Tuberculosis after heart transplantation: twenty years of experience in a single center in Taiwan.
The incidence of tuberculosis is slightly higher among heart transplantation cases than in the general population in Taiwan. Tuberculosis shows a high mortality rate ranging from 22% to 31% in transplant recipients. From October 1987 to October 2007, we performed 315 heart transplantations. Clinical records were reviewed for demographic data, clinical presentation, treatment, and outcome. Tuberculosis was diagnosed by cultures of any body sample in association with compatible symptoms and signs. Mortality was related to tuberculosis if there was evidence of active tuberculosis at the time of death and no other etiology accounted for death. Ten patients who had received heart transplants were diagnosed as tuberculosis. There were seven pulmonary lesions and seven extrapulmonary lesions. Treatment consisted of isoniazid, rifampin, ethambutol, pyrazinamide, streptomycin, ciprofloxacin, and levofloxacin. Seven patients completed the antituberculosis treatment: the median treatment duration was 1 year. Three patients developed hepatitis. There was no tuberculosis-related mortality. Ten out of a total of 315 patients (3.17%) represented a tuberculosis rate higher than that reported for the general Taiwan population (67/100,000). This high mortality of infection may be completely treated by a combination of at least three drugs except pyrzinamide because of side effects and tolerance.


Minimal Clinically Important Difference for PROMIS Physical Function and Pain Interference in Patients Following Surgical Treatment of Distal Radius Fracture.
We estimated the minimal clinically important difference (MCID) for the Patient-Reported Outcomes Measurement Information System (PROMIS) Physical Function (PF) and Pain Interference (PI) computer adaptive tests (CATs) following surgical treatment of distal radius fracture (DRF). Adult patients surgically treated between November 2017 and November 2020 for isolated DRF were identified. Demographic and patient-reported outcome data were extracted from the electronic health record. Outcomes of interest were the PROMIS PF and PI CATs. Inclusion criteria were met if: (1) PROMIS PF and PI scores were available at preoperative and postoperative visits; and (2) a postoperative clinical anchor question asking about overall response to treatment was answered. An anchor-based MCID estimate was determined by calculating the average absolute score change in PROMIS PF and PI for patients who indicated a mild change to the anchor question. A distribution-based MCID estimate was also calculated using the standard error of measurement and effect sizes of change. The changes in PROMIS PF and PI scores were significantly different between patients who gave responses of much change (n = 73), mild change (n = 51), and no change (n = 19) to the clinical anchor question. The average score changes in the mild change group for PROMIS PF and PI were 5.2 (SD, 3.7) and 6.8 (SD, 4.3) points, respectively, representing the anchor-based MCID estimates. The PROMIS PI anchor-based estimate was moderately correlated with the preoperative score (r = -0.41), time between visits (r = -0.39), and age (r = 0.30). The distribution-based MCID estimates were 3.8 (SD, 1.3) and 3.7 (SD, 1.3) points for the PROMIS PF and PI, respectively. The MCIDs were estimated as 5.2 and 6.8 for the PROMIS PF and PI CATs, respectively, following surgery for DRF. As reports continue to publish a consistent range of MCID values, researchers can be confident in these values and begin using them across a broader spectrum of conditions treated by hand surgeons.


ZnO-based Cu metal-organic framework (MOF) nanocomposite for boosting and tuning the photocatalytic degradation performance.
Although metal-organic frameworks (MOFs) are a viable choice for photocatalysts with large surface area and tunable pore structure, the rapid recombination of excited photogenerated charges results in low activity towards photodegradation. Aiming at improving the photocatalytic activities of MOFs, different strategies to incorporate MOF with light-harvesting semiconductors have been developed. In this research, we report an effective photocatalyst designed by incorporating Cu-MOF with ZnO for the photocatalytic degradation of Rose Bengal exhibiting excellent degradation efficiency of 97.4% in 45 min under natural sunlight with catalyst dosage of 320 mg/L. The optical, morphology and surface characteristics of the prepared nanocomposite were studied using scanning electron microscopy (SEM-EDX), high-resolution transmission electron microscopy (HRTEM), powder X-ray diffraction (PXRD), Brunauer-Emmett-Teller (BET) analysis, thermogravimetric (TGA) analysis, Fourier transform infrared spectroscopy (FTIR), X-ray photoelectron spectroscopy (XPS) and ultraviolet diffused reflectance spectroscopy (UV-DRS) techniques. Further studies showed that the degradation followed first-order kinetics with a rate constant of 0.077869 min-1. The degradation mechanism was investigated by photoluminescence (PL) study, XPS, zeta potential and quenching experiment in presence of different scavengers. Meanwhile, the fabricated composite displayed good recovery and reuse properties up to 5 cycles as revealed by XRD analysis proving itself a potential MOF-based photocatalyst towards environmental remediation process.


A large protein containing zinc finger domains binds to related sequence elements in the enhancers of the class I major histocompatibility complex and kappa immunoglobulin genes.
A cDNA from a B-cell library was previously isolated that encodes a sequence-specific DNA-binding protein with affinities for related sites in a class I major histocompatibility complex (MHC) and kappa immunoglobulin gene enhancers. We report here approximately 6.5 kilobases of sequence of the MBP-1 (MHC enhancer binding protein 1) cDNA. MBP-1 protein has a molecular weight predicted to be greater than 200,000. A DNA-binding domain with high affinity for the MHC enhancer sequence TGGGGATTCCCCA was localized to an 118-amino-acid protein fragment containing two zinc fingers of the class Cys2-X12-His2. Analysis of expression of MBP-1 mRNA revealed relatively high expression in HeLa cells and in a human retinal cell line, with lower levels in Jurkat T cells and in two B-cell lines. Interestingly, expression of MBP-1 mRNA was inducible by mitogen and phorbol ester treatment of Jurkat T cells and by serum treatment of confluent serum-deprived human fibroblasts.


Effect of internet support on the long-term maintenance of weight loss.
To investigate the efficacy of an Internet weight maintenance program. Two hundred fifty-five healthy overweight and obese adults (mean +/- SD BMI, 31.8 +/- 4.1 kg/m(2)) men (18%; mean +/- SD age, 45.8 +/- 8.9 yrs) participated in a 6-month behavioral weight control program conducted over interactive television. Treatment was followed by a 12-month weight maintenance program with three conditions: frequent in-person support (F-IPS), minimal in-person support (M-IPS) and internet support (IS). Main outcome measures included body weight, program adherence, and social influence components. There were no significant differences among the groups in weight loss (mean +/- SD) from baseline to 18 months (7.6 +/- 7.3 kg vs. 5.5 +/- 8.9 kg vs. 5.1 +/- 6.5 kg, p = 0.23 for the IS, M-IPS, and F-IPS, respectively). Participants assigned to an internet-based weight maintenance program sustained comparable weight loss over 18 months compared with individuals who continued to meet face-to-face. Therefore, the internet appears to be a viable medium for promoting long-term weight maintenance.


Oncocytomas of the kidney.
Fourteen cases of renal oncocytomas are presented. By definition these lesions are composed entirely of pink eosinophilic cells with abundant granular cytoplasm. No evidence of mitotic activity or necrosis was seen in any of the cases, although focal areas of nuclear pleomorphism were identified in two cases. Clinically the patients have remained asymptomatic and without evidence of metastatic or recurrent disease in a follow-up that ranges from 1-14 years. The clinical behavior of these tumors favors the benign nature of the lesion regardless of the tumor size.


Seasonal dynamics of polycyclic aromatic hydrocarbons between water and sediment in a tide-dominated estuary and ecological risks for estuary management.
Understanding the transportation of polycyclic aromatic hydrocarbons (PAHs) across the water-sediment interface can help researchers to partition their sources while being particularly important for managing PAH input. This study fully explored the PAH dynamics between water and sediment in a tide-dominated estuary. The monthly concentration of ΣPAHs in sediments ranged from 325.47 to 1098.49 ng/g (dry weight), while that in water varied from 154.00 to 725.80 ng/L. The PAH levels found in the present study were relatively high in comparison with other estuarine systems worldwide. The high-molecular-weight PAHs were more readily redissolved from sediment to water, while the low-molecular-weight PAHs were mostly in an unsaturated state with diffusion occurring from water to sediment. The seasonal differences of ΣPAHs were significant and were largely controlled by the changes in sediment properties, marine currents, and water temperature. The diagnostic ratios revealed that predominant sources of PAHs were pyrogenic processes and petrogenic inputs.


Hand preference and performance effects on line bisection.
Right- and left-handed subjects performed a visual line bisection task with each hand. When bisecting horizontal lines, both groups bisected left of true center regardless of hand used. Regardless of hand preference, bisections were significantly left of center only when subjects performed with their left hand. Left-handed subjects using their left hand deviated significantly further left than right-handed subjects using their left hand. Regardless of hand used, right-handers bisected vertical lines significantly above veridical center. Left-handed subjects were not significantly above center with either hand. The results require both hemispheric advantage and lateralized activation effects for a complete explanation.


Temozolomide therapy in patients with aggressive pituitary adenomas or carcinomas.
Temozolomide is effective in some patients with progressive pituitary adenoma or carcinoma. We report a survey study of Italian patients treated with Temozolomide because of aggressive pituitary adenoma or carcinoma resistant to standard therapies. Italian endocrinologists were surveyed and asked to participate into the study. A questionnaire was sent to all those who agreed and had used Temozolomide in at least one patient with pituitary tumor. Database was closed in December 2013. A literature review was also performed. Thirty-one patients were included into the analysis. Mean age at start of Temozolomide treatment was 58.3 ± 1.9 years (± standard error). Six of the 31 (19.4%) Italian patients had a pituitary carcinoma. Twenty-five patients (80.6%) had disease control during Temozolomide treatment, while 6 patients (19.4%) had disease progression. Median follow-up after beginning Temozolomide was 43 months. Thirteen patients had tumor growth after stopping Temozolomide. The 2-year progression-free survival was 47.7% (95% CI 29.5-65.9%), while the 2-year disease control duration was 59.1% (95% CI 39.1-79.1%). Eleven patients died of progressive disease and other two patients of unrelated causes. The 2-year and 4-year overall survival rates were 83.9% (95% CI 70.7-97.1%) and 59.6% (95% CI 40.0-79.2%), respectively. Temozolomide is an additional effective therapeutic option for the treatment of aggressive pituitary tumors. The drug is well tolerated and causes few severe adverse effects. Recurrence of the tumor can occur after an initial positive response and usually portends a grim outcome.


