A recurrent mutation in the tyrosine kinase domain of fibroblast growth factor receptor 3 causes hypochondroplasia.
Hypochondroplasia (MIM 146000) is an autosomal dominant skeletal dysplasia with skeletal features similar to but milder than those seen in achondroplasia. Within the past year, the achondroplasia locus has been mapped to 4p 16.3 (refs 5-7) and mutations in the fibroblast growth factor receptor 3 (FGFR3) gene have been identified in patients with the disorder. More than 95% of 242 cases reported so far are accounted for by a single Gly380Arg mutation. McKusick et al. proposed that achondroplasia and hypochondroplasia are allelic based on the similarities in phenotype between the two disorders and the identification of a severely dwarfed individual whose father had achondroplasia and whose mother had hypochondroplasia. There is also genetic linkage evidence that hypochondroplasia and achondroplasia map to the same locus. We therefore began a systematic screening of FGFR3 to detect mutations in patients with hypochondroplasia. We now report a single FGFR3 mutation found in 8 out of 14 unrelated patients with hypochondroplasia. This mutation causes a C to A transversion at nucleotide 1620, resulting in an Asn540Lys substitution in the proximal tyrosine kinase domain.


Developmental Trajectories of Adolescent Girls' Borderline Personality Symptoms and Sexual Risk Behaviors.
Adolescence is a developmental period during which youth tend to initiate sexual behavior, which may include sexual risk behavior. Symptoms of borderline personality disorder (BPD) are associated with increased rates of risky behaviors. However, little is known about longitudinal associations between BPD symptoms and sexual risk behaviors during adolescence. This study examines developmental trajectories of adolescent girls' BPD symptoms and sexual risk behaviors in a community sample of Black and White girls from the Pittsburgh Girls Study (n = 1620). Dual trajectory modeling provided insights into the temporal precedence and co-development of BPD symptoms and sexual risk behaviors from ages 14 to 18. In order to examine the unique association between BPD symptoms and sexual risk behaviors, analyses controlled for symptoms of depression and conduct disorder, as well as race, sexual orientation, and pubertal development. Girls with more BPD symptoms at age 14 showed steeper growth over time in sexual risk behaviors from ages 14 to 18. Additionally, adolescents who showed steeper increases in BPD symptoms over time also showed steeper increases in sexual risk behaviors across adolescence. Notably, however, sexual risk behavior at age 14 was not significantly associated with longitudinal trajectories of BPD symptoms. Results suggest that adolescent girls with early symptoms of BPD are at heightened risk for the development of sexual risk behaviors during adolescence, while the reverse association does not hold. Implications for adolescent development and sexual risk behavior are discussed.


Determinants of Hospital-Based Health Service Utilization in Cerebral Palsy: a Systematic Review.
To systematically review and synthesize evidence of determinants associated with hospital-based health service utilization among individuals with cerebral palsy (CP). Electronic databases MEDLINE, Embase, APA Psycinfo were searched from January 2000 to April 2020. Observational studies were included that described people with CP, reported quantitative measures of hospital-based health service utilization (inpatient, outpatient, emergency department), and based in high-income countries. We excluded studies that included only subsets of people with CP, or those that only reported therapy service utilization. After initial screen, 2 reviewers reviewed full texts for inclusion and performed data extraction and risk of bias assessment using the Newcastle-Ottawa scale. Determinants of health service utilization were identified and categorized using the Andersen behavioral model. Seventeen studies met inclusion criteria. Study quality was high. Twenty-six determinants were reported across 8 Andersen model characteristics. Individual predisposing factors such as sex showed no difference in health service utilization; inpatient admissions decreased with increasing age during childhood and was lower in adults. Increased health service utilization was associated with "individual need" including severe gross motor disability, epilepsy, developmental/ intellectual disability and gastrostomy-use across inpatient, outpatient and emergency department settings. There was little information reported on socio-demographic and health system contextual determinants. CP health service utilization is associated with age, severity and comorbidities. Improved understanding of determinants of health service utilization can support health service access for people with CP.


Healthcare Cost Implications of Utilizing a Dietary Intervention to Lower LDL Cholesterol: Proof of Concept Actuarial Analysis and Recommendations.
To determine if subsidizing the cost of a food-based intervention for managing hyperlipidemia could be cost-effective under commercial insurance and/or Medicare coverage scenarios. A large number of patients eligible for pharmaceutical treatment of hyperlipidemia either cannot or will not use lipid lowering drugs, leaving them at increased cardiovascular risk. Lipid levels can be modified by diet, but food has never enjoyed covered benefit status. We evaluated the financial implications of providing insurance coverage for a specifically formulated suite of food products previously documented to yield statistically significant lipid reductions, using multiple product uptake and lipid impact scenarios in both commercially covered and Medicare-covered populations. Even after controlling for multiple confounders, we noted positive payback on subsidizing the cost of lipid-lowering foods under all scenarios. Addressing a root cause of hyperlipidemia by directly encouraging dietary modification provides a cost-effective alternative for cholesterol management, especially for statin intolerant or statin unwilling patients.


Behavioural effects of anti-epileptic drugs.
There is increasing evidence that various types of behavioural disturbance, other than those described for phenytoin, for example, may occur from the use of anti-epileptic medication, and it has been suggested that these disturbances may not always be reversible. There are suspicions also that certain groups of patients--especially those with structural brain damage--are particularly susceptible. These and other factors relevant to the study of the effects of anti-epileptic drugs on behaviour are comprehensively reviewed. It is concluded that the psycho-pharmacology of anti-epileptic drugs is unsatisfactory at present because of inadequate and unsophisticated reporting of behavioural change and because of the common problem of polypharmacy, and that more accurate observations are needed on less heterogeneous groups of patients that have been described in the past.


Electrophysiologic behavior modification of frontal EMG in cerebral-palsied children.
Four cerebral-palsied children participated in the following ABAB design: speech and motor pre-electrophysiologic behavior modification (EMB) evaluation; frontal EMG EMB, six weeks; speech and motor post-EBM evaluation; six weeks no training; speech and motor reevaluation; EMG EBM, four weeks; speech and motor evaluation. Auditory and visual feedback of frontal EMG was monitored by cumulative integration of frontal EMG voltage. The children were shaped by setting a cumulative voltage threshold (CVT). If the child's cumulative integrated frontal EMG voltage fell below the CVT at the end of each 60-sec epoch, a reward was automatically dispensed from a Universal Feeder. Frontal EMG decreased significantly over the initial twelve trials. Correspondingly, improvement was noted for the children in speech and motor skills. Follow-up six weeks later showed increased frontal EMG voltage and deterioration of speech and motor function. Reinstitution of frontal EMG EBM produced reacquisition of low frontal EMG and some recovery of speech and motor function. Collectively, these results indicate that frontal EMG EBM shows promise as an additional treatment modality in the habilitation of cerebral palsy children with spasticity.


Autologous white blood cell transfusion: toward a younger immunity.
More and more cells and tissues of human origin are considered as unique medical bio-resources and are instrumental in the ongoing development of regenerative medicine. Although a better understanding of the genetic complexity of the major histocompatibility complex has contributed to develop allogeneic hematopoietic stem cell transplantation, the autologous setting was viewed early on only as a means to overcome myelodepression. The contribution of the immune system for adoptive immunotherapy was recognized in the 1990s, when donor lymphocyte infusion demonstrated an antileukemic effect of the transfused T cells. This led to the foundation and development of adoptive immunotherapy in the treatment and prevention of infectious diseases and cancer. The recognition that the immune system is undergoing a progressive decline and deterioration with age introduces a new challenge. Immunosenescence results in a well-documented increase in incidence and severity of infections, impaired responses to vaccines, and development of cancer. We propose and argue that autologous white blood cells collected and cryopreserved at a young age will represent a valuable bio-resource for the restoration of immunity and the successful development of adoptive immunotherapies in treating infections and cancer, and will pave the way to anticipatory medicine.


Suture or hemostatic agent during laparoscopic partial nephrectomy? A randomized study using a hypertensive porcine model.
To compare the efficacy of 3 biologic hemostatic devices with that of conventional suture during laparoscopic partial nephrectomy (LPN) in a hypertensive porcine model. Improving hemostasis, urinary tract closure, and the warm ischemia (WI) time are important in the development of LPN. A total of 40 pigs were randomized prospectively into 4 groups before bilateral LPN. Right LPN involved 30% of the renal parenchyma without a urinary tract opening, and left LPN involved 40% of the renal parenchyma with a urinary tract opening. The renal section was treated with fibrin/thrombin sealant, fibrin glue, thrombin/gelatin granules, and conventional suture in groups 1, 2, 3, and 4, respectively. At 10 days postoperatively, left retrograde pyelography was performed. The pigs were then killed and the kidneys sent for pathologic analysis. The main criteria were the estimated blood loss, perioperative WI time, leaking pressure during retrograde pyelography, and parenchyma necrotic-induced lesions. The estimated blood loss was lower in the pigs treated with either thrombin/gelatin granules or suture (P < .001). The use of thrombin/gelatin granules decreased the WI time compared with the use of suture (P < .001). However, the leaking pressure was greater in the pigs treated with suture (P < .01). The mean area of necrosis around the renal section was shorter when no suturing was performed (P < .01). The use of thrombin/gelatin granules alone controlled hemostasis as effectively as suture and significantly decreased the WI time. However, conventional suture of the urinary tract, when opened, should be considered. Additional evaluation in humans is required before any clinical recommendation can be made.


