TRPV4 ion channel is a novel regulator of dermal myofibroblast differentiation.
Scleroderma is a multisystem fibroproliferative disease with no effective medical treatment. Myofibroblasts are critical to the fibrogenic tissue repair process in the skin and many internal organs. Emerging data support a role for both matrix stiffness, and transforming growth factor β1 (TGFβ1), in myofibroblast differentiation. Transient receptor potential vanilloid 4 (TRPV4) is a mechanosensitive ion channel activated by both mechanical and biochemical stimuli. The objective of this study was to determine the role of TRPV4 in TGFβ1- and matrix stiffness-induced differentiation of dermal fibroblasts. We found that TRPV4 channels are expressed and functional in both human (HDF) and mouse (MDF) dermal fibroblasts. TRPV4 activity (agonist-induced Ca2+ influx) was induced by both matrix stiffness and TGFβ1 in dermal fibroblasts. TGFβ1 induced expression of TRPV4 proteins in a dose-dependent manner. Genetic ablation or pharmacological antagonism of TRPV4 channel abrogated Ca2+ influx and both TGFβ1-induced and matrix stiffness-induced myofibroblast differentiation as assessed by 1) α-smooth muscle actin expression/incorporation into stress fibers, 2) generation of polymerized actin, and 3) expression of collagen-1. We found that TRPV4 inhibition abrogated TGFβ1-induced activation of AKT but not of Smad2/3, suggesting that the mechanism by which profibrotic TGFβ1 signaling in dermal fibroblasts is modified by TRPV4 may be through non-Smad pathways. Altogether, these data identify a novel reciprocal functional link between TRPV4 activation and TGFβ1 signals regulating dermal myofibroblast differentiation. These findings suggest that therapeutic inhibition of TRPV4 activity may provide a targeted approach to the treatment of scleroderma.


Quantitative EEG Correlates of Outcome in Older Psychiatric Patients: Part II: Two-Year Follow-Up of Patients With Depression.
The authors examined quantitative electroencephalographc (QEEG) coherence in 37 depressed elderly patients and performed 2-year follow-up evaluations. All subjects had equivocal cognitive impairment, but none had delirium or dementia. More than 40% (16/37) recovered from depression, and 38% (14/37) remained well for 2 years. Twenty-four percent (n = 9) had died within 2 years, most from cardiac causes. Low trans-Rolandic coherence from the left hemisphere was strongly associated with mortality: 44% (7/16) of those with low coherence died, and 78% (7/9) of those who died had low coherence. Among survivors (n = 28) at follow-up, low coherence was significantly associated with lower functional status. These findings suggest that the coherence variable measures actual neurophysiology differences between groups of depressed patients and these differences are associated with the heterogeneous outcomes of depression in elderly patients.


[Knowledge and attitudes of Mexican population concerning solar radiation].
The effects of solar radiation in human health is dependent upon environment, behavior, and genetic characteristics. Identify phenotypic features, attitudes, knowledge and preventive measures concerning sun exposure among a local population. People older than 15 years were interviewed concerning time of sun exposure, photoprotection, and general knowledge about adverse effects of sun irradiation. 964 questionnaires were analyzed. White-skin population represented 7.4%, light-brown 24.8%, dark-brown 67.8%. Exposure time on working days was up to 15 min in 27.8%, and more than 60 min in 38.8%. On weekends, time exposure was similar. 30% did not take any preventive measures 41% wore hats and 11.8% used sunscreens. Among participants, 85.4% were aware that sun exposure caused skin cancer, 64. 1% knew that mortality is increased, 83.4% reported that excessive sun exposure is related to aging of the skin, and 26.5% believed tanning is healthy. In spite of thefact that a great majority of the population recognized that sun exposure produces aging and skin cancer, their exposure is widespread. This survey may be a valuable tool to design preventive public health campaigns that target high risk groups.


[The control of kennel cough].
Kennel cough is an infectious factorial disease with a multicausal genesis. The conventional methods (hygiene, management, chemotherapy, symptomatic therapy) are often insufficient in control of the disease. New methods were developed in collaboration with "problem kennels" (animal homes, dealer kennels etc.), which reduce the morbidity significantly. A so-called "synergistic combined vaccine" ("Candiflu", Behringwerke Marburg), which contains the basic viruses (reovirus, human influenza-A-virus, parainfluenza-2-virus), is recommended for prophylaxis. In problem kennels with a permanent changing of dogs the vaccination has to be supported by paramunization. Therapeutical success depends on the combination of conventional methods and the stimulation of the paraspecific immune system (paramunization). This new concept has been very successful in West Germany during the last years.


The presence of vitamin A in human tryptophan-rich prealbumin.
Human tryptophan-rich prealbumin has been isolated from serum and its homogeneity evaluated by immunoelectrophoresis and polyacrylamide-gel electrophoresis. The green fluorescence of the protein when exposed to ultraviolet light was shown to be due to the presence of vitamin A. It is suggested that trytophanrich prealbumin represents the hitherto unknown specific transport protein for vitamin A.


Novel domino cyclization of tryptophan-derived amino nitriles: scope and stereoselectivity.
[reaction: see text] The scope and stereoselectivity of the acid-promoted cyclization of new tryptophan-based alpha-amino nitriles derived from either ketones or aldehydes to novel hexahydropyrrolo[1',2',3':1,9a,9]imidazo[1,2-a]indoles is described. This cyclization involves the generation of two or three stereogenic centers. The time and stereoselectivity of this reaction mostly depended on both the steric volume of the substituents at the amino nitrile and its stereochemistry. Unhindered amino nitriles gave exclusively 2-exo-isomers, while hindered amino nitriles, which required higher reaction times, provided also these isomers under kinetic control. Under thermodynamic control, the 2-endo-isomer was the main reaction product, except for the benzaldehyde-derived alpha-amino nitriles, where a favorable electronic interaction between the phenyl and methoxycarbonyl groups in a relative cis-disposition might be responsible of the formation of the 2-exo-isomer as the only cyclization product.


Osteitis pubis in elite athletes: Diagnostic and therapeutic approach.
Osteitis pubis (OP) is a debilitating overuse syndrome characterizing by pelvic pain and local tenderness over the pubic symphysis commonly encountered in athletes often involved in kicking, twisting and cutting activities in sports such as soccer and rugby and to a lesser degree distance running. It is a common source of groin pain in elite athletes attributable to pubis sympysis instability as the result of microtrauma caused by repetitive muscle strains on pubic bones. Diagnosis is based mainly on detailed sports history and a meticulous clinical examination, although occasionally is difficult to distinguish this nosological entity from other pathologies affecting the involved area which may occur concomitantly in the same patient. Radiologic examinations such as plain radiographs, magnetic resonance imaging and 3 phase bone isotope scanning may be helpful to differentiate from other clinical entities with similar clinical presentation. Most cases respond well to conservative treatment which includes several physical modalities and especially a progressive rehabilitation programmed individualized to each one of patients diagnosed with OP. Local injection therapies have been also been proposed as a non-operative therapeutic option for the efficient management of these patients. In refractory cases, surgical therapeutic strategies are warranted. These include several open or minimally invasive surgical interventions such as arthroscopic or open symphysis curettage, wedge or total resection of pubic sympysis, polypropylene mesh placement and pubic fusion. In this review a critical analysis of OP in elite athletes is performed with special focus on current concepts of diagnosis and management of this source of athletic groin pain.


Positional Dependence of DNA Hole Transfer Efficiency in Nucleosome Core Particles.
Electron deficient "holes" migrate over long distances through the π-system in free DNA. Hole transfer efficiency (HTE) is strongly dependent on sequence and π-stacking. However, there is no consensus regarding the effects of nucleosome core particle (NCP) environment on hole migration. We quantitatively determined HTE in free DNA and NCPs by independently generating holes at specific positions in DNA. The relative HTE varied widely with respect to position within the NCP and proximity to tyrosine, which suppresses hole transfer. These data indicate that hole transfer in chromatin will be affected by the DNA sequence and its position with respect to histone proteins within NCPs.


The effect of farrowing environment and previous experience on the maternal behaviour of sows in indoor pens and outdoor huts.
Outdoor farrowing huts facilitate a less restricted maternal behaviour in sows compared with sows kept indoors in farrowing pens. The aim of our study was to investigate whether there are behavioural differences between primiparous sows kept outdoors in farrowing huts and indoors in pens, and whether the maternal behaviour during the second parity, when all sows were kept outdoors in farrowing huts, would differ between sows that have experienced the indoor or the outdoor environment, respectively, during their first parturition. A total of 26 Yorkshire×Swedish Landrace sows were studied. Of these, 11 sows were housed outdoors in farrowing huts during both parturitions (group=OUTOUT). The other 15 sows were kept indoors in a barn with single farrowing pens during their first parturition. During their second parturition, sows were kept outdoors in farrowing huts (group=INOUT). The behaviour was video recorded from 2 h prepartum to 48 h postpartum. The sows' responsiveness to playbacks of a piglet's screams was tested on days 2 to 3 postpartum. Parity 1: during the last 2 h prepartum, OUTOUT sows had a higher proportion of observations in the sternal lying position (P<0.01). During parturition, OUTOUT sows changed posture more often (P<0.05) and were lying less (P<0.05) than INOUT sows. All sows in both groups responded with 'lifting head' towards the playback of piglet scream, whereas 100% of OUTOUT sows and only 43% of INOUT sows thereafter were 'getting up' (P <0.01). Parity 2: There were no behavioural differences between INOUT and OUTOUT sows. In conclusion, it is not problematic for a second parity sow with initial maternal experience from an indoor farrowing pen to be kept outdoors in farrowing huts during its following farrowing.


ECG voltage modifications as response to gravity changes.
The aim of the study was to analyze ECG (QRS) voltage responses to body fluid shift due to gravity chances. Acute changes in gravity were created by two ways: 1) changes in gravity value during parabolic flights (within 27 subjects 45 ECG have been analyzed); 2) changes in gravity direction due to rotation of the body during postural tests (within 11 subjects 14 ECG have been analyzed). Results and conclusions. Gravity change leads to body fluid shift and changes of intrathoracic organs and tissues electroconduction. It influences on ECG voltage. During parabolic flights in up-right position: R amplitude in Z axis increases in hypergravity (+0.19 mV) and decreases in microgravity (-0.24 mV). During postural tests, R amplitude in Z axis increases in orthostatic position (+0.09 mV) and decreases in antiorthostatic position (-0.025 mV). Changes in QRS voltage during parabolic flights are more important than during postural tests. This could be due to more effective blood redistribution during parabolic flights.


