioWest TAH can be used in patients with a BSA between 1.5 m2 and 1.7 m2 with few fitting problems. In this group of patients, results are similar to those obtained in patients with a BSA greater than 1.8 m2.


The effect of short term contact lens wear on the tear film and ocular surface characteristics of tolerant and intolerant wearers.
The purpose of this study was to determine the effect of contact lens wear on the tear film and ocular surface of people tolerant or intolerant to contact lens wear. Twenty subjects participated; 11 tolerants and nine intolerants. Their baseline tear film (no lens wear) was analysed with a range of clinical measurements and protein analyses (lactoferrin, sIgA and lysozyme). The tests were then repeated at the end of 6h of contact lens wear during the day and while lenses were worn. Both tolerants and intolerants showed statistically significant increases in bulbar and overall conjunctival redness after 6h of lens wear. For tolerants only, there was a statistically significant increase in the tear film meniscus area (0.08 mm(2) +/- 0.04 compared to 0.14 mm(2) +/- 0.06 (p = 0.023)) and a statistically significant decrease in the non-invasive tear film break-up time (NI-TBUT; 21.3 s +/- 5.7 compared to 3.7 s +/- 4.3 (p = 0.003)) after 6h of lens wear. There were no changes in other tear film or ocular surface parameters. The protein concentration and lipid layer appearance did not change during lens wear for either population. Prior to lens wear, tolerant subjects had a statistically longer NI-TBUT, higher phenol red thread test and higher tear flow rate. After 6h of lens wear and while wearing lenses, all but NI-TBUT remained statistically different. Lens wear affected only a small number of clinical variables and 6h wear did not effect the concentration of those proteins measured in tears in this study.


Implementation of the HIF activator IOX-2 in routine doping controls - Pilot study data.
Early in 2020, racehorse doping cases revolved around the hypoxia-inducible factor (HIF) activator IOX-2. While the composition of IOX-2 has also been known and monitored in human doping controls for several years, the testing capability of routine sports drug testing methods was revisited for this newly surfaced doping agent. IOX-2 and the analytically well-established HIF activator roxadustat (FG-4592) share identical precursor/product ion pairs, enabling their co-detection in existing initial testing procedures in routine doping controls for the intact unconjugated analytes. In addition, hydroxylated IOX-2 and the corresponding glucuronic acid conjugates were identified as major metabolites in a microdose elimination study, contributing to enhanced initial testing and confirmation procedures.


Prospective Latin American cohort evaluating outcomes of patients with COVID-19 and abnormal liver tests on admission.
The independent effect of liver biochemistries as a prognostic factor in patients with COVID-19 has not been completely addressed. We aimed to evaluate the prognostic value of abnormal liver tests on admission of hospitalized patients with COVID-19. We performed a prospective cohort study including 1611 hospitalized patients with confirmed SARS-CoV-2 infection from April 15, 2020 through July 31, 2020 in 38 different Hospitals from 11 Latin American countries. We registered clinical and laboratory parameters, including liver function tests, on admission and during hospitalization. All patients were followed until discharge or death. We fit multivariable logistic regression models, further post-estimation effect through margins and inverse probability weighting. Overall, 57.8% of the patients were male with a mean age of 52.3 years, 8.5% had chronic liver disease and 3.4% had cirrhosis. Abnormal liver tests on admission were present on 45.2% (CI 42.7-47.7) of the cohort (n = 726). Overall, 15.1% (CI 13.4-16.9) of patients died (n = 244). Patients with abnormal liver tests on admission presented higher mortality 18.7% (CI 15.9-21.7), compared to those with normal liver biochemistries 12.2% (CI 10.1-14.6); P < .0001). After excluding patients with history of chronic liver disease, abnormal liver tests on admission were independently associated with death [OR 1.5 (CI 1.1-2.0); P = 0.01], and severe COVID-19 (2.6 [2.0-3.3], P < .0001), both adjusted by age, gender, diabetes, pneumonia and body mass index >30. The presence of abnormal liver tests on admission is independently associated with mortality and severe COVID-19 in hospitalized patients with COVID-19 infection and may be used as surrogate marker of inflammation. CLINICALTRIALS.GOV: NCT04358380.


In what sense is implicit memory "episodic"? The effect of reinstating environmental context.
We consider three aspects of the term episodic. Previous literature shows implicit memory does not make conscious autobiographical reference but does code an item's intrinsic context (e.g., perceptual detail). Here, we consider extrinsic context--namely, that not directly processed as part of item identification and not overtly relevant to the task. Study-test mismatch in environmental context (outdoors vs. indoors) reduced memory in an explicit stem-cued recall task but had no effect on repetition priming in an implicit stem completion task. This was true even for very low frequency words. We support the view that implicit memory reflects traces within perceptual (or semantic) knowledge-based systems that are instance specific but do not code the full spatiotemporal context information necessary to support conscious recollection. We also interpret our results as consistent with differences in environmental context specificity between free recall and recognition.