Repurposing radiotracers for myelin imaging: a study comparing 18F-florbetaben, 18F-florbetapir, 18F-flutemetamol,11C-MeDAS, and 11C-PiB.
Drugs promoting myelin repair represent a promising therapeutic approach in multiple sclerosis and several candidate molecules are currently being evaluated, fostering the need of a quantitative method to specifically measure myelin content in vivo. PET using the benzothiazole derivative 11C-PiB has been successfully used to quantify myelin content changes in humans. Stilbene derivatives, such as 11C-MeDAS, have also been shown to bind to myelin in animals and are considered a promising radiopharmaceutical class for myelin imaging. Fluorinated compounds from both classes are now commercially available and thus should constitute clinically useful myelin radiotracers. The aim of this study is to provide a head-to-head comparison of 18F-florbetaben, 18F-florbetapir, 18F-flutemetamol, 11C-MeDAS, and 11C-PiB with regard to brain kinetics and binding in white matter (WM). Four baboons underwent a 90-min dynamic PET scan for each radioligand. Arterial blood samples were collected during the exam for each radiotracer, except for 18F-florbetapir, to obtain a radiometabolite-corrected input function. Standardized uptake value ratio between 75 at 90 min (SUVR75-90), binding potential (BP) estimated with Logan method with input function, and distribution volume ratio (DVR) estimated with Logan reference method (using cerebellar gray matter as reference region) were calculated in WM and compared between tracers using mixed effect models. In WM, 18F-florbetapir had the highest SUVR75-90 (1.38 ± 0.03), followed by 18F-flutemetamol (1.34 ± 0.02), 18F-florbetaben (1.32 ± 0.07), 11C-MeDAS (1.27 ± 0.04), and 11C-PiB (1.25 ± 0.07). With regard to BP, 18F-florbetaben had the highest value (0.32 ± 0.06) compared with 18F-flutemetamol (0.20 ± 0.03), 11C-MeDAS (0.17 ± 0.03), and 11C-PiB (0.16 ± 0.03). No difference in DVR was detected between 18F-florbetaben (1.26 ± 0.06) and 18F-florbetapir (1.27 ± 0.03), but both were significantly higher in DVR than 18F-flutemetamol (1.17 ± 0.02), 11C-MeDAS (1.16 ± 0.03), and 11C-PiB (1.14 ± 0.02). Given their higher binding and longer half-life, our study indicates that 18F-florbetapir and 18F-florbetaben are promising tracers for myelin imaging which are readily available for clinical application in demyelinating diseases.


Extraskeletal Myxoid Chondrosarcoma with Molecularly Confirmed Diagnosis: A Multicenter Retrospective Study Within the Italian Sarcoma Group.
Extraskeletal myxoid chondrosarcoma (EMC) is a rare sarcoma of uncertain origin, marked by specific chromosomal translocations involving the NR4A3 gene, and usually characterized by an indolent course. Surgery (with or without radiotherapy) is the treatment of choice in localized disease. The treatment for advanced disease remains uncertain. In order to better evaluate prognostic factors and outcome, a retrospective pooled analysis of patients with EMC treated at three Italian Sarcoma Group (ISG) referral centers was carried out. All patients with localized EMC surgically treated from 1989 to 2016 were identified. Diagnosis was centrally reviewed according to WHO 2013. Only patients with NR4A3 rearrangement were included. Sixty-seven patients were identified: 13 (20%) female, 54 (80%) male. Median age was 56 years (range 18-84). Numbers and type of translocation were: 50 (80%) NR4A3-EWS, 10 (16%) NR4A3-TAF15, 1 (2%) NR4A3-TCF12, and 1 (2%) NR4A3-TFG. Median follow-up was 55 months (range 2-312). Five- and ten-year overall survival rates were 94% (86-100 95%CI) and 84% (69-98 95%CI). Thirty-five (52%) patients relapsed: 9 had local recurrence (LR) and 26 had distant metastasis (5 with concomitant LR). The 5- and 10-year disease-free survival rates (DFS) were 51% (38-65 95%CI) and 20% (7-33 95%CI). Size of the primary tumor was significantly related to distant metastasis-free survival (DMFS) (p = 0.004). Patients carrying the NR4A3-EWS translocation had a trend in favor of better DFS (p = 0.08) and DMFS (p = 0.09) compared with the patients with NR4A3-TAF15. Prolonged survival can be expected in patients with EMC, in spite of a high rate of recurrence. Size is significantly associated with distant relapse. The type of NR4A3 translocation could influence outcome.


Psychopathology and trauma in epileptic and psychogenic seizure patients.
Forty-one patients admitted to an inpatient epilepsy unit for intractable seizures were evaluated for the presence of Axis I and Axis II diagnoses and for a history of trauma by use of a structured clinical interview. Both the interviewer and the patient were blind to the seizure diagnosis. Following video and electroencephalographic evaluation, 27 patients were diagnosed with epileptic seizures, and 14 had psychogenic seizures. The history of Axis I and Axis II disorders did not distinguish the two groups of patients. A history of trauma was significantly more likely in the patients with psychogenic seizures. The experience of trauma appears to be an important factor in the development of psychogenic seizures. Sexual trauma alone, however, was not significantly associated with psychogenic seizures.


Efficient purification of somatomedin-C/insulin-like growth factor I using immunoaffinity chromatography.
Somatomedin-C/insulin-like growth factor I was purified from human plasma using a monoclonal antibody affinity column. Combining immunoaffinity chromatography with standard protein purification methods resulted in an overall recovery of 18%. The 35 micrograms of somatomedin-C/insulin-like growth factor I purified from 500 ml of plasma appeared as a single band when analyzed by polyacrylamide gel electrophoresis and could be used in radioimmunoassay and receptor binding studies.


The anxiogenic beta-carboline FG-7142 increases in vivo and in vitro tyrosine hydroxylation in the prefrontal cortex.
Systemic administration of the anxiogenic beta-carboline FG-7142, a benzodiazepine inverse agonist, results in a regionally selective increase in dopamine (DA) utilization in the anteromedial prefrontal cortex (PFC). We have examined both in vivo and in vitro tyrosine hydroxylation in the PFC and other mesotelencephalic DA system terminal fields in order to determine if FG-7142 effects changes in DA synthesis, and to determine if the beta-carboline biochemically activates certain DA neurons through an action occurring at the cell body level (impulse-dependent regulation) or at the terminal field level (presynaptic regulation). FG-7142 increased in vivo tyrosine hydroxylation in the PFC and in the ventral tegmental area, midbrain source of the DA innervation of the PFC; no changes were observed in mesolimbic or nigrostriatal regions. The beta-carboline also increased in vitro tyrosine hydroxylation in the PFC, but decreased tyrosine hydroxylation in striatal slices. The effects of FG-7142 were blocked by the benzodiazepine antagonist RO 15-1788. Another beta-carboline inverse agonist, methyl-beta-carboline-3-carboline-3-carboxylate, also increased in vitro tyrosine hydroxylation in the PFC. GABA exerted opposite effects to those of the beta-carbolines, decreasing in vitro tyrosine hydroxylation in the PFC and increasing DA synthesis in the CP. These data indicate that the benzodiazepine inverse agonists increase both in vivo and in vitro tyrosine hydroxylation in the PFC, and that the beta-carboline may act to increase DA synthesis at both the terminal field and the cell body level.


Application of electrospray ionization mass spectrometry for studying human immunodeficiency virus protein complexes.
Mass spectrometry (MS) with electrospray ionization (ESI) has shown utility for studying noncovalent protein complexes, as it offers advantages in sensitivity, speed, and mass accuracy. The stoichiometry of the binding partners can be easily deduced from the molecular weight measurement. In many examples of protein complexes, the gas phase-based measurement is consistent with the expected solution phase binding characteristics. This quality suggests the utility of ESI-MS for investigating solution phase molecular interactions. Complexes composed of proteins from the human immunodeficiency virus (HIV) have been studied using ESI-MS. Multiply charged protein dimers from HIV integrase catalytic core (F185K) and HIV protease have been observed. Furthermore, the ternary complex between HIV protease dimer and inhibitor pepstatin A was studied as a function of solution pH. Zinc binding to zinc finger-containing nucleocapsid protein (NCp7) and the NCp7-psi RNA 1:1 stoichiometry complex was also studied by ESI-MS. No protein-RNA complex was observed in the absence of zinc, consistent with the role of the zinc finger motifs for RNA binding.


Intrusion of retinal tacks.
We examined nine patients in whom retinal tacks intruded into the eye and lodged in the subretinal space, preretinal space, vitreous cavity, or anterior chamber. Complications included retinal pigment epithelium atrophy; retinal phlebitis; vitreous hemorrhage; focal corneal, iris, and retinal injury; and corneal edema. The intrusion of the retinal tacks did not apparently cause, but was associated with retinal redetachment in five patients. Factors associated with intrusion of the retinal tacks included absence of a barb at the end of the tack to anchor it to the sclera, absence of a groove in the tack, a short shaft, incomplete penetration of the retina, choroid, and sclera by the tack, self-inflicted trauma to the eye, placing a scleral buckle after inserting the tacks, and reproliferation of periretinal membranes. In four patients the intruded tacks did not cause any complications. In four patients the intruded tacks were removed without complications and in the remaining five patients, they were left in the eye.


[The use of magnetics and laser therapy in treating obliterating vascular diseases of the extremities].
The paper presents the results of treatment received by 60 patients suffering from lower limb vascular obliteration stage IIA-III. The treatment involved combined use of magnetic field and laser irradiation. Peripheral circulation and central hemodynamics were evaluated rheographically and using ultrasound Doppler sphygmomanometry. Combined application of the above two modalities produced a greater effect on central hemodynamics compared to them introduced alone.


The effect of long-acting injectable selenium formulations on blood and liver selenium concentrations and liveweights of red deer (Cervus elaphus).
To evaluate the efficacy of a new long acting injectable selenium ( Se ) formulation to increase the Se status and prevent Se deficiency in red deer. Groups of weaned red deer (four stags and six hinds/group) grazing pastures containing <30 mg Se/kg DM were injected subcutaneously with either 0.5, 1.0 or 2.0 mg Se/kg as a new formulation of BaSeO4 (Deposel Multidose), 1.0mgSe/kg of a current formulation (Deposel), or not treated. Blood Se concentrations and liveweight were measured nine times at intervals over 377 and 270 days, respectively. Both formulations of Se elevated blood Se concentrations from 105 nmol/l pre-injection for at least 377 days with peak levels of 1894, 1395 and 818 nmol/l for high, medium and low doses of Deposel Multidose, respectively, at 73141 days, and 1508 nmol/l at 73-141 days for the medium dose of Deposel, which persisted at similar levels for the duration of the study. Deposel Multidose produced fewer and less severe subcutaneous tissue reactions than Deposel. Pastures contained 10 to 30 mg Se/kg DM. There was no significant difference in growth rate between treated and control deer. There was a significant (p<0. 01) linear relationship (y = 1.25x + 71.6, R2=0.86) between blood (x) and liver (y) Se concentrations in the range of 120 - 2100 nmol/l for blood concentrations, and 200 - 3000 nmol/kg for liver concentrations. Injections of BaSeO4 in both formulations studied were effective in increasing the Se status of deer but the new formulation produced fewer and less-severe tissue reactions. Young growing red deer appear less sensitive to Se deficiency as measured by weight gain, than sheep and cattle, suggesting that reference ranges for those species are not appropriate for deer. There was a linear correlation between blood and liver selenium concentrations.