The effects of Le Fort I osteotomy with maxillary movement on articulation, resonance, and velopharyngeal function.
Articulation, resonance, and velopharyngeal function were evaluated before and after Le Fort I maxillary advancement in 16 patients (seven with cleft lip and palate, one with cleft lip only, and eight without clefts). On the postoperative evaluation, seven of 11 patients with preoperative articulation errors showed an improvement in articulation after surgery. Two patients without clefts showed slight changes in nasal resonance, and two patients (one with cleft lip and palate and one with cleft lip only) developed mild nasal emission. Nine patients showed diminished velopharyngeal contact during speech on videofluoroscopic studies. Compensatory changes in velopharyngeal function were also observed, which included velar stretching and lengthening and increased lateral pharyngeal wall movement.


Attenuation of Theileria lestoquardi infected cells and immunization of sheep against malignant ovine theileriosis.
Malignant ovine theileriosis caused by Theileria lestoquardi is an economically important disease infecting small ruminants in the Sudan. The disease causes massive losses among sheep in many regions of Northern Sudan. The present studies were done to isolate lymphoblastoid cells infected with malignant ovine theileriosis and attenuate them by passage using culture media to develop and produce schizonts candidate vaccine, then test its efficacy and safety by exposing immunized lambs to field challenge in an area endemic with T. lestoquardi. In the present experiments we isolated and established an in vitro culture of T. lestoquardi infected lymphoblast cell line. Long-term culture of T. lestoquardi infected lymphoplastoid cells was shown to result in attenuation of their virulence and lambs inoculated with different doses of such cells at passage 105 exhibited very mild reactions with fever that lasted for 1-5 days and parasitaemia of <0.2%. The experimental lambs immunized with this candidate vaccine were immune and protected when exposed to field challenge in an area endemic of ovine theileriosis, while morbidity and mortality among non-immunized animals reached 76.9% and 46.15%, respectively, and they exhibited the clinical signs of malignant ovine theileriosis that included, high fever, loss of appetite, enlargement of lymph nodes, jaundice, loss of weight and death. The present study demonstrates the efficacy and the safety of this attenuated cell line as a live attenuated candidate vaccine.


Correlation of Preoperative Renal Insufficiency With Mortality and Morbidity After Aortic Valve Replacement: A Propensity Score Matching Analysis.
Preoperative end-stage renal disease carries a high mortality and morbidity risk after aortic valve replacement (AVR), but the effect of renal insufficiency remains to be clarified. Through propensity score analysis, we compared the preoperative demographics, perioperative profiles, and outcomes between patients with and without renal insufficiency. From August 2005 to November 2014, 770 adult patients underwent AVR in a single institution. Patients were classified according to their estimated glomerular infiltration rate (eGFR) as renal insufficiency (eGFR: 30-89 mL/min/1.73 m) or normal (eGFR, ≥90 mL/min/1.73 m). Propensity scoring was performed with a 1:1 ratio, resulting in a matched cohort of 88 patients per group. Demographics, comorbidities, and surgical procedures were well balanced between the 2 groups, except for diabetes mellitus and eGFR. Patients with renal insufficiency had higher in-hospital mortality (19.3% versus 3.4%, P < 0.001), a greater need for postoperative hemodialysis (14.8% versus 3.1%, P = 0.009), and prolonged intubation times (>72 hour; 25% versus 9.1%, P = .008), intensive care unit stays (8.9 ± 9.9 versus 4.9 ± 7.5 days, P = .046), and hospital stays (35.3 ± 31.7 versus 24.1 ± 20.3 days, P = .008), compared with those with normal renal function. Multivariate analysis confirmed that preoperative renal insufficiency was an in-hospital mortality predictor (odds ratio, 2.33; 95% confidence interval, 1.343-4.043; P = .003), as were prolonged cardiopulmonary bypass time, intraaortic balloon pump support, and postoperative hemodialysis. The 1-year survival significantly differed between the 2 groups including (normal 87.5% versus renal insufficiency 67.9%, P < .001) or excluding in-hospital mortality (normal 90.7% versus renal insufficiency 82.1%, P = .05). Patients with preoperative renal insufficiency who underwent AVR had higher in-hospital mortality rates and increased morbidities, especially those associated with hemodynamic instabilities requiring intraaortic balloon pump support or hemodialysis. Earlier surgical intervention for severe aortic valve disease should be considered in patients who show deteriorating renal function during follow-up.


Pelvic organ function before and after laparoscopic bowel resection for rectosigmoid endometriosis: a prospective, observational study.
To assess urinary, sexual, and bowel function before and after laparoscopic bowel resection for rectosigmoid endometriosis. Prospectively collected data regarding the function of the pelvic organs. Tertiary endometriosis referral unit, Aarhus University Hospital. A cohort of 128 patients who underwent laparoscopic bowel resection for endometriosis. The International Consultation on Incontinence Questionnaire (ICIQ), Sexual Function-Vaginal Changes Questionnaire (SVQ), and the Low Anterior Resection Syndrome (LARS) questionnaire were answered before and after surgery. Non-invasive urodynamic testing was performed. Pre- and postoperative function of the pelvic organs was compared, and risk factors for improved/impaired function were identified. A total of 96.1% of the women completed the 1-year follow-up. A significant decrease (P = 0.002) in bladder filling problems (F-score) was observed 1 year after surgery, primarily caused by a significant decrease in bladder pain (P = 0.0001). No change for urodynamic parameters was observed. A significant increase in overall sexual satisfaction (P = 0.0001) and decrease in worries about sexual life (P = 0.001) was seen 1 year after surgery. Frequency of defecation was significantly increased 1 year after surgery (P = 0.0001), but the overall bowel function measured by LARS score was unchanged. Patients with anastomotic leakage had a significantly higher risk (odds ratio, OR 5.40; P = 0.002) of increased incontinence problems (I-score) 1 year after surgery. A significant and clinically relevant improvement in urinary and sexual function 1 year after laparoscopic bowel resection for endometriosis was found. Except for anastomotic leakage, this could be observed independent of any patient- or treatment-related factor. Apprehension about impairment of urinary and sexual function should not be a contraindication for bowel resection in endometriosis patients. Rectal resection for endometriosis does not impair urinary and sexual function 1 year after surgery.


Lack of spontaneous activity of cutaneous spinal dorsal horn neurons in awake, drug-free, spinally transected cats.
Extracellular single-unit activity was recorded from neurons with cutaneous input in the dorsal horn of the spinal cord (L4-L6) of awake, drug-free cats before (for several weeks) and after (day 1 through day 7) cord transection (T12). The spontaneous activity of the neurons was minimal or nonexistent in both recording conditions. The lack of spontaneous activity following spinal cord transection contrasts sharply with activity recorded in acute spinal-cord transected preparations in which high rates of spontaneous activity have been reported. This discrepancy may reflect an important difference between the chronic, awake, drug-free and acute preparations.


Molecular interactions of the redox-active accessory chlorophyll on the electron-donor side of photosystem II as studied by Fourier transform infrared spectroscopy.
A Fourier transform infrared (FTIR) difference spectrum upon photooxidation of the accessory chlorophyll (Chlz) of photosystem II (PS II) was obtained at 210 K with Mn-depleted PS II membranes in the presence of fericyanide and silicomolybdate. The observed Chlz+/Chlz spectrum showed two differential bands at 1747/1736 and 1714/1684 cm-1. The former was assigned to the free carbomethoxy C = 0 and the latter to the keto C = 0 that is hydrogen-bonded or in a highly polar environment. Also, the negative 1614 cm-1 band assignable to the macrocycle mode indicated 5-coordination of the central Mg. The negative 1660 cm-1 band, possibly due to the strongly hydrogen-bonded keto C = 0, may suggest oxidation of one more Chlz, although an alternative assignment, the amide I mode of proteins perturbed by Chlz oxidation, is also possible.


Safety of omitting routine bleeding tests prior to image-guided musculoskeletal core needle biopsy.
To evaluate the safety of withholding preprocedure international normalized ratio (INR) and platelet testing in patients undergoing musculoskeletal (MSK) core needle biopsy (CNB). Initially, a retrospective review of 1,162 consecutive patients undergoing MSK CNB with preprocedural INR and platelet testing was performed. Clinical (age, gender, bleeding disorder, liver disease, anticoagulation use, INR > 2, platelet count <50,000/ul) and biopsy factors (imaging modality, lesion type, biopsy needle gauge, number biopsy samples) were tested for association with bleeding complications. During the second phase, an additional 188 biopsies performed without preprocedural coagulation testing were studied. Categorical variables were compared using Chi-squared or Fisher's exact tests, continuous variables with a student t-test. Multivariate analysis was performed using logistic regression. In the first phase, there was a complication rate of 2.6%, 30/1162. Of the 11 clinical and biopsy factors, soft tissue lesions (p = 0.029) and lesions biopsied under ultrasound (p = 0.048) had a higher rate of bleeding than bone lesions or lesions biopsied under CT, respectively. Only three patients had an INR >2, 0.3% (3/1162) and only four patients had platelet count <50,000/ul, 0.3% (4/1162). No patient with a bleeding complication had an abnormal preprocedure bleeding test. In the second phase, there was a bleeding complication rate of 1.1% (2/188). Bleeding complications from MSK biopsy are low, even when preprocedure coagulation testing is omitted.