V-ATPase, ScNhx1p and yeast vacuole fusion.
Membrane fusion is the last step in trafficking pathways during which membrane vesicles fuse with target organelles to deliver cargos. It is a central cellular reaction that plays important roles in signal transduction, protein sorting and subcellular compartmentation. Recent progress in understanding the roles of ion transporters in vacuole fusion in yeast is summarized in this article. It is becoming increasingly evident that the vacuolar proton pump V-ATPase and vacuolar Na+/H+ antiporter ScNhx1p are key components of the vacuole fusion machinery in yeast. Yeast ScNhx1p regulates vacuole fusion by controlling the luminal pH. V-ATPases serve a dual role in vacuolar integrity in which they regulate both vacuole fusion and fission reactions in yeast. Fission defects are epistatic to fusion defects. Vacuole fission depends on the proton translocation activity of the V-ATPase; by contrast, the fusion reaction does not need the transport activity but requires the physical presence of the proton pump. V0, the membrane-integral sector of the V-ATPase, forms trans-complexes between the opposing vacuoles in the terminal phase of vacuole fusion where the V0trans-complexes build a continuous proteolipid channel at the fusion site to mediate the bilayer fusion.


Health-related quality of life and its socio-economic and cultural predictors among advanced cancer patients: evidence from the APPROACH cross-sectional survey in Hyderabad-India.
Patients with advanced cancer often experience poor health-related quality-of-life (HRQoL) due to cancer and treatment-related side-effects. With India's palliative care landscape in its infancy, there is a concern that advanced cancer patients, especially individuals who are from disadvantaged populations experience poor HRQoL outcomes. We aim to assess HRQoL of advanced cancer patients in terms of general well-being (physical, functional, emotional, and social/family well-being), pain experiences, psychological state, and spiritual well-being, and determine the relationship between belonging to a disadvantaged group and HRQoL outcomes. We hypothesize that patients from disadvantaged or minority backgrounds, identified in this paper as financially distressed, female, lower years of education, lower social/family support, minority religions, and Non-General Castes, would be associated with worse HRQoL outcomes compared to those who are not from a disadvantaged group. We administered a cross-sectional survey to 210 advanced cancer patients in a regional cancer center in India. The questionnaire included standardized instruments for general well-being (FACT-G), pain experiences (BPI), psychological state (HADS), spiritual well-being (FACT-SP); socio-economic and demographic characteristics. Participants reported significantly lower general well-being (mean ± SD) (FACT-G = 62.4 ± 10.0) and spiritual well-being (FACT-SP = 32.7 ± 5.5) compared to a reference population of cancer patients in the U.S. Patients reported mild to moderate pain severity (3.2 ± 1.8) and interference (4.0 ± 1.6), normal anxiety (5.6 ± 3.1) and borderline depressive symptoms (9.7 ± 3.3). Higher financial difficulty scores predicted most of the HRQoL domains (p ≤ 0.01), and being from a minority religion predicted lower physical well-being (p ≤ 0.05) and higher pain severity (p ≤ 0.05). Married women reported lower social/family well-being (p ≤ 0.05). Pain severity and interference were significant predictors of most HRQoL domains. Advanced cancer patients, especially those with lower financial well-being and belonging to minority religions, reported low physical, functional, emotional, social/family, and spiritual well-being, and borderline depressive symptoms. Future studies should be directed at developing effective interventions supporting vulnerable groups such as those with financial distress, and those belonging to minority religions.


Embouchure Dystonia as a Network Disease.
While the pathophysiology of embouchure dystonia, a sub-entity of musician's dystonia, is still not fully understood, recent research has shown that it involves alterations of several brain functions and networks. Maladaptive plasticity in sensorimotor integration, sensory perception, and deficient inhibitory mechanisms at cortical, subcortical, and spinal level seem to contribute to its pathophysiology. Furthermore, functional systems of the basal ganglia and the cerebellum are involved, clearly pointing toward a network disorder. We therefore propose a novel network model, based on electrophysiological and recent neuroimaging studies highlighting embouchure dystonia.


Clitoral cyst as a cause of ambiguous genitalia.
Ambiguous genitalia need appropriate evaluation, because a serious disease can manifest as this condition. A 28-year-old woman was referred with a "penis" present from age 12 years that enlarged throughout puberty but recently was unchanged. Differential diagnosis included true hermaphroditism; adrenal hyperplasia; clitoral, ovarian, and adrenal neoplasms; stromal hyperthecosis; polycystic ovarian syndrome; and exogenous androgen exposure. Free testosterone was not elevated. Dehydroepiandrosterone sulfate, 17-hydroxyprogesterone, total testosterone, androstenedione, deoxycorticosterone, 11-deoxycortisol, chromosomal analysis (46,XX), an intravenous pyelogram, and pelvic ultrasound were normal. The patient elected surgical removal. The mass was a chronic inflamed epidermoid cyst. If this patient had been appropriately evaluated earlier, she would have been spared anxiety and embarrassment over a simple epidermoid cyst.