Exercise and cancer: from "healthy" to "therapeutic"?
Exercise improves functional capacity and patient-reported outcomes across a range of cancer diagnoses. The mechanisms behind this protection have been largely unknown, but exercise-mediated changes in body composition, sex hormone levels, systemic inflammation, and immune cell function have been suggested to play a role. We recently demonstrated that voluntary exercise leads to an influx of immune cells in tumors, and a more than 60% reduction in tumor incidence and growth across several mouse models. Given the common mechanisms of immune cell mobilization in mouse and man during exercise, we hypothesize that this link between exercise and the immune system can be exploited in cancer therapy in particular in combination with immunotherapy. Thus, we believe that exercise may not just be "healthy" but may in fact be therapeutic.


FT-IR and DSC studies of poly(vinylidene chloride-co-acrylonitrile) complexed with LiBF4.
Poly(vinylidene chloride-co-acrylonitrile) (PVdC-co-AN) based solvent free electrolytes were prepared for different compositions of PVdC-co-AN and LiBF4 using solution casting technique. The ionic conductivity, thermal behavior, complexation and structure of polymer electrolytes have been investigated as a function of LiBF4 content at different weight ratios. DSC studies revealed that the glass transition temperature Tg decreases with the increase of salt concentration up to an optimum level. The change in the glass transition temperature (Tg) with respect to the LiBF4 concentration is reflected in the bulk resistance of the electrolytes and the sample containing 6 wt.% of LiBF4 exhibited minimum bulk resistance compared to other samples. FT-IR studies confirm the interaction of polymer and salt which is mainly between Li-cation and nitrogen atom of C≡N group. The crystalline phase of polymer host is completely changed on the addition of Li salt.


Atypical longitudinal self-inflicted incised wounds as a cause of death in an ecstasy user.
A 32-year-old chronic drug abuser was found dead at the entrance to his home, covered in blood. Pools of blood, bloody footprints and bloodstains were found across the apartment. A double-edged razor was recovered from the scene. Autopsy revealed multiple incised wounds: two on the palmar aspect of both forearms (37 cm and 33 cm long, oriented longitudinally). The cuts extended into the subcutaneous adipose tissue, muscles and blood vessels. There was an additional 30 cm cut extending across the middle of the torso anteriorly and two more cuts on the anteromedial aspect of the lower legs, set symmetrically (about 23 and 25 cm long). These three cuts were more shallow than the upper extremity wounds. No hesitation wounds were identified. Toxicological analysis identified MDMA (ecstasy). The cause of death was exsanguination. The deceased has been using ecstasy for the previous five years and had a history of inpatient psychiatric treatment due to psychosis with delusions and hallucinations. These self-inflicted incised wounds had many atypical features: location (torso, legs and arms), longitudinal orientation and symmetrical distribution, absence of hesitation injuries, use of both dominant and non-dominant hand. The absence of previous suicide attempts and suicide note suggest that these self-inflicted injuries were not planned beforehand, but were abrupt. We hypothesize that this injury pattern is associated with both acute and chronic effects of MDMA.


Impact of a laparoscopic renal surgery mini-fellowship program on postgraduate urologist practice patterns at 3-year followup.
To assist practicing urologists incorporate laparoscopic renal surgery into their practice we established a 5-day mini-fellowship program with a mentor, preceptor and a potential proctor at our institution. We report the impact of our mini-fellowship program at 3-year followup. A total of 106 urologists underwent laparoscopic ablative (44) or laparoscopic reconstructive (62) renal surgery training. The 1:2 teacher-to-attendee experience included tutorial sessions, hands-on inanimate and animate skills training, and clinical case observations. Participants were asked to complete a detailed questionnaire on laparoscopic practice patterns 1, 2 and 3 years after the mini-fellowship. The questionnaire response rate at 1 to 3 years was 77%, 65% and 68%, respectively. Of responders 72%, 71% and 71% performed laparoscopic renal surgery at 1 to 3 years, respectively. Of the 106 participants 32 (39%) had previous laparoscopic experience, including 78% who responded to the questionnaire at 3 years. Of those surgeons there was an increase in the practice of laparoscopic radical nephrectomy (88% vs 72%), nephroureterectomy (56% vs 13%), pyeloplasty (40% vs 6%) and partial nephrectomy (32% vs 6%) at 3 years. Of the 106 participants 74 (70%) were laparoscopy naïve, including 48 (65%) who responded to the questionnaire at 3 years. The take rate in this group was 76%, 52%, 34% and 23% for laparoscopic radical nephrectomy, nephroureterectomy, pyeloplasty and partial nephrectomy, respectively. Of the participants 90% indicated that they would recommend this training to a colleague. An intensive 5-day laparoscopic ablative and reconstructive renal surgery course enabled postgraduate urologists to effectively introduce and expand the volume and breadth of their laparoscopic renal surgery practice.


Probing the interaction of lipids with the non-annular binding sites of the potassium channel KcsA by magic-angle spinning NMR.
The activity of the potassium channel KcsA is tightly regulated through the interactions of anionic lipids with high-affinity non-annular lipid binding sites located at the interface between the channel's subunits. Here we present solid-state phosphorous NMR studies that resolve the negatively charged lipid phosphatidylglycerol within the non-annular lipid-binding site. Perturbations in chemical shift observed upon the binding of phosphatidylglycerol are indicative of the interaction of positively charged sidechains within the non-annular binding site and the negatively charged lipid headgroup. Site directed mutagenesis studies have attributed these charge interactions to R64 and R89. Functionally the removal of the positive charges from R64 and R89 appears to act synergistically to reduce the probability of channel opening.


Inactivation of MPF and MAP kinase by single electrical stimulus for parthenogenetic development of porcine oocytes.
This study was conducted to examine the activities of maturation-promoting factor (MPF) and mitogen-activated protein (MAP) kinase in the porcine oocytes after artificial activation. To determine optimal electrical activation condition, oocytes were exposed to single DC pulse in a variety of electric field strengths (120, 150, 180, and 210 V/mm) and pulse durations (15, 30, 45, and 60 microsec). After the artificial activation, 40-50 oocytes were cultured in a 50 microl drop of NCSU23 medium supplemented with 0.4% BSA at 39 degrees C, 5% CO2 in air for 6 days. No difference was detected in the preimplantation development of pocine oocytes and the mean nuclei number of blastocysts between electric field strengths. Under the 180 V/mm electric field strength, short pulse durations (15 and 30 microsec) showed a higher preimplantation developmental rate of the oocytes and mean nuclei number of blastocysts than an extended electric pulse (60 microsec) (P < 0.05). Single electrical stimulus (180 V/mm, 15 microsec) resulted in higher preimplantation development of porcine oocytes as compared to other chemical stimulators (P < 0.01). Western blot analyses showed the decrease of MPF and MAP kinase in the electrically-activated oocytes. After single electrical stimulus, the amounts of both cdc2 and ERK in porcine oocytes were remarkably reduced by 4 hr and then further decreased by 8 hr. However, the chemically-stimulated oocytes did not show any significant change at the levels of MPF and MAP kinase. Our results indicate that the optimal single electrical pulse is effective on the inactivation of MPF and MAP kinase, eventually leading to the parthenogenetic development of porcine oocytes.


Assessment of rabies exposure risk among Israeli travelers.
The decision whether or not to administer rabies pre-exposure prophylaxis (PEP) to travelers visiting endemic areas is a complex one. Paramount for making that decision is knowledge of the risk of animal bites during travel. This study attempts to estimate the risk of bites in travelers, and study the action they took before and after the incident. Travelers presenting for pre-travel immunizations during the period of August through December 2004, who planned a travel of >or= 1 month's duration were retrospectively identified, contacted and interviewed by a structured questionnaire. These travelers did not receive specific advice concerning rabies. The study cohort comprised of 815 travelers (median age=25), of who 13 (1.6%) were injured by a potentially rabid animal (mainly, dog=6; monkey=4). The incidence of potential rabies exposure was found to be of 2.66 per 1000 travelers per month. Those injured had significantly longer trips than the non-injured (6.9+/-3.8 vs. 4+/-5.0 months, p=0.037); notably, the injuries occurred after a median of 5 weeks from departure. Although seven travelers noted blood at the site of injury, only four (31%) of the injured sought medical attention following the exposure, and all four received post-exposure prophylaxis. An injury by potentially rabid animals is not rare among long-term travelers. As the injury may occur early in the itinerary, rabies PEP should be considered for this population. Educational efforts are required in light of the lack of understanding of the dismal consequences of rabies among travelers.


Type 1 ataxia with oculomotor apraxia with aprataxin gene mutations in two American children.
Ataxia and oculomotor apraxia are seen in ataxia-telangiectasia, type 1 ataxia with oculomotor apraxia, and type 2 ataxia with oculomotor apraxia; however, only type 1 ataxia with oculomotor apraxia is associated with aprataxin gene mutation. We report two American children, a sister and a brother, with type 1 ataxia with oculomotor apraxia and aprataxin gene mutations and briefly review type 1 ataxia with oculomotor apraxia.


Methyl jasmonate and ozone affect the antioxidant system and the quality of wine grape during postharvest partial dehydration.
Postharvest partial dehydration is a technique used in the production of important dry and sweet wines in Italy. An accurate management of the dehydration environmental parameters allows for the modulation of berry metabolism and the maintenance/improvement of the enochemical quality of grapes. As it is known that water loss induces oxidative processes in berries, our hypothesis was that methyl jasmonate (MeJA) and ozone (O3), as postharvest treatments before partial dehydration, might be beneficial for grape berry quality. Grape bunches were postharvest treated with 10 or 100 μM MeJA at 20 °C or with ozone gas at 10 °C, in 70% relative humidity (RH) and air flow, for 12 h; the control bunches were untreated and kept at 20 °C for 12 h. Subsequently, partial dehydration was performed at 10 °C until a 30% weight loss (w.l.) was reached. MeJA hastened grape berry water loss. Polyphenol and flavonoid contents at the end of the partial dehydration were lower in the MeJA-treated berries than in the control and ozone samples. Superoxide dismutase (SOD), catalase (CAT), ascorbate peroxidase (APX), and guaiacol peroxidase (GPX) activity rates increased in the treated samples. In contrast, lipoxygenase (LOX) and polyphenoloxidase (PPO) had lower activities in the MeJA-treated samples than in the controls. It would seem that MeJA accelerates grape water loss but at the same time activates the antioxidant system. Ozone does not accelerate grape water loss but induces the antioxidant system and increases polyphenol content.