Preoperative interscalene brachial plexus block aids in perioperative temperature management during arthroscopic shoulder surgery.
Hypothermia is common during arthroscopic shoulder surgery under general anesthesia, and anesthetic-impaired thermoregulation is thought to be the major cause of hypothermia. This prospective, randomized, double-blind study was designed to compare perioperative temperature during arthroscopic shoulder surgery with interscalene brachial plexus block (IBPB) followed by general anesthesia vs. general anesthesia alone. Patients scheduled for arthroscopic shoulder surgery were randomly allocated to receive IBPB followed by general anesthesia (group GB, n = 20) or general anesthesia alone (group GO, n = 20), and intraoperative and postoperative body temperatures were measured. The initial body temperatures were 36.5 ± 0.3℃ vs. 36.4 ± 0.4℃ in group GB vs. GO, respectively (P = 0.215). The body temperature at 120 minutes after induction of anesthesia was significantly higher in group GB than in group GO (35.8 ± 0.3℃ vs. 34.9 ± 0.3℃; P < 0.001). The body temperatures at 60 minutes after admission to the post-anesthesia care unit were 35.8 ± 0.3℃ vs. 35.2 ± 0.2℃ in group GB vs. GO, respectively (P < 0.001). The concentrations of desflurane at 0, 15, and 120 minutes after induction of anesthesia were 6.0 vs. 6.0% (P = 0.330), 5.0 ± 0.8% vs. 5.8 ± 0.4% (P = 0.001), and 3.4 ± 0.4% vs. 7.1 ± 0.9% (P < 0.001) in group GB vs. GO, respectively. The present study demonstrated that preoperative IBPB could reduce both the intraoperative concentration of desflurane and the reduction in body temperature during and after arthroscopic shoulder surgery.


[Detection of SOS response inhibitor with E. coli GW1104 and GW1107 and its mechanism].
E. coli GW1104 and GW1107 are temperature-sensitive strains carrying a fusion gene umu:: Mud(Ap,lac) with genotypes recA441 (tif-1) and recA441 (tif-1),lexA (Def) (spr), respectively. SOS response can be produced spontaneously at 32 degrees C in E. coli GW1107, and induced at 42 degrees C in both E. coli GW1107 and GW1104. To detect SOS response inhibitor and to study its mechanism, a quick-test-system was established based on their genetic characteristics of the two strains. It was found some kinds of Chinese herbal medicine, vegetables, and chemicals could inhibit SOS response in the strains to different extent with varied mechanisms. Shell of water chestnut could inhibit temperature-induced SOS response at 42 degrees C in E. coli GW1104, and spontaneously-produced one at 32 degrees C in E.coli GW1107. Chinese chives can only inhibit temperature-induced SOS response in E. coli GW1104. It suggested the former's inhibition effect on SOS response occurred at lexA gene or on the pathway of SOS response before lexA gene, and so did the latter's on the pathway after lexA gene.


The HL60 cell line: a model system for studying human myeloid cell differentiation.
The HL60 cell line was established in 1977 from a patient with acute myeloid leukaemia. The cells largely resemble promyelocytes but can be induced to differentiate terminally in vitro. Some reagents cause HL60 cells to differentiate to granulocyte-like cells, others to monocyte/macrophage-like cells. The HL60 cell genome contains an amplified c-myc proto-oncogene; c-myc mRNA levels are correspondingly high in undifferentiated cells but decline rapidly following induction of differentiation. These features have made the HL60 cell line an attractive model for studies of human myeloid cell differentiation. This review summarizes the major properties of HL60 cells, describes some aspects of the regulation of gene expression in differentiating HL60 cells, including a novel interaction between transcriptional and post-transcriptional controls, and discusses the possible involvement of c-myc in proliferation and differentiation.


[Gender and its impact on condom use among HIV male serodiscordant couples].
To study the gender-based factors which influence the condom use among the HIV serodiscordant couples in selected regions of China. Based on the analysis of the existing case reporting database and convenient sampling in the cross-sectional study, a total of 481 female HIV-negative spouses completed an interviewer-administered questionnaire regarding demographic characters, the knowledge, behaviors and the gender-based factors in five sites of four provinces Sichuan (Zhaojue), Yunnan (Dali), Henan (Weishi) and Guangxi (Lingshan and Luzhai), during June-September 2011. χ(2) analysis and logistic regression were used to study the gender-based factors influencing condom use among the participants. Among the 481 female HIV-negative spouses, the average age was (35.1 ± 6.7) years, and the proportion of Han and Yi nationality were high, 43.5% (209/481) and 41.8% (201/481), respectively. The awareness of knowledge related to HIV spousal transmission was high (≥ 79.6%). A total of 86.9% (418/481) used condom more frequently after informed the status of HIV infection of their spouses, and the condom use consistency was 56.6% (272/481). A total of 57.6% (277/481) reported low sexual relationship power; 34.5% (166/481) experienced forced sex in the past 1 year. And the proportion of condom use self-efficacy from 0 to 3 scores were 12.7% (61/481), 23.9% (115/481), 8.7% (42/481) and 54.7% (263/481), respectively (median = 3). Han and other nationality were significantly more likely to use condom consistently than Yi, with odds ratio (95%CI) of 0.01 (0.00 - 0.03) and 0.01 (0.00 - 0.04), and the female spouses with higher condom use self-efficacy used condom more consistently than the lower ones, with odds ratio (95%CI) of 0.20(0.11 - 0.34). The female spouses with higher condom use self-efficacy were more likely to use condom consistently after excluding the confounding effect of nationality.


Suture-related keratitis caused by Corynebacterium macginleyi.
We report two cases of suture-related keratitis following penetrating keratoplasty. In both cases, Corynebacterium macginleyi was isolated from corneal specimens. Scanning electron microscopy revealed that corynebacteria could aggregate and form a biofilm. The MICs of sulbenicillin and fluoroquinolones were high for both isolates. Our findings show that C. macginleyi can cause keratitis with biofilm formation.


Comparative Impact of Depressive Symptoms and FEV1% on Chronic Obstructive Pulmonary Disease.
Rationale: Individuals with chronic obstructive pulmonary disease (COPD) have a high prevalence of depression, which is associated with increased COPD hospitalizations and readmissions. Objectives: Examine the impact of depressive symptoms compared with FEV1% on COPD morbidity. Methods: Using longitudinal data from individuals with COPD in the Subpopulations and Intermediate Outcome Measures in COPD Study, longitudinal growth analysis was performed to assess COPD morbidity by assessing differences in baseline 6-minute walk distance and patient reported outcomes (PROs) and their rate of change over time explained by depressive symptoms or lung function, as measured by Hospital Anxiety and Depression Scale or FEV1% respectively. PROs consisted of in-person completion of St. George's Respiratory Questionnaire, COPD Assessment Test, Functional Assessment of Chronic Illness Therapy Fatigue, and Modified Medical Research Council Dyspnea Scale measures. Results: Of the individuals analyzed (n = 1,830), 43% were female, 81% Caucasian with mean ± SD age of 65.1 ± 8.1, and 52.7 ± 27.5 pack-years smoking. Mean ± SD FEV1% was 60.9 ± 23.0% and 20% had clinically significant depressive symptoms. Adjusted models showed higher Hospital Anxiety and Depression Scale scores and lower FEV1% each were associated with worse PROs at baseline (P ⩽ 0.001). Depression accounted for more baseline variance in St. George's Respiratory Questionnaire, COPD Assessment Test, and Functional Assessment of Chronic Illness Therapy Fatigue than FEV1%, explaining 30-67% of heterogeneity. FEV1% accounted for more baseline variance in Modified Medical Research Council Dyspnea Scale and 6-minute walk distance than depression, explaining 16-32% of heterogeneity. Depressive symptoms accounted for 3-17% variance in change over time in PROs. In contrast, FEV1% accounted for 1-4% variance over time in PROs. Conclusions: Depression is more strongly associated with many PROs at baseline and their change over time compared with FEV1%. Recognizing and incorporating the impact of depressive symptoms into individualized care may improve COPD outcomes.


Endocarditis due to Pseudomonas aeruginosa in a heroin addict. Successful treatment with trimethoprim-Sulfamethoxazole mixture plus colistin.
Endocarditis of the tricuspid valve due to Pseudomonas aeruginosa in a heroin addict failed to respond to therapy with gentamicin, carbenicillin, and amikacin. Clinical and bacteriologic cure was achieved with oral administration of a trimethoprim-sulfamethoxazole mixture plus parenteral therapy with colistin. In vitro synergism was demonstrated for the three drugs at concentrations achievable in the serum. Therapy for endocarditis due to Pseudomonas continues to be a major problem; however, the successful treatment of this patient warrants consideration for instituting therapy with a trimethoprim-sulfamethoxazole misture plus colistin in individuals with this infection who fail to respond to standard therapeutic regimens for severe infections with Pseudomonas.


Description of D-glucosamine immobilization kinetics onto poly(lactic acid) surface via a multistep physicochemical approach for preparation of novel active biomaterials.
Poly(lactic acid) (PLA) has shown much success in the preparation of tissue engineering scaffolds as it can be fabricated with a tailored architecture. However, the PLA surface has drawbacks including the lack of biofunctional motifs which are essential for high affinity to biological cells. Therefore, this study describes a multistep physicochemical approach for the immobilization of d-glucosamine (GlcN), a naturally occurring monosaccharide having many biological functions, on the PLA surface aiming at enhancing the cell proliferation activity. In this approach, poly(acrylic acid) (PAAc) spacer arms are first introduced into the PLA surface via plasma post-irradiation grafting technique. Then, covalent coupling or physical adsorption of GlcN with/on the PAAc spacer is carried out. Factors affecting the grafting yield are controlled to produce a suitable spacer for bioimmobilization. X-ray photon spectroscopic (XPS) analyses confirm the immobilization of GlcN on the PLA surface. The XPS results reveal also that increasing the yield of grafted PAAc spacer on the PLA surface increases the amount of covalently immobilized GlcN, but actually inhibits the immobilization process using the physical adsorption method. Contact angle measurements and atomic force microscopy (AFM) show a substantial increase of surface energy and roughness of PLA surface, respectively, upon the multistep modification procedure. The cytocompatibility of the modified surfaces is assessed using a mouse embryonic fibroblast (MEF) cell line. Observation from the cell culture basically demonstrates the potential of GlcN immobilization in improving the cytocompatibility of the PLA surface. Moreover, the covalent immobilization of GlcN seems to produce more cytocompatible surfaces if compared with the physical adsorption method. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 105A: 3176-3188, 2017.