Cross-regional transport of PM2.5 nitrate in the Pearl River Delta, China: Contributions and mechanisms.
Cross-regional transport potentially contributes to PM2.5 nitrate (pNO3), and this can occur as indirect transport, through which pNO3 precursors are transported to targeted regions, wherein they subsequently react with locally emitted ones to produce pNO3. However, the process has been rarely studied, which limits its comprehensive understanding. We applied the CMAQ model to study the contributions and mechanisms of pNO3 transport during autumn in the Pearl River Delta (PRD), a metropolitan region under the growing influence of cross-regional transport on PM2.5 pollution. Results showed that cross-regional transport contributed to 58% pNO3 monthly in the PRD, and this mostly occurred as indirect transport contributions (accounting for 43% among all contributions). For the first time, we identified the mechanism of indirect pNO3 transport in the PRD, which mainly involves transported O3 and locally emitted NOx reacting to produce pNO3 through N2O5 heterogeneous hydrolysis. pNO3 contributions in different periods and regions indicated differences in the indirect transport contributions to N2O5 heterogeneous hydrolysis under varying O3 availability conditions, which are determined by wind fields and the intensity of NOx emissions. On the regional scale, the pNO3 level is controlled by both transported O3 and local NOx emissions, but pNO3 sensitivity to these two precursors varies among cities. This study demonstrates the notable effect and complex process of cross-regional pNO3 transport in the PRD. Considering the important role of transported O3 for pNO3, O3 reduction within a larger scale is required to achieve PM2.5 pollution control target.


Genetic variation and covariation for resistance and tolerance to Cucumber mosaic virus in Mimulus guttatus (Phrymaceae): a test for costs and constraints.
Genetic variation for resistance and tolerance to pathogens may be maintained by costs represented as genetic tradeoffs between these traits and fitness. The evolution of resistance and tolerance also may be constrained by negative genetic correlations between these defense systems. Using a complete diallel, we measured genetic variation and covariation for and among performance, resistance, and tolerance traits in Mimulus guttatus challenged with a generalist pathogen, Cucumber mosaic virus (CMV). Viral coat protein was detected by enzyme-linked immunosorbent assay (ELISA) in all inoculated plants, indicating that all plants were susceptible to infection, although the ELISA absorbance varied quantitatively across plants. Plants inoculated with CMV had significantly reduced aboveground biomass and flower production relative to controls, although date of first flower was unaffected by infection. All three of these performance traits showed moderate to high narrow-sense heritability (h2 = 0.32-0.62) in both inoculated and control plants. We found phenotypic variation for both tolerance of and resistance to our strain of CMV, but both displayed very low narrow-sense heritability (h2 < 0.03). We found no evidence of a trade-off between resistance and tolerance. We also found no evidence for a cost of resistance or tolerance. In fact, a significant genetic correlation suggested that plants that were large when healthy had the greatest tolerance when infected. Significant, positive genetic correlations found between performance of uninfected and infected plants suggested that selection would likely favor the same M. guttatus genotypes whether CMV is present or not.


Quality of life and autonomy in emerging adults with early-onset neuromuscular disorders.
Emerging adulthood is an important period in the development of one's identity and autonomy. The ways in which identity and autonomy are viewed by emerging adults and how they impact quality of life (QoL) in individuals with early-onset neuromuscular conditions is not yet known. This study focused on understanding and exploring relationships between self-perceptions of emerging adulthood, autonomy, and QoL. Five previously validated measures were incorporated into an online survey and distributed to young adults with early-onset neuromuscular conditions and unaffected controls. Topics explored included individuals' views regarding their overall QoL, disease-specific QoL, components of emerging adulthood, and autonomy. We found that a sense of higher disease impact was associated with a lower Overall General QoL. Additionally, perceptions of key autonomy factors "negativity" and "instability" were uniquely associated with Overall General QoL in the case group as compared to controls, whereas "attitudinal autonomy" (attaining the ability to plan and follow through with goals) was important to this age group regardless of health status. The specific factors of emerging adulthood and autonomy that were significantly correlated with Overall General QoL can be used for developing targeted counseling and interventions to improve QoL for individuals and their families.


The makings of maleness: towards an integrated view of male sexual development.
As the mammalian embryo develops, it must engage one of the two distinct programmes of gene activity, morphogenesis and organogenesis that characterize males and females. In males, sexual development hinges on testis determination and differentiation, but also involves many coordinated transcriptional, signalling and endocrine networks that underpin the masculinization of other organs and tissues, including the brain. Here we bring together current knowledge about these networks, identify gaps in the overall picture, and highlight the known defects that lead to disorders of male sexual development.


Generation of a human induced pluripotent stem cell line (PHAi003) from a primary immunodeficient patient with CD70 mutation.
Primary immunodeficiency (PID) comprises a heterogeneous group of over 330 genetic disorders, caused mainly by single-gene mutations, such as CD70. We generated human induced pluripotent stem cell lines, PHAi003-A and PHAi003-B, from a PID patient carrying the homozygous frameshift CD70 mutation c.250delT. The CD70 c.250delT genotype results in a complete loss of expression variant. This patient is one of the five CD70 deficient individuals described to date, and presented hypogammaglobulinemia, EBV associated Hodgkin's lymphoma and susceptibility to other viral infections. The PHAi003-A and PHAi003-B lines are a unique resource for PID modeling and studying CD70-mediated immunity in human cells.


Pathophysiology of the kidney in rats with Heymann nephritis.
Alterations in kidney function were assessed early in the course of Heymann nephritis that was induced in rats by immunization with Fx1A, an extract prepared from rat kidney cortex. Whole kidney and single nephron function were evaluated by clearance and micropuncture techniques. Kidney function was studied in stage 1 of Heymann nephritis, before the onset of proteinuria, and in stage 2, when antibodies are deposited along the brush border of proximal tubules. Although overall kidney function was similar in rats in stage 1 and normal controls, glucose reabsorption was somewhat depressed in the first part of the proximal convoluted tubule in stage 1. Both whole kidney and single nephron glomerular filtration rates were depressed in stage 2. Proteinuria in stage 2 was characterized by an increased albumin sieving coefficient, which resulted in an elevated excretion of albumin. Furthermore, several proximal tubule functions (glucose and fluid reabsorption and PAH extraction) were substantially depressed in stage 2. These findings demonstrate that immunological injury to the proximal tubules in stage 2 of Heymann nephritis produces a significant impairment of proximal function.


Low-light image enhancement via adaptive frequency decomposition network.
Images captured in low light conditions suffer from low visibility, blurred details and strong noise, resulting in unpleasant visual appearance and poor performance of high level visual tasks. To address these problems, existing approaches have attempted to enhance the visibility of low-light images using convolutional neural networks (CNN). However, due to the insufficient consideration of the characteristics of the information of different frequency layers in the image, most of them yield blurry details and amplified noise. In this work, to fully extract and utilize these information, we proposed a novel Adaptive Frequency Decomposition Network (AFDNet) for low-light image enhancement. An Adaptive Frequency Decomposition (AFD) module is designed to adaptively extract low and high frequency information of different granularities. Specifically, the low-frequency information is employed for contrast enhancement and noise suppression in low-scale space and high-frequency information is for detail restoration in high-scale space. Meanwhile, a new frequency loss function are proposed to guarantee AFDNet's recovery capability for different frequency information. Extensive experiments on various publicly available datasets show that AFDNet outperforms the existing state-of-the-art methods both quantitatively and visually. In addition, our results showed that the performance of the face detection can be effectively improved by using AFDNet as pre-processing.


Characterization of a plasma membrane protein present in non-myelin-forming PNS and CNS glia, a subpopulation of PNS neurons, perineurial cells and smooth muscle in adult rats.
A plasma membrane protein common to non-myelin-forming peripheral glia, including non-myelin-forming Schwann cells, satellite cells and enteric glia, is recognized and defined by monoclonal antibody A5E3. It is not detectable immunohistochemically on myelin-forming Schwann cells. The antigen is also present in large amounts on smooth muscle cells and perineurial cells, on some PNS neurons, and at lower levels on astrocytes of adult rat. In neonatal but not adult animals, the antigen is present on skeletal muscle fibres and myoblasts. In immunoblots and immune precipitation experiments on smooth muscle and Schwann cell extracts the antigen is a polypeptide with an apparent molecular weight of 130 kd. In being present in some non-neural tissues, albeit very highly restricted in cell type, this antigen resembles several other cell surface glycoproteins found in large amounts in the nervous system.