Death After Crevasse Rescue in Antarctica.
We present a case report of a helicopter pilot who fell into a crevasse during a fuel delivery in Antarctica. He was trapped alone in the crevasse for 3 h while waiting for a rescue team to arrive, and a further 1 h during the extrication process. His condition deteriorated during the extrication and he lost consciousness and signs of life minutes after being dragged over the lip of the crevasse. He was then loaded into the rescue helicopter and treated with intermittent cardiopulmonary resuscitation during the 39-min return flight. Initial esophageal temperature on arrival at the Davis Base medical facility was 24.2°C. After 18 h of further treatment (mechanical ventilation with warm humidified O2, with internal and external warming) he was pronounced dead. The cause of death was hypothermia with minimal physical injury. This case highlights some of the extra challenges facing operational, rescue, and medical personnel in an isolated location. These complications include the tendency for flight crew to remove cold weather clothing during flight due to restricted mobility and excessive heat load from cabin heating; extended time for arrival of the rescue crew; extrication in a confined space; limited helicopter cabin space for transporting the rescue team and their rescue and medical equipment; and extended transport time to the nearest medical facility.


Elimination of erythromycin in milk after intramammary administration in cows with specific mastitis: relation to dose, milking frequency and udder health.
Elimination of erythromycin in milk following intramammary therapy of specific mastitis in cows was studied. Five cows received therapy in one quarter (G1), and eight in two quarters with five milked twice (G2) and three thrice a day (G3). Dose infused was 300 mg/quarter 12 h × 5 times. The drug concentrations in milk were determined using microbial assay technique with Micrococcus luteus as the test organism. Considerable variations occurred in the excretion of drug; levels for treated quarters being 8.25 to 37.61 μg/ml at first milking that declined rapidly at 24 h and no drug activity was observed beyond 36 h post treatment. In total, about 6-25% of the last infused dose appeared in the milk. Drug crossed to 1/15 quarter (G1), 6/10 quarters (G2) and all the six untreated quarters (G3). Crossover levels were significantly higher in mastitic quarters and for G3 cows, but duration of excretion remained same in all cases. It seems that crossover of erythromycin to untreated quarters is related to the udder health and dose infused.


Immunologic responses to a murine mammary adenocarcinoma. II. Monocyte effector activation by humoral factors.
Sera from DBA/2 mice bearing a syngeneic T1699 mammary adenocarcinoma not only induced specific antibody-dependent cellular cytotoxicity (ADCC) mediated by monocytes (and/or macrophages) but also armed (activated) such effector cells into specific killer cells in vitro. Removal of specific antitumor antibody (IgG2a subclass) by absorption with T1699 cells abolished ADCC activity at the level of target cell coating but did not alter the level of effector-arming activity. Fractionation on Sephadex G-20 indicated more than one factor capable of inducing specific monocyte-mediated lysis of target cells in vitro, including immune complexes, free IgG2a 7S antibody (ADCC), and another factor(s) with a molecular weight very close to that of 7S immunoglobulins.


Successful surgical management of penetrating cardiac injury.
A 60-year-old Asian man who suffered penetrating thoracoabdominal injuries was admitted to our hospital in a state of shock. Because the results of a chest computed tomogram (CT) strongly suggested a left ventricular injury, an emergency thoracotomy was performed. A laceration of the left ventricle (3 cm) was sutured and was closed without cardiopulmonary bypass, and coexisting lacerations of the superior mesenteric artery (SMA) and small bowel were surgically repaired. During the procedure, cardiac arrest occurred, but the patient recovered without any apparent neurologic deficit. Postoperative examinations using echocardiogram, CT, and cardiac catheterization revealed a delayed rupture of the left ventricle. On the 28th day after surgery, he was transferred to another hospital for elective cardiac surgery. Primary management of penetrating cardiac injury is discussed in this report.


Induction of antigen-specific tolerance through hematopoietic stem cell-mediated gene therapy: the future for therapy of autoimmune disease?
Based on the principle that immune ablation followed by HSC-mediated recovery purges disease-causing leukocytes to interrupt autoimmune disease progression, hematopoietic stem cell transplantation (HSCT) has been increasingly used as a treatment for severe autoimmune diseases. Despite clinically-relevant outcomes, HSCT is associated with serious iatrogenic risks and is suitable only for the most serious and intractable diseases. A further limitation of autologous HSCT is that relapse rates can be high, suggesting disease-causing leukocytes are incompletely purged or the environmental and genetic determinants that drive disease remain active. Incorporation of antigen-specific tolerance approaches that synergise with autologous HSCT could reduce or prevent relapse. Further, by reducing the requirement for highly toxic immune-ablation and instead relying on antigen-specific tolerance, the clinical utility of HSCT could be significantly diversified. Substantial progress has been made exploring HSCT-mediated induction of antigen-specific tolerance in animal models but studies have focussed on primarily on prevention of autoimmune diseases. However, as diagnosis of autoimmune disease is often not made until autoimmune disease is well developed and populations of autoantigen-specific pathogenic effector and memory T cells have become well established, immunotherapies must be developed to address effector and memory T-cell responses which have traditionally been considered the key impediment to immunotherapy. Here, focusing on T-cell mediated autoimmune diseases we review progress made in antigen-specific immunotherapy using HSCT-mediated approaches, induction of tolerance in effector and memory T cells and the challenges for progression and clinical application of antigen-specific 'tolerogenic' HSCT therapy.


Pregnancy outcome in women with antiphospholipid antibodies.
The association of antiphospholipid antibodies (APA) or lupus anticoagulant (LA) and recurrent fetal loss (RFL) is well established; however, the spectrum of pregnancy outcome in relation to various therapeutic approaches versus placebo is unknown. We studied 49 women with RFL, 14 with immune thrombocytopenia (ITP) 13 of whom without a history of RFL, and 32 controls (all in the first trimester of pregnancy) for the presence of APA. Tests for APA were positive in 15/49 women with RFL (30%), 6/14 ITP (43%) and 2/32 controls (6%). Treatment in the APA positive patients consisted of: no treatment for the 8 patients who had no history of RFL (Group A; all 34 previous pregnancies successful), aspirin alone (Group B, 5 patients; all 30 previous pregnancies unsuccessful), aspirin with prednisolone (Group C, 9 patients; 69/80 previous pregnancies unsuccessful), or aspirin, prednisolone and immunoglobulin G for resistant cases (Group D, 4 patients, previously in Group C). 10/11 (90.9%), 3/7 (43%), 7/13 (53.8%) and 4/7 (57.1%) pregnancies were successful in Group A, B, C and D, respectively. There was a total of 19/45 (42%) failures including 3 pregnancies in one patient who failed to respond to all forms of therapy. This open study with small subgroups of patients draws attention to a wide range of pregnancy outcome in women with APA and to the fact that APA may serve only as a marker for a wide range of pathological conditions with variable degrees of disease severity. More studies are, however, needed to explore the real mechanism of RFL in women with APA and RFL, especially those who are resistant to therapy.


In vivo and in vitro responses to poly(ethylene terephthalate-co-diethylene glycol terephthalate) and polyethylene oxide blends.
Although biocompatible polymeric compounds are generally nontoxic, nonimmunogenic, and chemically inert, implants made from these materials may trigger acute and chronic inflammatory responses. These inflammatory reactions may induce degeneration of implanted biopolymer. Interactions between implanted biomaterial and inflammatory cells are mediated by many cellular events involving cellular adhesion and activation. We studied the inflammatory responses in vivo and in vitro to samples of biopolymers composed of poly(ethylene terephthalate-co-diethylene glycol terephthalate) plus 0, 5, 25% of polyethylene oxide. We observed that these biopolymers did not induce inflammatory responses when implanted in the peritoneal cavity of mice for 28 days. However we observed deposition of hyaluronic acid at the surface of implanted biomaterial, suggesting that tolerance to biomaterial occurred after surgical implantation. No significant adhesion of inflammatory cells such as mononuclear phagocytes and peripheral leukocytes were observed in vitro, when poly(ethylene terephthalate-co-diethylene glycol terephthalate) blends were used as substratum to cellular adhesion. These results suggest that blends composed of poly(ethylene terephthalate-co-diethylene glycol terephthalate) induce low inflammatory cell adhesion, since no rejection of biopolymer was observed when implanted in experimental animal models.


Seasonal changes in median eminence dopamine in male Syrian hamsters: role of the gonads and duration of exposure to short days.
Median eminence dopamine concentrations are reduced in male hamsters housed in a short photoperiod for 12 weeks, but tyrosine hydroxylase activity and dopamine metabolism are unaffected. The mechanism responsible for this decrease in dopamine is unclear. The purpose of the experiments presented here was to examine the effects of gonadal steroids on this decline in median eminence dopamine concentrations, and to characterize the time course over which this change occurs. Experiment 1 examined the effects of short day exposure on median eminence dopamine concentrations and tuberoinfundibular dopamine neuronal activity (i.e., accumulation of 3,4-dihydroxyphenylanine) in castrated male hamsters. The results of that experiment suggest that the short-day induced decline in median eminence dopamine concentrations is maintained in the absence of gonadal steroids. In Experiments 2 and 3, tuberoinfundibular dopamine neuronal activity (accumulation of 3,4-dihydroxyphenylalanine and 3,4-dihydroxyphenylacetic acid concentrations, respectively), median eminence dopamine concentrations and circulating prolactin levels were measured in animals housed in short days for varying lengths of time. This was done to determine when the decline in median eminence dopamine concentrations occurs and if the decline is preceded by a change in tuberoinfundibular dopamine neuronal activity. The results of these two experiments suggest that median eminence dopamine concentrations and circulating prolactin levels decline after approximately 4 weeks of short-day exposure, and that these photoperiod induced changes are not associated with changes in tuberoinfundibular dopaminergic neuronal activity.


Anaerobic digestate water for Chlorella pyrenoidosa cultivation and employed as co-substrate with cow dung and chicken manure for methane and hydrogen production: A closed loop approach.
In rural India, unpleasant atmosphere, anthropogenic gas emission, air and soil pollution are caused due to disposal of livestock's wastes (cow dung and chicken waste) in open environment. This study provides zero emission concept for waste disposal and value addition of these wastes for renewable green energy production. In this study, biogas production was carried out with varying proportion of cow dung to chicken waste (1:0, 0:1, 1:1, 2:1, 1:2, 3:1 and 1:3) for duration of 40 days. Chlorella pyrenoidosa was cultivated from digestate water and used as co-substrate in digester in varying proportions (2:1:1, 2:1:2 and 2:1:3) to study its role on biogas distribution. The effect of pH, feedstock ratio, time and C/N ratio for biogas production were evaluated. The maximum methane and hydrogen yield was 68% (30th day) and 29% (10th day) for 2:1:2 ratio respectively. The slurry possessed nitrogen (1.7%), phosphate (0.8%) and potassium (0.4%) respectively.


