Renal handling of amylase and immunoreactive trypsin in pancreatic cancer and chronic pancreatitis.
In order to evaluate the renal metabolism of amylase and immunoreactive trypsin (IRT) in chronic pancreatic disease, we assayed amylase, IRT and creatinine in serum and urine and gamma-glutamyl transferase (GGT) in dialyzed urine as well as alpha-glucosidase (AGL) and ribonuclease (RNase) in 24 control subjects, 34 patients with pancreatic cancer, 52 with chronic pancreatitis and 32 with extra-pancreatic diseases. Urinary amylase and IRT outputs were found to be more elevated in chronic pancreatitis than in control subjects. The levels of serum amylase, its renal inputs and outputs were correlated with the corresponding IRT values. Multiple regression analyses (dependent on amylase or IRT urinary outputs, circulating levels of the two enzymes, creatinine clearance and the excretion of GGT, AGL and RNase predictor variables) showed significant correlations. The standardized partial regression coefficients found to be significant were: GGT, RNase and serum amylase for amylase, and GGT and RNase for IRT. No difference was found between amylase and IRT outputs in patients with chronic pancreatitis, taking the presence or the absence of alcohol abuse, exocrine insufficiency and pancreatic pseudocysts into consideration. Urinary GGT excretion correlated with serum amylase and IRT levels.(ABSTRACT TRUNCATED AT 250 WORDS)


Microalbuminuria is related to marked end organ damage in previously untreated, elderly hypertensive patients.
We wondered whether, in an elderly hypertensive population in a primary prevention setting, free from diabetes mellitus and clinical atherosclerosis, differences between end organ damage and microalbuminuria (MA) could be found using a lower level of urinary albumin excretion than that of classically defined MA. From a population survey of 173 previously untreated hypertensive patients (4x blood pressure systolic > or = 160 and < or = 220 mmHg, and/or diastolic > or = 95 and < or = 115 mmHg), mean age 67 +/- 4 years, were screened for MA (defined as albumin excretion between 20 and 300 mg/24 h). End organ damage was determined by B-mode ultrasound scanning of carotid and femoral arteries and echocardiography. Out of 173 hypertensives, 14 showed MA (8%). These hypertensives had a significantly higher intima media thickness (IMT; 1.01 +/- 0.21 vs 0.88 +/- 0.6 mm, p < 0.05) and increased left ventricular mass index (118 +/- 31 vs 103 +/- 22 g/m2, p < 0.05) than hypertensives without MA. Linear regression analysis showed that MA, age, male gender and diastolic blood pressure were independently related to IMT, while systolic blood pressure, male gender and body mass index were independently related to left ventricular mass. Even using lower levels of urinary albumin excretion rate, patients with MA had significantly higher IMT and increased left ventricular mass. Moreover, MA was independently related to IMT in these elderly hypertensives. These results suggest that the threshold value for MA should be reconsidered in hypertension.


Small biopsies in the head and neck: Bone and soft tissue.
Bone and soft tissue lesions in the head and neck encompass not only a broad morphologic spectrum but also significant inherent clinicopathologic overlap. Epidemiology, radiology, and location - similar to the diagnostic assessment in other sites - are especially important considerations in the context of an established mesenchymal proliferation. Herein, the approach towards diagnosis is stratified by morphology (spindle, sarcomatoid, epithelioid, round cell), cellular lineage (fibroblastic, nerve sheath, rhabdomyogenic), and tumor grade (benign, low- to high-grade malignant) as the basis of further immunohistochemical or molecular investigation.


Fine-needle aspiration cytology in pancreatic endocrine tumors.
Pancreatic endocrine tumors (PETs) are relatively uncommon neoplasms. Although their histologic patterns have been widely studied, their cytologic features as they appear in fine-needle aspiration (FNA) specimens have rarely been reported. In this study, aspirates of seven PETs, four primary and three metastatic lesions (two to liver and one to bone), are described. The tumors occurred in seven men ranging in age from 37 to 72 yr. Six tumors presented as nonfunctioning masses and one produced Zollinger-Ellison syndrome. Three were located in the head of the pancreas and four in the body and tail. The pancreatic and liver aspirations were performed under computed tomographic guidance and the bone lesion, under fluoroscopy. The aspiration specimens were hypercellular. The tumor cells occurred singly and in small clusters. In three cases, there was a tendency toward acinar formations. In two cases, there were prominent, thin-walled, branching blood vessels with tumor cells attached to the vascular walls. The cells were round or polygonal with a moderate amount of finely granular, well-defined cytoplasm. The nuclei were eccentrically located and round-to-oval--with one or two small nucleoli and finely granular, evenly-dispersed chromatin. The diagnosis was confirmed by immunocytochemistry (two cases) and electron microscopy (four cases) of the aspirated material and histology sections of the resected tumors (two cases). The results of this study demonstrate that FNA is a useful method to establish the diagnosis of PETs.


Evaluation of two absorbed enzyme-linked immunosorbent assays and a complement fixation test as replacements for fecal culture in the detection of cows shedding Mycobacterium avium subspecies paratuberculosis.
Control of paratuberculosis in dairy herds is based on preventing the transmission of Mycobacterium avium subsp. paratuberculosis (Mptb) from cows to calves by management measures, supported by removal of cows excreting these bacteria by the fecal route (Mptb shedders). Fecal culture is the most accurate test for identifying Mptb shedders, but this technique is expensive and takes up to 16 weeks for results to be available. Serologic tests are inexpensive, rapid, and easy to perform. Of serologic tests, the complement fixation test (CFT) and absorbed enzyme-linked immunosorbent assay (ELISA) are the serologic tests used most frequently; the CFT is considered less accurate than the ELISA with respect to sensitivity and specificity. The commonly accepted absorbed ELISA is from the Australian Central Serum Laboratory. However, a European supplier has marketed a second ELISA that is supposed to be more sensitive in detecting Mptb shedders. These 2 absorbed ELISAs, designated ELISA-A and ELISA-B, and an in-house CFT were compared with data from 2 serum panels. The Mptb shedding panel consisted of sera from 198 culture-positive cows from 53 infected herds. The method used for culture of fecal samples was a modified Jørgensen method on individual samples. The Mptb shedder detection rate by the 3 serologic tests ranged from 29.8% to 39.4%. Detection rate for ELISA-A was lower than that for ELISA-B and CFT. For all 3 tests, detection rate was dependent on the level of Mptb shedding and the age of the animals. Detection rates increased as cattle age increased to 4 years. The specificity panel was initially composed of sera from 811 cows randomly selected from 41 herds without clinical paratuberculosis that were negative for Mptb based on whole-herd fecal culture. The modified Jørgensen method for culture was used on pooled fecal samples. Serologic test specificity ranged from 93.4% to 99.8%. The specificity of ELISA-A was higher than that of ELISA-B and CFT. Specificity of ELISA-B between herds was 75-100%. Specificity of CFT between herds was 62-100%. The low specificity of ELISA-B and CFT could not be explained by a higher sensitivity for Mptb-infected cows before onset of shedding, because in the 19 herds with 8 more subsequent negative whole-herd fecal cultures in the 4 years after sampling, specificity was not improved. The insufficient specificity of ELISA-B was not corrected sufficiently by heightening the cutoff value because Mptb shedder detection rate was lowered to 28.9%, equal to that of ELISA-A, and specificity only rose to 97%, much lower than that of ELISA-A. Taking into account the different test characteristics, serologic tests are a cost-effective alternative to fecal culture in high-prevalence herds. For certification programs, only ELISA-A is recommended because in a large number of nonsuspect herds specificity remained almost 100%.


A review of projective test findings with older adults.
The projective test literature on aging is reviewed. It was concluded that, while much critical research remains to be done and many of the studies are flawed, projective testing has contributed a great deal to the understanding of the aging process and has yielded a core of consistent findings. Suggestions for future research which would help resolve some current ambiguities were made.


Magnetic Resonance Imaging of Pelvic Masses: A Compartmental Approach.
Magnetic resonance imaging (MRI) is often "one stop shop" for evaluating female pelvic masses that helps in diagnosis, staging, and restaging of these tumors. A pelvic mass can arise from any tissue present within the pelvis. Although most masses in the female pelvis arise from the reproductive organs, masses may also arise from the gastrointestinal tract, urinary system, adjacent soft tissues, peritoneum, etc. It may not always be possible to determine the site of origin or distinguish these masses based on imaging characteristics. However, familiarity with the clinicopathologic and MRI features of most common pelvic masses helps in narrowing the differential diagnosis. Diagnosis of these masses needs a holistic approach as required for any tumor including clinical history, laboratory data, and imaging characteristics. We focus on MRI characteristics of commonly encountered pelvic masses. A compartmental imaging approach is discussed in this article that helps in identifying and characterizing these masses.


Prevalence, risk indicators, and clinical characteristics of peri-implant mucositis and peri-implantitis for an internal conical connection implant system: A multicenter cross-sectional study.
Peri-implant disease prevalence is associated with a multifactorial etiology and distinct clinical characteristics of inflammation. The present study aimed to assess the prevalence of peri-implant diseases, identify related risk indicators, and associate specific clinical characteristics to peri-implant biological complications in the medium term. Peri-implant diseases were classified according to established case criteria. Patients' data, implant and/or prosthetic features, and maintenance records were collected. Clinical characteristics such as bleeding on probing (BOP), suppuration (SUPP), keratinized mucosa (KM), probing depth (PD), marginal recession (MR), and modified plaque index (mPI) were recorded. Ninety-nine patients with 266 implants with a mean functional duration of 30.26 months were evaluated. Peri-implant mucositis and peri-implantitis prevalence totaled to 49.5% and 15.15% (patient level), respectively. Peri-implant mucositis was associated with osteoporosis (odds ratio [OR] 6.09), age (OR 0.97), diabetes mellitus (OR 3.09), cemented-retained prosthesis (OR 3.81), and partial prosthesis (OR 2.21). Peri-implantitis was associated with osteoporosis (OR 7.74) and periodontitis (OR 2.74), cemented prosthesis (OR 10.12), partial and full arch prostheses (OR 12.35 and 19.86), implant diameter (OR 3.64), abutment transmucosal height (OR 3.39), and hygiene difficulty (OR 3.14). Furthermore, mPI score 3 (OR 3.27) and PD scores (OR 1.64) were associated with peri-implant mucositis, while mPI score 3 (OR 16.42), KM (OR 1.53), PD (OR 1.81), MR (OR 2.61), and the relationship between KM and PD (OR 0.63) were associated with peri-implantitis. In the medium term, peri-implant diseases were correlated with factors inherent to the patient's conditions, presurgical treatment plan, and hygiene maintenance care. The knowledge of the mentioned factors and featured clinical characteristics can be crucial for disease prevention and establishment of a superior implant therapy prognosis.