Breath isoprene--aspects of normal physiology related to age, gender and cholesterol profile as determined in a proton transfer reaction mass spectrometry study.
This study was performed to clarify variations in breath isoprene concentrations with age, gender, body mass index (BMI) and total serum cholesterol. Our cohort consisted of 205 adult volunteers of different smoking background without health complaints. Total cholesterol in blood serum was measured in 79 of these volunteers. Mixed expiratory exhaled breath was sampled using Tedlar bags. Concentrations of isoprene were then determined using proton transfer reaction-mass spectrometry. Isoprene concentrations ranged from 5.8 to 274.9 ppb, with an overall geometric mean (GM) of 99.3 ppb. There was no statistically significant difference in mean isoprene in breath between males and females (GM 105.4 and 95.5 ppb, respectively). Ageing led to a decrease in concentration in men, with an estimated slope of the regression line for log-transformed isoprene concentrations of -0.0049, but did not influence isoprene levels in women. We did not observe any significant correlation between isoprene breath content and cholesterol level in blood, even after adjusting for the possible influence of age. Similarly, no correlation was found between isoprene levels and BMI. Isoprene concentrations in exhaled breath showed gender-specific correlations with respect to age. Further investigations are necessary to clarify the relation between isoprene concentrations in exhaled breath and cholesterol levels and synthesis rates in blood.


Preoperative TNM-classification is a better prognostic indicator for recurrence of hepatocellular carcinoma after liver transplantation than albumin mRNA in peripheral blood. Liver Transplant Oncology Group.
Survival after orthotopic liver transplantation for hepatocellular carcinoma is limited by a high rate of tumor recurrence. A polymerase chain reaction assay based on the detection of albumin mRNA expression in peripheral blood for detection of hematogenous micrometastasis of hepatocellular carcinoma has been described, which may help to select candidates for orthotopic liver transplantation. The prognostic value of a highly sensitive nested reverse transcription-polymerase chain reaction assay was evaluated in comparison with the TNM-classification of the International Union against Cancer in a population of liver transplant candidates. Eighty patients with liver disease and 42 control patients were evaluated. Six of 21 patients with hepatocellular carcinoma and 11 of 59 patients with other diseases of the liver were positive for albumin reverse transcription-polymerase chain reaction, making this assay an indicator of ongoing liver damage without absolute specificity for hepatocellular carcinoma. Twelve patients with hepatoma were followed after liver transplantation and seven of those patients had a tumor recurrence within 12 months. Six of these patients with recurrence had International Union against Cancer stage IV A tumors preoperatively, while only one of them was positive for albumin reverse transcription-polymerase chain reaction before transplantation. Only one patient with a stage I to III tumor had a recurrence within 12 months. Detection of albumin mRNA in peripheral blood by reverse transcription-polymerase chain reaction seems to be an unreliable marker for assessing hematogenous spread of hepatocellular carcinoma. With International Union against Cancer stage IV A being a much better predictor of tumor recurrence, the practical value of albumin mRNA reverse transcription-polymerase chain reaction for patient selection in liver transplant candidates seems to be very limited.


Plasma Epstein-Barr virus DNA as a biomarker for nasopharyngeal carcinoma.
Nasopharyngeal carcinoma (NPC) is common in southern China and Southeast Asia. Epstein-Barr virus (EBV) infection is an important etiology for NPC, and EBV genome can be detected in almost all tumor tissues of NPC in this region. Plasma EBV DNA, when quantitatively analyzed using real-time polymerase chain reaction (PCR), has been developed as a biomarker for NPC. In this review, the different clinical applications of plasma EBV DNA in the management of NPC, including screening, monitoring, and prognostication, are discussed. In addition, the biological issues of circulating EBV DNA, including the molecular nature and clearance kinetics, are also explored.


Gravity-oriented microfluidic device for uniform and massive cell spheroid formation.
We propose a simple method for forming massive and uniform three-dimensional (3-D) cell spheroids in a multi-level structured microfluidic device by gravitational force. The concept of orienting the device vertically has allowed spheroid formation, long-term perfusion, and retrieval of the cultured spheroids by user-friendly standard pipetting. We have successfully formed, perfused, and retrieved uniform, size-controllable, well-conditioned spheroids of human embryonic kidney 293 cells (HEK 293) in the gravity-oriented microfluidic device. We expect the proposed method will be a useful tool to study in-vitro 3-D cell models for the proliferation, differentiation, and metabolism of embryoid bodies or tumours.


A Perforated Colonic Neuroendocrine Tumor with Liver Metastasis: A Case Report and Literature Review.
BACKGROUND Neuroendocrine neoplasms (NENs) originate from cells of the endocrine and nervous systems, and they are rarely encountered in colorectal cases with no specific symptoms. The incidence and prevalence of NENs of the large bowel are increasing. Malignant colonic types are known to have poor diagnosis. The mean age of colonic NENs is the seventh decade, and the risk of NENs is increased 4-fold with affected first-degree family members. CASE REPORT A 57-year-old male patient presented to our Emergency Department with a 5-day history of severe generalized abdominal pain associated with worsening abdominal distension, history of night sweats, and weight loss. A CT scan of the abdomen and pelvis demonstrated a large heterogeneously enhancing neoplastic mass lesion involving the splenic flexure of the colon surrounded by fat stranding with a small contained leak, in addition to multiple metastatic hypodense focal hepatic lesions. Multiple lymph nodes under 1 cm in size were also noted. The patient underwent exploratory laparotomy, subtotal colectomy, ileostomy creation, and washout. The histopathological exam revealed high-grade invasive colonic neuroendocrine carcinoma, which was pT4N2bM1c, while the peritoneal lesion was metastatic carcinoma. The patient was then referred to the multidisciplinary tumor board. CONCLUSIONS Unusual presentation of neuroendocrine tumors is shown to be expected. Since colorectal NECs are rare, highly aggressive diseases and usually discovered very late, individualization of management, as well as additional research, is required.


An NMR determination of CO diffusion on platinum electrocatalysts.
We report the first direct measurement of CO diffusion on nanoparticle Pt electrocatalysts at the solid/liquid interface, carried out using 13C nuclear magnetic resonance (NMR) with a spin-labeling pulse sequence. Diffusion parameters were measured in the temperature range of 253-293 K for CO adsorbed on commercial Pt-black under saturation coverage. 2H NMR of the same system indicates that the electrolyte remains in the liquid state at temperatures where the CO diffusion experiments were performed. The CO diffusion parameters follow typical Arrhenius behavior with an activation energy of 6.0 +/- 0.4 kcal/mol and a pre-exponential factor of (1.1 +/- 0.6) x 10-8 cm2/s. Exchange between different CO populations, driven by a chemical potential gradient, is suggested to be the main mechanism for CO diffusion. The presence of the electrolyte medium considerably slows down the diffusion of CO as compared to that seen on surfaces of bulk metals under UHV conditions. This work opens up a new approach to the study of surface diffusion of adsorbed molecules on nanoparticle electrode catalysts, including the possibility of correlating diffusion parameters to catalytic activity in real world applications of broad general interest.


Long-working-distance 3D measurement with a bionic curved compound-eye camera.
The bionic curved compound-eye camera is a bionic-inspired multi-aperture camera, which can be designed to have an overlap on the field of view (FOV) in between adjacent ommatidia so that 3D measurement is possible. In this work, we demonstrate the 3D measurement with a working distance of up to 3.2 m by a curved compound-eye camera. In that there are hundreds of ommatidia in the compound-eye camera, traditional calibration boards with a fixed-pitch pattern arrays are not applicable. A batch calibration method based on the CALTag calibration board for the compound-eye camera was designed. Next, the 3D measurement principle was described and a 3D measurement algorithm for the compound-eye camera was developed. Finally, the 3D measurement experiment on objects placed at different distances and directions from the compound-eye camera was performed. The experimental results show that the working range for 3D measurement can cover the whole FOV of 98° and the working distance can be as long as 3.2 m. Moreover, a complete depth map was reconstructed from a raw image captured by the compound-eye camera and demonstrated as well. The 3D measurement capability of the compound-eye camera at long working distance in a large FOV demonstrated in this work has great potential applications in areas such as unmanned aerial vehicle (UAV) obstacle avoidance and robot navigation.


Labeo rohita Mx1 exhibits the critical structural motifs of the family of large GTPases of mammals and is activated by rhabdovirus vaccination and bacterial RNA stimulations.
Myxovirus resistance (Mx) proteins belonging to the dynamin superfamily of high molecular weight GTPases exist in various isoforms and play crucial role in innate immunity. In addition to the isoforms, Mx1 also plays important role in exerting its anti-viral actions against a broad range of animal RNA viruses. In rohu (Labeo rohita), mx1 full-length cDNA sequence consists of 2440 nucleotides (nt) encoding 628 amino acids (aa) polypeptide of 71.289 kDa. Structurally, it belongs to the family of large GTPases with one DYNc domain (13-257aa) comprising of dynamin family motifs (LPRGSGIVTR) and the tripartite GTP-binding motifs (GDQSSGKS, DLPG and TKPD) at the N-terminal and one GED domain (537-628aa) at C-terminus. Rohu Mx1 is closely related to zebrafish Mx1 and is widely expressed in gill, liver, kidney, spleen and blood. In response to rhabdovirus vaccinations, poly I:C stimulation and bacterial infections, mx1 gene expression in rohu was significantly (p < 0.05) induced in majority of the tested organs/tissues. Stimulation of rohu gill cell line with bacterial RNA also induced mx1 gene expression. Together these data suggest the important role of Mx1 in innate immunity in rohu against wide spectrum of fish pathogens.


[Susceptibilities of bacteria isolated from patients with lower respiratory infectious diseases to antibiotics (2005)].
From October 2005 to September 2006, we collected the specimen from 366 patients with lower respiratory tract infections in 12 institutions in Japan, and investigated the susceptibilities of isolated bacteria to various antibacterial agents and patients' characteristics. Of 411 strains that were isolated from specimen (mainly from sputum) and assumed to be bacteria causing in infection, 406 strains were examined. The isolated bacteria were: Staphylococcus aureus 70, Streptococcus pneumoniae 85, Haemophilus influenzae 78, Pseudomonas aeruginosa (non-mucoid) 46, P. aeruginosa (mucoid) 14, Klebsiella pneumoniae 21, and Moraxella subgenus Branhamella catarrhalis 40. Of 70 S. aureus strains, those with 2 microg/ml or less of MIC of oxacillin (methicillin-susceptible S. aureus: MSSA) and those with 4 microg/ml or more of MIC of oxacillin (methicillin-resistant S. aureus: MRSA) were 38 (54.3%) and 32 (45.7%) strains, respectively. Against MSSA, imipenem had the most potent antibacterial activity and inhibited the growth of 37 strains (97.4%) at 0.063 microg/ml or less. Against MRSA, arbekacin and vancomycin showed the most potent activity and inhibited the growth of all the strains at 1 microg/ml. Carbapenems showed the most potent activities against S. pneumoniae and in particular, panipenem inhibited the growth of all the strains at 0.063 microg/ml or less. Faropenem also had a preferable activity and inhibited the growth of all the strains at 0.25 microg/ml. In contrast, there were high-resistant strains (MIC: over 128 microg/ml) for erythromycin (38.1%) and clindamycin (22.6%). Against H. influenzae, levofloxacin showed the most potent activity and its MIC90 was 0.063 microg/ml or less. Meropenem showed the most potent activity against P. aeruginosa (mucoid) and its MIC90 was 0.5 microg/ml. Against P. aeruginosa (non-mucoid), arbekacin had the most potent activity and its MIC90 was 8 microg/ml. Against K. pneumoniae, cefozopran was the most potent activity and inhibited the growth of all the strains at 0.063 microg/ml or less. Also, all the antibacterial agents except ampicillin generally showed a potent activity against M. (B.) catarrhalis and the MIC90 of them were 2 microg/ml or less. The approximately half the number (53.6%) of the patients with respiratory infection were aged 70 years or older. Bacterial pneumonia and chronic bronchitis accounted for 44.3% and 29.8% of all the respiratory infection, respectively. The bacteria frequently isolated from the patients with bacterial pneumonia were S. aureus (15.4%), S. pneumoniae (23.4%), and H. influenzae (21.3%). S. aureus (25.4%) and S. pneumoniae (18.0%) also were frequently isolated from the patients with chronic bronchitis. Before the drug administration, the bacteria frequently isolated from the patients were S. pneumoniae (22.0%) and H. influenzae (21.4%). The bacteria frequently isolated from the patients treated with macrolides were S. pneumoniae and P. aeruginosa, and their isolation frequencies were each 35.3%.