Understanding NSCLC, one cell at a time.
Lung cancers are very heterogeneous, a feature that in part emanates from the tumor microenvironment. In this issue, Salcher et al. provide a comprehensive analysis of hundreds of patients with non-small cell lung cancer (NSCLC) at the single-cell level to discover extreme immune diversity and define neutrophil populations associated with treatment outcome.


A new dominant selection marker for transformation of Pichia pastoris to soraphen A resistance.
Despite the considerable progress molecular genetics of filamentous fungi has made during the past decade, there is still an urgent need for efficiently working selectable markers for fungal transformation. Using Pichia pastoris as a host, we describe the development of a new dominant selectable marker of prokaryotic origin. This system, termed sor(R), is based upon the resistance of the bacterial enzyme acetyl-CoA carboxylase (ACCase) to the macrocyclic polyketide soraphen A, a potent inhibitor of fungal ACCase produced by the myxobacterium Sorangium cellulosum. In this study, we firstly demonstrate that the integration of a single sor(R) cassette into the P. pastoris genome confers resistance to elevated concentrations of soraphen A. Furthermore, it has been shown that the versatility of this marker can be considerably increased by splitting the sor(R) cassette, especially when successive transformations are performed on the same strain. As pronounced sensitivity to soraphen A is the rule among filamentous fungi, we expect the sor(R) marker to be a widely applicable tool for fungal transformation.


Exploring "fringe" consciousness: the subjective experience of perceptual fluency and its objective bases.
Perceptual fluency is the subjective experience of ease with which an incoming stimulus is processed. Although perceptual fluency is assessed by speed of processing, it remains unclear how objective speed is related to subjective experiences of fluency. We present evidence that speed at different stages of the perceptual process contributes to perceptual fluency. In an experiment, figure-ground contrast influenced detection of briefly presented words, but not their identification at longer exposure durations. Conversely, font in which the word was written influenced identification, but not detection. Both contrast and font influenced subjective fluency. These findings suggest that speed of processing at different stages condensed into a unified subjective experience of perceptual fluency.


Noninvasive monitoring of oxygenation during one-lung ventilation: a comparison of transcutaneous oxygen tension measurement and pulse oximetry.
Oxygenation was monitored concomitantly by measurement of transcutaneous oxygen tension and by pulse oximetry, and the data were compared with arterial blood oxygen tension and saturation values in 10 patients who became hypoxemic when undergoing thoracotomy and one-lung ventilation. A steep decrease in arterial blood oxygen tension was obvious immediately after the institution of one-lung ventilation, reaching the lowest mean value of 63 +/- 2 mm Hg (+/- SEM) at 12 minutes. Despite significant correlation between transcutaneous oxygen tension and arterial blood oxygen tension during one-lung ventilation (r = 0.75; P less than 0.001), the delay in the transcutaneous oxygen tension response resulted in underestimation of the severity of hypoxemia at the beginning of one-lung ventilation. In contrast, the decrease in arterial blood oxygen saturation from 97.9 +/- 0.3% to 92.2 +/- 0.8% as measured by CO-Oximeter was accurately followed by pulse oximetry with almost beat-to-beat response, bringing about a highly significant linear correlation between the two methods (r = 0.93; P less than 0.001). We conclude that pulse oximetry is a simpler and more rapidly responding method than measurement of transcutaneous oxygen tension for detection of hypoxemia during one-lung ventilation in adults.


Experimental verification of the modified Gran methods applicable to redox systems.
This study describes the application of the modified Gran I and II methods for determination of equivalence volume in redox titrations and for calibration, i.e. for determination of the correct slope of the redox indicator electrodes, which appears to be a major problem in using these electrodes. The four new versions of the Gran II method, denoted as MG(II)B, MG(II)C, MG(II)D and MG(II)E methods, in which the problem of calibration and determination of equivalence volume are considered simultaneously are suggested and compared with MG(I)S and MG(II)A methods known hitherto. All the methods are experimentally tested and discussed.


Correction: Correction: AIG1 affects in vitro and in vivo virulence in clinical isolates of Entamoeba histolytica.
[This corrects the article DOI: 10.1371/journal.ppat.1007091.].


Interacting proteins as genetic modifiers of Huntington disease.
Huntington disease is caused by polyglutamine expansion in huntingtin, a 350 kD protein that is ubiquitously expressed and widely distributed at the subcellular level. Recently, Kaltenbach et al. identified a large collection of novel huntingtin-interacting proteins, several of which modify mutant huntingtin toxicity in Drosophila. Thus, the interaction of mutant huntingtin with certain protein partners can influence its toxicity and therefore the severity and/or progression of Huntington disease.


Dealing with RV-oversensing; separate sensitivity settings for brady and tachy sensing.
An 81-year-old male with a history of systolic heart failure due to an underlying ischemic cardiomyopathy with a left ventricular ejection fraction of 13% and QRS duration of 130 ms had undergone an uncomplicated cardiac resynchronization therapy defibrillator implantation (Quadra Assura MP, St. Jude Medical, LV lead (SJM Quartet 1458Q-86), RA lead (Biotronik Safio S53) and RV shocklead (Biotronik Linox Smart S65 ProMRI) in 2015.


Hepatitis B virus X protein modulates renal tubular epithelial cell-induced T-cell and macrophage responses.
Renal tubular epithelial cells (RTECs) have an active role in renal inflammation, functioning as antigen-presenting cells as they constitutively express major histocompatibility complex-II and co-stimulatory molecules that can activate T cells and macrophages. Previous studies indicate that inflammatory cell infiltration and tubulointerstitial fibrosis are present in renal biopsies from Hepatitis B virus (HBV)-associated glomerulonephritis (HBV-GN) patients. We hypothesized that disorder RTECs may be involved in the progression of HBV-GN. Here, we measured renal function and inflammatory cells infiltration in C57BL/6J-TgN mice, and data showed that in C57BL/6J-TgN mice HBV x protein (HBx) mainly deposited in RTECs, and CD4(+) T cells and macrophages infiltrated into the interstitium. In vitro HBx upregulated CD40 expression in RTECs. In HK-2/CD4(+) T cells co-culture system, we found that HBx-stimulated HK-2 cells could activate CD4(+) T cells, promote their proliferation, and lead to an imbalance of interleukin (IL)-4 and interferon-γ. In HK-2/macrophages co-culture system, we found that HBx-stimulated HK-2 cells also increased macrophage adherent capacity and promoted MCP-1 and tumor necrosis factor-α and IL-1β secretion. These immune dysfunction may contribute to the pathogenesis of HBV-GN.


Comparison of embryo morphokinetics after in vitro fertilization-intracytoplasmic sperm injection in smoking and nonsmoking women.
To evaluate the impact of female smoking on early embryo development in vitro using a time-lapse system. Retrospective analysis of prospectively collected database. Assisted reproductive technology (ART) program. A total of 135 infertile couples undergoing IVF-intracytoplasmic sperm injection (ICSI) cycle. Embryo culture in a time-lapse incubator (Embryoscope, Unisense Fertilitech). Embryo morphokinetic parameters. Of 135 women, 139 and 729 oocytes were cultured in 23 smokers and 112 nonsmokers, respectively. Basal characteristics and ovarian stimulation parameters were comparable in both groups. Serum antimüllerian hormone level and antral follicle count were significantly lower in smokers than in nonsmokers. Conventional embryologic parameters were comparable in both groups, but time-lapse analysis showed that most cleavage events occurred significantly later in smokers than in nonsmokers, leading to poor cycle outcome in smokers. Female smoking impairs early embryo development, as reflected by time-lapse analysis. This might contribute to the dramatic decrease in pregnancy rates (PRs) in smokers undergoing IVF. Time lapse is a useful tool for the identification of deleterious components impairing early embryo development.


Physical activity (PA) influences the risk of depression associated with long working hours.
Growing evidences showed that long working hours is associated with depression epidemic, but few studies investigate whether physical activity (PA) could modify the risk of depression associated with long working hours, which was the purpose of the present study. A cross-sectional data obtained from the National Health and Nutrition Examination Survey 2015-2018. According to the criteria of International Labour Organization, long working hours was defined as >40 h/wk. The Nine-item Patient Health Questionnaire (PHQ-9) was used to identify depression. Binary logistic regression and restricted cubic spline (RCS) models were used to estimate the associations between long working hours and depression, furthermore to estimate the association of PA. 5958 participants were included in the study. The results indicated that 3074 (51.6 %) of participants worked >40 h/wk. The prevalence of depression was 7.7 %. Logistic regression analysis indicated a positive association between long working hours and depression [OR = 1.738, 95 CI (1.427, 2.117)], and the results were still robust after controlling other confounding factors. RCS models indicated that the high intensity PA group had the lowest risk of depression, followed by low intensity PA group and no PA group. Long working hours probably be associated with depression, while PA can modify the risk to some degree.


Renal type I inositol 1,4,5-trisphosphate receptor is reduced in streptozotocin-induced diabetic rats and mice.
The mechanisms underlying glomerular hypertrophy and hyperfiltration in diabetes remain unclear. We have previously demonstrated that the cytokine transforming growth factor-beta1 (TGF-beta1) is increased in early diabetic kidney disease and TGF-beta1 inhibits the expression of the inositol 1,4,5-trisphosphate (IP3)-gated calcium channel, the type I IP3 receptor (IP3R), in mesangial cells. To test the hypothesis that reduced type I IP3R may be important in diabetic kidney disease, we evaluated type I IP3R expression in the kidney of streptozotocin-induced diabetic rats and mice. Two-week-old diabetic rats have decreased renal type I IP3R protein and mRNA levels. Immunostaining of normal rat kidney demonstrated presence of type I IP3R in glomerular and vascular smooth muscle cells, whereas diabetic rats had reduced staining in both compartments. Reduction of type I IP3R also occurred in parallel with renal hypertrophy, increased creatinine clearance, and increased renal TGF-beta1 expression in the diabetic rats. Two-week-old diabetic mice also had reduced renal type I IP3R protein and mRNA expression in association with renal hypertrophy and increased TGF-beta1 mRNA expression. These findings demonstrate that there is reduced type I IP3R in glomerular and vascular smooth muscle cells in the diabetic kidney, which may contribute to the altered renal vasoregulation and renal hypertrophy of diabetes.