[A study of expression of p53, c-myc and PCNA in retinoblastoma].
To investigate the expressions of p53, c-myc (oncogene) and proliferating cell nuclear antigen (PCNA) in retinoblastoma (Rb) and the relationships of the expression to the degree of differentiation and optic nerve infiltration. The expressions of p53, c-myc and PCNA in Rb tissues of 31 cases were analyzed by using LSAB immunohistochemical method. The positive rates of p53, c-myc and PCNA in Rb were respectively 51.6%, 45.2% and 67.7% and all the expressions were significantly related to the differentiation degree of Rb (all P < 0.05). The expression of PCNA was significantly related to the optic nerve infiltration of Rb (P < 0.05). Both the expressions of p53 and c-myc in Rb were markedly correlated with the expression of PCNA (all P < 0.05). The occurrence of Rb is the result of multiple gene mutations. The determinations of p53, c-myc and PCNA are of significance for evaluating the histologic characteristics and biological behavior of Rb.


C-type natriuretic peptide is a potent stimulator of cyclic GMP production in cultured mouse astrocytes.
The effect of C-type natriuretic peptide (CNP), a novel member of the natriuretic peptide family, on cyclic GMP (cGMP) generation was studied in primary cultures of mouse astrocytes. CNP stimulated cGMP production by mouse astrocytes in a dose-dependent fashion, with an EC50 of 32 nM and a maximal stimulatory concentration of greater than 1 microM, which induced a rise of cGMP level from a baseline of 1.0 +/- 0.1 pmol/mg of protein to 196.2 +/- 22.0 pmol/mg of protein. Compared with our previously reported atrial and brain natriuretic peptide-induced cGMP responses, CNP had a lower EC50 and was 10-20 times more efficacious in its maximal effect on cGMP stimulation. These data lend support to the concept of a significant role of CNP in neuromodulation/neurotransmission.


Congenital Tricuspid Valve Calcification Necessitating Neonatal Surgical Intervention.
We report a case of isolated idiopathic congenital tricuspid valve calcification that necessitated urgent neonatal surgical intervention. Hemodynamic analysis revealed circular shunt caused by severe tricuspid regurgitation, pulmonary regurgitation, and a hypoplastic right ventricle. The patient successfully underwent tricuspid valve repair at postnatal day 10. Although intervention for neonatal tricuspid valve is challenging, hemodynamic evaluation and early surgical intervention are necessary in patients with this rare cardiac calcification.


Mitochondria spatially and temporally modulate VSMC phenotypes via interacting with cytoskeleton in cardiovascular diseases.
Cardiovascular diseases caused by atherosclerosis (AS) seriously endanger human health, which is closely related to vascular smooth muscle cell (VSMC) phenotypes. VSMC phenotypic transformation is marked by the alteration of phenotypic marker expression and cellular behaviour. Intriguingly, the mitochondrial metabolism and dynamics altered during VSMC phenotypic transformation. Firstly, this review combs VSMC mitochondrial metabolism in three aspects: mitochondrial ROS generation, mutated mitochondrial DNA (mtDNA) and calcium metabolism respectively. Secondly, we summarized the role of mitochondrial dynamics in regulating VSMC phenotypes. We further emphasized the association between mitochondria and cytoskelton via presenting cytoskeletal support during mitochondrial dynamics process, and discussed its impact on their respective dynamics. Finally, considering that both mitochondria and cytoskeleton are mechano-sensitive organelles, we demonstrated their direct and indirect interaction under extracellular mechanical stimuli through several mechano-sensitive signaling pathways. We additionally discussed related researches in other cell types in order to inspire deeper thinking and reasonable speculation of potential regulatory mechanism in VSMC phenotypic transformation.


[A systematic review of diagnosis of Helicobacter pylori infection by Helicobacter pylori stool antigen test].
To evaluate the accuracy of Helicobacter pylori (Hp) stool antigen test for diagnosing Hp infection. Articles related to diagnosis of Hp infection by Hp stool antigen test, published before March 2004, were retrieved in the databanks such as CBMdisc, CMCC, CNKI, and VIP. Related journals were searched manually. Meta-analysis was performed by SROC curve recommended by Diagnostic and Screening Group of the Cochrane Collaboration Web with the parameters such as sensitivity, specificity, accuracy, predictive values, and likelihood ratio. In total 19 studies including 3123 patients met the inclusion criteria. The sensitivity of Hp stool antigen for the diagnosis of Hp infection was 94% and its specificity was 93%. Helicobacter pylori stool antigen examination is a simple, noninvasive and highly accurate method in diagnosis of Hp infection.


Immunological functioning in Alzheimer's disease: differential effects of relative left versus right temporoparietal dysfunction.
The cerebral hemispheres are differentially involved in regulating immunological functioning and the neuropathology associated with Alzheimer's disease (AD) is asymmetrical. Thus, subgroups of AD patients may exhibit different patterns of immunological dysfunction. We explored this possibility in a group of AD patients and found that patients with low white blood cell counts and low lymphocyte numbers exhibited better performance on tests of right temporoparietal functioning. Also, a significant positive relationship exists between lymph numbers and performance on a test of left temporoparietal functioning. Thus, some AD patients have greater immunological dysfunction based on relative left versus right temporoparietal functioning.