[The dilated vestibular aqueduct syndrome].
The authors analyse the clinical, radiological and audiometric findings in a population of 89 ears of 49 patients. There was no correlation between bone malformation and auditory deficit which was often profound. This anomaly occurs during the 7th week of embryogenesis and represents one facet of the dysplasia of Mondini.


Beyond mean-field approximations for accurate and computationally efficient models of on-lattice chemical kinetics.
Modeling the kinetics of surface catalyzed reactions is essential for the design of reactors and chemical processes. The majority of microkinetic models employ mean-field approximations, which lead to an approximate description of catalytic kinetics by assuming spatially uncorrelated adsorbates. On the other hand, kinetic Monte Carlo (KMC) methods provide a discrete-space continuous-time stochastic formulation that enables an accurate treatment of spatial correlations in the adlayer, but at a significant computation cost. In this work, we use the so-called cluster mean-field approach to develop higher order approximations that systematically increase the accuracy of kinetic models by treating spatial correlations at a progressively higher level of detail. We further demonstrate our approach on a reduced model for NO oxidation incorporating first nearest-neighbor lateral interactions and construct a sequence of approximations of increasingly higher accuracy, which we compare with KMC and mean-field. The latter is found to perform rather poorly, overestimating the turnover frequency by several orders of magnitude for this system. On the other hand, our approximations, while more computationally intense than the traditional mean-field treatment, still achieve tremendous computational savings compared to KMC simulations, thereby opening the way for employing them in multiscale modeling frameworks.


[Galactography].
Spontaneous single duct discharge is the main indication for galactography. This abnormality has in most cases a benign aetiology (> 90%). With a meticulous technique and sufficient experience, the ducts can be cannulated in 95% of the cases. A nipple adenoma with a blood stained discharge is seldom to pass for cannulation. Because cytology of the nipple discharge is not always positive in case of intraductal proliferations, microdochectomy must be used to obtain the differential diagnosis. Galactography shows multiple normal duct variations, depending on age, surrounding tissue, and a possible history of lactation. Pathologic images can be seen in dystrophic breasts, solitary papillomas, (juvenile) papillomas or (intraductal) carcinomas. In addition to high frequency ultrasonography (> or = 10 MHz), which is able to visualise the retro-areolar and superficial ducts, galactography can give a more detailed and better overview of the pathology.


Lipocalin 2 regulates retinoic acid-induced activation of beige adipocytes
Lipocalin-2 (LCN2) has been previously characterized as an adipokine regulating thermogenic activation of brown adipose tissue and retinoic acid (RA)-induced thermogenesis in mice. The objective of this study was to explore the role and mechanism for LCN2 in the recruitment and retinoic acid-induced activation of brown-like or 'beige' adipocytes. We found LCN2 deficiency reduces key markers of thermogenesis including uncoupling protein-1 (UCP1) and peroxisome proliferator-activated receptor gamma coactivator 1α (PGC-1α) in inguinal white adipose tissue (iWAT) and inguinal adipocytes derived from Lcn2 −/− mice. Lcn2 −/− inguinal adipocytes have attenuated insulin-induced upregulation of thermogenic gene expression and p38 mitogen-activated protein kinase (p38MAPK) signaling pathway activation. This is accompanied by a lower basal and maximal oxidative capacity in Lcn2 −/− inguinal adipocytes, indicating mitochondrial dysfunction. Recombinant Lcn2 was able to restore insulin-induced p38MAPK phosphorylation in both WT and Lcn2 −/− inguinal adipocytes. Rosiglitazone treatment during differentiation of Lcn2 −/− adipocytes is able to recruit beige adipocytes at a normal level, however, further activation of beige adipocytes by insulin and RA is impaired in the absence of LCN2. Further, the synergistic effect of insulin and RA on UCP1 and PGC-1α expression is markedly reduced in Lcn2 −/− inguinal adipocytes. Most intriguingly, LCN2 and the retinoic acid receptor-alpha (RAR-α) are concurrently translocated to the plasma membrane of adipocytes in response to insulin, and this insulin-induced RAR-α translocation is absent in adipocytes deficient in LCN2. Our data suggest a novel LCN2-mediated pathway by which RA and insulin synergistically regulates activation of beige adipocytes via a non-genomic pathway of RA action.


Novel probe-based melting curve assays for the characterization of fluoroquinolone resistance in Mycoplasma genitalium.
Mycoplasma genitalium infection is a sexually transmitted infection that has rapidly become resistant to mainstay treatments. While individualized treatment approaches have been recommended and adopted for macrolides, individualized therapy for fluoroquinolones has not yet been explored, due to a lack of commercial molecular assays and a lack of confidence in specific mutations associated with resistance. In another recent study, we defined a clear role and diagnostic utility in focusing on the absence of resistance mutations to inform microbial cure with fluoroquinolone antimicrobials. We developed two proof-of-concept molecular tests that focus on detection of M. genitalium and characterization of WT parC sequences that are strongly linked to fluoroquinolone susceptibility. We screened a total of 227 M. genitalium-positive samples using novel molecular beacon and dual hybridization probe assays. These assays were able to detect M. genitalium and characterize fluoroquinolone susceptibility in 143/227 (63%) samples, based on clear differences in melting peak temperatures. The results of these molecular assays were in 100% agreement with 'gold standard' Sanger sequencing. Additionally, WT parC sequences were readily distinguished from M. genitalium samples harbouring parC mutations of known or suspected clinical significance. The ability of the assays to successfully characterize fluoroquinolone susceptibility and resistance was reduced in low M. genitalium load samples. These proof-of-concept assays have considerable potential to improve individualized treatment approaches and rationalize tests of cure for M. genitalium infection. The ability to initiate individualized treatment in up to two-thirds of cases will enhance antimicrobial stewardship for this challenging pathogen.


[Resection of carcinoid tumors of the small intestine is still indicated in the presence of disseminated hepatic metastases].
The authors report their experience with resection of small bowel carcinoid tumors associated with diffuse hepatic metastases. Nine patients were operated during the last ten years. A carcinoid syndrome was present biologically in every case and clinically in 8 cases. The tumor was removed in every case, either by right hemicolectomy (n = 6), or by small bowel resection (n = 3). Postoperative mortality and morbidity were nil. Adjuvant therapy included hepatic chemo-embolization and long-term therapy by a long-acting somatostatin analog. Five patients died during the period of follow-up and 4 patients were alive at the end of the study. Resection of small bowel carcinoid tumor is indicated even when the liver is involved by diffuse metastases to prevent the risk of small bowel occlusion, and to promote hepatic chemoembolization as subsequent therapy against the carcinoid syndrome and metastatic spread. Moreover, the procedure can participate in the selection of cases for orthotopic liver transplantation, when conservative therapy fails to control the carcinoid syndrome.


Characteristics of specific unresponsiveness toward kidney and skin allografts in adult rats inoculated at birth with allogenic bone marrow or kidney cells across a strong H-1 barrier.
Specific unresponsiveness inducible in newborn Lewis (Le) rats by injection of bone marrow or kidney cells from (Bu x Le)F1 hybrids was tested in adults by allografting of skin or kidneys from strongly incompatible Buffalo (Bu) strain donors. High doses of bone marrow cells (10(7) or more) proved quite effective in procuring indefinite survival of subsequent Bu kidney allografts, but not Bu skin allografts. Kidney allografts remained fully functional without modulation of their inherent immunogenicity regardless whether skin allografts were acutely rejected before or after kidney grafting on bone marrow-tolerant recipients. Lower doses of bone marrow cells were either near threshold for induction of specific Bu kidney allograft tolerance (5 x 10(6)) or, conversely, led to increased immunity(1-5 x 106). A strikingly different pattern of reactivity was found in adult Le recipients of Bu skin allografts as shown by only a moderate, but stepwise increase in survival times as a function of increasing allogeneic cell dosage at birth. Allogeneic kidney cells at all doses were surprisingly ineffective in inducing tolerance of either kidney or skin allografts, so the existence of kidney-specific transplantation antigens remains problematical. Lymphocytes from kidney allograft-tolerant recipients showed much reduced but still significant antidonor activity in several tests of cell-mediated immunity in vitro and in vivo. Blocking antibody activity was also demonstrable in these animals. Acquired tolerance (i.e., essential nonreactivity) may not only exist in degrees in either T or B cell pathways but may coexist with specific immunoblocking reactions in a dynamic equilibrium. Instead of tolerance versus enhancement, a new concept of selective specific immunoregulation emerges.


Adherence of alloreactive lymphocytes to human arterial endothelial cell monolayers.
Early events of cellular infiltration during allograft rejection involve interactions between alloreactive lymphocytes and vascular endothelium. These interactions have been studied in an in vitro model of lymphocyte adherence to human arterial endothelial cell (HAEC) monolayers. Alloreactive lymphocytes primed against donor HLA antigens (DPL) or unrelated HLA antigens from a third party (TPL) were studied for their adherence to HAEC derived from organ transplant donors. DPL exhibited a degree of adherence to donor HAEC which was nearly twice that of the TPL population and developed a morphologically blastoid appearance. DPL adherence was dependent on the recognition of donor HLA antigens expressed on the HAEC surface and investigation of DPL and TPL adherence at various lymphocyte concentrations showed that the binding of DPL and TPL to HAEC was saturable. Monoclonal antibody (MoAb) directed against HLA class I antigens showed inhibition of only DPL adherence to HAEC monolayers expressing donor class I HLA antigens, whereas MoAb directed against other HAEC surface antigens failed to inhibit either the DPL or TPL populations. The results of this study suggest that in a transplant situation, lymphocyte activation and adherence to the graft endothelium is increased in the context of allorecognition.