Is there a hormonal network in Tetrahymena? A systematic investigation of hormonal effects on the hormone content.
The effect of six hormones (histamine, serotonin, insulin, epidermal growth factor (EGF), oxytocin and gonadotropin) was studied on the hormone (histamine, serotonin, adrenocorticotropic hormone [ACTH], endorphin and triiodothyronine [T(3)]) content of Tetrahymena. The hormones were given in 10(-9) or 10(-12) M concentrations or as 0.1 and 0.001 I.U. ml(-1) (in the case of oxytocin and gonadotropin) for 1 h. The hormones in picomolar concentration, i.e. at levels which can be present also in natural conditions, influence the amount of other hormones inside the cell. Their effect is not a general one: it is individual, the level of one of the hormones was elevated, while that of the others diminished under the effect of the same hormonal stimulus. Insulin was the only hormone, which influenced the concentration of other hormones in one direction, elevating them. This effect could have a role in the life-saving property of this hormone in Tetrahymena, but the hormones were not studied from this point of view. Usually there is no difference between the effect of the two concentrations used, but there are situations when the effect of the two concentrations is opposite. This means that there is a possible concentration dependence and this could influence differently the cells which are far from or near to the secretor cell. Considering earlier observations, the duration of the treatment can also influence the result. The results give new data to the hormonal regulation at unicellular level (which can be the base of regulation at higher evolutionary levels) and point to the possibility of a hormonal network.


Seagrass and green macroalgae Halimeda as biomonitoring tools for metal contamination in Chuuk, Micronesia: Pollution assessment and bioaccumulation.
In this study, we evaluated metal accumulation in different species and tissues of seagrasses and green macroalgae Halimeda and assessed metal pollution levels in Chuuk, Micronesia. In seagrass, the concentrations of Ni, Cu, Zn, Cd, Pb, and Hg were higher in leaves than in roots, whereas Cr and As concentrations were higher in roots. Halimeda had higher concentrations of Ni than of the other metals, and the mean Ni concentration was approximately 2.1 times higher in Halimeda than in seagrass leaves. The concentrations of Cr, As, Cu, Pb, and Hg in Halimeda were similar to those in seagrasses, whereas the Zn and Cd concentrations in Halimeda were very low. Significant correlations in metal concentrations between sediment and both seagrasses and Halimeda were observed for Cr, Ni, Cu, Zn, and Pb. This study suggests that seagrasses and Halimeda are useful indicators for monitoring metal pollution in coastal environments.


Development and characterization of a suturable biomimetic patch for cardiac applications.
3D scaffolds used to repair damaged tissues should be able to mimic both composition and functions of natural extracellular matrix, which is mainly composed of polysaccharides and proteins. In our previous research new biomimetic sponges, based on blends of alginate with gelatin, were produced and characterized for myocardial tissue engineering applications. It was observed that these scaffolds can potentially function as a promising cardiac extracellular matrix substitute, but a reinforcement is required to improve their suturing properties. Aim of the present work was the development of a suturable biomimetic patch by the inclusion of a synthetic mesh within an alginate/gelatin scaffold. The mesh, produced by dry spinning, was made of eight superimposed layers of polycaprolactone microfibers, each one rotated of 45° with respect to the adjacent one. Reinforced scaffolds were obtained through the use of a mold, specially designed to place the fibrous mesh exactly in the center of the sponge. Both the reinforcement mesh and the reinforced scaffold were characterized. A perfect integration between the mesh and the sponge was observed. The fibrous mesh reduced the capacity of the sponge to absorb water, but the degree of hydrophilicity of the material was still comparable with that of natural cardiac tissue. The reinforced system showed a suitable stability in aqueous environment and it resulted much more resistant to suturing than not reinforced scaffold and even than human arteries. Polycaprolactone mesh was not cytotoxic and the reinforced scaffold was able to support cardiomyocytes adhesion and proliferation. Overall, the obtained results confirmed that the choice to modify the alginate/gelatin sponges through the insertion of an appropriate reinforcement system turned out to be correct in view of their potential use in myocardial tissue engineering.


Tissue Doppler is more sensitive and reproducible than spectral pulsed-wave Doppler for fetal right ventricle myocardial performance index determination in normal and diabetic pregnancies.
The aim of this study was to compare the reproducibility, agreement, and sensitivity of pulsed-wave Doppler tissue imaging (DTI) versus spectral Doppler assessment of right ventricular (RV) myocardial performance index (MPI) in midgestation fetuses in both a normal and a disease state. RV MPI was calculated using pulsed-wave DTI and spectral Doppler in normal pregnancies (n = 69) and in women with pregestational diabetes (n = 51). Intraobserver and interobserver variability and agreement were evaluated using Bland-Altman analysis. Student's t tests were used for comparisons of differences. In normal fetuses, RV MPI derived by the two methods showed no statistical difference, were interchangeable (DTI, 0.51 ± 0.10; spectral Doppler, 0.50 ± 0.12; P = .686), and were in agreement by Bland-Altman analysis. However, in fetuses of mothers with diabetes, the two methods produced different RV MPI measurements (DTI, 0.56 ± 0.10; spectral Doppler, 0.51 ± 0.12; P < .001). Intraobserver and interobserver bias was lower for DTI. The DTI method of measuring fetal RV MPI is more sensitive, has less variability and more precision, and is better able to demonstrate subtle abnormalities in cardiac function than the spectral Doppler method in diabetic versus normal pregnancies.


Correction to: The MINDMAP project: mental well-being in urban environments : Design and first results of a survey on healthcare planning policies, strategies and programmes that address mental health promotion and mental disorder prevention for older people in Europe.
Correction to: Z Gerontol Geriat 2017 https://doi.org/10.1007/s00391-017-1290-7 The article "The MINDMAP project: mental well-being in urban environments. Design and first results of a survey on healthcare planning policies, strategies and programmes that address mental health promotion and mental disorder prevention for older people in …The original article was corrected.


A genome-wide search for alleles and haplotypes associated with autism and related pervasive developmental disorders on the Faroe Islands.
The involvement of genetic factors in the etiology of autism has been clearly established. We undertook a genome-wide search for regions containing susceptibility genes for autism in 12 subjects with childhood autism and related pervasive developmental disorders (PDDs) and 44 controls from the relatively isolated population of the Faroe Islands. In total, 601 microsatellite markers distributed throughout the human genome with an average distance of 5.80 cM were genotyped, including 502 markers in the initial scan. The Faroese population structure and genetic relatedness of cases and controls were also evaluated. Based on a combined approach, including an assumption-free test as implemented in CLUMP, Fisher's exact test for specific alleles and haplotypes, and IBD(0) probability calculations, we found association between autism and microsatellite markers in regions on 2q, 3p, 6q, 15q, 16p, and 18q. The most significant finding was on 3p25.3 (P(T1)=0.00003 and P(T4)=0.00007), which was also supported by other genetic studies. Furthermore, no evidence of population substructure was found, and a higher degree of relatedness among cases could not be detected, decreasing the risk of inflated P-values. Our data suggest that markers in these regions are in linkage disequilibrium with genes involved in the etiology of autism, and we hypothesize susceptibility genes for autism and related PDDs to be localized within these regions.


Effects of subacute opioid administration during late pregnancy in the rat on the initiation, duration and outcome of parturition and maternal levels of oxytocin and arginine vasopressin.
1. The effects, on parturition in the rat, of subacute and acute opioid administration were studied. Further experiments investigated the role of modulation of maternal plasma and pituitary oxytocin (OXY) and arginine vasopressin (AVP) levels in these effects. 2. Subacute opioid (M320, buprenorphine or bremazocine) administration prolonged the gestation of rats. This was accompanied by toxic effects on the offspring. Acute subcutaneous (s.c.) M320 (10 micrograms/kg) administration was accompanied by prolonged gestation without toxic effects. 3. Subacute M320 (10 micrograms/kg, s.c., twice daily) treatment was accompanied by increased interbirth intervals in parturient rats. 4. Maternal OXY but not AVP release, as assessed by measurement of plasma and pituitary immunoreactivity, was elevated during and up to 1 h after the completion of parturition. Subacute M320 treatment did not inhibit this elevated OXY release.


Does radiofrequency ablation (RFA) epiphysiodesis affect adjacent joint cartilage?
To test the hypothesis that epiphysiodesis made with radiofrequency ablation (RFA) is a safe procedure that disrupts the growth plate without damaging the adjacent joint articular cartilage. RFA epiphysiodesis was done during 8 min in vivo in 40 growing pig tibia physis. In addition, three tibiae were ablated for 16 min and three more for 24 min. As a burned cartilage reference, six tibiae were ablated on the joint articular cartilage for 8 min. After the procedure, the animals were terminated and the tibiae were harvested. Magnetic resonance imaging (MRI) was done ex vivo to evaluate the joint articular cartilage in all samples. We used T1-weighted, T2-weighted, and water content sequences under a 1.5 T magnetic field. On the burned articular cartilage, intensity changes were observed at MRI. We found no evidence of articular cartilage damage on the 40 8-min RFA procedures. The tibiae ablated for 16 min and 24 min showed intact joint cartilage. Epiphysiodesis using RFA is safe for the adjacent articular cartilage. This study shows that RFA can be done safely in the growing physis of pigs, even with triple duration procedures.


The proteasome/multicatalytic-multifunctional proteinase. In vivo function in the ubiquitin-dependent N-end rule pathway of protein degradation in eukaryotes.
Proteinase yscE, the proteasome/multicatalytic-multifunctional proteinase of yeast had been shown to function in stress response and in the degradation of ubiquitinated proteins [(1991) EMBO J. 10, 555-562]. A well-defined set of proteins degraded via ubiquitin-mediated proteolysis are the substrates of the N-end rule pathway [(1986) Science 234, 179-186; (1989) Science 243, 1576-1583]. We show that mutants defective in the chymotryptic activity of proteinase yscE fail to degrade substrates of the N-end rule pathway. This gives further proof of the proteasome being a central catalyst in ubiquitin-mediated proteolysis.


The Effects of the Respiratory Rehabilitation Program on Perceived Self-Efficacy and Dyspnea in Patients with Lung Cancer.
This study aims to examine the effects of the respiratory rehabilitation program on perceived self-efficacy and dyspnea in patients with lung cancer. This is a quasi-experimental research study with a two-group repeated measures design with the pretest and post-test at Week 4 and Week 8. The theory of self-efficacy by Bandura was used as the conceptual framework. The sample consisted of patients with non-small-cell lung cancer Stage 4 who visited the oncology clinic in a university hospital. Twenty-eight patients were enrolled and equally allocated to the control group and experimental group. The control group received routine nursing care only, whereas the experimental group received the respiratory rehabilitation program. The program comprised dyspnea educating, breathing exercise, using handheld fans, effective coughing, respiratory strengthening training, and follow-up by phone in the third and sixth week. Data for perceived self-efficacy and dyspnea were collected before the program start and reassessment in the fourth and eighth week. Instrumentation was composed of the respiratory rehabilitation program, demographic data, perceived self-efficacy assessment for respiratory rehabilitation, and the Cancer Dyspnea Scale. Data were analyzed using descriptive statistics and one-factor repeated measures analysis of variance and by comparing means between groups. The result revealed that almost all of the patients in the sample were men, and the mean age of the experimental group and control group was 65.80 years (standard deviation = 8.80) and 73.00 years (standard deviation = 7.60), respectively. There was significant different in the mean score of perceived self-efficacy and dyspnea between the experimental group and the control group (p < .050). Based on the findings of the study, the respiratory rehabilitation program should be used to promote self-efficacy and relieve dyspnea in patients with lung cancer.