Immunohistochemical expression of endothelial markers CD31, CD34, von Willebrand factor, and Fli-1 in normal human tissues.
Few systematic studies have been published comparing the expression and distribution of endothelial cell (EC) markers in different vascular beds in normal human tissues. We investigated by immunohistochemistry the expression of CD31, CD34, von Willebrand factor (vWF), and Fli-1 in EC of the major organs and large vessels. Tissue samples obtained from autopsies and biopsy specimens were routinely processed and stained immunohistochemically for CD31, CD34, and vWF. Biopsy material was also stained immunohistochemically for Fli-1, D2-40, and Lyve-1. The expression pattern of the markers was heterogeneous in some of the organs studied. In the kidney, fenestrated endothelium of the glomeruli strongly expressed CD31 and CD34 but was only focally positive or completely negative for vWF. Alveolar wall capillaries of the lung strongly stained for CD31 and CD34 but were usually negative for vWF. The staining intensity for vWF increased gradually with the vessel caliber in the lung. Sinusoids of the spleen and liver were diffusely positive for CD31. They were negative for CD34 in the spleen and only expressed CD34 in the periportal area in the liver. Fli-1 was expressed in all types of EC but also in lymphocytes. D2-40 stained lymphatic endothelium only. Lyve-1 immunostaining was too variable to be applied to routinely processed tissues. The expression of EC markers CD31, CD34, and vWF in the vascular tree is heterogeneous with a specific pattern for individual vessel types and different anatomic compartments of the same organ. D2-40 labels lymphatic EC only.


Parathyroid hormone-related protein in human term placenta and membranes.
Parathyroid hormone-related protein (PTHrP), the hypercalcaemia of malignancy factor, is expressed in the tissues of the human uteroplacental unit, including the placenta, amnion and chorion. We have used three region-specific immunoassays to quantitate and compare the distribution of PTHrP in tissues obtained at term following spontaneous labour and vaginal delivery or elective Caesarean section. In non-labouring women highest PTHrP(1-86) and (37-67) immunoreactivity was found in amnion covering the placenta, rather than the decidua parietalis of the uterus (reflected amnion) (median 1020 vs 451 fmol/g; 2181 vs 1444 fmol/g respectively). In labouring women, the PTHrP(1-86) concentration in reflected amnion was inversely correlated with the interval between rupture of the membranes and delivery. Tissue PTHrP(1-86) concentrations were lower in placenta than in chorion and amnion (medians 12, 109 and 664 fmol/g respectively) and, in all tissues, PTHrP(1-34) and (37-67) concentrations were significantly higher than that of PTHrP(1-86). Bioactive PTHrP(1-34) was detected in placenta, chorion and amnion using the ROS cell bioassay. The PTHrP(1-86) concentration (mean +/- S.E.M. = 41.4 +/- 4.5 pmol/l) was high in amniotic fluid at term, although in maternal and cord plasma levels were only modestly increased. The molecular forms of PTHrP present in tissues and amniotic fluid were investigated by column chromatography which confirmed its molecular heterogeneity and suggested that processing is tissue-specific and occurs at both amino- and carboxy-terminals of the peptide.


The efficacy of functional surgery associated with early intensive rehabilitation therapy in Charcot-Marie-Tooth Type 1A disease.
Charcot-Marie-Tooth (CMT) is a genetically and clinically heterogeneous disorder, and it is caused by alterations in genes with different loci that encode for proteins, resulting into metabolic and structural defects. The most common form of the disease is type 1A. Treatment of the disease, due to the absence of an effective pharmacological therapy, mainly relies on surgical treatment and rehabilitative therapy. However, the literature is still poor of evidences on this subject. The aim of the study was to describe a treatment protocol based on the integration of functional surgery and early intensive neurorehabilitation in CMT1A disease patients. Five patients with CMT1A (2 females, 3 males), 19-57 years, age 36.8±14 years (mean±SD) are described in the paper. Pre - and post-treatment clinical and quantitative evaluation including muscle and balance score, patient questionnaires, and gait analysis was held. Treatment consisted in functional surgery followed (after the removal of the cast) by a three weeks intensive neurorehabilitation treatment during which patients were hospitalized. The post-treatment examination documented an overall improvement of walking and balance, and reduction of pain. A smaller reduction of fatigue and cramps was observed. Gait analysis showed decreased foot-drop, increased ankle power, and increased knee flexion as a compensatory mechanism. Even considering the heterogeneity of patients in CMT disease this clinical series study confirms that functional surgery followed by intense neurorehabilitation might be considered a valid approach to improve patients with CMT1A. Clinical impact of the study mainly relies on the detailed description of an effective method of evaluation, surgical and rehabilitative treatment of patients with CMT disease. Even taking into account the heterogeneity of CMT patients, this case series study confirms that functional surgery integrated with early intensive neurorehabilitation might be considered a valid approach to improve the performances of patients with CMT1A.


Life history variation in the heavy metal tolerant plant Thlaspi caerulescens growing in a network of contaminated and noncontaminated sites in southern France: role of gene flow, selection and phenotypic plasticity.
* Here we explore life history differences in a set of neighbouring metallicolous and nonmetallicolous populations of the heavy metal tolerant plant Thlaspi caerulescens. * We contrasted data from field observations and from a common garden experiment, in which soil zinc (Zn) concentration and light availability were manipulated, and data on microsatellite molecular variation. * The two ecotypes showed few differences in life history in the field, but large differences in their response to Zn concentration in the common garden. Soil toxicity affected most characters in nonmetallicolous plants, while it had no effect on metallicolous plants. The two ecotypes responded similarly to light. Genetic differentiation for quantitative characters between ecotypes contrasted with the absence of differentiation for microsatellites. Conversely, populations of the same ecotype showed similar responses to Zn, despite their high differentiation for molecular markers. * We conclude that divergent selection related to soil toxicity has had a predominant role in shaping life history differences between ecotypes, gene flow weakly opposing local adaptation despite geographical proximity.


Squamous cell carcinoma of the eyelid.
A total of 24 patients (12 men and 12 women) with squamous cell carcinoma of the eyelid were identified from pathology records at Wills Eye Hospital from 1978 through 1987. Squamous cell carcinoma accounted for 24 of 648 (3.7%) malignant eyelid lesions submitted during the 10-year study period. The median age of patients at the time of diagnosis was 72 years (range, 55 to 96 years). Initial therapy of all tumors involved surgical excision. Four patients developed clinical recurrence of squamous cell carcinoma in a median of 7.5 months after surgery. There were no tumor recurrences when frozen section techniques were applied during the initial surgical excision. The data suggest that the risk of persistence or recurrence of tumor was increased for patients who delayed seeking medical care after the lesion was first noticed and when frozen section control was not used during surgery. None of the patients were known to have developed metastases, and there were no tumor-related deaths.


Pharmacotherapy in Bronchopulmonary Dysplasia: What Is the Evidence?
Bronchopulmonary Dysplasia (BPD) is a multifactorial disease affecting over 35% of extremely preterm infants born each year. Despite the advances made in understanding the pathogenesis of this disease over the last five decades, BPD remains one of the major causes of morbidity and mortality in this population, and the incidence of the disease increases with decreasing gestational age. As inflammation is one of the key drivers in the pathogenesis, it has been targeted by majority of pharmacological and non-pharmacological methods to prevent BPD. Most extremely premature infants receive a myriad of medications during their stay in the neonatal intensive care unit in an effort to prevent or manage BPD, with corticosteroids, caffeine, and diuretics being the most commonly used medications. However, there is no consensus regarding their use and benefits in this population. This review summarizes the available literature regarding these medications and aims to provide neonatologists and neonatal providers with evidence-based recommendations.


Cryopreservation of Zebrafish Spermatogonia by Whole Testes Needle Immersed Ultra-Rapid Cooling.
Current trends in science and biotechnology lead to creation of thousands of new lines in model organisms thereby leading to the necessity for new methods for safe storage of genetic resources beyond the common practices of keeping breeding colonies. The main purpose of this study was to adapt the needle immersed vitrification (NIV) procedure to cryopreserve whole zebrafish testes. Cryopreservation of early-stage germ cells by whole testes NIV offers possibilities for the storage of zebrafish genetic resources, especially since after transplantation they can mature into both male and female gametes. Testes were excised, pinned on an acupuncture needle, equilibrated in two cryoprotective media (equilibration solution containing 1.5 M methanol and 1.5 M propylene glycol; and vitrification solution containing 3 M dimethyl sulfoxide and 3 M propylene glycol) and plunged into liquid nitrogen. Samples were warmed in a series of three consequent warming solutions. The main advantages of this technique are (1) the lack of spermatozoa after digestion of warmed testes thus facilitating downstream manipulations; (2) ultra-rapid cooling enabling the optimal exposure of tissues to liquid nitrogen therefore maximizing the cooling and reducing the required concentration of cryoprotectants, thereby reducing their toxicity; (3) synchronous exposure of several testes to cryoprotectants and liquid nitrogen; and (4) repeatability demonstrated by obtaining viability of above 50% in five different zebrafish strains.


Prevalence of prostate cancer in end-stage renal disease patients.
We aimed to assess the prevalence of prostate cancer in end-stage renal disease (ESRD) patients by a large-scale, multicentric and prospective study, and to show the difference between ESRD patients and normal healthy subjects. The level of serum prostate-specific antigen (PSA) was measured in 724 male ESRD patients undergoing dialysis. Those patients whose serum PSA level was over 4.0 ng/ml underwent a second screening test. After diagnosis, the prevalence of prostate cancer was subsequently calculated following adjustments by logistic-regression analysis. The prevalence of prostate cancer was also assessed in three control groups who had undergone health checks. The prevalence of prostate cancer in ESRD patients was found to be 1.4%. Those of the control groups (after correction for age) were 0.4, 1.4 and 0.8%. The odds ratios were 3.49, 0.96 and 1.71. The prevalence of prostate cancer in ESRD patients was equal or higher compared with that of normal healthy subjects. The result strongly indicates that the use of the serum PSA assay contributes to the early detection of prostate cancer in ESRD patients.