[Clarity and legal authority in decisions to limit therapy].
The decision to limit a patient's therapy can lead to conflicts in the therapeutic team if their views have not been carefully weighed. Further problems also result if they are not clearly and logically documented. The legal authority of patient will, medical indication, and interaction of the care-giving team for arriving at a common decision are examined here. Using a case history as an example, we discuss ethical and legal questions of documentation and obligations on those faced with concrete decisions whether to continue medical procedures. To widen the basis for such decisions, discussion must include the viewpoints of all participants. The final decision must then be clearly documented without any unclarity or ambivalence. Those finally required to carry out that prospective decision, however, must decide whether it actually applies to the situation at hand.


Changes in unbound sex steroids and sex hormone binding globulin--binding capacity during oral and vaginal progestogen administration.
Four groups of five cycling women each received either a contraceptive vaginal ring containing a combination of either levonorgestrel or norethindrone with estradiol or oral contraceptives containing a combination of either dl-norgestrel or norethindrone with ethinyl estradiol. Pretreatment as well as 2- and 7-week treatment serum samples were assayed for sex hormone binding globulin-binding capacity (SHBG-BC), estradiol, non-SHBG-bound estradiol, testosterone, and non-SHBG-bound testosterone, d-norgestrel, non-SHBG-bound d-norgestrel, and norethindrone. SHBG-BC was significantly increased in the norethindrone oral contraceptive group, unchanged in the norgestrel oral contraceptive group, and significantly reduced in both contraceptive vaginal ring groups. These findings indicate that the positive effect of oral ethinyl estradiol on SHBG-BC offsets the suppressive effects of d-norgestrel on SHBG-BC, while the estradiol in the d-norgestrel or norethindrone contraceptive vaginal rings is insufficient to alter the suppressive effect of d-norgestrel or norethindrone on SHBG-BC. In contrast, the ethinyl estradiol in the norethindrone oral contraceptive overcame the suppressive effect of norethindrone on SHBG-BC, resulting in a significantly increased SHBG-BC level. Although total circulating estradiol was significantly decreased in the contraceptive vaginal ring groups, the percentage of unbound serum estradiol was significantly increased in both contraceptive vaginal ring groups and significantly reduced in the norethindrone oral contraceptive group. Although total circulating testosterone was significantly reduced only in the norgestrel oral contraceptive group, the percentage and mass of unbound testosterone were significantly decreased in the norethindrone oral contraceptive group, while the percentage of unbound testosterone was significantly reduced in the norgestrel oral contraceptive group and significantly increased in the norethindrone contraceptive vaginal ring group. As levels of unbound (biologically active) steroid differ markedly from levels of total steroid, it is essential to measure levels of non-SHBG-bound estradiol and testosterone in order to determine effects of steroidal contraceptives on physiologically active circulating endogenous steroids.


Reactions of Bili-Uele chimpanzees to humans in relation to their distance from roads and villages.
In order to assess the impact of human activities on chimpanzee behavior, we compared reactions to humans of Eastern chimpanzees (Pan troglodytes schweinfurthii) living in proximity to and at a distance from roads and settlements in the Bili-Uele landscape in Northern Democratic Republic of the Congo (DRC). We found that chimpanzees in the remote Gangu Forest were more likely to show curious or neutral reactions to us and were less likely to flee than those living closer to roads. In addition, arboreal contact durations with Gangu chimpanzees lasted significantly longer than elsewhere. The most likely explanation for this phenomenon is that with increasing distance from roads, chimpanzees have in the recent past had fewer negative encounters with humans, and thus never learned to fear them. The discovery of this population of "naïve chimpanzees" presents us with an important research and conservation opportunity that may result in the installation of a long-term research site and increased protection of the population.


A comparison of the SPRINT and CAPS assessment scales for posttraumatic stress disorder.
The Clinician-Administered PTSD Scale for DSM-IV (CAPS) is a widely used assessment tool for (posttraumatic stress disorder) (PTSD). However, a shorter assessment tool may be beneficial for clinical work. Here, we compare such a tool, the Short PTSD Rating Interview (SPRINT) to the CAPS. We found that the SPRINT rating scale performs similarly to the CAPS rating scale in the assessment of PTSD symptom clusters and total scores, and that the SPRINT takes significantly less time to administer than the CAPS.


MDR1 polymorphisms G2677T in exon 21 and C3435T in exon 26 fail to affect rhodamine 123 efflux in peripheral blood lymphocytes.
P-glycoprotein (Pgp) is a member of the ABC-transporter family, and in humans, is encoded by the MDR1 gene. Recently, several single-nucleotide polymorphisms in the MDR1 gene were identified. The aim of the present study was to evaluate the effect of the MDR1 genetic polymorphisms G2677T and C3435T on Pgp activity in CD56+ and CD4+ peripheral blood cells. Using flow cytometry, rhodamine 123 (Rh123) efflux was determined in 46 male healthy volunteers. Median Rh123 fluorescence in control sample, after baseline dye uptake, was set as 100%. Rh123 fluorescence in efflux samples, exposed to different efflux periods, was used to calculate the percentage of Rh123 retained in the cells in comparison with control. There was no significant difference in Rh123 efflux in CD56+ cells after 5, 10, 15, and 30 min efflux between individuals with different MDR1 genotypes. Also, in CD4+ cells after 15, 30, 60, and 90 min, Rh123 efflux did not reveal statistically different results for the three genotypes at 2677 and 3435. Rh123 efflux was not enhanced by a 10-day rifampin administration, as determined in 15 individuals before and after rifampin treatment. In conclusion, we found no impact of the MDR1 G2677T and C3435T polymorphisms on Pgp activity in CD56+ and CD4+ peripheral blood lymphocytes.


Experimental models for the study of prostatic adenocarcinoma.
The Dunning R3327H transplantable rat tumor is a well differentiated prostatic adenocarcinoma. The biological properties of this tumor have been characterized, and it appears that this animal model is well suited for studying the nature of prostatic cancer. The established tumor responds to castration therapy and this is subsequently followed by relapse to a predominant state of hormone insensitivity. Cell kinetic studies indicate that 70 to 90 per cent of the total tumor cells are hormonally sensitive, and a subpopulation of 8 to 30 per cent are hormone insensitive. The therapeutic relapse to androgen deprivation represents the continued growth of the clone of cells, which were hormone insensitive. It appears that this animal mimics the relapse of phenomenon observed in the hormone control of human prostatic cancer.


Prevalence of myopia in school children in Vanuatu.
The onset of myopia typically occurs in childhood and increases during puberty. We studied the vision and refractive errors of 977 school children (ages 6 to 17 years) in 1983. Myopia in the group was extremely low; 97% had vision of 6/6, and 1.3% had myopia greater than 0.25D. Regression analysis revealed a change in mean refraction of -0.016D/year for males and -0.024D/year for females. There were no significant differences between males and females. These children engaged in about 8 hours of school work per day, and we conclude that genetic factors predominate over environmental factors in the determination of myopic refractive errors for this group.


The synthesis of a new type of anthracene DNA intercalator.
A new type of DNA intercalator based on anthracene 3 was synthesized. Preliminary binding studies show high affinity of this probe to CT-DNA. Higher binding constant of this compound (4.0 x 10(4) M-1) as compared with that known for 9-aminomethylanthracene, is caused presumably by enhanced electrostatic interaction.


Allograft inflammatory factor-1 enhances inflammation and oxidative stress via the NF-κB pathway in diabetic kidney disease.
Inflammation and glomerular endothelial dysfunction promote diabetic kidney disease (DKD) progression, but the mechanisms are not fully understood. Allograft inflammatory factor-1 (AIF-1) is a protein that regulates inflammatory reactions and immune responses. This study aimed to explore the mechanism of AIF-1 in a DKD animal model and mouse renal glomerular endothelial cells (MRGECs). We injected AIF-1-shRNA into the tail vein to knockdown AIF-1 in db/db mice. Metabolic index, renal pathological changes and inflammatory factors were measured in each group. Lentiviral transfection was used to overexpress AIF-1 in MRGECs. Inflammatory factors, oxidative stress and nuclear factor-κB (NF-κB) pathway-related proteins were examined. AIF-1 expression was upregulated in glomerular endothelial cells in renal tissues of db/db mice. Knockdown of AIF-1 reversed kidney injury and renal inflammation in db/db mice. In a 30 mM high-glucose environment, overexpression of AIF-1 in MRGECs activated the NF-κB pathway and induced inflammation and oxidative stress. Moreover, this damage could be attenuated by the addition of an NF-κB inhibitor (BAY 11-7082). In conclusion, AIF-1 facilitates glomerular endothelial cell inflammation and oxidative stress in DKD via the NF-κB signaling pathway. Our results provide evidence for the molecular mechanism of DKD and may offer a potential target for DKD treatment.


Prostacyclin-lipoprotein interactions. Studies on human platelet aggregation and adenylate cyclase.
The in vitro effects of different lipoprotein fractions (VLDL, LDL and HDL) on human washed platelet aggregation, induced by collagen and thrombin, were evaluated in the presence and absence of PGI2. Although VLDL and LDL increased the platelet aggregation while HDL showed an opposite effect, none of the tested lipoprotein fractions affected the potency of PGI2 as inhibitor of platelet aggregation (IC50). In addition, studies were performed to evaluate the effects of lipoproteins on adenylate cyclase activity in human platelet membranes. The three lipoprotein classes inhibited both basal and PGI2-stimulated adenylate cyclase without affecting the EC50 for PGI2. This inhibitory activity was not specifically elicited by any protein or lipid since neither bovine serum albumin nor a lipid emulsion (Intralipid) displayed any inhibition. The effect on adenylate cyclase elicited by VLDL, LDL and HDL does not seem to be correlated with the activity on platelet aggregation. It is concluded that mediators other than cAMP might be involved in the control of platelet function by lipoproteins.