Physicians' beliefs about placebo and nocebo effects in antidepressants - an online survey among German practitioners.
While substantial placebo and nocebo effects have been documented in antidepressant clinical trials, physicians' awareness of the nonspecific effects in routine antidepressant treatment remains unclear. The study investigated physicians' beliefs and explanatory models regarding the desired effects and undesired side effects of antidepressants, with specific emphasis on nonspecific effects accounted for by placebo and nocebo mechanisms. An online survey was conducted among 87 physicians (40.2% psychiatrists, 25.3% neurologists, 24.1% general practitioners, 12.6% internists, 21.8% other). The survey assessed the physician's beliefs in antidepressant effectiveness, as well as 6 explanatory models regarding antidepressant effectiveness and 8 explanatory models for the occurrence of side effects. Most physicians (89.7%) believed in the effectiveness of antidepressants while acknowledging a considerable role of the placebo effect by attributing around 40% of the total effects to nonspecific factors. For both antidepressant effectiveness and the occurrence of side effects, pharmacological effects were rated as most important (93.1% and 80.5% agreement), but physicians also attributed a substantial role to the patients' expectations (63.2% and 58.6%) and experiences (60.9% and 56.3%). Concerning the physician's own role in promoting nonspecific effects in antidepressant effectiveness, highest endorsements were found for the quality of the physician-patient-relationship (58.6%) and own expectations (41.4%). When asked about side effects, fewer participants agreed that informing the patient about known side effects (25.2%) or the physicians' expectations themselves (17.2%) could induce side effects. Physicians, when prescribing antidepressants, are generally open towards nonspecific treatment mechanisms. However, they consider their own influence as less important than the patient's side, especially when it comes to the explanation of unwanted side effects. Awareness of the possible beneficial as well as malicious role of nonspecific mechanisms should be fostered as the first step towards optimizing antidepressant treatment by promoting placebo while avoiding nocebo effects.


Effect of fosfomycin alone and in combination with N-acetylcysteine on E. coli biofilms.
Four slime-producing uropathogenic Escherichia coli strains were used to investigate the activity of fosfomycin and N-acetylcysteine (NAC) against biofilms developed on 96-well polystyrene tissue culture plates. Biofilms aged, respectively, 5 (initial) and 48 h (mature) and two fosfomycin concentrations (128 and 2000 mg/l) were used. The effect of various levels (0.007-8 mg/ml) of NAC alone and in combination with fosfomycin on the formation or disruption of biofilms was assessed. Following exposure to the drugs, the percentage of residual slime relative to the control, ranged from 62.5-100 to 26.2-64.1% in the presence of 0.007 and 8 mg/ml of NAC. After treatment of pre-formed biofilms with NAC at the highest concentrations used, the remaining exopolysaccharide matrix was reduced to 25-68% of the amount found with the untreated control. Exposure to fosfomycin at 2000 mg/l reduced biofilms 40-57 and 41-49% for the initial and mature forms, respectively. Fosfomycin was more active at 2000 mg/l combined with NAC 2 mg/ml. Under these conditions initial and mature biofilms were reduced 66-80 and 60-73%, respectively. NAC, when used in combination, enhanced fosfomycin bactericidal activity producing a 99-99.9% reduction in viable cells. Fosfomycin and NAC at concentrations achievable in urine displayed a synergistic effect promoting both the formation of biofilms and reduction of sessile cell viability.


Elucidating Adsorptive Fractions of Natural Organic Matter on Carbon Nanotubes.
Natural organic matter (NOM) is a heterogeneous mixture of organic compounds that is omnipresent in natural waters. To date, the understanding of the adsorption of NOM components by carbon nanotubes (CNTs) is limited because of the limited number of comprehensive studies in the literature examining the adsorption of NOM by CNTs. In this study, 11 standard NOM samples from various sources were characterized, and their adsorption behaviors on four different CNTs were examined side-by-side using total organic carbon, fluorescence, UV-visible spectroscopy, and high-performance size-exclusion chromatography (HPSEC) analysis. Adsorption was influenced by the chemical properties of the NOM, including aromaticity, degree of oxidation, and carboxylic acidity. Fluorescence excitation-emission matrix (EEM) analysis showed preferential adsorption of decomposed and terrestrial-derived NOM compared to freshly produced and microbial-derived NOM. HPSEC analysis revealed preferential adsorption of fractions in the molecular weight range of 0.5-2 kDa for humic acids but in the molecular weight range of 1-3 kDa for all fulvic acids and reverse-osmosis isolates. However, the smallest characterized fraction (MW < 0.4 kDa) in all samples did not adsorb on the CNTs.


Screening, brief intervention, and referral to treatment: public health training for primary care.
The purpose of this study was to elucidate changes in attitudes, experiences, readiness, and confidence levels of medical residents to perform screening, brief intervention, and referral to treatment (SBIRT) and factors that moderate these changes. A cohort of 121 medical residents received an educational intervention. Self-reported experience, readiness, attitude, and confidence toward SBIRT-related skills were measured at baseline and at follow-up. Analyses were conducted to evaluate the effects of medical specialization. The intervention significantly increased experience (P<.001), attitude (P<.05), readiness (P<.001), and confidence (P<.001). Residents were more likely to report that their involvement influenced patients' substance use. However, experience applying SBIRT skills varied by country of birth, specialty, and baseline scores. This study suggested that SBIRT training was an effective educational tool that increased residents' sense of responsibility. However, application of skills might differ by specialization and other variables. Future studies are needed to explore and evaluate SBIRT knowledge obtained, within the context of cultural awareness and clinical skills.


Conjugated Polymeric Materials in Biological Imaging and Cancer Therapy.
Conjugated polymers (CPs) have attracted much attention in the fields of chemistry, medicine, life science, and material science. Researchers have carried out a series of innovative researches and have made significant research progress regarding the unique photochemical and photophysical properties of CPs, expanding the application range of polymers. CPs are polymers formed by the conjugation of multiple repeating light-emitting units. Through precise control of their structure, functional molecules with different properties can be obtained. Fluorescence probes with different absorption and emission wavelengths can be obtained by changing the main chain structure. By modifying the side chain structure with water-soluble groups or selective recognition molecules, electrostatic interaction or specific binding with specific targets can be achieved; subsequently, the purpose of selective recognition can be achieved. This article reviews the research work of CPs in cell imaging, tumor diagnosis, and treatment in recent years, summarizes the latest progress in the application of CPs in imaging, tumor diagnosis, and treatment, and discusses the future development direction of CPs in cell imaging, tumor diagnosis, and treatment.


Short-term clinical importance of osseous injuries diagnosed at MR imaging in patients with anterior cruciate ligament tear.
To determine the association between osseous injuries and short-term clinical outcome in patients with anterior cruciate ligament (ACL) tear. The retrospective study was performed with institutional review board approval, and the requirement to obtain informed consent was waived. The study group consisted of 114 patients (57 male and 57 female patients with a mean age of 26.1 and 25.1 years, respectively) with ACL tear who underwent magnetic resonance (MR) imaging and ACL reconstruction surgery and who filled out International Knee Documentation Committee (IKDC) knee evaluation questionnaires before and 1 year after surgery. All MR images were independently reviewed by two radiologists to determine the presence of a cortical depression fracture on each surface of the knee joint. Bone marrow edema volume was quantified by using segmentation software. Correlation coefficients were used to determine the association between bone marrow edema volume and IKDC score. A multivariate analysis model was used to compare IKDC scores in patients without fracture, patients with a single fracture, and patients with multiple fractures. There was no significant association between total bone marrow edema volume and preoperative or postoperative IKDC score (P = .32 and P = .91, respectively). The mean preoperative and postoperative IKDC scores were 53.4 ± 18.6 and 93.0 ± 5.0, respectively, for patients without fracture, 54.8 ± 13.6 and 87.3 ± 10.8 for patients with a single fracture, and 53.1 ± 17.2 and 83.4 ± 12.7 for patients with multiple fractures. Patients with single and multiple fractures had similar (P = .91) preoperative IKDC scores but significantly lower (P < .001) postoperative IKDC scores compared to patients without fracture. Cortical depression fractures in patients with ACL tear are associated with decreased clinical outcome scores 1 year after ACL reconstruction surgery.


Validated quantitation of underivatized amino acids in human blood samples by volatile ion-pair reversed-phase liquid chromatography coupled to isotope dilution tandem mass spectrometry.
Quantitation of amino acids in complex matrixes without derivatization is advantageous; however, difficulties exist in both the separation and the detection of those compounds. A validated method that is based on the use of volatile ion-pair liquid chromatography coupled to stable isotope dilution tandem mass spectrometry has been developed for the simple and accurate quantitation of underivatized amino acids in biological samples. Sufficient separation of 22 underivatized amino acids was achieved on a C18 column in 36 min using perfluoroheptanoic acid (PFHA) and trifluoroacetic acid (TFA) as mobile phase modifiers. The collisionally activated dissociation spectra of the amino acids were investigated and the transitions of [M + H]+ --> [M + H - 46]+, which are specific to alpha-amino acids, were used for the detection of most amino acids and their stable isotopes. The calibration curves were linear over the range of 0.10-100 microg/mL, and the detection limits were 0.03-20 pmol on column. The quantitative results by this method were compared with those by an established OPA-derivatization HPLC method in the assay of 8 human serum samples, and better recovery and precision data of this method were observed. The method was also applied to the neonatal screening for phenylketonuria (PKU) with dry blood spots, and the results were satisfactory. This is the first time that all proteinogenic amino acids have been quantified directly from biological extracts without any kind of derivaization. The technique shows potential for routine determination of amino acids and analogous compounds in complex matrixes.


Amolimogene bepiplasmid, a DNA-based therapeutic encoding the E6 and E7 epitopes from HPV, for cervical and anal dysplasia.
MGI Pharma Biologics is developing amolimogene bepiplasmid as a potential therapy for HPV-associated diseases, including cervical dysplasia. Amolimogene bepiplasmid is a polymer-encapsulated DNA vaccine consisting of a plasmid expressing a chimeric peptide comprising immunogenic hybrid epitopes from HPV-16 and HPV-18 E6 and E7 proteins and an HLA-DRalpha intracellular trafficking peptide. In phase I and I/II clinical trials of ZYC-101 (the precursor of amolimogene bepiplasmid containing a single epitope from HPV-16 E7) in patients with cervical dysplasia and patients with anal dysplasia, ZYC-101 produced significant histological regression and was safe and well tolerated. Results from this trial led to a phase II clinical trial of amolimogene bepiplasmid in patients with cervical dysplasia. This phase II trial demonstrated that treatment with amolimogene bepiplasmid resolution of disease was not significantly superior to placebo except in the predefined group of women who were less than 25 years of age. A phase II/III clinical trial was ongoing at the time of publication examining amolimogene bepiplasmid in this patient population.