Differences over the life span in daily life-style regularity.
A diary-based instrument-the Social Rhythm Metric (SRM)-was used to assess the level of stability of daily social and behavioral rhythms in a group of 239 healthy subjects (112 male, 127 female) ranging in age from 20 to 89 years. Each subject completed the instrument for two consecutive weeks, which were averaged to yield one measure (SRM score) of life-style regularity [range 0 (least regular) to 7 (most regular)] and another of activity level index (ALI), corresponding to the number of (diary listed) activities done per week (max. = 119). SRM score increased reliably with age group at an average rate of 0.018 units per year. ALI showed an "inverted U"-shaped function with a maximum at about 50 years. SRM changes appeared not to be related to demographic differences between the age groups, although ALI differences may have been so related. No main effects or interactions were found with gender. Life-style regularity appears to increase over the life span in response to both biological and psychosocial changes and may represent an adaptation to age-related changes in the circadian system's sensitivity to entraining agents. Regular behavioral rhythms may be conducive to continued good health and well-being.


Expression of recombinant growth hormone in Escherichia coli: effect of the region between the Shine-Dalgarno sequence and the ATG initiation codon.
We constructed a synthetic Escherichia coli expression system in which various promoter elements can be changed easily. In this study we investigated the effect of a number of portable Shine-Dalgarno regions (SD regions) on the synthesis of two modified recombinant human growth hormones (hGH). The production of these modified hGH was measured during exponential growth and after the bacteria had reached stationary phase. The results show that the optimal distance between the SD region (AGGAGG) and the ATG start codon is approximately 11 nucleotides. However, the nucleotide sequence in this region also influences expression: 6-10 adenines result in comparable expression levels despite the varying lengths. Two overlapping SD regions reduce expression of the growth hormones considerably, whereas two potential ATG start codons do not affect expression. Having a SD-ATG region partly or totally complementary to the 5' end of the 16S ribosomal RNA does not alter translation efficiency. Estimation of the delta G values for the association between the 16S rRNA and the ribosome-binding region suggests that these are not indicators of expression efficiency.


[Changes in the paravertebral musculature following a traditional herniated lumbar diskectomy. A computed tomographic and magnetic resonance study].
On the basis of previous EMG data, a retrospective study was carried out on the CT and MR features of the paravertebral musculature after lumbar spine surgery through the posterior approach. The authors reviewed the CT scans and some MR images of 35 symptomatic patients hospitalized 7 months to 42 years after operation for disc herniation. Changes in the paraspinal musculature were apparent in all of them on the surgical side. The changes were minimal or very slight in 14 patients, moderate in 13 and severe in 8. A close correlation was observed between the above changes and the surgical procedure used in every single case. Histology showed atrophy and degeneration of the muscle fibres and fibrofatty substitution. The possible responsible causes of damage to the postvertebral muscles during spinal surgery are briefly mentioned and practical implications discussed.


[Results of Monitoring of the Plan of Measures Directed to Reduction of Ischemic Heart Disease in North Caucasus Republics. Analysis of Dynamics of Cardio-Vascular Mortality].
Comparative analysis of dynamics of cardiovascular mortality in Russia and foreign countries as well as main directions of development of cardiological service in Russia are presented in this review article. Plan of measures for reduction of mortality from ischemic heart disease (IHD) was created in 2015. This plan comprises 4 blocks of assessment of the following measures: directed at improvement of primary IHD prevention (1), directed at secondary prevention of complications of IHD (2); directed at improvement of efficacy of medical care of patients with IHD (3), and directed at monitoring of some demographic parameters (4). The article also contains results of monitoring of realization of the plan of IHD reduction in republics of North Caucasus. Realization of the program on healthy life style (HLS) lacks coordination between ministries. Mass information media are not sufficiently involved in propaganda of HLS. Mean achievement of target levels of main risk factors does not exceed 30-35%. First stage of prophylactic medical examination (dispanserization) has been fulfilled in 65%. High technology care is available both in federal and regional centers. Organization of effective urgent medical service, drug supply, and rehabilitation of patients with IHD are important aspects of improvement of secondary prevention in the region.


Application of immersion B-scan ultrasonography in diagnosis of complex retinal detachment, persistent hyperplastic primary vitreous and intraocular tumors.
To evaluate the diagnostic value of panoramic immersion B-scan ultrasonography (Pano-immersion B-scan, PIB) in complex retinal detachment (RD), persistent hyperplastic primary vitreous (PHPV) and intraocular tumors. The clinical data of 44 patients collected from May 2012 to December 2019 in Chinese PLA General Hospital was retrospectively studied. All of these patients underwent PIB of the eye, because it was difficult to diagnose by routine ocular fundus examination, conventional ultrasound or/and ultrasonic biomicroscope (UBM) due to opacity of refractive media, pupillary occlusion, large involvement or special location of the lesion. The imaging features of difficult cases in PIB were analyzed. The diagnosis accuracy rating of PIB were evaluated and contrasted with conventional ultrasound or UBM by the standard of intraoperative diagnosis or/and pathological results. According to intraoperative diagnosis or pathological results as gold standard, among the 44 cases, there were 19 cases missed diagnosis, misdiagnosed or difficult-to-diagnose by conventional ultrasound or UBM, including 4 cases of long-standing RD difficult to diagnose, 4 cases misdiagnosed, and 11 cases incompletely observed or miss diagnosed. The diagnostic accuracy rate of PIB and conventional ultrasound or UBM were 100% (44/44) and 56.82% (25/44), and the sensitivity of them were 100% and 56.82%. All the patients underwent PIB and were diagnosed as RD (15 cases), retinal and choroidal detachment (4 cases), subchoroidal hematocele (1 case), vitreous opacity and/or organic membrane formation (4 cases), PHPV (12 cases), iris and/or ciliary body tumors (3 cases), and choroidal tumors (6 cases). According to the intraoperative diagnosis or pathological results, the diagnostic coincidence rate of PIB was 100%, which was significantly higher than conventional ultrasound and UBM. PIB can help to accurately diagnose complex RD, PHPV, and intraocular masses with special location or/and excessive size. It has important diagnostic value for patients with equivocal findings at conventional ultrasound examination.


Recent progress of circular RNAs in different types of human cancer: Technological landscape, clinical opportunities and challenges (Review).
Circular RNAs (circRNAs) are a novel class of endogenous non‑coding RNAs that have been recently regarded as functionally active. CircRNAs are remarkably stable and known to possess several biological functions such as microRNA sponging, regulating transcription and splicing and occasionally acting as polypeptide‑producing templates. CircRNAs show tissue‑specific expression and have been reported to be associated with the progression of several types of malignancies. Given the recent progress in genome sequencing and bioinformatics techniques, a rapid increment in the biological role of circRNAs has been observed. Concurrently, the patent search from different patent databases shows that the patent number of circRNA is increasing very quickly. These phenomena reveal a rapid development of the technological landscape. In the present review, the recent progress on circRNAs in various kinds of cancer has been investigated and their function as biomarkers or therapeutic targets and their technological landscape have been appreciated. A new insight into circRNAs structure and functional capabilities in cancer has been reviewed. Continually increasing knowledge on their critical role during cancer progression is projecting them as biomarkers or therapeutic targets for various kinds of cancer. Thus, recent updates on the functional role of circRNAs in terms of the technological landscape, clinical opportunities (biomarkers and therapeutic targets), and challenges in cancer have been illustrated.


The mechanisms of action of Plasmodium infection against cancer.
Our murine cancer model studies have demonstrated that Plasmodium infection activates the immune system that has been inhibited by cancer cells, counteracts tumor immunosuppressive microenvironment, inhibits tumor angiogenesis, inhibits tumor growth and metastasis, and prolongs the survival time of tumor-bearing mice. Based on these studies, three clinical trials of Plasmodium immunotherapy for advanced cancers have been approved and are ongoing in China. After comparing the mechanisms of action of Plasmodium immunotherapy with those of immune checkpoint blockade therapy, we propose the notion that cancer is an ecological disease and that Plasmodium immunotherapy is a systemic ecological counterattack therapy for this ecological disease, with limited side effects and without danger to public health based on the use of artesunate and other measures. Recent reports of tolerance to treatment and limitations in majority of patients associated with the use of checkpoint blockers further support this notion. We advocate further studies on the mechanisms of action of Plasmodium infection against cancer and investigations on Plasmodium-based combination therapy in the coming future. Video Abstract.


Fifteen-minute consultation: Recognition and management of the child or young person who has ingested a novel psychoactive substance.
Intoxicated children and young people (CYP) attending the paediatric emergency department (PED) are typically under the influence of alcohol or established recreational agents such as cannabis or ecstasy. The last decade or so has seen an increase in the numbers of CYP in PED who have used novel psychoactive substances (NPS). In this review, we describe four different functional classes of NPS, their legal status, clinical effects, acute management and interventions to reduce harm.


POCT in Developing Countries.
Point of Care Technology (POCT) means acquiring clinical parameters from the place where the patient is, thus generating faster test results leading to a faster turnaround time. However, improvements in patient outcomes depend on how healthcare delivery professionals and system utilize faster turnaround times. Thus, POCT, by itself, does not lead to better clinical outcomes. Throughout the last two decades, advances in POCT have been impressive, but its impact on developing countries depends on the present healthcare infrastructure. Presently, in most developing countries, POCT is delivered in remote locations or Physicians chamber or Hospital setup of Emergency rooms, Operation Theaters, ICU. It is applied for therapeutic aid (for treatment of certain diseases like diabetes or myocardial infarction), preventive measures (for targeted screening in high-risk groups) or surveillance measures (monitoring of routine blood parameters). There are several challenges in implementing POCT like poor patient demographics, lack of workforce, training, lacking healthcare infrastructure, reluctance in physicians to accept new technology and certain technological limits. Although it may take time, solutions to these challenges will lead to a proper implementation of POCT in the developing nations. Further, integrating it with mobile phone technology will lead to higher acceptance and application. The boom of POCT will depend on the overall improvement and capacity building in the healthcare infrastructure of developing nations.


Occupational morbidities and their association with nutrition and environmental factors among textile workers of desert areas of Rajasthan, India.
In Rajasthan 21,000 workers are engaged in hand processing textile industries (process gray/raw cotton cloth). They are exposed to hazards of the textile industries besides the harsh conditions of the desert which contributes to adverse effects on their health. To explore the occupational health problems of the desert textile workers and their association with nutrition and environmental factors, investigations were carried-out in two districts, Jodhpur and Pali. Data on occupational disease conditions, environmental factors, nutritional deficiency signs and anemia were collected for a total of 1,240 individuals out of which 845 were textile workers and 395 were comparative group workers of the same age groups. The main disease conditions, i.e. aches (19.4%), respiratory (12.1%) and fever (7.7%), were higher in textile workers than the comparative group. Dyeing group workers suffered the most (25.5%) from aches, significantly higher than the comparative group (11.6%), may be due to a higher percentage of severe anemia, besides physical labour. Printing and bleaching group workers suffered from respiratory problems (15.5%) almost twice as much as the comparative group, possibly due to exposure to fumes of acids and use of chemical dyes. Housing conditions, personal hygiene and education showed negative associations with disease conditions but positive associations with anemia. The study revealed that in the textile industry, disease conditions vary with the categorization of work. The findings suggest the need for implementation of safety measures according to the type of work in textile industries, besides extension of health and nutrition education and welfare programs.