Moral intuitions and political orientation: similarities and differences between South Korea and the United States.
Koreans and Americans were compared in terms of political ideology and moral attitudes. The pattern found among U.S. participants is that liberals rated moral concerns about harm and unfairness higher than Korean conservatives, but conservatives rated moral concerns about betrayals of the ingroup and violations of social hierarchies and physical/spiritual purity higher. Compared with U.S. data (in which concerns about purity and disgust showed the strongest relation to ideology), Korean data revealed higher purity concerns overall, and a weaker relationship between purity concerns and ideology. Results suggested that while the patterns of ideological difference in moral concerns are the same, the magnitude of the differences depends upon the particular histories, traditions, and socioecological factors of these different cultures. They also emphasize a consistent pattern of overall moral structure: liberals discounted concerns related to group cohesiveness (rating them at best "slightly relevant") and rated only individualistic concerns as "somewhat" to "very" relevant, while conservatives rated all moral concerns in the latter range, nearly equating individual and group moral concerns.


Focal Spinal Nondisjunctional Disorders: Including a Discussion on the Embryogenesis of Cranial Focal Nondisjunctional Lesions.
The publication of a comprehensive report on limited dorsal myeloschisis by the senior author (DP) in 2010 has brought full attention to the concept of limited myeloschisis that he first formulated in 1992 and ignited interests in the whole spectrum of focal spinal nondisjunctional disorders. Now that focal nondisjunctional disorders have become well known, new clinical reports on these conditions or relevant subjects are frequently seen. Here we present an updated review on the full spectrum of focal spinal nondisjunctional disorders and extend the scope to include a discussion on the embryogenesis of cranial focal nondisjunctional malformations.


Methanol extract of Codium fragile inhibits tumor necrosis factor-α-induced matrix metalloproteinase-9 and invasiveness of MDA-MB-231 cells by suppressing nuclear factor-κB activation.
To evaluate whether the methanol extract of Codium fragile (MECF) regulates tumor necrosis factor-α (TNF-α)-induced invasion of human breast cancer MDA-MB-231 cells by suppressing matrix metalloproteinase-9 (MMP-9). Reverse transcription-polymerase chain reaction (RT-PCR) and western blot analysis were performed to analyze the expression of MMP-9 and nuclear factor-κB (NF-κB) subunits, p65 and p50, and IκB in MDA-MB-231 cells. 3-(4,5-Dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay was used for cell viability. MMP-9 activity and invasion were measured by gelatin zymography and a matrigel invasion assay, respectively. NF-κB activity was measured by an electrophoretic mobility shift assay and luciferase activity. MECF had no effect on cell viability up to a concentration of 100 μg/mL in human breast cancer MDA-MB-231 cells regardless of the presence of TNF-α. MDA-MB-231 cells that were stimulated with TNF-α showed a marked increase of invasion compared to the untreated control, whereas pretreatment with MECF downregulated the TNF-α-induced invasion of MDA-MB-231 cells. Additionally, zymography, western blot analysis, and RT-PCR confirmed that MECF decreased TNF-α-induced MMP-9 expression and activity which is a key regulator for cancer invasion. According to an electrophoretic morbidity shift assay, pretreatment with MECF in MDA-MB-231 cells significantly decreased the TNF-α-induced DNA-binding activity of NF-κB, which is an important transcription factor for regulating cancer invasion-related genes such as MMP-9. Furthermore, treatment with MECF sustained the expression of p65 and p50 in response to TNF-α in the cytosolic compartment. The luciferase assay demonstrated that MECF attenuated TNF-α-induced NF-κB luciferase activity. MECF exhibited its anti-invasive capability by downregulating TNF-α-induced MMP-9 expression, resulting from the suppression of NF-κB activity in the human breast cancer cell line MDA-MB-231.


A novel acridone akaloid from Atalantia buxifolia.
Study of the chemical constituents of ethanol extract from the aerial parts of Atalantia buxifolia led to the identification of a new acridone alkaloid named as buxifoliadine (1), along with known compounds citrusinine--I (2), N-methylatalaphylline (3), Severinolid (4) and cycloseverinolide (5). Structural elucidation of compound 1 was carried out by a combination of mass spectrometry and (1)H and (13)C NMR spectroscopy analyses.


Promoting the consumer voice in palliative care: exploring the possibility of using consumer impact statements.
It can be difficult to engage consumers in health decision making. This is particularly so in the area of palliative care, where consumers are very unwell and are unlikely to become involved in long-term programmes that promote consumer input. This paper explores the possibility of using 'Consumer Impact Statements' to facilitate the inclusion of the viewpoint of people at the end of life in the process of policy and decision making, particularly in the area of subsidy of pharmaceuticals used in palliative care. A broad search was conducted to find information about the use of impact statements in any health field. The health literature and grey literature were searched to explore the use of Consumer Impact Statements to date. No papers were found describing the use of Consumer Impact Statements in the palliative care setting. Health impact assessment is used in the areas of environmental health and community health. Impact statements are less commonly used in other areas of health, especially policy development, and no formal description of a Consumer Impact Statement was found. There is considerable scope for developing the use of Consumer Impact Statements to promote the consumer viewpoint in health decision making, because it will allow people who are otherwise unlikely to contribute to the public debate to have their views heard by decision makers. The use of Consumer Impact Statements is particularly suited to palliative care, given that consumers are often otherwise unable to contribute to the public debate.


[Effects of Klebsiella pneumoniae on the expression of cytokines by polymorphonuclear neutrophil granulocytes in mice].
To observe the effect of Klebsiella pneumoniae (Kle.p) on the expression of cytokines in mouse polymorphonuclear neutrophil granulocytes (PMNs). Mouse models of acute pneumonia were induced by intranasal inoculation of 30 microl PBS containing 1 x 10(7) Kle.p (heat-inactivated at 60 degrees C for 1.5 h). The mRNA and protein expressions of the cytokines in the isolated and purified PMNs were assayed by reverse transcriptional (RT)-PCR, Western blotting and enzyme- linked immunosorbent assay (ELISA), respectively. Kle.p infection induced the mRNA expressions of tumor necrosis factor (TNF)-alpha and interleukin (IL)-1beta in the early stage, and TNF-alpha mRNA reached its peak at 6 h and IL-1beta mRNA at 12 h after infection, both of which decreased 24 h after infection. Western blot analysis showed that the protein expressions of TNF-alpha and IL-1beta were the highest at 6 h, and decreased obviously at 24 h after infection. ELISA showed that the secretion of TNF-alpha peaked at 6 h and decreased obviously at 24 h after infection, while the peak of IL-1beta production occurred at 12 h and maintained the high level till 24 h after the infection. TNF-alpha may participate in the immune defense of PMN against Kle.p infection mainly in the early stage of infection while IL-1beta mainly in the later stage.


Histogenesis of the gallbladder carcinoma induced by methylcholanthrene beeswax pellets in hamsters.
Gallbladder carcinoma was induced in hamsters by inserting methylcholanthrene beeswax pellets into the gallbladder lumen. The histogenesis and mode of development of the cancer was studied. The mode of development was classified into four; the infiltrative, the polypoid, the para-adenoma, and the mixed type. Twenty-one gallbladder carcinoma included six of the infiltrative type, seven of the polypoid type, three of the para-adenoma type (each case was accompanied by the infiltrative type), and eight of the mixed type (containing three of the infiltrative plus the para-adenoma type, and five of the infiltrative plus the polypoid type). Concerning histogenesis, the infiltrative type developed as de novo cancer. The polypoid and the para-adenoma type developed from adenomatous hyperplasia or adenoma.


Low-affinity nerve-growth factor receptor (P75NTR) can serve as a receptor for rabies virus.
A random-primed cDNA expression library constructed from the mRNA of neuroblastoma cells (NG108) was used to clone a specific rabies virus (RV) receptor. A soluble form of the RV glycoprotein (Gs) was utilized as a ligand to detect positive cells. We identified the murine low-affinity nerve-growth factor receptor, p75NTR. BSR cells stably expressing p75NTR were able to bind Gs and G-expressing lepidopteran cells. The ability of the RV glycoprotein to bind p75NTR was dependent on the presence of a lysine and arginine in positions 330 and 333 respectively of antigenic site III, which is known to control virus penetration into motor and sensory neurons of adult mice. P75NTR-expressing BSR cells were permissive for a non-adapted fox RV isolate (street virus) and nerve growth factor (NGF) decreased this infection. In infected cells, p75NTR associates with the RV glycoprotein and could be precipitated with anti-G monoclonal antibodies. Therefore, p75NTR is a receptor for street RV.