Structural, electronic and kinetic properties of the phase-change material Ge2Sb2Te5 in the liquid state.
Phase-change materials exhibit fast and reversible transitions between an amorphous and a crystalline state at high temperature. The two states display resistivity contrast, which is exploited in phase-change memory devices. The technologically most important family of phase-change materials consists of Ge-Sb-Te alloys. In this work, we investigate the structural, electronic and kinetic properties of liquid Ge2Sb2Te5 as a function of temperature by a combined experimental and computational approach. Understanding the properties of this phase is important to clarify the amorphization and crystallization processes. We show that the structural properties of the models obtained from ab initio and reverse Monte Carlo simulations are in good agreement with neutron and X-ray diffraction experiments. We extract the kinetic coefficients from the molecular dynamics trajectories and determine the activation energy for viscosity. The obtained value is shown to be fully compatible with our viscosity measurements.


HYBRID ZONES WITH DOBZHANSKY-TYPE EPISTATIC SELECTION.
Dobzhansky's model of epistatic selection assumes that viable genotypes form "clusters" in genotype space so that populations can evolve from one state to a reproductively isolated state following a "ridge" of well-fit genotypes without crossing any deep adaptive valleys. Recently, the importance of Dobzhansky-type models in evolutionary studies has been reemphasized by Gavrilets (1997a) and Gavrilets and Gravner (1997) who argue that the existence of "ridges" of well-fit genotypes connecting reproductively isolated genotypes is actually a general property of multidimensional adaptive landscapes. Using rigorous techniques and numerical simulations, I analyze clines in the frequencies of selected and neutral alleles maintained by a balance of migration and Dobzhansky-type epistatic selection acting on two diallelic loci. I show that Dobzhansky-type epistatic selection can build up a very strong barrier to neutral gene flow. I describe properties of clines that are indicative of Dobzhansky-type selection.


Detection of typhoid carriers by duodenal fluid culture in a tertiary care hospital, Karachi: A cross-sectional study.
We aimed to detect typhoid carriers by performing duodenal fluid culture in patients in a tertiary care hospital in Pakistan. A cross-sectional study was conducted during 2017 at the Aga Khan University Hospital, Karachi. Patients who underwent upper gastrointestinal endoscopy were included. Participants were interviewed, and duodenal fluid samples were taken for culture to detect Salmonella typhi (S. typhi) and paratyphi. A polymerase chain reaction on 100 randomly selected sub-samples was also conducted. A total of 477 participants were enrolled. The mean age was 42.4±15.5 years. History of typhoid fever was present in 73 (15.3%) participants. Out of the 477 duodenal fluid cultures tested for various micro-organisms, 250 (52.4%) were positive. Neither S. typhi nor paratyphi were isolated. S. typhi was also not detected by PCR. To better detect S. typhi carriage in general population, future studies should target people with gall bladder diseases and screen them using culture and PCR based methods.


[Clinical evaluation in 69 cases with neurogenic bladder].
Clinical evaluation was made in 69 cases of neurogenic bladder experienced during the past 3 years. Thirty seven of the patients were male and 32 female, and they ranged in age from 4 to 88 years with an average of 63.2 years, The basic diseases of neurogenic bladder were brain lesions in 27 cases, spinal cord lesions in 18 cases, and peripheral nerve lesions in 13 cases. Three cases were of the mixed type and the basic disease was unknown in 8 cases. Cerebrovascular diseases were the most frequent, followed by spinal cord injuries and intrapelvic operations. Duration from the onset of urological symptoms to the first visit to our clinic was less than 1 month in half of the patients. The chief complaints at the first visit were pollakisuria in 25 cases (25.8%), incontinence in 18 cases (18.6%), urinary difficulty in 25 cases (25.8%) and urinary retention in 13 cases (13.4%). Urological conditions at the first visit were spontaneous urination in 53 cases (76.8%), indwelling catheterization in 12 cases (17.4%) and clean intermittent catheterization in 4 cases (5.8%). Urological complications seen at the first examination were urinary tract infections (UTI) in 27 cases (39.1%) and chronic renal failure in 2 cases (2.9%). The patients were classified by cystometrography into 3 patterns: 42 cases (60.9%) with underactive detrusor, 21 cases (30.4%) with overactive detrusor and 6 cases (8.7%) with normal detrusor. Detrusor sphincter dyssynergia was observed in 29 cases (42.0%), 40.7% had brain lesions, 44.4% spinal cord lesions, and 46.2% peripheral nerve lesions.(ABSTRACT TRUNCATED AT 250 WORDS)


Health and health care access among California women ages 50-64.
This policy brief examines the health issues and health care access of women ages 50-64.While the need for effective and accessible health care applies to all women, there are distinct social, economic and health issues within each age group. Women ages 50-64 often face new and accelerated health issues and have more concern for management of health conditions. Using data from the 2007 California Health Interview Survey (CHIS 2007) this brief examines several of the health issues for women in this age group and the role of health insurance coverage.


Density-functional description of water condensation in proximity of nanoscale asperity.
We apply nonlocal density-functional formalism to describe an equilibrium distribution of the waterlike fluid in the asymmetric nanoscale junction presenting an atomic force microscope tip dwelling above an arbitrary surface. The hydrogen bonding dominating in intermolecular attraction is modeled as a square-well potential with two adjustable parameters (energy and length) characterizing well's depth and width. A liquid meniscus formed inside the nanoscale junction is explicitly described for different humidity. Furthermore, we suggest a simple approach using polymolecular adsorption isotherms for the evaluation of an energetic parameter characterizing fluid (water) attraction to substrate. This model can be easily generalized for more complex geometries and effective intermolecular potentials. Our study establishes a framework for the density-functional description of fluid with orientational anisotropy induced by nonuniform external electric field.


[The secret of red eyes].
"Red eye" is a sign and the same time a symptom frequently met in the ophthalmological practice. The "red eye" is not always the clinical manifestation of a common conjunctivitis. We will present a case report of a patient who accused conjunctival hyperemia, lacrimation, foreign--body sensation; she was also describing recurrent conjunctivitis for the past year. After an detailed ophthalmologic examination and interdisciplinary consultations. She was diagnosed with Basedow Disease and paraselar meningioma with invasion in the pterigoid fossa. The authors are suggesting that there is an indirect left carotid - cavernous fistula.


Simultaneous quantification of vortioxetine, carvedilol and its active metabolite 4-hydroxyphenyl carvedilol in rat plasma by UPLC-MS/MS: Application to their pharmacokinetic interaction study.
To establish a rapid and sensitive ultra performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS) method for the determination of vortioxetine, carvedilol and its metabolite 4-hydroxyphenyl carvedilol in rat plasma. The analytes and the internal standard (diazepam) were separated on an Acquity UPLC BEH C18 chromatography column (2.1mm×50mm, 1.7μm) using gradient elution with a mobile phase of acetonitrile and 0.1% formic acid in water at a flow rate of 0.4mL/min. The detection was performed on a triple quadrupole tandem mass spectrometer by multiple reaction monitoring (MRM) mode to monitor the precursor-to-product ion transitions of m/z 299.2→150.1 for vortioxetine, m/z 407.2→100.3 for carvedilol, m/z 423.2→100.1 for 4-hydroxyphenyl carvedilol and m/z 285.2→193.1 for diazepam (IS) using a positive electrospray ionization interface. The method was validated over a concentration range of 0.5-100ng/mL for vortioxetine, 0.5-1000ng/mL for carvedilol and 0.1-50ng/mL for 4-hydroxyphenyl carvedilol. Total time for each chromatograph was 3.0min. The intra- and inter-day precision and accuracy of the quality control samples at low, medium, and high concentration levels exhibited relative standard deviations (RSD)<11.6% and the accuracy values ranged from -12.2% to 11.3%. The analytical method was successfully applied to a pharmacokinetic interaction study of vortioxetine and carvedilol after oral administration vortioxetine and carvedilol in rats. Results suggested that the co-administration of vortioxetine and carvedilol results in a significant drug interaction in rats.


Combined preauricular, retroauricular bilobed flap for earlobe reconstruction.
The earlobe is an important anatomical structure that has a significant role in aesthesis. An absent ear lobule may be congenital or acquired due to the result of trauma, infection or malignancy. Its surgical repair places a challenge due to the difficulty of obtaining a natural-appearing and durable outcome. Many procedures have been described for reconstruction including the Gavello and Zenteno Alanis techniques. We have described a new method which is single staged, easy to perform and aesthetically acceptable.


Electrochemical performance of porous diamond-like carbon electrodes for sensing hormones, neurotransmitters, and endocrine disruptors.
Porous diamond-like carbon (DLC) electrodes have been prepared, and their electrochemical performance was explored. For electrode preparation, a thin DLC film was deposited onto a densely packed forest of highly porous, vertically aligned multiwalled carbon nanotubes (VACNT). DLC deposition caused the tips of the carbon nanotubes to clump together to form a microstructured surface with an enlarged surface area. DLC:VACNT electrodes show fast charge transfer, which is promising for several electrochemical applications, including electroanalysis. DLC:VACNT electrodes were applied to the determination of targeted molecules such as dopamine (DA) and epinephrine (EP), which are neurotransmitters/hormones, and acetaminophen (AC), an endocrine disruptor. Using simple and low-cost techniques, such as cyclic voltammetry, analytical curves in the concentration range from 10 to 100 μmol L(-1) were obtained and excellent analytical parameters achieved, including high analytical sensitivity, good response stability, and low limits of detection of 2.9, 4.5, and 2.3 μmol L(-1) for DA, EP, and AC, respectively.


[Nursing care of patients with acute pulmonary edema].
Nursing care of patients with acute lung edema is vital, as well as their timely diagnosis and treatment. The nurse, through the corresponding evaluation, diagnoses and accelerates the treatment avoiding death of the patient by detecting the event appropriately and providing treatment to stabilize the patient. The care of a multidisciplinary medical team is required to solve this emergency that can be of cardiogenic or non-cardiogenic origin. Injury of the capillary endothelium and blockade of lymphatic vessels are its main causes. In acute lung edema occurs and accumulation of serous liquid in the alveoli of the lung, which produces severe hypoxia. Nurse interventions, in order of priorities, are aimed primarily at resolving, the oxygenation needs of the patient.