Investigation of the Relationship between Electronic Structures and Bioactivities of Polypyridyl Ru(II) Complexes.
Ruthenium (Ru)-based organometallic drugs have gained attention as chemotherapeutic and bioimaging agents due to their fewer side effects and excellent physical optical properties. Tuning the electronic structures of Ru complexes has been proven to increase the cytotoxicity of cancer cells and the luminescent efficiency of the analytical probes. However, the relationship between electronic structures and bioactivities is still unclear due to the potential enhancement of both electron donor and acceptor properties. Thus, we investigated the relationship between the electronic structures of Ru(II) complexes and cytotoxicity by optimizing the electron-withdrawing (complex 1), electron-neutral (complex 2), and electron-donating (complex 3) ligands through DFT calculations, bioactivities tests, and docking studies. Our results indicated that it was not sufficient to consider only either the effect of electron-withdrawing or electron-donating effects on biological activities instead of the total electronic effects. Furthermore, these complexes with electron-donating substituents (complex 3) featured unique "off-on" luminescent emission phenomena caused by the various "HOMO-LUMO" distributions when they interacted with DNA, while complex with electron-withdrawing substituent showed an "always-on" signature. These findings offer valuable insight into the development of bifunctional chemotherapeutic agents along with bioimaging ability.


Superficial mycoses among psychiatric patients in Mathari Hospital, Nairobi, Kenya.
To determine the prevalence of superficial mycoses among psychiatric patients. Randomised Prospective study Mathari Mental Hospital, and Jomo Kenyatta University of Agriculture and Technology, Nairobi Kenya. A study was conducted on prevalence of superficial fungal infections among psychiatric patients in Mathari Hospital, Nairobi, Kenya during the period of July to November 2009. 152 patients were assessed and samples collected from 25 patients with clinically suggestive symptoms of dermatomycosis revealed a 12.5% prevalence of superficial mycosis. There was no significant difference between males and females with superficial mycosis (P>0.05). Twenty percent of the patients who were on topical application had no viable organisms. Microsporum was the predominant species isolated while the skin was the site most commonly affected (64 %). Epidermophyton was the least prevalent. Terbinafin was the most effective antifungal while ketoconazole was the least effective. All patients admitted at Mathari hospital should be screened for fungal infection and treated. Terbinafin can be used as first line treatment of dermatomycosis after screening all psychiatric patients in Mathari Mental Hospital.


Changes in subset specificity of anti-T cell autoantibodies in systemic lupus erythematosus.
Relative reactivity of anti-lymphocyte autoantibodies (ALA) from patients with systemic lupus erythematosus (SLE) against CD4+ and CD8+ T cells was studied using C-dependent microcytotoxicity assay. Of 46 SLE sera screened for anti-T cell autoantibodies, 27 sera (59%) showed significant cytotoxic reactivity. Of these, positive correlation between the titer of anti-T cell antibody and CD4/CD8 killing ratio (p < 0.01) was demonstrated. In time course study of individual patients, the CD4/CD8 killing ratio increased and decreased as the disease flared and subsided and was accompanied by parallel changes in the titer of anti-T cell antibody titer. Moreover, as sera were serially diluted, the CD4/CD8 killing ratio decreased in 5 out of 10 sera. These results suggest that discrepancy among reports concerning the subset specificity of anti-T cell antibodies may be due, in part, to differences in the titer of ALA in the sera studied and to the dilution of serum used.


Nonionic surfactant-based vesicular system for transdermal drug delivery.
The objective of this study was to formulate and evaluate the Ibuprofen niosomal formulation as a transdermal drug delivery system. Niosomes were prepared by a modified ethanol injection method, using Span 60, Tween 60 and Tween 65 as well as cholesterol with various cholesterol:surfactant molar ratios. The prepared vesicles were characterized for entrapment efficiency (EE), particle size, zeta potential and in vitro release study. Skin permeation studies were conducted using modified Franz diffusion cell, and excised rat skin was treated with niosomal, liposomal and conventional Carbopol 914 gel of Ibuprofen. The results showed that the type of surfactant and molar ratio of cholesterol:surfactant altered the EE, size and in vitro drug release of niosomes. Higher EE was obtained with the niosomes prepared with cholesterol and Span 60 at molar ratio of 0.5:1. It has been observed that both niosomal and liposomal formulations enhanced the drug permeation and the percentage of accumulated dose in the skin compared to control conventional gel formulation. However, niosomes prepared by Span 60 and Tween 65 exhibited higher permeation and retention of Ibuprofen, respectively. Our results suggested that niosomal formulations could be used as a promising carrier for the Ibuprofen transdermal delivery system.


Cell surface expression of 5-hydroxytryptamine type 3 receptors is promoted by RIC-3.
RIC-3 has been identified as a molecule essential for the recruitment of functional nicotinic acetylcholine receptors composed of alpha7, but it exhibits inhibitory effects on alpha4beta2 or alpha3beta4 receptors. In this study, we investigated the role of RIC-3 in the recruitment of 5-hydroxytryptamine type 3A (5-HT(3A)) receptors to the cell surface. Although RIC-3 is not essential for the surface transport of 5-HT(3A) receptors, we found that its presence enhances both receptor transport and function in a concentration-dependent manner. RIC-3 is localized to the endoplasmic reticulum, as evidenced by co-localization with the chaperone molecule, binding protein (BiP). RIC-3 is not detected at significant levels on the cell surface when expressed alone or in the presence of 5-HT(3A). RIC-3 and 5-HT(3A) show a low level interaction that is transient (<4 h). That RIC-3 can interact with an endoplasmic reticulum-retained 5-HT(3A) construct, combined with the transient interaction observed and lack of significant surface-expressed RIC-3, suggests that RIC-3 may play a role in 5-HT(3A) receptor folding, assembly, or transport to the cell surface.


[Analysis of pregnancy outcomes of polycystic ovary syndrome patients after frozen embryo transfer].
Objective: To investigate pregnancy outcomes of the patients with polycystic ovary syndrome (PCOS) after frozen embryo transfer (FET) . Methods: Data of 2 367 PCOS patients received in vitro fertilization-embryo transfer [including fresh embryo transfer (fET) and FET] from January 2009 to December 2015 in Peking University Third Hospital were evaluated retrospectively. The basal characteristics, pregnancy complications and outcomes were analyzed, then identified the relative factors followed. Results: Totally 2 367 patients received in vitro fertilization-embryo transfer: 1 106 were treated with fET, and the rest 1 261 cases were treated with FET. The incidence of gestational diabetes mellitus (GDM) was lower in FET group [4.04%(51/1 261) versus 6.15%(68/1 106)], the difference was statistically significant (P<0.05). Singletons born after FET had higher birth weight than fET [(3 406±548) versus (3 360±533) g], the difference was statistically significant (P<0.05). There was no difference of other pregnancy complications between the two groups (all P>0.05). fET was an independent risk factor for GDM (adjusted OR=1.570, 95%CI: 1.075-2.294). Conclusion: Compared with fET, FET could decrease the risk of GDM and receive better neonatal outcomes in patients with PCOS.


Objectively measured physical activity and sedentary time in children with overweight, obesity and morbid obesity: a cross-sectional analysis.
Limited physical activity (PA) and a high level of sedentary time (ST) are associated with childhood obesity and are a target for intervention. This study aimed to assess objectively measured PA and ST in Dutch children across weight categories, age groups and sex. 202 children with overweight, obesity and morbid obesity (55% girls, 12 ± 3y of age, BMI z-score + 3.15 ± 0.73), referred to the Centre for Overweight Adolescents and Children's Healthcare (COACH, Maastricht UMC+) were included. PA (total PA, light PA and moderate to vigorous PA (MVPA)) and ST were measured with the GT3X Actigraph accelerometer. Wear time validation was set to include at least four days, 480 min/day, including one weekend day. PA levels in children with morbid obesity were higher compared to children with obesity, also after correction for age and sex (corrected difference (B) 118 counts per minute (cpm), p = .006). ST was lower in children with morbid obesity compared to children with obesity (B - 51 min/day, p = .018). Girls performed significantly less MVPA than boys (B - 11 min/day, p < .001) and for each year increase of age, children performed less PA (B - 46 cpm, p < .001) and ST increased (B 18 min/day, p < .001). PA and ST is different in subgroups of children with overweight, obesity and morbid obesity, depending on sex, age and overweight severity. In particular, children with obesity perform less PA and more ST compared to children with morbid obesity. Future research could explore the preferences and needs for PA and ST in children in the different weight categories. The trial is registered with Clinicaltrials.gov NCT02091544 at March 19, 2014.


Structural and magnetic properties of hexagonal perovskites La1.2Sr2.7MO7.33 (M = Ru, Ir) containing peroxide ions.
The structures of the new compound La(1.2)Sr(2.7)IrO(7.33) and the recently discovered La(1.2)Sr(2.7)RuO(7.33) have been solved using a combination of X-ray and neutron diffraction. Both compounds crystallize in the trigonal space group Rm and consist of isolated MO6 (M = Ru, Ir) octahedra, which are arranged in well-defined hexagonal perovskite slabs. These slabs are separated by (Sr2O(1+delta)) layers containing both O2- and (O2)2- ions. The composition can therefore be written as La(1.2)Sr(2.7)MO(7-delta)(O2)delta with delta = 0.33. Results of the magnetic susceptibility and XANES measurements show that the transition metal cations are in a pentavalent state. While in La(1.2)Sr(2.7)RuO(7.33) an antiferromagnetic interaction between the Ru5+ ions is found, La(1.2)Sr(2.7)IrO(7.33) shows a very small temperature-independent paramagnetism down to 1.8 K due to the strong spin-orbit coupling characteristic for the 5d element iridium.


A simple method to generate arbitrary laser shapes for stimulated Raman adiabatic passage.
Stimulated Raman adiabatic passage (STIRAP) is an effective technique to transfer state coherently with the features of both high fidelity and robustness in the field of quantum information and quantum precise measurement. In this note, we present a simple method to generate arbitrary laser shapes for STIRAP by controlling the modulation depth of the electro-optic modulator (EOM) and the diffraction efficiency of the acoustic-optic modulator (AOM) simultaneously. The EOM and AOM are used to control the power ratio between the two Raman lasers (pumping laser and Stokes laser) and the total power, respectively. Compared with the traditional method by combining two Raman lasers separated in space, this method has the advantage of simple structure and insensitivity to the environment disturbance, which would degrade the relative phase noise between two Raman lasers.