Factors associated with depression among elderly Koreans: the role of chronic illness, subjective health status, and cognitive impairment.
The objective of this cross-sectional study was to investigate the relationship between depression in elderly individuals and chronic illness, subjective health status, and cognitive impairment. This study used the dataset of the Survey of Living Conditions and Welfare Needs of Korean Older Persons, which was conducted by the Korea Institute for Health and Social Affairs in 2011. Participants (n = 10,674) were randomly selected from a pool of individuals aged 65 years and older. Elderly depression was evaluated by the short version of the Geriatric Depression Scale. Multivariate logistic regression was used to investigate factors associated with depression in terms of their sociodemographic and health-related characteristics. Our results revealed that chronic illness, subjective health status, and cognitive impairment were significant factors associated with depression. In particular, subjective health status showed the highest odds ratio (OR) (OR for bad subjective health status = 4.290, P < 0.001), followed by chronic illness (OR for three or more chronic illnesses = 1.403, P < 0.01) and cognitive impairment (OR = 1.347, P < 0.001) in the final model. Interestingly, the significant association between chronic illness and depression was attenuated (OR for three or more chronic illnesses = 1.403, P = 0.01) or even disappeared (OR for two chronic illnesses = 1.138, P = 0.274; OR for one chronic illnesses = 0.999, P = 0.996) after adjustment for subjective health status in the final model; this may be attributable to the close relationship among the variables studied: chronic illness, subjective health status, and depression. Development and implementation of prevention strategies, including management of chronic illness, individual's perception of health status, and cognitive impairment, could possibly reduce the impact of depression.


Reduced ADP off-rate by the yeast CCT2 double mutation T394P/R510H which causes Leber congenital amaurosis in humans.
The CCT/TRiC chaperonin is found in the cytosol of all eukaryotic cells and assists protein folding in an ATP-dependent manner. The heterozygous double mutation T400P and R516H in subunit CCT2 is known to cause Leber congenital amaurosis (LCA), a hereditary congenital retinopathy. This double mutation also renders the function of subunit CCT2, when it is outside of the CCT/TRiC complex, to be defective in promoting autophagy. Here, we show using steady-state and transient kinetic analysis that the corresponding double mutation in subunit CCT2 from Saccharomyces cerevisiae reduces the off-rate of ADP during ATP hydrolysis by CCT/TRiC. We also report that the ATPase activity of CCT/TRiC is stimulated by a non-folded substrate. Our results suggest that the closed state of CCT/TRiC is stabilized by the double mutation owing to the slower off-rate of ADP, thereby impeding the exit of CCT2 from the complex that is required for its function in autophagy.


Cognitive coping and goal adjustment are associated with symptoms of depression and anxiety in people with acquired hearing loss.
The present study examined the joint influence of cognitive coping strategies and goal adjustment on symptoms of depression and anxiety in people with acquired hearing loss (AHL). The study had a cross-sectional design in which participants were asked to fill in written questionnaires. The sample consisted of 119 individuals with moderate to profound AHL, acquired in adulthood. Symptoms of depression and anxiety, cognitive coping strategies, and goal-related coping processes were assessed. Relationships between these variables were statistically tested by Pearson correlations and multiple regression analyses. The results showed that ruminative and catastrophizing ways of coping were related to the reporting of more symptoms of depression and/or anxiety. In contrast, refocusing attention to more pleasant issues, disengaging from unattainable goals, and re-engaging in alternative, meaningful goals were related to the reporting of less symptomatology. These results provide us with important targets for prevention and intervention of mental health problems in people with AHL.


Effects of Moringa oleifera Lam. Supplementation on Inflammatory and Cardiometabolic Markers in Subjects with Prediabetes.
Different parts of the Moringa oleifera Lam. (MO) tree are consumed as food or food supplements for their nutritional and medicinal value; however, very few human studies have been published on the topic. The current work was aimed to provide ancillary analysis to the antidiabetic effects previously reported in a double-blind, randomized, placebo-controlled, parallel group intervention conducted in patients with prediabetes. Thus, the effect of MO leaves on blood and fecal inflammatory markers, serum lipid profile, plasma antioxidant capacity and blood pressure was studied in participants who consumed 6 × 400 mg capsule/day of MO dry leaf powder (MO, n = 31) or placebo (PLC, n = 34) over 12 weeks. Differences between groups were assessed using each biomarker's change score with, adjustment for fat status and the baseline value. In addition, a decision tree analysis was performed to find individual characteristics influencing the glycemic response to MO supplementation. No differences in the biomarker's change scores were found between the groups; however, the decision tree analysis revealed that plasma TNF-α was a significant predictor of the subject's HbA1c response (improvement YES/NO; 77% correct classification) in the MO group. In conclusion, TNF-α seems to be a key factor to identify potential respondents to MO leaf powder.