Intra-islet glucagon-like peptide 1.
Glucagon-like peptide-1 (GLP-1) is originally identified in the gut as an incretin hormone, and it is potent in stimulating insulin secretion in the pancreas. However, increasing evidence suggests that GLP-1 is also produced locally within pancreatic islets. This review focuses on the past and current discoveries regarding intra-islet GLP-1 production and its functions. There has been a long-standing debate with regard to whether GLP-1 is produced in the pancreatic α cells. Early controversies lead to the widely accepted conclusion that the vast majority of proglucagon is processed to form glucagon in the pancreas, whereas an insignificant amount is cleaved to produce GLP-1. With technological advancements, recent studies have shown that bioactive GLP-1 is produced locally in the pancreas, and the expression and secretion of GLP-1 within islets are regulated by various factors such as cytokines, hyperglycemia, and β cell injury. GLP-1 is produced by the pancreatic α cells, and it is fully functional as an incretin. Therefore, intra-islet GLP-1 may exert insulinotropic and glucagonostatic effects locally via paracrine and/or autocrine actions, under both normal and diabetic conditions.


Celebrating INVAM: 35 years of the largest living culture collection of arbuscular mycorrhizal fungi.
The International Culture Collection of (Vesicular-) Arbuscular Mycorrhizal Fungi-INVAM-the largest living culture collection of arbuscular mycorrhizal fungi (AMF) celebrated its 35th year in 2020. The authors record here the mission and goals of INVAM, its contribution as a living culture collection, some historical aspects of INVAM, and describe the advances in mycorrhizology and AMF systematics after INVAM moved to West Virginia University. This commentary emphasizes the importance of a living culture collection to preserve germplasm and to educate and assist researchers in mycorrhizal science.


Studies on the opiate receptor-mediated inhibition of K+-stimulated cholecystokinin and substance P release from cat hypothalamus in vitro.
The addition of 50 mM K+ to the perfusate of cat hypothalamic slices results in a 3.4- and 5.5-fold increase in the levels of cholecystokinin (CCK) and substance P (sP) like immunoreactivity, respectively. The addition of morphine (10(-11)-10(-8) M; a mu receptor agonist) and D-Ala2-D-Leu5-enkephalin (DADL: 10(-12)-10(-10) M; a delta receptor agonist) resulted in a dose-dependent suppression of the K+-evoked release. SKF10047 (a sigma receptor ligand) and U50488H (a kappa receptor ligand) had no effect in doses up to 10(-6) M. Naloxone added with the lowest dose of agonist producing a maximal inhibition produced a dose-dependent reversal of the anti-release effects of morphine and DADL. The IC50 of naloxone for the antagonism by DADL and morphine of the release of CCK were similar, whereas the naloxone IC50 was lower for morphine than DADL in the reversal of the effects of the agonist in sP release. Within the constraints of receptor selectivity of the several ligands, these data suggest that at least two populations of opioid receptors (mu and delta) may be discriminated which govern the release of hypothalamic sP.


Effect of age on cytokine production in humans.
Aging is accompanied by many changes in immune response, with the most consistent and dramatic alterations occurring within the T cell compartment. Since cytokines are central to immune cell communications, age-associated changes in cytokine production may contribute to these alterations. While data from murine studies suggest a switch from a Th1 (IL-2, IFNγ) to a Th2 (IL-4, IL-6, IL-10) cytokine response, this model has not been as clearly established in humans. In addition, this current review of over 50 studies in humans suggests that age-associated changes in cytokine production are not consistent.


Pathogenetic role of Yersinia pseudotuberculosis endotoxin in hemostasis and microcirculation disturbances.
We studied the role of Y. pseudotuberculosis endotoxin (LPS) in the pathogenesis of hemostasis and microcirculation disorders. It was found that changes in the hemostasis system after injection of LPS had biphasic character corresponding to the stages of DIC syndrome development. Pathomorphological findings in animals with endotoxemia induced by Y. pseudotuberculosis LPS attested to increased permeability and destruction of the vascular endothelium in the microcirculatory bed and focal degenerative and necrotic changes in cells of the target organs (kidney, liver, and lungs) progressing with increasing the duration of the pathological process, which was determined by microcirculation disturbances and development of multiple organ failure.


Increasing accuracy of antenatal ultrasound diagnosis of cleft lip with or without cleft palate, in cases referred to the North Thames London Region.
To determine the accuracy of antenatal ultrasound diagnosis of cleft lip with or without cleft palate (CL +/- P) and isolated cleft palate (CP). This was a retrospective review of 256 surviving cases referred in 2002-2003 for treatment of CL +/- P. We had referrals from 36 maternity units, 27 of which were in our local catchment area. There were 154 cases of CL +/- P, of which five had microform CL. Of the remaining 149, 88 (59%) were diagnosed on antenatal ultrasound examination. Among these 88 cases there were minor reporting errors in 22 (25%). These errors were in describing the side and type of the lip cleft in 10 cases, predicting if there was a CP in 10 cases, and recognizing the anomaly in two cases. There were 102 cases referred with isolated CP, of which 92 had overt CP and 10 submucous CP. None of these was diagnosed by antenatal ultrasound imaging. There was no significant difference in the accuracy of ultrasound diagnosis between district hospitals and teaching/tertiary units. There is a good awareness and ability to detect CL +/- P by obstetric units from which referrals are received. Inaccuracies in antenatal ultrasound reports occur frequently when attempting to determine the type of CL and when predicting if there is a CP. We recommend that families should continue to be referred to specialist centers for counseling immediately after antenatal diagnosis, and comprehensive advice should always be given about clefts of the lip and palate.


Exogenous insulin-like growth factor 1 accelerates growth and maturation of follicles in human cortical xenografts and increases ovarian output in mice.
To measure the influence of exogenous insulin-like growth factor 1 (IGF1) on follicle growth and maturation in human ovarian cortical xenografts. Xenotransplantation model. University-based research laboratory. Ovarian tissue was donated with consent and institutional review board approval by brain-dead organ donors or patients undergoing ovarian tissue cryopreservation for fertility preservation. Cortical fragments were transplanted into immunocompromised mice. Cryopreserved ovarian cortical fragments from four women (aged 19, 25, 33, and 46 years) were transplanted into the gluteus muscle of immunocompromised mice in a fibrin matrix containing endothelial cells that were transduced with lentiviral particles encoding secreted IGF1. Xenografts were recovered after 3, 8, and 14 weeks. In addition, C57/Bl6 mice underwent intraovarian injection of saline or recombinant IGF1 (60 μg), followed by superovulation, analysis of ethynyl-deoxyuridine incorporation, and ribonucleic acid sequencing of the whole ovaries. For xenografts: follicle count and distribution; antral follicle count; and corpora lutea/albicans count. For mice: follicle count and distribution; oocyte yield, ethynyl-deoxyuridine incorporation (granulosa cell proliferation); and ovarian transcriptomic signature. At 3 weeks, xenografts in the IGF1 condition revealed a decreased percentage of primary follicles and increased percentage of secondary follicles that were concentrated in the preantral subtype; at 8 weeks, an increase in secondary follicles was concentrated in the simple subtype; after 14 weeks, primordial follicles were reduced, and while the number of advanced follicles did not power the experiment to demonstrate significance, antral follicles reduced and corpora lutea increased. Supporting experiments in mice revealed an increase in normal oocytes following intraovarian injection of recombinant IGF1 (60 μg) as well as increased proliferative index among follicles of secondary and preantral stages. Ribonucleic acid sequencing analysis of the whole ovaries following injection of recombinant IGF1 (25 μg) revealed an acute (24 hours) upregulation of transcripts related to steroidogenesis and luteinization. Exogenous IGF1 advances the pace of growth among primordial, primary, and secondary stage follicles but results in near absence of antral stage follicles in long-term (14 weeks) xenografts. In mice, acute administration of IGF1 promotes follicle advance and increased oocyte yield. The results suggest that while superphysiological IGF1 alone advances the pace of growth among early/preantral follicles, a sustained and/or later-stage influence undermines antral follicle growth/survival or promotes premature luteinization. These findings provide a temporal framework for interpreting follicle growth/mobilization and may be useful in understanding the clinical application of human growth hormone in the context of assisted reproduction.


Strategies for the chemoenzymatic preparation of optically active 1-alkyn-3-ols.
A series of (R)- and (S)-1-alkyn-3-ols, chiral building units for the synthesis of leukotrienes and pheromones, were prepared via enantioselective hydrolysis of their racemic esters. While the majority of biocatalysts employed (lipases, fermenting or freeze-dried microorganisms) failed in discriminating between enantiomers, lyophilized cells of baker's yeast (Saccharomyces cerevisiae Hansen) gave (S)-1-alkyn-3-ols and their corresponding (R)-esters with greater than 90% e.e.