Method to detect functional estrogen receptor expression using estrogen receptor probing compound.
A novel method to detect functional estrogen receptor expression with estrogen receptor probing compound (ERPC) has been established. ERPC is composed of estradiol-BSA-biotin. ERPC can be used to detect functional estrogen receptor expression in both Western blot and immunohistochemistry. ERPC based techniques are non-radioactive, sensitive, relatively inexpensive, and can be used with all species. The use of both ERPC and ERalpha- or ERbeta-specific antibodies provides complementary information in characterizing estrogen receptors' expression and functional binding to ligand.


Pleomorphic adenoma of lacrimal gland: diagnosis based on fine needle aspiration cytology.
A 48 years old male patient presented with a mass in the supratemporal quadrant of orbit. Fine needle aspiration (FNAC) revealed a cellular tumour with a chondrimyxoid background and epithelial cells intermingled with mesenchymal cells in a fibrillary matrix. A diagnosis of pleomorphic adenoma of the lacrimal gland was made which was confirmed on histopathology. FNA is a rapid and accurate method in diagnosis of lacrimal gland tumours.


Wavelength-selective dual p- and n-type carrier transport of an organic/graphene/inorganic heterostructure.
A novel organic/graphene/inorganic -heterostructure, consisting of a graphene layer encapsulated by n- and p-type photoactive materials with complementary absorptions, enables the control of dual n- and p-typed transport behaviors of a graphene transistor under selective UV or visible light illumination. A graphene-based p-n junction created by spatially patterned wavelength-selective illumination using the organic/graphene/inorganic heterostructure is also demonstrated.


Melasma in men.
Melasma is an acquired hypermelanosis that results in localized hyperpigmentation, commonly found on the face. This condition is much more common in women than men. There are some features of melasma in men that seem to differ from those seen in women. However, there is a paucity of data on this topic. The aim of this article is to review the etiology, clinical presentation, and treatment of melasma in men. It is important for dermatologists to understand some unique aspects of melasma in this group to provide appropriate care for patients who suffer from this frustrating condition.


Biologically inspired virtual aperture extension method of small aperture HFSWR multielement array.
We propose a method for extending the virtual aperture of the small aperture high-frequency surface wave radar multielement array inspired by a fly namedOrmia ochracea. Despite the tremendous incompatibility between its ear and the incoming wavelength,Ormiacan accurately local the sound of its host cricket. This ability benefits from the coupled structure ofOrmia's ears which have been modelled as a mechanical vibration system. In this paper, we first design a two-degree of freedom biologically inspired coupled system by mimickingOrmia's coupled ears. We quantitatively analyze its extension capability to the array aperture and construct the received signal model of the virtual array. We then analyze its response characteristic and available frequency band. To achieve the applications of arbitrary desired frequencies, we propose a frequency conversion algorithm. Moreover, we design two multi-degree of freedom biologically inspired coupled systems for the multielement array We summarize the criteria for extending the degree of freedom and optimize these two systems to address their respective shortcomings. Numerical results give the optimal system parameters for our desired frequency and validate the frequency conversion algorithm. By comparing the radiation pattern of the inspired arrays (arrays with the proposed systems) with that of an ordinary array, we demonstrate the virtual aperture extension capability of our proposed method. We also verify the effectiveness of proposed method by processing the actual received signals of the array.


Determinants of antibody response after recombinant gp160 boosting in vaccinia-naive volunteers primed with gp160-recombinant vaccinia virus. The National Institute of Allergy and Infectious Diseases AIDS Vaccine Clinical Trials Network.
Priming with a live recombinant vector followed by subunit boosting is a promising strategy for human immunodeficiency virus (HIV) immunization. Twenty-nine vaccinia-naive volunteers were primed with gp160-recombinant vaccinia virus (HIVAC-1e) and boosted with recombinant (r) gp160 to define factors associated with the magnitude and specificity of antibody response after booster immunization. A longer interval between inoculation and boost, two inoculations of HIVAC-1e with lesion formation occurring after the first, and Western blot-detectable antibody to gp160 after inoculation were significantly associated with higher neutralizing antibody titers and fusion-inhibiting activity after boosting. HIVAC-1e-primed vaccinees were more likely to have antibody to V3- and CD4-binding regions of gp120 and less likely to have antibody to constant regions 2 and 3 than vaccinees immunized with rgp160 alone. Priming volunteers with HIVAC-1e was a key determinant of the epitope specificity and magnitude of functional antibody responses induced by rgp160 boosting.


Molecular characterization of a new mosaic Simian Immunodeficiency Virus in a naturally infected tantalus monkey (Chlorocebus tantalus) from Cameroon: a challenge to the virus-host co-evolution of SIVagm in African green monkeys.
African green monkeys (AGMs) represent the most widely distributed non-human primates species in Africa. SIVagm naturally infects four of the 6 AGMs species at high prevalence in a species-specific manner. To date, only limited information is available on molecular characteristics of SIVagm infecting Chlorocebus tantalus. Here, we characterized the full-length genome of a virus infecting a naturally infected captive C. tantalus from Cameroon by amplifying and sequencing sub-genomic PCR fragments. The isolate (SIVagmTAN-CM545) is 9923bp long and contained all canonical genes of a functional SIV. SIVagmTAN-CM545 showed a mosaic structure, with gag, pol, nef and accessory genes closely related to SIVagmSAB infecting Chlorocebus sabaeus monkeys from west Africa, and the env gene, closely related to SIVagmTAN infecting tantalus monkeys from Central Africa. Thus SIVagmTAN-CM545 is SIVagmSAB/SIVagmTAN recombinant. These unexpected findings suggest that the evolution of SIVagm is more complex than previously thought and warrant further studies.


Electrostatic Linear Ion Trap Optimization Strategy for High Resolution Charge Detection Mass Spectrometry.
Single ion mass measurements allow mass distributions to be recorded for heterogeneous samples that cannot be analyzed by conventional mass spectrometry. In charge detection mass spectrometry (CD-MS), ions are detected using a conducting cylinder coupled to a charge sensitive amplifier. For optimum performance, the detection cylinder is embedded in an electrostatic linear ion trap (ELIT) where trapped ions oscillate between end-caps that act as opposing ion mirrors. The oscillating ions generate a periodic signal that is analyzed by fast Fourier transforms. The frequency yields the m/z, and the magnitude provides the charge. With a charge precision of 0.2 elementary charges, ions can be assigned to their correct charge states with a low error rate, and the m/z resolving power determines the mass resolving power. Previously, the best mass resolving power achieved with CD-MS was 300. We have recently increased the mass resolving power to 700, through the better optimization of the end-cap potentials. To make a more dramatic improvement in the m/z resolving power, it is necessary to find an ELIT geometry and end-cap potentials that can simultaneously make the ion oscillation frequency independent of both the ion energy and ion trajectory (angular divergence and radial offset) of the entering ion. We describe an optimization strategy that allows these conditions to be met while also adjusting the signal duty cycle to 50% to maximize the signal-to-noise ratio for the charge measurement. The optimized ELIT provides an m/z resolving power of over 300 000 in simulations. Coupled with the high precision charge determination available with CD-MS, this will yield a mass resolving power of 300 000. Such a high mass resolving power will be transformative for the analysis of heterogeneous samples.


Influence of Preeclampsia on Induction of Labor at Term: A Cohort Study.
Even though vaginal delivery is a feasible option in patients with preeclampsia, the cesarean section rate in those patients is high. The aim of this study was to evaluate the influence of preeclampsia on induction of labor at term. This historical cohort study analyzed inductions of labor in women at term having preeclampsia versus women who were induced due to other reasons. The primary outcome measure was the cesarean section rate. The cesarean section rate was higher in the preeclampsia group for both nulliparous and multiparous women after induction of labor but failed to reach statistical significane. The induction-to-delivery interval was longer in nulliparous women and the rate of vaginal birth within 48 h was lower in the nulliparous patiens with preeclampsia. However, the impact of preeclampsia on the cesarean section rate was not significant in the multivariable analysis following adjustment for BMI and parity. Preeclampsia at term did not influence the cesarean section rate in nulliparous and parous women when labor was induced.


Unilateral cross-incompatibility between Camellia oleifera and C. yuhsienensis provides new insights for hybridization in Camellia spp.
Camellia yuhsienensis was used to cross with Camellia oleifera to improve the resistance of oil camellia anthracnose. However, unilateral cross-incompatibility (UCI) between C. oleifera and C. yuhsienensis was found during the breeding process. Five C.oleifera cultivars and four C. uhsienensis materials were tested to confirm the UCI between C. oleifera and C. yuhsienensis. 'Huashuo' (HS) and 'Youza 2' (YZ2) were used to represent these two species to characterize the UCI, including pollen tube growth, fertilization and fruit development. The results demonstrated that UCI was prevalent between C. oleifera and C. yuhsienensis. The asynchronous flowering period was a pre-pollination barrier that limited mating between these two species under natural conditions. Interspecific pollen tubes were observed through the styles of these two plants, though the growth rates differed considerably. At 96 hours after pollination, the pollen tube of YZ2 barely entered the ovule, but remained at the base of the style and became swollen. However, the HS pollen tube entered the ovule 48 hours after pollination, double fertilization was observed, and the fruit and seeds developed commonly. Relative to compatible combinations, most unfertilized ovules in incompatible combinations failed to grow, turned brown 150 days after pollination, and the fruits were smaller than expected with uneven enlargement. Investigations on both semi-in vivo and in vitro pollen tubes gave us new idea for thought: the HS style has a stronger inhibitory effect on the interspecific pollen tubes, while calcium alleviates the inhibitory of styles but failed to prevent the appearance of abnormal pollen tube morphology. This study provides useful information on interspecific hybridization between C. oleifera and C. yuhsienensis for understanding reproductive isolation mechanisms and breeding programs in genus Camellia.