Effects of photobiomodulation therapy on the local experimental envenoming by Bothrops leucurus snake.
Bothrops leucurus is the major causative agent of snakebites in Brazil's Northeast. The systemic effects of its venom are effectively neutralized by antivenom therapy, preventing bitten patients' death. However, antivenom fails in neutralizing local effects that include intense pain, edema, bleeding, and myonecrosis. Such effects can lead to irreversible sequels, representing a clinically relevant issue for which there is no current effective treatment. Herein, the effects of photobiomodulation therapy (PBMT) were tested in the local actions induced by B. leucurus venom (BLV) in mice (n = 123 animals in 20 experimental groups). A continuous emission AlGaAs semiconductor diode laser was used in two wavelengths (660 or 780 nm). Mechanical nociceptive thresholds were assessed with the electronic von Frey apparatus. Local edema was determined by measuring the increase in paw thickness. Hemorrhage was quantified by digital measurement of the bleeding area. Myotoxicity was evaluated by serum creatine kinase (CK) activity and histopathological analysis. PBMT promoted anti-hypernociception in BLV-injected mice; irradiation with the 660 nm laser resulted in faster effect onset than the 780 nm laser. Both laser protocols reduced paw edema formation, whether irradiation was performed immediately or half an hour after venom injection. BLV-induced hemorrhage was not altered by PBMT. Laser irradiation delayed, but did not prevent myotoxicity caused by BLV, as shown by a late increase in CK activity and histopathological alterations. PBMT was effective in the control of some of the major local effects of BLV refractory to antivenom. It is a potential complementary therapy that could be used in bothropic envenoming, minimizing the morbidity of these snakebite accidents.


Pulmonary Manifestations of Rheumatic Diseases in Children.
Children with rheumatic disease have rare pulmonary manifestations that may cause significant morbidity and mortality. These children are often clinically asymptomatic until disease has significantly progressed, so they should be screened for pulmonary involvement. There has been recent recognition of a high mortality-related lung disease in systemic-onset juvenile idiopathic arthritis; risk factors include onset of juvenile idiopathic arthritis less than 2 years of age, history of macrophage activation syndrome, presence of trisomy 21, and history of anaphylactic reaction to biologic therapy. Early recognition and treatment of lung disease in children with rheumatic diseases may improve outcomes.


Functional dissection of transmembrane domains of human TAP-like (ABCB9).
An ABC transporter, TAP-Like (TAPL), was dissected into its amino-terminal transmembrane domain and the following core domain. When these domains were transiently expressed as tagged proteins with a His6- or Myc-epitope tag, the amino-terminal ones (Met(1)-Lys(182)) could not associate with each other, or with the full-length transporter (Met(1)-Ala(766)). However, both the core domain (Arg(141)-Ala(766)) and full-length protein mutually interacted. The amino-terminal domain (Met(1)-Arg(141)) as well as the full-length transporter fused with fluorescent protein GFP was sorted to lysosomal membranes upon their stable expression, as visualized by means of fluorescent microscopy, while the core domain (Arg(141)-Ala(766)) was broadly distributed in the intra-cellular membranes. These results suggest that the sorting signal for lysosomes is present within the amino-terminal transmembrane domain (Met(1)-Arg(141)) of the TAPL molecule.


Partitioning of electrostatic and conformational contributions in the redox reactions of modified cytochromes c.
The reduction of acetylated, fully succinylated and dicarboxymethyl horse cytochromes c by the radicals CH3CH(OH), CO2.-, O2.-, and e-aq' and the oxidation of the reduced cytochrome c derivatives by Fe(CN)3-6 were studied using the pulse radiolysis technique. Many of the reactions were also examined as a function of ionic strength. By obtaining rate constants for the reactions of differently charged small molecules redox agents with the differently charged cytochrome c derivatives at both zero ionic strength and infinite ionic strength, electrostatic and conformational contributions to the electron transfer mechanism were effectively partioned from each other in some cases. In regard to cytochrome c electron transfer mechanism, the results, especially those for which conformational influences predominate, are supportive of the electron being transferred in the heme edge region.


Long-term survival in adult mediastinal neuroblastoma.
Neuroblastoma rarely occurs in adults, in whom prognosis is poor. Here we report on the effective use of multimodal therapy to achieve long-term survival in adult mediastinal neuroblastoma. In a 33-year-old male with severe pain radiating from the left hypochondrium to the back area, no abnormal shadow was detected on first examination; the shadow appeared in chest X-ray only 10 months later when the severe pain recurred. The patient was then referred to our department for further examination. Chest X-rays and chest CT scans revealed a posterior mediastinal mass beside the thoracic vertebrae. Diagnosis was confirmed after surgical resection, which was followed by outpatient adjuvant therapy through radiation and chemotherapy. The patient has survived 8 years and 8 months without recurrence or metastasis.


A comparison audit of a genitourinary medicine colposcopy service against nationally agreed quality standards.
The National Health Service Cervical Screening Programme (NHSCSP) recently published their document Standards and Quality in Colposcopy outlining recommendations for standards in the service provided by colposcopists. In this first audit of colposcopic practice measured against these agreed UK national guidelines, the authors discuss the standards, their attainability, and their relevance to genitourinary medicine (GUM) colposcopy services.


EAP Service Use in a Managed Behavioral Health Care Organization: From the Employee Perspective.
Contemporary employee assistance program (EAP) services are typically provided in broad-brush programs delivered by large external vendors in a network model. Yet research has not kept pace with EAP evolution, including in terms of how EAP clients themselves view services. We surveyed a random sample of EAP service users from a national provider (361 respondents). About one-third of respondents reported getting help for workplace issues. Most learned about the EAP through employer communications such as the company website. The large majority reported that the EAP helped them "a lot" or "some," suggesting they valued this benefit.