Contrasting effects of SH-compounds on oxidative DNA damage: repair and increase of damage.
The non-radical singlet oxygen (1O2) and the OH radical (.OH) are the major damaging oxidative species that can be generated inside cells during normal aerobic metabolism and by processes such as photosensitization. Both reactive oxygen species fulfill essential prerequisites to be a genotoxic agent. Due to their continuous production they represent an ever-present threat to all vital cellular molecules, especially DNA. As might be anticipated from the difference in character between these reactive species (non-radical versus radical) the pattern of DNA modifications caused by singlet oxygen is different from that produced by OH radicals. All cells possess an elaborate defense system against oxidative damage. This paper focuses mainly on the effect of thiols such as glutathione, which are thought to play a role as antioxidants. Under certain conditions thiols can repair chemically, probably by H-donation, some of the DNA damage caused by .OH; for instance breaks can be rather easily prevented in this way. This process will compete with fixation of damage by oxygen. However, there is ample evidence that H-atom donation does not always lead to 'correct' repair. Moreover under aerobic conditions thiyl peroxy radicals might increase DNA damage. Although the repair/fixation process could not be examined in the case of 1O2 yet, it could be demonstrated that reactive species can be formed out of the reaction of thiols with 1O2 capable of enhancing the number of DNA modifications such as 8-oxoguanine and single-strand breaks, probably arising from different pathways. Although it is quite clear that thiols are to some extent excellent antioxidants they possess unexpected properties which, depending on the conditions, can have genotoxic consequences.


Ensnaring webs and nets: ethical issues in Internet-based research.
The Internet is a relatively new medium for research that few nurse researchers have embraced. While it offers countless opportunities for nursing research, it also is prey to many perils. In the crucible of cyberspace, the very nature of not only the research process, but also that of the participant researcher relationship is transmuted. This paper critically examines the major and often unique ethical issues of online research, and argues these must be adequately addressed if online nursing research is to effectively protect participants and researchers from harm, and optimally meet the profession's and society's best interests.


Mechanism of growth inhibitory effect of Blumea balsamifera extract in hepatocellular carcinoma.
Blumea balsamifera is known to improve physiological disorders such as rheumatism and hypertension, but its anticancer activity has not been well elucidated. In this study, we found that Blumea balsamifera MeOH extract (BME) induced growth-inhibitory activity in rat and human hepatocellular carcinoma cells without cytotoxicity in rat hepatocytes which were used as a normal cell model. BME induced cell cycle arrest at the G1 phase via decreases in the expression of cyclin-E and phosphorylation of retinoblastoma protein. Furthermore, BME reduced the level of a proliferation-inducing ligand, that stimulates tumor cell growth. These findings suggest that BME has possible therapeutic potential in hepatoma cancer patients and that depletion of cellular APRIL is an important mechanism in the growth-inhibitory effect of BME.


Lessons from fatal re-expansion pulmonary oedema: case series.
The goal of this study was to investigate the extent of the alveolar-capillary membrane porosity in patients with severe re-expansion pulmonary oedema. The biochemistry of airway fluid of two patients who died of re-expansion oedema was compared to their blood biochemistry. The airway fluid was comparable to plasma, while no blood cells were observed across the alveolar-capillary membrane. The membrane was linked to a fishnet that traps cells on one side, while plasma sieved through.


Surgical treatment for early breast cancer: should the patient decide?
Conservative surgery followed by a course of radiotherapy has been shown to be as effective as mastectomy in terms of survival and disease-free interval. This has led to an increase in the number of surgeons who undertake conservative surgery for early breast cancer. However, some studies have shown that, when offered a choice of surgery, some women elect mastectomy. Such results highlight the need for patients to be fully involved in the decision made about surgery, especially in the circumstances where there is more than one surgical option and a choice of surgery can be offered.


Anterior lingual thyroglossal cyst: antenatal diagnosis, management, and long-term outcome.
To describe the long-term outcome of a large anterior lingual thyroglossal duct cyst, diagnosed antenatally by ultrasound that completely obstructed the oral cavity and had almost completely replaced the anterior two-thirds lingual musculature. Longitudinal observation. Anticipated airway obstruction at birth did not occur. Complete cyst removal occurred at day 2 of life with a rim of lingual muscle observed present only on the left side. Complete and safe oral feeding was achieved by day 11 of life. Progressive muscle mass development and function with mild asymmetry was observed during sequential assessments. Vigorous speech therapy was started at age 7 months achieved 80-100% intelligible speech with minimal misarticulations at age 33 months. This case demonstrates the remarkable compensatory ability of the tongue to achieve almost normal function with minimal anterior musculature that is critical to deglutition and articulation. Early speech therapy appears key to improving functional outcomes of speech. A strong central nervous system basis for suckle development is suggested by the rapid development of a safe and effective suckle and swallow soon after cyst resection and in spite of in utero tongue fixation.


The first case of invasive EEG monitoring for the surgical treatment of epilepsy: historical significance and context.
Controversy persists about when EEG became a fundamental tool in the preoperative investigation for epilepsy surgery. We revisit Penfield's first use of invasive EEG monitoring, emphasizing its historical importance for the evolution of epilepsy surgery. Patients' hospital charts and articles published before 1940 regarding EEG and epilepsy or EEG and cerebral lesions were reviewed to evaluate the historical context of the surgery. In April 1939, Penfield performed trephination over both temporal regions and placed electrodes on the dura, intending to lateralize seizure origin in a patient with bitemporal epilepsy. The patient underwent serial EEGs with this technique. The final report of the recordings from epidural leads was "continued random delta activity in the left temporal region indicating a cortical lesion on this side." The pneumoencephalogram showed "the presence of diffuse cerebral atrophy, particularly in the left cerebral hemisphere." Based on these findings, the patient underwent surgery on April 21, revealing a meningocerebral scar in the posterior part of the left temporal lobe. Brain stimulation and electrocorticography delineated the extent of resection, while preserving the speech area. Seizures did not improve. We revisit the first case of epidural EEG monitoring for epilepsy surgery and show that the concept of EEG-directed surgery was already present at the Montreal Neurological Institute in the late 1930s.


Neoliberalist influences on nursing hospital work process and organization.
To describe and analyze the influence of the neoliberal economic and political model on the nursing hospital work process and organization. Qualitative descriptive research, having as its scenery a university hospital. The subjects were 34 nursing workers. The data collection took place from March to July 2013, through semi-structured interview. The data treatment technique used was content analysis, which brought up the following category: working conditions precariousness and its consequences to the hospital work process and organization in the neoliberal context. The consequences of neoliberalism on hospital work process and organization were highlighted, being observed physical structure, human resources and material inadequacies that harms the assistance quality. In addition to wage decrease that cause the need of second jobs and work overload. There is a significant influence of the neoliberal model on hospital work, resulting on working conditions precariousness. Descrever e analisar a influência do modelo econômico e político neoliberal na organização e no processo de trabalho hospitalar de enfermagem. Pesquisa qualitativa e descritiva, tendo como cenário um hospital universitário. Os participantes foram 34 trabalhadores de enfermagem. A coleta ocorreu de março a julho de 2013, por meio de entrevista semiestruturada. A técnica de tratamento dos dados foi a análise de conteúdo, que fez emergir a seguinte categoria: precarização das condições laborais e suas repercussões para organização e processo de trabalho hospitalar no contexto neoliberal. Evidenciaram-se repercussões do neoliberalismo na organização e no processo de trabalho hospitalar, verificando-se inadequações na estrutura física, nos recursos humanos e materiais, que afetavam a qualidade da assistência. Além de perdas salariais que levam à necessidade de outros empregos e sobrecarga de trabalho. Há forte influência do modelo neoliberal no trabalho hospitalar, resultando na precarização das condições laborais.


[Length of operation with video-assisted thoracoscopic lobectomy].
To determine the duration of the resection of pulmonary lobe (RPL) and the effect of video-assisted thoracoscopic surgery (VATS) procedure on the duration of RPL. The records of 126 patients who had VATS lobectomy from October 2009 to October 2010 with a single-direction thoracoscopic procedure in one hospital were reviewed. The patients included 65 (52%) men and 61 (48%) women with a mean age of 56 years (range, 15 years to 82 years). Four cases were excluded because of intraoperative complication. The average length of operation of RPL in the 122 patients without intraoperative complications was 38.98 min +/- 13.243 min (range, 17 min to 100 min), and the average length of the entire operation was 153.36 min +/- 39.64 min (range, 70 min to 245 min). Regardless which lobes, the average length of a single RPL remained the same (P > 0.05). The RPL of bilobectomies took longer than a single lobectomy (P < 0.05). However, no significant differences in the length of the entire operations were found between bilobectomy and single lobectomy (P > 0.05). The length of RPL reflects the difficulties of the core step of thoracoscopic lobectomy. Single-direction thoracoscopic lobectomy is an easy procedure to manipulate.


2-Amino-3-ketobutyrate CoA ligase of Escherichia coli: stoichiometry of pyridoxal phosphate binding and location of the pyridoxyllysine peptide in the primary structure of the enzyme.
Pure 2-amino-3-ketobutyrate CoA ligase from Escherichia coli, which catalyzes the cleavage/condensation reaction between 2-amino-3-ketobutyrate (the presumed product of the L-threonine dehydrogenase-catalyzed reaction) and glycine + acetyl-CoA, is a dimeric enzyme (Mr = 84,000) that requires pyridoxal 5'-phosphate as coenzyme for catalytic activity. Reduction of the hololigase with tritiated NaBH4 yields an inactive, radioactive enzyme adduct; acid hydrolysis of this adduct allowed for the isolation and identification of epsilon-N-pyridoxyllysine. Quantitative determinations established that 2 mol of pyridoxal 5'-phosphate are bound per mol of dimeric enzyme. After the inactive, tritiated enzyme adduct was digested with trypsin, a single radioactive peptide containing 23 amino acids was isolated and found to have the following primary structure: Val-Asp-Ile-Ile-Thr-Gly-Thr-Leu-Gly-Lys*-Ala-Leu-Gly-Gly-Ala-Ser-Gly-Gly -Tyr-Thr-Ala-Ala-Arg (where * = the lysine residue in azomethine linkage with pyridoxal 5'-phosphate). This peptide corresponds to residues 235-257 in the intact protein; 10 residues around the lysine residue have a high level of homology with a segment of the primary structure of 5-aminolevulinate synthase from chicken liver.