Synthesis and In Vitro Biological Evaluation of Psoralen-Linked Fullerenes.
Photodynamic therapy (PDT) is a widely used medicinal treatment for the cancer therapy that utilizes the combination of a photosensitizer (PS) and light irradiation. In this study, we synthesized two novel C60 fullerene derivatives, compounds 1 and 2, with a psoralen moiety that can covalently bind to DNA molecules via cross-linking to pyrimidine under photoirradiation. Along with several fullerene derivatives, the biological properties of several novel compounds have been evaluated. Compounds 1 and 2, which have been shown to induce the production of hydroxyl radicals using several ROS detecting reagents, induced DNA strand breaks with relatively weak activities in the in vitro detection system using a supercoiled plasmid. However, the psoralen-bound fullerene with carboxyl groups (2) only showed genotoxicity in the genotoxicity assay system of the umu test. Compound 2 was also seen to have cytotoxic activities in several cancer cell lines at higher doses compared to water-soluble fullerenes.


Predictive value of LDH kinetics in bevacizumab treatment and survival of patients with advanced NSCLC.
The combination of bevacizumab and chemotherapy is still one of the standard treatments for advanced non-small-cell lung cancer (NSCLC) patients in the new era of targeted therapy. Although a high level of baseline lactate dehydrogenase (LDH) was found to predict survival benefit from bevacizumab in patients with metastatic colorectal cancer, the predictive value of serum level of LDH in NSCLC patients treated with bevacizumab has not been investigated yet. Moreover, dynamic evaluation of serum level of LDH changes may be more informative and promising in predicting patients' prognosis. We thus sought to analyze LDH kinetics and evaluate its predictive role in the response and survival of advanced NSCLC patients treated with bevacizumab. We retrospectively collected and analyzed a total of 161 advanced NSCLC patients who had undergone treatment with bevacizumab. Univariate and multivariate logistic regression analyses of serum level of LDH were used for response analyses, and Cox models for both overall survival (OS) and progression-free survival analyses (PFS). Longitudinal analysis of LDH was performed using a mixed-effect regression model. On multivariate Cox models, increase of serum level of LDH after 4 cycles with bevacizumab (INC4) treatment was shown to be the independent risk factor for OS (hazard ratio =2.17, 95% CI: 1.21-3.90, P=0.009), and the serum level of LDH after 2 cycles (LDH2) and the increase of LDH after 6 cycles with bevacizumab (INC6) treatment were the predictive factors for PFS (hazard ratio =2.33, 95% CI: 1.38-3.93, P=0.001; hazard ratio =1.96, 95% CI: 1.27-3.03, P=0.002, respectively). Patients with increase of serum level of LDH after 2 cycles of treatment with bevacizumab (INC2) (odds ratio =3.75, 95% CI: 1.83-7.68, P<0.001) were more likely to attain stable disease/progressive disease on multivariate logistic regression analyses, while patients with complete response (CR)/partial response (PR) experienced a reduction of serum level of LDH every 2 cycles (Coef =-0.076, std error =0.017, P<0.001) over time. Dynamic changes of LDH were superior to baseline LDH in predicting prognosis of NSCLC patients treated with bevacizumab. Serum level of LDH reducing over time was a potential biomarker for patients to achieve good clinical response (CR/PR) to bevacizumab.


Does Improvised Waterbed Reduce the Incidence of Pressure Ulcers in Patients with Spinal Injury?
Pressure ulcers are lesions caused by unrelieved pressure over bony prominences, resulting in damage to underlying tissues. The etiology is multifactorial including prolonged immobility. They usually complicate spinal cord injuries with long periods of bed confinement. The use of bed replacements markedly reduces the incidence of pressure ulcers, but the unaffordability of these replacements in low-income countries has necessitated the need to explore cheaper alternatives. The aim of this study was to ascertain whether the use of our cheap and locally improvised waterbeds would reduce the incidence of pressure ulcers in patients on prolonged bed confinement due to spinal injury. Over a 16-month period, 51 patients (age range 1-80 years) with spinal injuries were managed conservatively in our service using improvised waterbeds in 21 (41.2%), while using the regular hospital bed/foam in 30 (58.8%). Biodata, the time interval between injury and presentation to the hospital, nature of the injury, use of improvised waterbed and development of pressure ulcer, were collected, collated, and analyzed. Statistical significance was calculated with the Chi-square test. Most were males (98%), in the age range of 21-30 years (25.5%), and due to fall from heights (35.3%). Of 21 patients who were managed on improvised waterbeds, 6 (28.6%) had pressure ulcers, and of the 30 who did not use the waterbed, 17 (56.7%) developed ulcers. The χ(2) = 3.9381, while P = 0.0472. This difference was statistically significant. The improvised waterbed, which is much cheaper than the standard waterbed, was observed to have significantly reduced the incidence of pressure ulcers among our patients. Nonetheless, further studies would still be needed to confirm this observation.


Hidden imperfect synchronization of wall turbulence.
Instantaneous amplitude and phase concept emerging from analytical signal formulation is applied to the wavelet coefficients of streamwise velocity fluctuations in the buffer layer of a near wall turbulent flow. Experiments and direct numerical simulations show both the existence of long periods of inert zones wherein the local phase is constant. These regions are separated by random phase jumps. The local amplitude is globally highly intermittent, but not in the phase locked regions wherein it varies smoothly. These behaviors are reminiscent of phase synchronization phenomena observed in stochastic chaotic systems. The lengths of the constant phase inert (laminar) zones reveal a type I intermittency behavior, in concordance with saddle-node bifurcation, and the periodic orbits of saddle nature recently identified in Couette turbulence. The imperfect synchronization is related to the footprint of coherent Reynolds shear stress producing eddies convecting in the low buffer.


[Relationship between the experience of steroids side effects and noncompliance with oral steroids treatment in collagen disease patients].
To analyze the relationship between the experience of side effect and the compliance with oral steroids drug treatment of the patients in Collagen Disease Clinic. A questionnaire survey through interview was conducted on 165 outpatients with various collagen disease at Saga Medical School Hospital. 94 patients (57%) had a history of noncompliance to the steroids drug. 49 patients (52.1%) adventitiously had forgotten to take the steroids as ordered and 45 patients (47.9%) intentionally had regulated their steroids dose or had discontinued the steroids drug treatment. Over 80% of the patients had experienced side effects of the steroids. The patients who experienced one or more of the following side effects, osteoporosis, bone fractures, menstrual disorders, moon face, central obesity, alopecia, acnelike eruption, manic-depressive state, and insomnia, intentionally regulated, or discontinued the steroids therapy. In addition, the patients who were not made cognizance about side effects of the steroids by their physicians and nurse tended to noncompliance group. To increase the compliance rate with oral steroids drug treatment, we must make conscious efforts to inform the patients on the condition of their medical states, the efficacy of the prescribed drugs, and the side effects and risk concerning discontinuation of the steroids. It is Also necessary to establish "Drug information and counseling day" in outpatient Department.


Reactivation of human herpesviruses 6 and 7 in Kawasaki disease.
Objectives: Kawasaki disease (KD) is one of the most common childhood vasculitides. Some serological studies have suggested an etiological relationship between KD and human herpesvirus (HHV)-6 or HHV-7. However, primary or reactivated HHV-6 and -7 has not been fully investigated in patients with KD. Methods: Twenty-three patients with KD were prospectively enrolled in this study. Peripheral blood was collected in the acute and convalescence phases, and HHV-6 and -7 viral loads were measured by real-time PCR. Results: In the acute phase, HHV-6 and -7 DNA was detected in 7 (30%) patients each, compared to 13 (57%) and 9 (39%) patients in the convalescence phase, respectively. HHV-6 and -7 DNA loads were significantly higher in the convalescence phase than in the acute phase. Significant increases in HHV-6 and -7 DNA loads were not observed in disease control patients. Taking into account HHV-6 and -7 serostatus, reactivation of HHV-6 and -7 was observed in 7 and 9 patients, respectively. KD patients with HHV-6 reactivation showed higher C-reactive protein levels and more frequently required steroid therapies than patients without reactivation. Conclusion: HHV-6 and -7 reactivation is frequent in KD patients. HHV-6 reactivation might exacerbate the severity of KD.


Controlled trial of distal radial fractures treated with a resorbable bone mineral substitute.
This randomized trial compared the use of hydroxyapatite cement with Kapandji wiring in distal radial fractures. Two groups of nine patients with distal radial fractures were either treated by reduction and fixation with wires or insertion of the cement into the fracture void. There was no difference between the groups before operation, on reduction or at day 1. Dorsal angle in the hydroxyapatite group was significantly worse at 6, 12 and 26 weeks. Grip strength and palmar flexion were poor in the hydroxyapatite cement group. All the clinical parameters and X-ray variables were worse at 12 and 26 weeks in the hydroxyapatite cement group. We conclude from this trial that there is nothing to support the use of this hydroxyapatite cement, without the use of additional fixation, in distal radial fractures.


Transforming G protein-coupled receptors block insulin and ras-induced adipocytic differentiation in 3T3-L1 cells: evidence for a PKC and MAP kinase independent pathway.
We have used the expression of muscarinic m1 receptors in the preadipocytic 3T3-L1 cell line for dissecting the nature of the G protein-linked pathways governing adipocytic differentiation, a complex process controlled by many stimuli and their downstream targets. 3T3-L1 cells can be differentiated by insulin or by ras oncogenes, and MAP kinase has been implicated in this process. However, m1 stimulation failed to induce differentiation of 3T3-L1 cells. Furthermore, it prevented insulin or v-ras-induced adipocytic differentiation, utilizing a protein kinase C-independent pathway. m1 stimulation did not alter the phosphorylation state of the insulin receptor substrates IRS-1 and SHC, nor the recruitment of Grb-2. Interestingly, whereas m1 receptors potently activated MAP kinase, another differentiation-inhibitor, TNF alpha, did not affect it. These results suggest that the control of adipocytic differentiation can occur utilizing a biochemical route independent of protein kinase C, and acting downstream, or independently from the Ras-MAP kinase pathway.


[The Short-term Outcome and Safety of Laparoscopic Colorectal Cancer Resection in Very Elderly Patients].
Due to the recent increase in elderly population, laparoscopic surgery is more frequently performed in the elderly. This study aimed to compare the short-term outcomes of laparoscopic colorectal cancer surgery between the very elderly group (VEG), categorized as those with age over 80 years and the elderly group (EG), categorized as those with age 65 to 79 years. We retrospectively compared 48 very elderly patients with 96 elderly patients (1:2 matched) who underwent laparoscopic resection for colorectal cancers at our institution between March 2010 and December 2014. The clinicopathologic parameters, surgical characteristics and short term outcomes were compared. There was no statistically significant difference in clinicopathologic characteristics between VEG and EG. Postoperative pain score (7 points vs. 6 points, p=0.264), time to first flatus (3 days vs. 3 days, p=0.335), hospital stay (15 days vs. 16.5 days, p=0.361), complication rates (47.9% vs. 26.0%, p=0.147) and major complication rate (25% vs. 20.8%, p=0.681) were not statistically different between the two groups. Before surgery, VEG had higher rate of neurologic underlying disease, such as dementia or cerebrovascular disease, than EG (25.0% vs. 7.3%, p=0.007). There was no significant difference in the clinicopathologic characteristics, short-term outcomes, and complication rates for laparoscopic colorectal resection between VEG and EG, except delirium. Age over 80 years may be relevant for the application of laparoscopic colorectal cancer resection.