Development and evaluation of a problem-based learning simulation module for home-visit nursing.
Although home-visit healthcare programs in Korea are expected to expand, providing hands-on experience to nursing students may be limited. This study aimed to develop and evaluate a problem-based learning (PBL) simulation module that reflects home-visit healthcare services provided by public health centers for pre-frail older adults. The simulation module, including PBL as prebriefing, was developed by the researchers and revised based on expert reviews. The module was evaluated using a mixed-method embedded one-group post-test-only design with focus group interviews (FGIs). Quantitative data (n = 29) were collected between April and June, 2021. FGIs (n = 10) were conducted twice in June 2021, and qualitative data were analyzed using an inductive content analysis approach. The average score of the Simulation Design Scale was 4.67 ± 0.36. The overall mean score of the Educational Practices Questionnaire was 4.75 ± 0.37. Three themes emerged from the FGIs: immersive learning experience, changes in perspective on nursing, and enhanced nursing competency. This PBL-based simulation module was evaluated as a systematic learning process in which nursing students could become self-directed learners, interacting and collaborating with colleagues, instructors, and environments. The module encourages them to practice home visit services.


Subclassification of small bowel Crohn's disease using magnetic resonance enterography: a review using evidence-based medicine methodology.
Magnetic resonance enterography (MRE) has a growing role in imaging small bowel Crohn's disease (SBCD), both in diagnosis and assessment of treatment response. Certain SBCD phenotypes respond well to biologic therapy and others require surgery; MRE has an expanding role in triaging these patients. In this review, we evaluate the MRE signs that subclassify SBCD using evidence-based medicine (EBM) methodology and provide a structured approach to MRE interpretation.


Activation of BAG3 by Egr-1 in response to FGF-2 in neuroblastoma cells.
The co-chaperone protein, BAG3, which belongs to the BAG protein family, has an established antiapoptotic function in different tumor cell lines. Here we demonstrated that treatment of the human neuroblastoma cell line, SK-N-MC, with fibroblast growth factor-2 (FGF-2) results in induction of BAG3 expression. Induction of BAG3 protein by FGF-2 occurs at the transcriptional level; it requires the extracellular regulated kinase1/2 pathway and is dependent on the activity of Egr-1 upon the BAG3 promoter. Targeted suppression of BAG3 by small-interfering RNA results in dysregulation of cell-cycle progression most notably at S and G(2) phases, which corroborates the decreased level of cyclin B1 expression. These observations suggest a new role for BAG3 in regulation of the cell cycle.


Membrane technology as a promising alternative in biodiesel production: a review.
In recent years, environmental problems caused by the use of fossil fuels and the depletion of petroleum reserves have driven the world to adopt biodiesel as an alternative energy source to replace conventional petroleum-derived fuels because of biodiesel's clean and renewable nature. Biodiesel is conventionally produced in homogeneous, heterogeneous, and enzymatic catalysed processes, as well as by supercritical technology. All of these processes have their own limitations, such as wastewater generation and high energy consumption. In this context, the membrane reactor appears to be the perfect candidate to produce biodiesel because of its ability to overcome the limitations encountered by conventional production methods. Thus, the aim of this paper is to review the production of biodiesel with a membrane reactor by examining the fundamental concepts of the membrane reactor, its operating principles and the combination of membrane and catalyst in the catalytic membrane. In addition, the potential of functionalised carbon nanotubes to serve as catalysts while being incorporated into the membrane for transesterification is discussed. Furthermore, this paper will also discuss the effects of process parameters for transesterification in a membrane reactor and the advantages offered by membrane reactors for biodiesel production. This discussion is followed by some limitations faced in membrane technology. Nevertheless, based on the findings presented in this review, it is clear that the membrane reactor has the potential to be a breakthrough technology for the biodiesel industry.


Malignant Hilar Biliary Obstruction: Treatment by Means of Placement of a Newly Designed Y-Shaped Branched Covered Stent.
To evaluate the technical feasibility and clinical efficacy of placement of a newly designed Y-shaped branched covered stent for palliative treatment of malignant hilar biliary obstruction. From June 2011 to September 2014, 34 consecutive patients with malignant hilar biliary obstruction underwent percutaneous placement of a Y-shaped branched covered stent for palliative treatment. Technical and clinical success, complications, cumulative patient survival, and stent patency were evaluated. Stent placement was technically successful in all patients. All patients showed adequate biliary drainage on the follow-up cholangiogram. Mean serum bilirubin level (10.9 mg/dl) decreased significantly 1 week (5.7 mg/dl) and 1 month (2.6 mg/dl) after stent placement (p < 0.01). Complications associated with the procedure included hemobilia (n = 3) and biloma (n = 1). During the mean follow-up period of 225 (range 12-820) days, nine patients (26.5%) developed stent occlusion caused by tumor overgrowth (n = 8) and sludge (n = 1). Two of them underwent coaxial placement of a second stent with good results. The median survival time was 281 days and median primary stent patency was 337 days. There were no significant differences in the patient survival and stent patency rates in relation to age, sex, or Bismuth type. Percutaneous placement of the Y-shaped branched covered stent seems to be technically feasible and clinically effective for palliative treatment of malignant hilar biliary obstruction.