Embolization Tactics of Spinal Epidural Arteriovenous Fistulas.
Spinal epidural arteriovenous fistulas (SEDAVFs) show an epidural venous sac often with venous congestive myelopathy (VCM) due to intradural reflux at a remote level to which a transarterial approach would be difficult. We present 12 cases of SEDAVF with VCM and describe 3 main tactics for effective transarterial embolization. Among 152 patients with spinal vascular malformations diagnosed in our tertiary hospital between 1993 and 2019, 12 SEDAVF patients with VCM were included. Three different transarterial embolization tactics were applied according to the vascular configuration and microcatheter accessibility. We evaluated treatment results and clinical outcomes before and after treatment. Transarterial embolization with glue (20-30%) was performed in all patients. The embolization tactics applied in 12 patients were preferential flow (n=2), plug-and-push (n=6), and filling of the venous sac (n=4). Total occlusion of the SEDAVF, including intradural reflux, was achieved in 11 (91.7%) of 12 patients, and partial occlusion was achieved in 1 patient. No periprocedural complications were reported. Spinal cord edema was improved in all patients for an average of 18 months after treatment. Clinical functional outcome in terms of the pain, sensory, motor, and sphincter scale and modified Rankin scores improved during a mean 25-month follow-up (6.3 vs. 3.3, P=0.002; 3.6 vs. 2.3, P=0.002, respectively). Endovascular treatment for 12 SEDAVF patients with VCM achieved a total occlusion rate of 91.7% without any periprocedural complication. The combined embolization tactics can block intradural reflux causing VCM, resulting in overall good clinical outcomes.


The role of drugs in the treatment of alcoholism.
Many drugs are used in alcoholism treatment with the aim of reducing alcohol consumption and correcting alcohol-related psychosocial problems that lead to excessive drinking or result from it. Alcohol-sensitising drugs are used to reduce alcohol consumption with the expectation that improvement in other problem areas will follow. Drugs that share sedative-hypnotic actions with and cross-dependence to alcohol are often used during acute alcohol withdrawal reactions for symptomatic relief, to prevent major withdrawal symptoms, and to prevent and treat seizures. Alcohol abuse may be a form of self-medication, and treatment of an underlying psychiatric disorder, such as depression (with antidepressants), anxiety (with anxiolytics) or psychosis (with antipsychotics), is expected to reduce alcohol consumption. Pretreatment medical and psychiatric assessment of the patient is necessary to ensure that the drug therapy is appropriate to the patient's therapeutic goals and medical/psychological status. Use of the drug must be systematic and carefully monitored; the duration of treatment is determined individually for each patient on the basis of the response to the treatment as well by the development of adverse clinical effects. Ideally, the drug therapy allows the patient to establish resources necessary for continued abstinence after the drug treatment is stopped.


Vitamin D Serum Levels in Type 2 Diabetic Patients: A Cross-Sectional Study.
Background and objective Type 2 diabetes mellitus (T2DM) is a chronic metabolic disorder characterized by hyperglycemia. It is linked with an increase in morbidity (e.g., blindness, kidney failure, stroke, cardiovascular diseases, limb amputations), premature mortality, high healthcare costs, and is quickly becoming a global epidemic disorder. Several studies have shown that vitamin D supplements reduce insulin resistance in T2DM and improve insulin secretion and sensitivity. In this study, we aimed to determine the prevalence of vitamin D deficiency in T2DM patients in Saudi Arabia. Methods This was a retrospective cross-sectional study conducted at the King Faisal University Health Centre in Saudi Arabia. The study used patient data during the period from October 2014 to January 2021. After obtaining approval from the King Faisal University Polyclinic Administration, we collected patient data from the King Faisal University Health Centre. The Ethics and Research Committee at the College of Medicine of King Faisal University granted ethical approval with the approval number (2020-11-82). The relevant patient data were collected, including age, gender, nationality, and blood test findings (vitamin D and HbA1c levels). Results A total of 191 T2DM patients participated in this study. The mean age of the patients was 56.1 ± 11.4 years (range: 21-85 years); 107 (56%) patients were females, and 137 (71.7%) were Saudis. There were 134 (70.2%) patients with vitamin D deficiency, 53 (27.7%) with vitamin D insufficiency, and only four (2.1%) with normal vitamin D levels. Conclusion Based on our findings, the prevalence of vitamin D deficiency among T2DM patients is highly associated with poor diabetic control.


Molecular response to nilotinib in a patient with imatinib-intolerant e19a2-positive chronic myeloid leukemia.
The BCR-ABL1 fusion gene is the molecular marker of chronic myeloid leukemia (CML). The e19a2 transcript is a rare variant associated with various clinical presentations and courses of CML. We herein present a case of e19a2-positive CML who was intolerant to initial treatment with imatinib and successfully responded to subsequent nilotinib therapy. She achieved a major molecular response and has since be able to sustain it. According to the literature, achieved molecular response by imatinib monotherapy has not yet been reported in e19a2-positive CML patients. Second generation tyrosine kinase inhibitors may therefore be a more effective treatment for e19a2-positive CML patients.


[Hematologic and surgical problems connected with splenectomy in elderly patients].
The authors carried out a clinical analysis of problems connected with splenectomy in elderly patients treated surgically at the Institute of Haematology in the years 1965-1972. Out of 24 patients aged above 60 years 12 were analysed clinically (8 females and 4 males). Splenectomy was done in these patients from haematological indications (haemolytic anaemia, thrombocytopenia, pancytopenia). In all these cases indications to splenectomy, the course of operation and postoperative period as well as late therapeutic results were assessed. The analysis of these elderly patients showed that the criteria of indications for splenectomy were the same as in other age groups. The choice of surgical method depended in these cases on the clinical and haematological findings, a lack of permanent improvement after conservative treatment, contraindications to immunosuppressive treatment and results of isotope investigations (particularly the values of the spleen-liver index). In most splenectomized patients there were no complications during the operation and in the postoperative period. In 2 cases only acute circulatory failure was observed immediately after the operation. Evaluation of late results showed that the effects of the operation were similar to those in other age groups.


Overexpression of ezrin and galectin-3 as predictors of poor prognosis of cervical cancer.
The aim of this study was to explore the correlation of ezrin and galectin-3 expressions with prognosis in cervical cancer. The immunohistochemical method was applied to detect ezrin and galectin-3 expressions in normal cervix tissues (n=30), cervicitis tissues (n=28), cervical intraepithelial neoplasia (CIN) tissues (classified as I-III, n=89), and cervical carcinoma tissues (n=84). Follow-up was conducted for 5 to 78 months to analyze the correlation of protein expressions with prognosis. Ezrin and galectin-3 expressions in cervical cancer were significantly higher than in normal cervix, cervicitis and CIN (all P<0.05), and expressions in CIN were significantly higher than in normal cervix and cervicitis (both P<0.05). The expressions of ezrin and galectin-3 were both related with histological grade, deep myometrial invasion and lymph node metastasis (all P<0.05). Spearman analysis showed that ezrin expression was positively correlated with galectin-3 expression in cervical cancer (r=0.355, P<0.05). The survival rate of patients with high expressions of ezrin and galectin-3 was significantly lower than those with low expressions of proteins (both P<0.05). The expressions of ezrin and galectin-3, histological grade, depth of stromal invasion, and lymph node metastasis are risk factors affecting the survival rate of patients with cervical cancer. The expressions of ezrin and galectin-3 were correlated with the development of cervical cancer, and overexpressions of those proteins were indicative of poor prognosis in patients with cervical cancer.


Multi-crystal native SAD analysis at 6 keV.
Anomalous diffraction signals from typical native macromolecules are very weak, frustrating their use in de novo structure determination. Here, native SAD procedures are described to enhance signal to noise in anomalous diffraction by using multiple crystals in combination with synchrotron X-rays at 6 keV. Increased anomalous signals were obtained at 6 keV compared with 7 keV X-ray energy, which was used for previous native SAD analyses. A feasibility test of multi-crystal-based native SAD phasing was performed at 3.2 Å resolution for a known tyrosine protein kinase domain, and real-life applications were made to two novel membrane proteins at about 3.0 Å resolution. The three applications collectively serve to validate the robust feasibility of native SAD phasing at lower energy.


Dual structures of chaos and turbulence, and their dynamic scaling laws.
The decay form of the time correlation function Un(t) of a state variable un(t) with a small wave number kn has been shown to take the algebraic decay 1/{1+(gammanat)2} in the initial regime t<taun(gamma) and the exponential decay alphane exp(-gammanet) in the final regime t>taun(gamma), where taun(gamma) denotes the decay time of the memory function Gamman(t). This dual structure of Un(t) is generated by the deterministic short orbits in the initial regime and the stochastic long orbits in the final regime, thus giving the outstanding features of chaos and turbulence. The kn dependence of gammana, alphane, and gammane is obtained for the chaotic Kuramoto-Sivashinsky equation, and it is shown that if kn is sufficiently small, then the dual structure of Un(t) obeys a hydrodynamic scaling law in the final regime t>tau(gamma) with scaling exponent z=2 and a dynamic scaling law in the initial regime t<taun(gamma) with scaling exponent z=1. If kn is increased so that the decay time taun(u) of Un(t) becomes equal to the decay time taun(gamma), then the decay form of Un(t) becomes the power-law decay t-3/2 in the final regime.


Selecting the appropriate digital planning pathway for computer-guided implant surgery.
The incorporation of virtual engineering into our profession and the digitalization of information are allowing us new perspectives and innovative alternatives for dental treatment modalities. The use of computer-guided implant-planning software allows the radiographic, prosthetic, surgical, and laboratory fields to be combined under a common virtual scenario, permitting complete virtual treatment planning. Different alternatives for the digital workflow have been described for computer-guided implant placement. In this article, we present a recommendation for selecting the appropriate digital workflow depending on the clinical situation to achieve precise computer-guided implant planning and a predictable treatment outcome.


Single-cycle gap soliton in a subwavelength structure.
We demonstrate that a single subcycle optical pulse can be generated when a pulse with a few optical cycles penetrates through resonant two-level dense media with a subwavelength structure. The single-cycle gap soliton phenomenon in the full Maxwell-Bloch equations without the frame of the slowly varying envelope and rotating wave approximations is observed. Our study shows that the subwavelength structure can be used to suppress the frequency shift caused by intrapulse four-wave mixing in continuous media and supports the formation of single-cycle gap solitons even in the case when the structure period breaks the Bragg condition. This suggests a way toward shortening high-intensity laser fields to few- and even single-cycle pulse durations.


Inheritance of apospory in bahiagrass, Paspalum notatum.
Previous studies on the inheritance of aposporous apomixis in bahiagrass showed a wide range of segregation ratios in crosses involving sexual and aposporous apomictic plants. The F1 progenies were classified through a visual progeny test carried out on few F2 plants. The number of sexual F1s highly exceeded the apomictics leading to the conclusion that apomixis was controlled by a few recessive genes. The present study examines the inheritance of apospory in bahiagrass. A sexual plant was self-pollinated and crossed with an aposporous apomictic plant as pollen donor. Backcross and F2 progenies were obtained in several combinations. All self-pollinated sexual plants or sexual x sexual crosses produced progenies free of apospory. All crosses involving a sexual and an apomictic plant produced approximately three times more apospory-free plants than plants with apospory. Bahiagrass is of autotetraploid origin and hence is expected to display tetrasomic inheritance. The most widely accepted genetic model for inheritance of apospory in tropical grasses is a single dominant gene with tetrasomic inheritance. In the present experiments none of the apospory-free F1s segregated for the apospory trait indicating that it is most likely a dominant character. However, the observed results fit better a modified model: tetrasomic inheritance of a single dominant gene with pleiotropic effect and incomplete penetrance. The excess of apospory-free plants in the F1 progeny could be ascribed to some distortion in the segregation pattern due to a pleiotropic lethal effect of the dominant A allele with incomplete penetrance. Alternatively, partial lethality of factors linked to aposporous gene may account for segregation distortion against apospory.