Chiral separation of polychlorinated biphenyls using a combination of hydroxypropyl-gamma-cyclodextrin and a polymeric chiral surfactant.
Chiral separation of moderately to highly hydrophobic polychlorinated biphenyls (PCBs) using a conventional chiral micelle or a polymeric chiral surfactant, as the single chiral selector is very difficult since the hydrophobic interactions between the chiral PCB and the monomeric or polymeric surfactant is very strong. Combined use of a polymeric chiral surfactant, polysodium N-undecanoyl-D-valinate (poly-D-SUV) with hydroxypropyl-gamma-cyclodextrin (HP-gamma-CD) was successful in cyclodextrin modified electrokinetic chromatography (CD-EKC) enantioseparation of PCB congeners. Addition of HP-gamma-CD to the background electrolyte containing poly-D-SUV functioned to improved chiral resolution for the PCBs and reduce the analysis time for these congeners. In addition, concentration of methanol, concentration of 2-(N-cyclohexylamino) ethanesulfonic acid (CHES) buffer and separation voltage was also varied to optimize multicomponent separation of five chiral PCBs. Simultaneous separation and enantioseparation of all five PCBs was possible in less than 50 min under optimized conditions that requires a 5 mM CHES solution buffered at about pH 10 with 1.5% w/v (ca. 60 mM) poly-D-SUV and 16 mM HP-gamma-CD. In addition, 1 M urea and 20% v/v methanol should be added as organic modifier and the capillary temperature maintained at 45 degrees C. As expected the polymeric surfactant showed improved chiral resolution of PCBs over conventional micelles of SUV. Under optimized conditions, when CD-EKC of chiral PCBs using poly-D-SUV was compared to sodium dodecyl sulfate (SDS), better resolution, higher efficiency and shorter analysis time was achieved with poly-D-SUV.


[Boerhaave syndrome: a rare cause of acute thoracic pain].
In a 74-year old female patient suffering from acute thoracic pain, vomiting, and dyspnoea, the diagnosis of Boerhaave's syndrome was made. After medical treatment the patient was dismissed in a sufficiently satisfactory condition. If symptoms like vomiting, severe thoracic pain, pneumomediastinum, pneumothorax or hydropneumothorax on the left side occur, a rupture of the oesophagus should be taken into account especially in case of abuse of alcohol. The early diagnosis is decisive for the course of the disease and a lethality reduction.


Proceedings of the Second Annual Deep Brain Stimulation Think Tank: What's in the Pipeline.
The proceedings of the 2nd Annual Deep Brain Stimulation Think Tank summarize the most contemporary clinical, electrophysiological, and computational work on DBS for the treatment of neurological and neuropsychiatric disease and represent the insights of a unique multidisciplinary ensemble of expert neurologists, neurosurgeons, neuropsychologists, psychiatrists, scientists, engineers and members of industry. Presentations and discussions covered a broad range of topics, including advocacy for DBS, improving clinical outcomes, innovations in computational models of DBS, understanding of the neurophysiology of Parkinson's disease (PD) and Tourette syndrome (TS) and evolving sensor and device technologies.


Sex-related differences of acetohexamide reductase activities in the liver and kidney of various mammalian species.
Sex-related differences of acetohexamide reductase activities in cytosol and microsomes from the liver and kidney of the rat, mouse, guinea pig, hamster and rabbit were examined. Among animal species tested, the rat, guinea pig and rabbit exhibited sex-related differences in the activities. The activities in liver cytosol of the rat and rabbit were higher in the females than in the males, whereas the activity in kidney cytosol of the rabbit was higher in the male than in the female. Furthermore, the activities in liver and kidney microsomes of the rat and that in kidney microsomes of the guinea pig were much higher in the males than in the females. It is interesting to note that significant sex-related differences of acetohexamide reductase activities are found in some animal species other than the rat.


Chronic cavitary Pneumocystis carinii pneumonia in a patient with AIDS.
A 39-year-old man with AIDS presented with cough, chest pain, dyspnea on exertion, fever, and a cavitary lesion in the upper lobe of the left lung. The cavity increased in size over the next five months with disease involvement limited to the left upper lobe. Pneumocystis carinii infection was then diagnosed. Symptoms and cavity resolved with trimethoprim/sulfamethoxazole therapy.


The confluence of mental, physical, social, and academic difficulties in middle childhood. II: developing the Macarthur health and Behavior Questionnaire.
(1) To evaluate the psychometric properties of the MacArthur Health and Behavior Questionnaire (HBQ) in two studies of 4- to 8-year-old children and (2) to explore the empirical and theoretical implications of HBQ-based study findings. Samples of children were recruited from (1) mental health clinics (n = 53) and community schools (n = 67) for a case-control study in three research sites and (2) a Wisconsin-based community cohort study of families and work, comprising children with high levels of internalizing and/or externalizing behavior problems and asymptomatic children (N = 122). Combinations of mothers, fathers, and teachers completed the HBQ at one or two time points in four geographically and culturally distinctive settings. Assessment of HBQ reliability showed high test-retest stability and cross-informant agreement. The instrument discriminated strongly and significantly among symptom groups (i.e., high internalizing, high externalizing, high both, and low both) and showed moderate to large effect sizes for between-group differences. Substantial covariance was also found among the HBQ mental, physical, social, and academic problem subscales. The HBQ is a reliable and valid parent- and teacher-report instrument for assessing multiple dimensions of health and dysfunction in middle childhood and for identifying children on whom more intensive diagnostic procedures may be warranted. Confluences among the four health dimensions suggest phenomenological and perhaps etiological commonalities among traditionally partitioned childhood difficulties and suggest possible artificiality in the conventional distinction between pediatric and child psychiatric morbidities.


[Conceptual review of oncocytic lesions].
Updating of a series of entities which significance is not always pathological, or it is poorly known, and which are related to oxyphilic transformation of epithelial cells. Review of concepts such as "oncocytosis", "oncocytic hyperplasia" and "oncocytoma", establishing a hypothetical continuum of damage which could actually be contemplated within the evolution spectrum of hyperplasia-adenoma-carcinoma. Also, both the changes occurring at subcellular level and the hypothesis considered to explain them are commented.


[Sense and nonsense of tumor markers in practice].
Tumor markers can be used for screening, diagnosis, planning and monitoring of therapy, for early detection of relapse and for psychological reasons. Unfortunately none of the currently available tumor markers can be used for all these purposes. An ever increasing number of tumor markers can be determined; however, the advantage for the individual patient's management is less obvious. We therefore critically review the routine use of some tumor markers such as CEA, AFP, beta-HCG, LDH, CA-125, CA 19-9, prostate acid phosphatase, prostate specific antigen and CA 15-3. The use of tumor markers requires a sound knowledge of the biology of the marker, the neoplastic disease and the available treatment. When tumor markers do not add new information and have no diagnostic or therapeutic consequences, their use becomes an expensive medical nonsense!


Metformin-associated Lactic Acidosis: An Unexpected Scenario.
According to the National Diabetes Statistics Report (2017) by Centers for Disease Control and Prevention (CDC), 9.4% of the US population, approximately 30.3 million people had diabetes while 84.1 million had pre-diabetes as of 2015. In addition to lifestyle changes, the American Diabetes Association recommends metformin as the first-line treatment for type 2 diabetes. Hence, not surprisingly, metformin is a commonly prescribed medication by most healthcare providers in all clinical settings. As a result, it remains essential that all medical professionals be aware of any adverse effects as a result of metformin therapy, no matter how uncommon. We present the case of a 42-year-old lady with type 2 diabetes mellitus who required initial admission to intensive care unit (ICU) after presenting with unilateral back and lower abdominal pain with dysuria and was noted to have an acute kidney injury with a creatinine of 7.45 mg/dL and severe metabolic acidosis with a pH of 6.7 and an anion gap more than 50 mmol/L. Lactic acid was elevated at 24.2 mmol/L. Serum metformin levels were high at 14 mcg/mL (therapeutic range: 1-2 mcg/mL). She required emergent dialysis but subsequently, renal functions recovered. Risk of metformin-associated lactic acidosis (MALA) is reported to be an estimated 6.3 per 100,000 patient-years. Commonly encountered clinical scenarios such as hypoxemia, sepsis, alcohol abuse, renal injury, and shock can precipitate MALA. Early recognition allows timely initiation of appropriate therapy and reduces associated morbidity.


"Bone Development" Is an Ontology Group Upregulated in Porcine Oocytes Before In Vitro Maturation: A Microarray Approach.
Mammalian cumulus-oocyte complexes (COCs) reach full developmental capability during folliculogenesis and oogenesis. It is well recognized that only gametes achieving MII stage after in vivo or in vitro maturation (IVM) are successfully fertilized by a single spermatozoon. Although the process of oocyte nuclear and/or cytoplasmic maturation in pigs is well determined, there exist many differences that promote these processes in vivo and in vitro. Therefore, this study aimed to investigate the differences in RNA expression profiles between porcine oocytes before and after IVM using microarray and real-time quantitative polymerase chain reaction (RT-qPCR) assays. Experiments were performed on oocytes isolated from 55 pubertal crossbred Landrace gilts. The oocytes were analyzed both before and after IVM and only Brilliant Cresyl Blue (BCB)-positive gametes were used for subsequent microarray analysis (Affymetrix) and RT-qPCR analysis. The microarray assay, which measures expression of 12,258 transcripts, revealed 419 differentially expressed transcripts in porcine oocytes, from which 379 were downregulated and 40 were upregulated before IVM compared to those analyzed after IVM. After DAVID analysis, we found eight different transcripts, including IHH, BMP1, WWTR1, CHRDL1, KLF10, EIF2AK3, MMP14, and STC1. Their expression is related to the "bone development" ontology group and was further subjected to hierarchical clusterization. Using RT-qPCR analysis, we confirmed the results of the microarray assay, showing increased expression of the eight genes in oocytes before IVM compared to oocytes after maturation in vitro. It has been suggested that "bone development" belongs to one ontological group involving genes substantially upregulated in porcine oocytes before IVM. We suggest that the gamete mRNA expression profile before IVM may comprise stored transcripts, which are templates for protein biosynthesis following fertilization. We also hypothesize that these mRNAs may be a specific "fingerprint" of folliculogenesis and oogenesis in pigs.