Designing a health outcomes research study in infusion nursing practice. How to get from a great idea to research results.
In infusion nursing practice, outcomes research involves identifying and measuring outcomes sensitive to, and most consistent with, current infusion nursing practice and theory. This article discusses what outcomes should be measured in infusion nursing; how to frame the study problem, develop a working research question, and define study variables; and how to design the method for sampling, variable measurement, data collection, and proposed data analysis. The article concludes with a discussion of how to apply research components using retrospective descriptive-comparative and prospective experimental approaches, and details how to write up the final research report.


Predictability and outcomes of photoastigmatic keratectomy using the Nidek EC-5000 excimer laser.
To evaluate the effect of astigmatic correction on the accuracy of the myopic and astigmatic correction in patients having photorefractive astigmatic keratectomy (PARK) and in those having photorefractive keratectomy (PRK). Specialist excimer laser refractive clinic. This prospective consecutive case series comprised 6097 eyes with a preoperative mean spherical equivalent (MSE) of -4.63 diopters (D) +/- 1.95 (SD) (range -0.75 to -13.00 D) and a mean cylinder of -1.13 +/- 0.73 D (range -0.50 to -6.00 D) having PARK with a Nidek EC-5000 excimer laser. Visual and refractive outcomes were assessed 12 months postoperatively and compared with those in 3004 eyes that had spherical PRK. At 12 months, the MSE was -0.02 +/- 0.79 D and the mean cylinder was -0.49 +/- 0.47 D in the PARK group; the MSE was -0.07 +/- 0.66 D in the PRK group. An MSE within +/-0.05 D of emmetropia was achieved by 69.8% and within +/-1.00 D, by 87.9%. The uncorrected visual acuity (UCVA) was 20/20 or better in 42.6% and 20/40 or better in 91.2%. Statistical significance (P <.001, analysis of variance) was achieved for MSE, sphere, cylinder, haze, and visual acuity (best corrected [BCVA] and UCVA) based on the preoperative cylinder. The loss of BCVA varied from 1.1% to 5.8% depending on the degree of astigmatism treated. Accuracy varied with the attempted myopic correction and the attempted astigmatic correction. Excimer laser PARK was an effective treatment for compound myopic astigmatism, but predictability decreased and complications increased as the attempted astigmatic correction increased.


Closed-loop control of a GaAs-based singlet-triplet spin qubit with 99.5% gate fidelity and low leakage.
Semiconductor spin qubits have recently seen major advances in coherence time and control fidelities, leading to a single-qubit performance that is on par with other leading qubit platforms. Most of this progress is based on microwave control of single spins in devices made of isotopically purified silicon. For controlling spins, the exchange interaction is an additional key ingredient which poses new challenges for high-fidelity control. Here, we demonstrate exchange-based single-qubit gates of two-electron spin qubits in GaAs double quantum dots. Using careful pulse optimization and closed-loop tuning, we achieve a randomized benchmarking fidelity of (99.50±0.04)% and a leakage rate of 0.13% out of the computational subspace. These results open new perspectives for microwave-free control of singlet-triplet qubits in GaAs and other materials.


Fluorescence detection of intracellular cadmium with Leadmium Green.
Leadmium Green is a commercially available, small molecule, fluorescent probe advertised as a detector of free intracellular cadmium (Cd(2+)) and lead (Pb(2+)). Leadmium Green has been used in various paradigms, such as tracking Cd(2+) sequestration in plant cells, heavy metal export in protozoa, and Pb(2+) absorption by vascular endothelial cells. However very little information is available regarding its affinity and selectivity for Cd(2+), Pb(2+), and other metals. We evaluated the in vitro selectivity of Leadmium Green using spectrofluorimetry. Consistent with manufacturer's claims, Leadmium Green was sensitive to Cd(2+) (KD ~600 nM) and also Pb(2+) (KD ~9.0 nM) in a concentration-dependent manner, and furthermore proved insensitive to Ca(2+), Co(2+), Mn(2+) and Ni(2+). Leadmium Green also responded to Zn(2+) with a KD of ~82 nM. Using fluorescence microscopy, we evaluated Leadmium Green in live mouse hippocampal HT22 cells. We demonstrated that Leadmium Green detected ionophore-mediated acute elevations of Cd(2+) or Zn(2+) in a concentration-dependent manner. However, the maximum fluorescence produced by ionophore-delivered Zn(2+) was much less than that produced by Cd(2+). When tested in a model of oxidant-induced liberation of endogenous Zn(2+), Leadmium Green responded weakly. We conclude that Leadmium Green is an effective probe for monitoring intracellular Cd(2+), particularly in models where Cd(2+) accumulates rapidly, and when concomitant fluctuations of intracellular Zn(2+) are minimal.