Thymol-based submicron emulsions exhibit antifungal activity against Fusarium graminearum and inhibit Fusarium head blight in wheat.
Fusarium graminearum is a very destructive fungal pathogen that leads to Fusarium head blight (FHB) in wheat, a disease which costs growers millions of dollars annually both in crop losses and in remediation efforts. Current countermeasures include the deployment of wheat varieties with some resistance to FHB in conjunction with timed fungicide treatments. In this article, we introduce a fungicide based on thymol, a naturally occurring plant phenolic derived from essential oils. To overcome the hydrophobicity of thymol, the thymol active was incorporated into a low-surfactant submicron emulsion with and without a carrier oil. The minimum fungicidal concentration of F. graminearum was found to be both 0·02% for thymol emulsions with and without an oil component. Time-to-kill experiments showed that thymol emulsions were able to inactivate F. graminearum in as little as 10 s at concentrations above 0·06%. Spraying the thymol emulsions (~0·1% range) on the wheat variety Bobwhite demonstrated significant reductions in FHB infection rate (number of infected spikelets). However, with 0·5% thymol, the wheat heads exhibited premature senescence. Transmission and scanning electron micrographs suggest that the mechanism of antifungal action is membrane mediated, as conidia exposed to thymol showed complete organelle disorganization and evidence of lipid emulsification. The collective experimental data suggest that thymol emulsions may be an effective naturally derived alternative to the current thymol treatments, and chemical fungicides in ameliorating FHB. This is the first thymol-derived nanoemulsion particles resuspended into water and not DMSO, exhibiting the same antibacterial/antifungal activity as previously described thymol and thyme oil treatments. This drastically reduces the environmental footprint thymol will leave if utilized as a fungicide treatment on field crops.


Associations between gait speed and well-known fall risk factors among community-dwelling older adults.
Exercise interventions are effective at preventing falls in community-dwelling older adults, especially before disability is present. Gait speed below 1.0 m/s is a strong predictor for falls in the elderly. However, evidence is sparse for gait speed alone being sufficient to identify individuals at a high risk of falling. This study aimed to describe the prevalence of fall risk factors among community-dwelling older adults in their late 70s and to investigate the associations between these risk factors and low gait speed in this population. This cross-sectional cohort study comprised 108 elderly living in a small Norwegian municipality, born between 1936 and 1938. Exclusion criteria were living in residential care, inability to walk 4 m, and severe cognitive impairment. Measurements included gait speed, depressive symptoms, executive functions, fear of falling, vision function, fall history, body mass index, medications, and comorbidity. Gait speed was dichotomized using a cut-off of 1 m/s, and associations between different risk factors and low gait speed was explored using logistic regression analysis. Mean gait speed was 1.0 ± 0.3 m/s. In 44.4% of the participants, gait speed was below 1.0 m/s, indicating increased fall risk. Low gait speed was significantly associated with a history of multiple falls (odds ratio [OR] = 3.70, 95% CI [1.18, 11.65]), low educational level (OR = 3.58, 95% CI [1.10, 11.66]), higher number of medications (OR = 4.28, 95% CI [1.63, 11.2]), and higher number of depressive symptoms (OR = 1.31, 95% CI [1.09, 1.58]). We found no significant associations between gait speed and comorbidity, sex, vision, executive functions, or fear of falling. Our results indicate that gait speed with cut-off 1.0 m/s could represent a useful tool for identifying individuals who are vulnerable but not yet disabled and could benefit from fall-preventive exercise. However, extended assessment is probably needed to personalize interventions.


Radioiodinated dechloro-4-iodofenofibrate: a hydrophobic model drug for molecular imaging studies.
Radiolabeling is a valuable option for tracking drug molecules in biodistribution experiments. In the development of innovative drug delivery systems the influence of the pharmaceutical formulation on the drugs' pharmacokinetics has to be investigated. The hypolipidemic agent fenofibrate is an ideal model drug for testing the performance of drug delivery systems designed for poorly soluble compounds. Herein, we report a de novo synthesis of a fenofibrate derivative, dechloro-4-iodofenofibrate, as well as its conversion into its radioiodinated derivatives containing (125)I or (131)I. The enzymatic stability of the radiolabeled compounds synthesized was determined in vitro. A scintigraphic imaging study supplemented by biodistribution experiments and analysis of excreted metabolites revealed the stability required for in vivo applications and its similarity to fenofibrate. Therefore a convenient method is presented to synthesize radioiodinated derivatives of fenofibrate. These tracers show excellent in vitro and in vivo properties to study the behavior of lipophilic drugs.


Correlation between elevation of serum antinuclear antibody titer and decreased therapeutic efficacy in the treatment of Behçet's disease with infliximab.
Infliximab, an anti-TNF-α monoclonal antibody, administered to Behçet's disease (BD) patients in Japan with refractory intraocular inflammation, has shown excellent clinical results. However, some patients demonstrate a decreased response to infliximab during the course of the treatment. In the present study, we investigated the correlation between this reduced therapeutic effect and elevation of the serum antinuclear antibody (ANA) titers in patients with BD who were undergoing infliximab therapy. Seventeen patients (14 males and three females) with uveitis in BD who were undergoing treatment with infliximab for 2 years or longer were enrolled. Their blood test results and clinical histories were obtained from medical records. One patient (5.9%) was ANA-positive prior to the initiation of infliximab, and 11 patients (64.7%) developed positive ANA during the therapy. The appearance of ANA was observed 6 months after the initiation of the infliximab therapy, and its titers gradually increased. None of the patients showed lupus symptoms. Five patients (29.4%) have suffered from ocular inflammatory attacks since the sixth month from the initiation of infliximab treatment and all of them were ANA-positive. In contrast, four patients (23.5%) who were ANA-negative experienced no ocular attacks during the follow-up period. Here we report the positive conversion and subsequent elevation of serum ANA titers in some patients with BD after the initiation of infliximab therapy. Since all recurrences of uveitis were shown only in the ANA-positive patients, serum ANA titer may be a helpful biomarker for predicting the recurrence of ocular attacks in BD patients treated with anti-TNF-α antibody therapies.


Platelet-to-hemoglobin ratio as a valuable predictor of long-term all-cause mortality in coronary artery disease patients with congestive heart failure.
The platelet-to-hemoglobin ratio (PHR) has emerged as a prognostic biomarker in coronary artery disease (CAD) patients after PCI but not clear in CAD complicated with congestive heart failure (CHF). Hence, we aimed to assess the association between PHR and long-term all-cause mortality among CAD patients with CHF. Based on the registry at Guangdong Provincial People's Hospital in China, we analyzed data of 2599 hospitalized patients who underwent coronary angiography (CAG) and were diagnosed with CAD complicated by CHF from January 2007 to December 2018. Low PHR was defined as ˂ 1.69 (group 1) and high PHR as ≥ 1.69 (group 2). Prognosis analysis was performed using Kaplan-Meier method. To assess the association between PHR and long-term all-cause mortality, a Cox-regression model was fitted. During a median follow-up of 5.2 (3.1-7.8) years, a total of 985 (37.9%) patients died. On the Kaplan-Meier analysis, patients in high PHR group had a worse prognosis than those in low PHR group (log-rank, p = 0.0011). After adjustment for confounders, high PHR was correlated with an increased risk of long-term all-cause mortality in CAD patients complicated with CHF. (adjusted hazard ratio [aHR], 1.31; 95% confidence interval [CI], 1.13-1.52, p < 0.0001). Elevated PHR is correlated with an increased risk of long-term all-cause mortality in CAD patients with CHF. These results indicate that PHR may be a useful prognostic biomarker for this population. Meanwhile, it is necessary to take effective preventive measures to regulate both hemoglobin levels and platelet counts in this population.


Doping with artificial oxygen carriers: an update.
There is a long history of science seeking to develop artificial substitutes for body parts damaged by disease or trauma. While defective teeth and limbs are commonly replaced by imitations without major loss of functionality, the development of a substitute for red blood cells has proved elusive. There is a permanent shortage of donor blood in western societies. Nevertheless, despite whole blood transfusions carrying measurable risks due to immunogenicity and the transmission of blood-borne infectious diseases, red blood cells are still relatively inexpensive, well tolerated and widely available. Researchers seeking to develop products that are able to meet and perhaps exceed these criteria have responded to this difficult challenge by adopting many different approaches. Work has focussed on two classes of substances: modified haemoglobin solutions and perfluorocarbon emulsions. Other approaches include the creation of artificial red cells, where haemoglobin and supporting enzyme systems are encapsulated into liposomes. Haemoglobin is ideally suited to oxygen transport when encased by the red cell membrane; however, once removed, it rapidly dissociates into dimers and is cleared by the kidney. Therefore, it must be stabilised before it can be safely re-infused into humans. Modifications concomitantly alter the vascular half-life, oxygen affinity and hypertensive characteristics of raw haemoglobin, which can be sourced from outdated blood stores, genetically-engineered Escherichia coli or even bovine herds. In contrast, perfluorocarbons are entirely synthetic molecules that are capable of dissolving oxygen but biologically inert. Since they dissolve rather than bind oxygen, their capacity to serve as a blood substitute is determined principally by the oxygen pressure gradients in the lung and at the target tissue. Blood substitutes have important potential areas of clinical application including red cell replacement during surgery, emergency resuscitation of traumatic blood loss, oxygen therapeutic applications in radiography (oxygenation of tumour cells is beneficial to the effect of certain chemotherapeutic agents), other medical applications such as organ preservation, and finally to meet the requirements of patients who cannot receive donor blood because of religious beliefs. Given the elite athlete's historical propensity to experiment with novel doping strategies, it is likely that the burgeoning field of artificial oxygen carriers has already attracted their attention. Scientific data concerning the performance benefits associated with blood substitutes are virtually nonexistent; however, international sporting federations have been commendably proactive in adding this category to their banned substance lists. The current situation is vulnerable to exploitation by immoral athletes since there is still no accepted methodology to test for the presence of artificial oxygen carriers.