Passive immunization with anti-ganglioside antibodies directly inhibits axon regeneration in an animal model.
Recent studies have proposed that neurite outgrowth is influenced by specific nerve cell surface gangliosides, which are sialic acid-containing glycosphingolipids highly enriched in the mammalian nervous system. For example, the endogenous lectin, myelin-associated glycoprotein (MAG), is reported to bind to axonal gangliosides (GD1a and GT1b) to inhibit neurite outgrowth. Clustering of gangliosides in the absence of inhibitors such as MAG is also shown to inhibit neurite outgrowth in culture. In some human autoimmune PNS and CNS disorders, autoantibodies against GD1a or other gangliosides are implicated in pathophysiology. Because of neurobiological and clinical relevance, we asked whether anti-GD1a antibodies inhibit regeneration of injured axons in vivo. Passive transfer of anti-GD1a antibody severely inhibited axon regeneration after PNS injury in mice. In mutant mice with altered ganglioside or complement expression, inhibition by antibodies was mediated directly through GD1a and was independent of complement-induced cytolytic injury. The impaired regenerative responses and ultrastructure of injured peripheral axons mimicked the abortive regeneration typically seen after CNS injury. These data demonstrate that inhibition of axon regeneration is induced directly by engaging cell surface gangliosides in vivo and imply that circulating autoimmune antibodies can inhibit axon regeneration through neuronal gangliosides independent of endogenous regeneration inhibitors such as MAG.


IGF-1 and retinopathy of prematurity in the preterm infant.
Retinopathy of prematurity (ROP) continues to be a major cause of blindness in children. Although ablation of the retina reduces the incidence of blindness by suppressing the neovascular phase of ROP, the visual outcomes after treatment are often poor. Preventive therapy is required and will likely come from a better understanding of the pathophysiology of the disease. To study the role of insulin-like growth factor 1 (IGF-1) and vascular endothelial growth factor (VEGF) in both the proliferative phase of ROP (phase II) and in the early phase when blood vessels are lost. Using both a mouse model of ROP and clinical studies the relationship between IGF-1, VEGF and both vessel loss and vessels proliferation in the retina was studied. IGF-1 is required for maximum VEGF activation of vascular endothelial cell proliferation and survival pathways. IGF-1 levels are deficient after premature birth, setting the stage for retinal vascular loss and ROP. Restoration of IGF-1 to levels found in utero may help prevent ROP.


Construction and application of a stoichiometric displacement model for retention in chiral recognition of molecular imprinting.
To do an extensive investigation of the chiral recognition mechanism of the molecular imprinting technique, two kinds of enantio-selective molecularly imprinted polymers (MIPs), N-tert-butoxycarbonyl-L-tryptophan (N-Boc-L-Trp) and N-tert-butoxycarbonyl-L-tyramine (N-Boc-L-Tyr), were synthesized by photo-induced and thermal-induced polymerization, respectively, and were employed as the stationary phase in liquid chromatography. A stoichiometric displacement model for retention (SDM-R) was successfully constructed and applied to evaluate the chiral separation of the MIPs. The simulation results showed that the values of ln k' in the proposed SDM-R could be employed to characterize the efficiency of the MIP's total separation, and the value of n could be used to denote the space effect of the enantiomers interacting with the MIPs when the interaction between the solutes and MIPs was a hydrogen-bonding interaction. Further studies showed that the suitability of the MIP cavity structure mainly determined the chiral-recognition ability of the imprinting system, when a strong hydrogen-bond competitive solvent was added into the mobile phase.


Size and ionic currents of unexcitable cells coupled to cardiomyocytes distinctly modulate cardiac action potential shape and pacemaking activity in micropatterned cell pairs.
Cardiac cell therapies can yield electric coupling of unexcitable donor cells to host cardiomyocytes with functional consequences that remain unexplored. We micropatterned cell pairs consisting of a neonatal rat ventricular myocyte (NRVM) coupled to an engineered human embryonic kidney 293 (HEK293) cell expressing either connexin-43 (Cx43 HEK) or inward rectifier potassium channel 2.1 (Kir2.1) and Cx43 (Kir2.1+Cx43 HEK). The NRVM-HEK contact length was fixed yielding a coupling strength of 68.9±9.7 nS, whereas HEK size was systematically varied. With increase in Cx43 HEK size, NRVM maximal diastolic potential was reduced from -71.7±0.6 mV in single NRVMs to -35.1±1.3 mV in pairs with an HEK:NRVM cell surface area ratio of 1.7±0.1, whereas the action potential upstroke ([dV(m)/dt](max)) and duration decreased to 1.6±0.7% and increased to 177±32% in single NRVM values, respectively (n=21 cell pairs). Pacemaking occurred in all NRVM-Cx43 HEK pairs with cell surface area ratios of 1.1 to 1.9. In contrast, NRVMs, coupled with Kir2.1+Cx43 HEKs of increasing size, had similar maximal diastolic potentials, exhibited no spontaneous activity, and showed a gradual decrease in action potential duration (n=23). Furthermore, coupling single NRVMs to a dynamic clamp model of HEK cell ionic current reproduced the cardiac maximal diastolic potentials and pacemaking rates recorded in cell pairs, whereas reproducing changes in (dV(m)/dt)(max) and action potential duration required coupling to an HEK model that also included cell membrane capacitance. Size and ionic currents of unexcitable cells electrically coupled to cardiomyocytes distinctly affect cardiac action potential shape and initiation with important implications for the safety of cardiac cell and gene therapies.


Reductive activation of potential antitumor mitosene compounds.
The reductive activation of mitosene compounds was studied with cyclic voltammetry and HPLC analysis. Reduction of mitosenes, possessing good leaving groups at C-1 and C-10, was shown to result in loss of these groups at pH 7.0 and pH 6.0. The loss of leaving groups from mitosenes occurred faster at lower pH. Mitosenes without good leaving groups were found to be stable upon reduction. In the presence of acetoxy groups at C-1 and C-10, the C-10 site is the most reactive site upon reductive activation. This is opposite to the case of mitomycin C, where the C-1 site is the first to react upon reduction. At pH 6.0 without reduction, acid degradation also caused the loss of leaving groups of mitosenes, although at a very slow rate. In contrast to reductive activation, upon acid degradation of a diacetoxymitosene the C-1 group appeared to be lost faster. Electrochemical as well as dithionite reduction of a bifunctional (diacetoxy) mitosene compound in the presence of calf thymus DNA at pH 5.5 resulted in the formation of DNA interstrand cross-links. Depending on activation method, this diacetoxymitosene was at least as efficient in DNA cross-linking as mitomycin C under comparable conditions.


[Establishment of an animal model of intrauterine growth retardation (IUGR)].
This paper reports the establishment of animal model of IUGR by injecting Actinomycin to pregnant rats at 0.1 micrograms/g on the tenth, eleventh and twelfth day after pregnancy. The rats were divided into control, test A, B and C groups. The body weight of test A group rats was obviously lowered than the controls (P less than 0.01). The fetal weight, placental function and serum total proteins of A group rats were also markedly lowered (P less than 0.01). IUGR incidence in test A, B and C groups were 66.2%, 41.2% and 27.8%, respectively. It may be seen that establishment of animal model of IUGR by giving Actinomycin on the 10th day after pregnancy of the rat produced the best results and the most cases of IUGR.


P/Q-type calcium channel modulators.
P/Q-type calcium channels are high-voltage-gated calcium channels contributing to vesicle release at synaptic terminals. A number of neurological diseases have been attributed to malfunctioning of P/Q channels, including ataxia, migraine and Alzheimer's disease. To date, only two specific P/Q-type blockers are known: both are peptides deriving from the spider venom of Agelenopsis aperta, ω-agatoxins. Other peptidic calcium channel blockers with activity at P/Q channels are available, albeit with less selectivity. A number of low molecular weight compounds modulate P/Q-type currents with different characteristics, and some exhibit a peculiar bidirectional pattern of modulation. Interestingly, there are a number of therapeutics in clinical use, which also show P/Q channel activity. Because selectivity as well as the exact mode of action is different between all P/Q-type channel modulators, the interpretation of clinical and experimental data is complicated and needs a comprehensive understanding of their target profile. The situation is further complicated by the fact that information on potency varies vastly in the literature, which may be the result of different experimental systems, conditions or the splice variants of the P/Q channel. This review attempts to provide a comprehensive overview of the compounds available that affect the P/Q-type channel and should help with the interpretation of results of in vitro experiments and animal models. It also aims to explain some clinical observations by implementing current knowledge about P/Q channel modulation of therapeutically used non-selective drugs. Chances and challenges of the development of P/Q channel-selective molecules are discussed.


Artificial Intelligence-Assisted Early Detection of Retinitis Pigmentosa - the Most Common Inherited Retinal Degeneration.
The purpose of this study was to detect the presence of retinitis pigmentosa (RP) based on color fundus photographs using a deep learning model. A total of 1670 color fundus photographs from the Taiwan inherited retinal degeneration project and National Taiwan University Hospital were acquired and preprocessed. The fundus photographs were labeled RP or normal and divided into training and validation datasets (n = 1284) and a test dataset (n = 386). Three transfer learning models based on pre-trained Inception V3, Inception Resnet V2, and Xception deep learning architectures, respectively, were developed to classify the presence of RP on fundus images. The model sensitivity, specificity, and area under the receiver operating characteristic (AUROC) curve were compared. The results from the best transfer learning model were compared with the reading results of two general ophthalmologists, one retinal specialist, and one specialist in retina and inherited retinal degenerations. A total of 935 RP and 324 normal images were used to train the models. The test dataset consisted of 193 RP and 193 normal images. Among the three transfer learning models evaluated, the Xception model had the best performance, achieving an AUROC of 96.74%. Gradient-weighted class activation mapping indicated that the contrast between the periphery and the macula on fundus photographs was an important feature in detecting RP. False-positive results were mostly obtained in cases of high myopia with highly tessellated retina, and false-negative results were mostly obtained in cases of unclear media, such as cataract, that led to a decrease in the contrast between the peripheral retina and the macula. Our model demonstrated the highest accuracy of 96.00%, which was comparable with the average results of 81.50%, of the other four ophthalmologists. Moreover, the accuracy was obtained at the same level of sensitivity (95.71%), as compared to an inherited retinal disease specialist. RP is an important disease, but its early and precise diagnosis is challenging. We developed and evaluated a transfer-learning-based model to detect RP from color fundus photographs. The results of this study validate the utility of deep learning in automating the identification of RP from fundus photographs.