The clinical impact of single inhaler therapy in asthma.
Low-dose budesonide/formoterol combination used in the SMART fashion with symptom-reactive supplemental dosing has been reported to reduce asthma exacerbations as compared to the use of budesonide alone or to lower doses of budesonide/formoterol without supplemental dosing. We undertook to review the non-exacerbation outcomes of SMART therapy and to assess the patient education implications of this treatment strategy. Systematic review. Patients treated with this strategy appear to be under-treated in that the majority fail to achieve guideline-defined control standards. The SMART strategy has not been tested against equivalent or higher doses of budesonide/formoterol given in symptom-prevention fashion. Existing educational strategies that focus on recognition of poor disease control may not be applicable with SMART therapy and the use of action plans has not been clarified with this symptom-reactive strategy. There is some evidence from that the current clinical use of SMART therapy may be contaminated frequently by the concurrent prescription of short-acting bronchodilators. There is no information on long-term outcomes with a symptom-reactive ICS/LABA strategy but the use of the strategy for one year has been associated with rising sputum and airway biopsy eosinophil counts. Despite fewer severe exacerbations with SMART therapy as compared to ICS monotherapy or lower dose ICS/LABA therapy, the strategy produces poor day-to-day control of symptoms and is associated with increasing inflammation. The symptom-reactive strategy described as SMART therapy is associated with poor symptom control of asthma.


Labelling 'unexpected' deaths on a neurology service.
We wrote a list of descriptive phrases to dichotomize admissions to a neurology service by a priori perceptions of risk of death within 30 days as "higher than average" versus "lower than average." In 500 consecutive admissions, the higher-risk list carried a 17-fold relative risk of death for the 20% of admissions so classified. The list is a valid and informative predictor of 30-day outcome that supports a classification of deaths as "expected" or "unexpected."


Expanding the Chemistry Palette for Radiotracer Synthesis.
The synthesis, characterisation and application of radiolabelled compounds for use in diagnostic and therapeutic medicine requires a diverse skill set. This article highlights a selection of our ongoing projects that aim to provide new synthetic methods and radiochemical tools for building molecular imaging agents with various radionuclides.


[Cryogenic surgery of prostatic adenoma: an enrichment of our surgical possibilities?].
On the basis of our experience of 410 operations and constant contact with the most prominent exponents of this new method we feel able to draw the following conclusion; cryosurgery of prostate adenomas with good equipment is a palliative method with little danger which can be used to advantage in maximum-risk patients with indwelling catheters and large adenomas. The success rate is 70-80%, whereby this falls to 50% after 5 years. Since it is difficult to classify patients as "maximum-risk" from an internal point of view, we must reckon that the evaluation is too unfavourable in around 20%.


Augmentation of in vitro pituitary biotransformation of testosterone due to orchidectomy and its relation to serum gonadotropins in the rat.
The biotransformation of testosterone to its metabolites by the anterior pituitary gland and the relation between the products formed and the circulating levels of LH and FSH were examined in male rats at various stages of sexual maturation. The animals were either intact controls or castrated 4 and 7 days prior to the investigation. Castration greatly increased testosterone biotransformation to its 5alpha-reduced products, but did not affect the formation of androstendione. It was concluded that castration and the eventual rise of LH-RH stimulated the 5alpha-reductase activity but not the 17beta-ol-dehydrogenase system. This is reflected in the significant relationship between the circulating gonadotropins and 5alpha-metabolites of testosterone but not androstendione.


Subchondral involvement in osteonecrosis of the femoral head: insight on local composition, microstructure and vascularization.
To determine changes of subchondral bone composition, micro-structure, bone marrow adiposity and micro-vascular perfusion in end-stage osteonecrosis of the femoral head (ONFH) compared to osteoarthritis (OA) using a combined in vivo and ex vivo approach. Male patients up to 70 years old referred for total hip replacement surgery for end-stage ONFH were included (n = 14). Fifteen patients with OA were controls. Pre-operative MRI was used to assess bone perfusion (dynamic contrast-enhanced (DCE) sequences) and marrow fat content (chemical shift imaging). Three distinct zones of femoral head subchondral bone - necrotic, sclerotic, distant - were compared between groups. After surgery, plugs were sampled in these zones and Raman spectroscopy was applied to characterize bone mineral and organic components (old and newly-formed), and contrast-enhanced micro-computed tomography (CE-μCT) to determine bone micro-structural parameters and volume of bone marrow adipocytes, using conventional 2D histology as a reference. In the necrotic zone of ONFH patients compared to OA patients: 1) the subchondral plate did not exhibit significant changes in composition nor structure; 2) the volume fraction of subchondral trabecular bone was significantly lower; 3) type-B carbonate substitution was less pronounced, 4) collagen maturity was more pronounced; and 5) bone marrow adipocytes were significantly depleted. The sclerotic zone from the ONFH group showed greater trabecular thickness, and higher DCE-MRI AUC and Ktrans. Volume fraction of subchondral bone, trabecular number, and Kep were significantly lower in the distant zone of the ONFH group. This study demonstrated alterations of subchondral bone microstructure, composition, perfusion and/or adipose content in all zones of the femoral head.