An Unroofing Method to Observe the Cytoskeleton Directly at Molecular Resolution Using Atomic Force Microscopy.
An improved unroofing method enabled the cantilever of an atomic force microscope (AFM) to reach directly into a cell to visualize the intracellular cytoskeletal actin filaments, microtubules, clathrin coats, and caveolae in phosphate-buffered saline (PBS) at a higher resolution than conventional electron microscopy. All of the actin filaments clearly exhibited a short periodicity of approximately 5-6 nm, which was derived from globular actins linked to each other to form filaments, as well as a long helical periodicity. The polarity of the actin filaments appeared to be determined by the shape of the periodic striations. Microtubules were identified based on their thickness. Clathrin coats and caveolae were observed on the cytoplasmic surface of cell membranes. The area containing clathrin molecules and their terminal domains was directly visualized. Characteristic ridge structures located at the surface of the caveolae were observed at high resolution, similar to those observed with electron microscopy (EM). Overall, unroofing allowed intracellular AFM imaging in a liquid environment with a level of quality equivalent or superior to that of EM. Thus, AFMs are anticipated to provide cutting-edge findings in cell biology and histology.


Clinicopathological and prognostic value of CD24 expression in breast cancer: a meta-analysis.
A number of studies have been conducted to explore the relationship between CD24 expression and the prognosis of breast cancer; however, the results remain inconsistent. Therefore, we performed this meta-analysis to clarify the impact of CD24 expression on clinicopathological features and prognosis of breast cancer. A comprehensive literature search for relevant studies was performed, and statistical analysis was conducted using Stata software. Twenty studies, including 5,179 cases, were included in this meta-analysis. The pooled analysis indicated that CD24 expression was associated with lymph node invasion (odds ratio [OR] = 0.68, for negative vs. positive, 95% confidence interval [95% CI], 0.53-0.87, p = 0.002) and TNM stage (OR = 0.63, for I + II vs. III + IV, 95% CI, 0.49-0.81, p<0.001). The prognosis analysis also suggested CD24 overexpression indicated a poorer 5-year overall survival (OS) rate (relative risk ratio [RR] = 0.93, 95% CI, 0.86-0.99, p = 0.03) and 5-year disease-free survival (DFS) rate (RR = 0.90, 95% CI, 0.83-0.98, p = 0.02). However, CD24 expression had no correlation with tumor size, tumor grade, distance metastasis, estrogen receptor (ER) status, progesterone receptor (PR) status, or HER2 status. Our results suggest that higher CD24 expression is significantly associated with lower OS rate, lower DFS rate and some clinicopathological factors such as lymph node invasion and TNM stage. This meta-analysis suggested that CD24 is an efficient prognostic factor in breast cancer.


The effect of acetylcholine on early postoperative intraocular pressure.
We randomly assigned 36 patients undergoing extracapsular cataract extraction and posterior chamber lens implantation to two groups. The 18 patients in the treatment group received intracameral acetylcholine during the operative procedure, and the 18 patients in the control group received only balanced salt solution. In all other respects the patients were treated identically. Intraocular pressures were measured preoperatively, and at three, six, nine, and 24 hours postoperatively. Preoperatively, the mean intraocular pressures were 16.5 mm Hg in the treatment group and 16.8 mm Hg in the control group. Three hours postoperatively, the mean pressures were 11.9 mm Hg in the treatment group and 21.8 mm Hg in the control group. Six hours postoperatively the respective pressures were 15.4 mm Hg and 22.3 mm Hg. These differences in the mean pressures between the two groups were statistically significant. At nine and 24 hours postoperatively, the pressures in the treatment group remained lower than pressures in the control group, but these differences were no longer significant.


Cervical Joint Position Sense in Individuals With Type 2 Diabetes and Its Correlations With Glycated Hemoglobin Levels: A Cross-Sectional Study.
This study aimed to compare cervical joint position sense (JPS) between individuals with type 2 diabetes (T2D) and healthy individuals and to assess the correlation between glycated hemoglobin (HbA1c) values and cervical JPS in individuals with T2D. Ninety-seven individuals with T2D (mean age: 59.0 ± 6.8 years; men = 63 [67.02%], women = 34 [32.98%], and 117 healthy individuals without T2D (mean age: 57.3 ± 6.9 years; men = 70 [79.80%], women = 44 [20.20%]) were recruited into this study. Cervical JPS was evaluated using a cervical range of motion device in cervical flexion, extension, and rotation in left and right directions. Participants were required to relocate their heads actively to a predefined target position with eyes closed, and their reposition accuracy was measured in degrees as joint reposition error (JRE). The HbA1c test was performed on all participants with T2D to determine their average blood sugar level over the previous 2 to 3 months. Cervical JREs were compared and correlated with HbA1c values. The participants with T2D showed significantly larger cervical JREs in all directions compared with the healthy group (flexion: d = 1.23, P < .001; extension: d = 1.85, P < .001; left rotation: d = 1.70, P < .001; right rotation: d = 2.60, P < .001). Pearson correlation coefficient (r) showed significant moderate positive association between HbA1c and cervical JREs in flexion (r = 0.41, P = .001), extension (r = 0.48, P < .001), left rotation (r = 0.38, P < .001), and right rotation (r = 0.37, P < .001) in participants with T2D. The magnitude of cervical JPS impairment was significant in individuals with T2D. In addition, HbA1c levels showed a significant negative correlation with cervical JPS.


Preperitoneal fat thickness by ultrasonography and obesity-related disorders.
To determine optimal cutoff values for preperitoneal fat thickness measured by ultrasonography as indicators for obesity-related disorders. We studied 276 men aged 60 ± 13 years and 307 women aged 64 ± 11 years. Participants were consecutively enrolled from inpatients aged ≤75 years. Demographic data were collected and maximal preperitoneal fat thickness (PFTmax) and carotid intima-media thickness were evaluated on B-mode ultrasonography. Receiver operating characteristic (ROC) curve analysis was performed to determine optimal cutoff values for PFTmax. Multiple regression analysis using one or more obesity-related disorders as an objective variable showed that the tertile on the basis of PFTmax was a significant independent contributing factor in both men and women. Receiver operating characteristic curve analysis identified the cutoff points of 6.1 mm for PFTmax in men (sensitivity, 66.7%; specificity, 62.5%) and 8.7 mm for PFTmax in women (sensitivity, 56.6%; specificity, 63.6%) as discriminator values corresponding to the presence of one or more obesity-related disorders. Using the new criteria to diagnose visceral obesity, we found that adjusted carotid intima-media thickness was significantly higher in men and women with visceral obesity and two or more obesity-related disorders than in those without them. These findings suggested that PFTmax measured on ultrasonography was useful in screening for indicators of cardiovascular risk factors.


Glucose handling in streptozotocin-induced diabetic rats is improved by tyramine but not by the amine oxidase inhibitor semicarbazide.
A soluble form of semicarbazide-sensitive amine oxidase (SSAO) circulating in plasma is known to increase in type 1 and 2 diabetes. This cuproenzyme generates hydrogen peroxide, ammonia, and aldehydes when oxidizing circulating biogenic or exogenous amines. Based on the angiotoxicity of these products, inhibition of SSAO has been proposed to prevent vascular complications of diabetes. However, substrates of SSAO and monoamine oxidase (MAO) have been recently evidenced to activate glucose utilisation in insulin-sensitive tissues and to exhibit antihyperglycemic actions. To determine whether amine oxidase blockade or activation could be beneficial for diabetes, we aimed at comparing the influence of prolonged treatments with semicarbazide (SSAO-inhibitor), pargyline (MAO-inhibitor), or tyramine (amine oxidase substrate) on amine oxidase activities and glycemic control in streptozotocin-induced diabetic rats. The increase in plasma SSAO was confirmed in diabetic rats, while MAO and SSAO were decreased in subcutaneous adipose tissue when compared with normoglycemic controls. Among the diabetic rats, only those receiving tyramine exhibited slightly decreased hyperglycemia and improved glucose tolerance. Adipocytes from untreated or treated diabetic rats shared similar sensitivity to insulin. However glucose uptake activation and lipolysis inhibition in response to amine oxidase substrates combined with vanadate were impaired in rats treated with amine oxidase inhibitors. Thus, amine oxidase inhibition does not improve metabolic control while prolonged administration of tyramine slightly improves glucose disposal. It is therefore concluded that amine oxidase activation by increased substrate supply elicits insulin-like actions that may be more beneficial in diabetes than SSAO inhibition formerly proposed to prevent vascular complications.


A rare case of extensive cutaneous spider angioma in Zieve's syndrome: A case report and review of literature.
Chronic alcoholism is a global public health problem showing increasing trends throughout the world. Alcoholic liver disease is one of the most important causes of mortality worldwide. Cutaneous features are one of the most frequent manifestations of liver disease and can often be a presenting feature. Spider angioma is one of the cutaneous manifestations in liver diseases. More than six spider nevi are considered abnormal. Here we present a case of a gentleman with a history of chronic alcohol intake and diagnosed with Zieve's syndrome, who presented with extensive cutaneous spider angioma.


The radical soft-tissue mobilization (Kelly repair) for bladder exstrophy.
The radical soft-tissue mobilization (RSTM) technique has been proposed as an alternative for staged reconstruction of bladder exstrophy. In this video, we demonstrate the successive steps of this technique. A newborn male with classic bladder exstrophy underwent bladder closure without pelvic osteotomies at birth; he then underwent RSTM at 1 year of age. Mobilization: The RSTM involved simultaneous intra-pelvic and perineal dissection, aiming at full mobilization of potential urethral sphincter striated structures, levatores ani muscles, pudendal pedicles and corpora cavernosa from their attachment on the pubic bones. From the perineal approach, a periosteum incision was performed on the antero-medial aspect of the pubic bones, and the periosteum was peeled from the ischio-pubic ramus, lifting the corpora from the bone and providing control on the pudendal pedicles. The attachments of all striated muscular structures on the lower aspects of the posterior corpora (transverse perinei, bulbo-spongiosus, ischio-cavernosus muscles) were released to allow adequate re-approximation around the reconstructed urethra. Reconstruction: After ureteric reimplantation, a funnel-shaped cervicoplasty was performed and continued by urethroplasty over an 8-Fr catheter. The muscular structures mobilized from the corpora and the bones were wrapped around the neo-urethra, which was transposed ventrally in the scrotal position, creating a temporary hypospadiac urethrostomy. After abdominal wall closure, the corpora were then de-rotated, and secured to the neo-symphisis with non-absorbable sutures, and the penile skin shaft was reconstructed. At the 12-month follow-up, the boy was asymptomatic, still in nappies, with non-dilated upper-tracts on renal ultrasound, and dryness intervals of 90 min. Radical soft-tissue mobilization allows a tension-free bladder-neck reconstruction, and may favour development of physiological continence mechanisms independent of the inevitable pubic symphisis re-enlargement. Creation of temporary hypospadias is most often needed to maximize penile length. This technically demanding procedure requires thorough knowledge of detailed anatomy of the bladder exstrophy pelvis, as demonstrated in this video.