Laparoscopic entry techniques.
Laparoscopy is a common procedure in many surgical specialties. Complications arising from laparoscopy are often related to initial entry into the abdomen. Life-threatening complications include injury to viscera (e.g. bowel, bladder) or to vasculature (e.g. major abdominal and anterior abdominal wall vessels). No clear consensus has been reached as to the optimal method of laparoscopic entry into the peritoneal cavity. To evaluate the benefits and risks of different laparoscopic entry techniques in gynaecological and non-gynaecological surgery. We searched the Cochrane Gynaecology and Fertility (CGF) Group trials register, CENTRAL, MEDLINE, Embase, PsycINFO, and trials registers in January 2018. We also checked the references of articles retrieved. We included randomised controlled trials (RCTs) that compared one laparoscopic entry technique versus another. Primary outcomes were major complications including mortality, vascular injury of major vessels and abdominal wall vessels, visceral injury of bladder or bowel, gas embolism, solid organ injury, and failed entry (inability to access the peritoneal cavity). Secondary outcomes were extraperitoneal insufflation, trocar site bleeding, trocar site infection, incisional hernia, omentum injury, and uterine bleeding. Two review authors independently selected studies, assessed risk of bias, and extracted data. We expressed findings as Peto odds ratios (Peto ORs) with 95% confidence intervals (CIs). We assessed statistical heterogeneity using the I² statistic. We assessed the overall quality of evidence for the main comparisons using GRADE methods. The review included 57 RCTs including four multi-arm trials, with a total of 9865 participants, and evaluated 25 different laparoscopic entry techniques. Most studies selected low-risk patients, and many studies excluded patients with high body mass index (BMI) and previous abdominal surgery. Researchers did not find evidence of differences in major vascular or visceral complications, as would be anticipated given that event rates were very low and sample sizes were far too small to identify plausible differences in rare but serious adverse events.Open-entry versus closed-entryTen RCTs investigating Veress needle entry reported vascular injury as an outcome. There was a total of 1086 participants and 10 events of vascular injury were reported. Four RCTs looking at open entry technique reported vascular injury as an outcome. There was a total of 376 participants and 0 events of vascular injury were reported. This was not a direct comparison. In the direct comparison of Veress needle and Open-entry technique, there was insufficient evidence to determine whether there was a difference in rates of vascular injury (Peto OR 0.14, 95% CI 0.00 to 6.82; 4 RCTs; n = 915; I² = N/A, very low-quality evidence). Evidence was insufficient to show whether there were differences between groups for visceral injury (Peto OR 0.61, 95% CI 0.06 to 6.08; 4 RCTs; n = 915: I² = 0%; very low-quality evidence), or failed entry (Peto OR 0.45, 95% CI 0.14 to 1.42; 3 RCTs; n = 865; I² = 63%; very low-quality evidence). Two studies reported mortality with no events in either group. No studies reported gas embolism or solid organ injury.Direct trocar versus Veress needle entryTrial results show a reduction in failed entry into the abdomen with the use of a direct trocar in comparison with Veress needle entry (OR 0.24, 95% CI 0.17 to 0.34; 8 RCTs; N = 3185; I² = 45%; moderate-quality evidence). Evidence was insufficient to show whether there were differences between groups in rates of vascular injury (Peto OR 0.59, 95% CI 0.18 to 1.96; 6 RCTs; n = 1603; I² = 75%; very low-quality evidence), visceral injury (Peto OR 2.02, 95% CI 0.21 to 19.42; 5 RCTs; n = 1519; I² = 25%; very low-quality evidence), or solid organ injury (Peto OR 0.58, 95% Cl 0.06 to 5.65; 3 RCTs; n = 1079; I² = 61%; very low-quality evidence). Four studies reported mortality with no events in either group. Two studies reported gas embolism, with no events in either group.Direct vision entry versus Veress needle entryEvidence was insufficient to show whether there were differences between groups in rates of vascular injury (Peto OR 0.39, 95% CI 0.05 to 2.85; 1 RCT; n = 186; very low-quality evidence) or visceral injury (Peto OR 0.15, 95% CI 0.01 to 2.34; 2 RCTs; n = 380; I² = N/A; very low-quality evidence). Trials did not report our other primary outcomes.Direct vision entry versus open entryEvidence was insufficient to show whether there were differences between groups in rates of visceral injury (Peto OR 0.13, 95% CI 0.00 to 6.50; 2 RCTs; n = 392; I² = N/A; very low-quality evidence), solid organ injury (Peto OR 6.16, 95% CI 0.12 to 316.67; 1 RCT; n = 60; very low-quality evidence), or failed entry (Peto OR 0.40, 95% CI 0.04 to 4.09; 1 RCT; n = 60; very low-quality evidence). Two studies reported vascular injury with no events in either arm. Trials did not report our other primary outcomes.Radially expanding (STEP) trocars versus non-expanding trocarsEvidence was insufficient to show whether there were differences between groups in rates of vascular injury (Peto OR 0.24, 95% Cl 0.05 to 1.21; 2 RCTs; n = 331; I² = 0%; very low-quality evidence), visceral injury (Peto OR 0.13, 95% CI 0.00 to 6.37; 2 RCTs; n = 331; very low-quality evidence), or solid organ injury (Peto OR 1.05, 95% CI 0.07 to 16.91; 1 RCT; n = 244; very low-quality evidence). Trials did not report our other primary outcomes.Other studies compared a wide variety of other laparoscopic entry techniques, but all evidence was of very low quality and evidence was insufficient to support the use of one technique over another. Overall, evidence was insufficient to support the use of one laparoscopic entry technique over another. Researchers noted an advantage of direct trocar entry over Veress needle entry for failed entry. Most evidence was of very low quality; the main limitations were imprecision (due to small sample sizes and very low event rates) and risk of bias associated with poor reporting of study methods.


Clinical manifestation score and characterization of cytokines and lymphocytes of dimethylacetamide-induced toxic hepatitis in spandex workers.
Occupational exposure to dimethylacetamide (DMAc) has been reported to cause toxic hepatitis. Sixty spandex workers were included in this study to research the clinical manifestations and expression of cytokines and lymphocytes in DMAc-induced toxic hepatitis. Chinese drugs (reduced glutathione and Hugan tablets) were used to treat them. The manifestations including jaundice, asthenia, appetite, nausea, emesis, abdominal distension, yellow urine, and dizziness were scored. The percentages of patients rated as 0-3, 4-6, 7-9, and 10-12 points were 33.3%, 43.3%, 21.7%, and 1.7%, respectively, before treatment, and all patients showed 0-3 points after the treatment. The ultrasonic and CT imaging revealed diffuse intrahepatic hypodensity, intrahepatic calcification, signs of liver injury, and splenomegaly, which improved after therapy. Blood analysis showed that ALT, AST, TBIL, IL-6, IL-10, TNF-α, IFN-γ, CD3+%, and CD4+/CD8+ statistically decreased after drug treatment. Correlation analysis demonstrated positive linear correlations between ALT and TBIL, AST and TBIL, IL-10 and ATL, IL-10 and AST, IL-10 and TBIL, IFN-γ and IL-6, IFN-γ and TNF-α, and CD3+% and ALT. Pro-inflammatory cytokines and lymphocytes in DMAc-induced toxic hepatitis reflected an active immune state that decreased after treatment. IL-10 may inhibit the immune response in this disease, as a protective mechanism.


Modafinil Improves Episodic Memory and Working Memory Cognition in Patients With Remitted Depression: A Double-Blind, Randomized, Placebo-Controlled Study.
Cognitive dysfunction is a core feature of depression and tends to persist even after mood symptoms recover, leading to detrimental effects on clinical and functional outcomes. However, most currently available treatments have not typically addressed cognition. Modafinil has been shown to have beneficial effects on cognitive function and therefore has the potential to improve cognition in depression. The objective of this double-blind, placebo-controlled study was to investigate the effects of modafinil on cognitive functions in patients with remitted depression. In total, 60 patients with remitted depression participated in the study. Cognitive functions were evaluated with tests of working memory, planning, attention, and episodic memory from the Cambridge Neuropsychological Test Automated Battery at the baseline session and after treatment. A double-blind, randomized, placebo-controlled, parallel groups design was used to assess the effects of single-dose (200 mg) modafinil (n = 30) or placebo (n = 30) on cognition and fatigue. The main outcome measures were neurocognitive test scores from the Cambridge Neuropsychological Test Automated Battery. Visual analogue scales for subjective feelings and fatigue were used as secondary measures. The modafinil group had significantly better performance on tests of episodic memory (p = .01, ηp2 = .10) and working memory (p = .04, ηp2 = .06). Modafinil did not improve planning or sustained attention. This study suggested that modafinil (200 mg) could improve episodic memory and working memory performance in patients with remitted depression. Modafinil may have potential as a therapeutic agent to help remitted depressed patients with persistent cognitive difficulties.


Depression of home cage wheel running is an objective measure of spontaneous morphine withdrawal in rats with and without persistent pain.
Opioid withdrawal in humans is often subtle and almost always spontaneous. In contrast, most preclinical studies precipitate withdrawal by administration of an opioid receptor antagonist such as naloxone. These animal studies rely on measurement of physiological symptoms (e.g., wet dog shakes) in the period immediately following naloxone administration. To more closely model the human condition, we tested the hypothesis that depression of home cage wheel running will provide an objective method to measure the magnitude and duration of spontaneous morphine withdrawal. Rats were allowed access to a running wheel in their home cage for 8days prior to implantation of two 75mg morphine or placebo pellets. The pellets were removed 3 or 5days later to induce spontaneous withdrawal. In normal pain-free rats, removal of the morphine pellets depressed wheel running for 48h compared to rats that had placebo pellets removed. Morphine withdrawal-induced depression of wheel running was greatly enhanced in rats with persistent inflammatory pain induced by injection of Complete Freund's Adjuvant (CFA) into the hindpaw. Removal of the morphine pellets following 3days of treatment depressed wheel running in these rats for over 6days. These data demonstrate that home cage wheel running provides an objective and more clinically relevant method to assess spontaneous morphine withdrawal compared to precipitated withdrawal in laboratory rats. Moreover, the enhanced withdrawal in rats with persistent inflammatory pain suggests that pain patients may be especially susceptible to opioid withdrawal.