Characterization of mild and severe post-radical nephrectomy renal functional deterioration utilizing histopathological evaluation of non-neoplastic nephrectomized renal parenchyma.
We investigated factors affecting mild (MRFD) and severe renal functional deterioration (SRFD) after radical nephrectomy with a special focus on the histopathology of nephrectomized non-neoplastic renal parenchyma. MRFD was defined as a postoperative decline of percent estimated glomerular filtration rate (eGFR) lower than the value of the mean minus standard deviation (SD). SRFD was defined as a rate greater than the value of the mean plus SD. The histopathological factors of global glomerulosclerosis (GS) and arteriosclerosis in non-neoplastic renal parenchyma and multiple clinical factors were analyzed to determine whether they affected postoperative renal functional deterioration in 100 renal cell carcinoma cases. The prognoses, including non-cancer mortality, were collected from long-term follow-up data. A higher preoperative eGFR and a higher global GS extent in non-neoplastic renal parenchyma were independently associated with MRFD and SRFD, respectively. The cardiovascular disease-specific survival rates of the SRFD group and the group with global GS extent >14 % were significantly worse than those of their counterparts. This is the first report to identify global GS extent in nephrectomized non-neoplastic renal parenchyma as a factor affecting the development of life-threatening post-nephrectomy renal functional deterioration. Moreover, we are the first to advocate the importance of the characterization of favorable post-nephrectomy renal functional deterioration. The identification of MRFD and SRFD by histopathological evaluation of nephrectomized non-neoplastic renal parenchyma will contribute to personalized postoperative follow-up. It may improve follow-up of individual patients with SRFD by permitting collaboration with other clinical departments such as cardiology.


D-galactosamine-induced cell damage enhances specific binding of prostaglandin E1 to rat hepatocytes.
Specific bindings of [3H]prostaglandin E1 ([3H]PGE1), 125I-glucagon and [3H]norepinephrine to D-galactosamine (GalN)-treated rat hepatocytes in primary culture were investigated. After a two hour-treatment with GalN (1 and 10mg/ml), hepatocytes showed an enhanced specific binding to [3H]PGE1, whereas 125I-glucagon binding was little affected and [3H]norepinephrine binding was strongly diminished. Scatchard plot analysis indicated an increase of binding sites of [3H]PGE1. This unusual manner of [3H]PGE1 binding is suggested to indicate a special property of PGE1 receptor and may be associated with the cytoprotective effect of prostaglandins.


Inattentional blindness for a gun during a simulated police vehicle stop.
People often fail to notice unexpected objects and events when they are focusing attention on something else. Most studies of this "inattentional blindness" use unexpected objects that are irrelevant to the primary task and to the participant (e.g., gorillas in basketball games or colored shapes in computerized tracking tasks). Although a few studies have examined noticing rates for personally relevant or task-relevant unexpected objects, few have done so in a real-world context with objects that represent a direct threat to the participant. In this study, police academy trainees (n = 100) and experienced police officers (n = 75) engaged in a simulated vehicle traffic stop in which they approached a vehicle to issue a warning or citation for running a stop sign. The driver was either passive and cooperative or agitated and hostile when complying with the officer's instructions. Overall, 58% of the trainees and 33% of the officers failed to notice a gun positioned in full view on the passenger dashboard. The driver's style of interaction had little effect on noticing rates for either group. People can experience inattentional blindness for a potentially dangerous object in a naturalistic real-world context, even when noticing that object would change how they perform their primary task and even when their training focuses on awareness of potential threats.


Native mass spectrometry of photosynthetic pigment-protein complexes.
Native mass spectrometry (MS), or as is sometimes called "native electrospray ionization" allows proteins in their native or near-native states in solution to be introduced into the gas phase and interrogated by mass spectrometry. This approach is now a powerful tool to investigate protein complexes. This article reviews the background of native MS of protein complexes and describes its strengths, taking photosynthetic pigment-protein complexes as examples. Native MS can be utilized in combination with other MS-based approaches to obtain complementary information to that provided by tools such as X-ray crystallography and NMR spectroscopy to understand the structure-function relationships of protein complexes. When additional information beyond that provided by native MS is required, other MS-based strategies can be successfully applied to augment the results of native MS.


Estimates of distance by claudicants and vascular surgeons are inherently unreliable.
Claudication distance and maximum walking distance are both measures of disability. Estimates of the distances which a patient with intermittent claudication can walk are commonly used by vascular surgeons as surrogate measures of handicap. We studied how accurately distance was estimated by 70 patients with intermittent claudication, and by 100 British vascular surgeons. Patients and vascular surgeons estimated actual distances of 30 m and 34 m, respectively. Estimates were 46 m median (range 2.7-402 m) for claudicants, and 46 m median (range 15.2-186 m) for vascular surgeons, median over estimates of 52% and 34% respectively. Claudicants' errors can easily be eliminated by accurate and appropriate measurement of claudication and maximum walking distances but interpretation of the data by surgeons is dependent on their own ability to estimate distance. Flawed perceptions by patients and their surgeons of the disability of reduced walking distance illustrates the need for reliable measures of handicap on which to base therapeutic decisions in patients with intermittent claudication.


Why lightning strikes twice: postpartum resumption of sexual activity during adolescence.
To describe the circumstances surrounding the postpartum resumption of sexual activity in a cohort of teenage mothers. The goal was to shed new light on the reasons why teenagers who have just given birth put themselves at risk for conception. A racially and ethnically diverse group of 267 poor, predominantly unmarried, primiparous, 13-21 year olds was enrolled consecutively at delivery and followed through the third postpartum month. The primary outcome measure was weeks postpartum at resumption of sexual activity, further categorized as protected or unprotected. The analysis controlled for factors thought to influence the postpartum resumption of sexual activity among adult couples and the use of contraception during adolescence. The Kaplan-Meier method was used to estimate the time to end point and Cox proportional-hazards regression analysis to compute relevant relative risks (RR). By the end of the third postpartum month, 58% of the teenagers had had sexual intercourse and the majority (80%) used contraception when they did so. The median time to first coitus, 10.7 weeks, was unrelated to contraceptive use but was significantly shorter among teenagers who lived with their boyfriends (RR: 2.4; 95%CI: 1.7-3.4) and those who delivered prior to term (RR: 2.1; 95%CI: 1.3-3.6). The analysis revealed that the teenagers who did not use contraception at first postpartum sexual intercourse exhibited more theorized risk factors for conception than those who did and those who remained sexually abstinent. This new empirical evidence that coital activity resumes soon after delivery should dispel the normative belief that contraception is unnecessary during the puerperium. Early contraceptive vigilence may also decrease the frequency and rapidity with which teen mothers conceive, as the differences in the prevalence of teen pregnancy risk factors we uncovered suggest that decisions about using contraception (not sexual intercourse) determine the risk of rapid repeat conception. Teens with live-in boyfriends and premature babies are especially apt to benefit from the new information in this report as they resume sexual activity sooner than their peers and are less apt to use contraception when they do so.


Responsive and biocompatible chitosan-phytate microparticles with various morphology for antibacterial activity based on gas-shearing microfluidics.
Chitosan microparticles are frequently used for the encapsulation of ingredients, owing to their pH-responsive, renewable, biocompatible and antimicrobial properties. Herein, pH-responsive antibacterial encapsulation carriers in chitosan-phytate (CS-PA) microparticles with various morphologies were prepared by gas-shearing microfluidics. Microparticles sizes were tuned by gas flow rate in production, and the CS and PA concentration significantly dominated the morphology of microparticles. Additionally, microparticles exhibit great storage stability, lyophilizing rehydration performance, pH-responsive behavior, as well as antibacterial and biocompatible effect, indicating that CS-PA microparticles are expected to become an ideal carrier for the actives encapsulation in pharmaceutical, food and cosmetic industries.


The correlation of atherosclerosis and triglyceride glucose index: a secondary analysis of a national cross-sectional study of Japanese.
Few studies examined the relationship between triglyceride/glucose index (TyG index) and atherosclerosis in Japanese adults. Therefore, this study evaluated their relationship, as measured based on the brachial-ankle pulse wave velocity (baPWV) in Japanese adults. A total of 912 participants was selected from the NAGALA (NAFLD in Gifu Area, Longitudinal Analysis) study conducted from 2004 to 2012. The relationship between the TyG index and baPWV was estimated through a logistic model. Subgroup analyses by sex, age, body mass index (BMI), total cholesterol, low-density lipoprotein cholesterol, estimated glomerular filtration rate (eGFR), and fatty liver was performed. The formula for TyG index was ln (½fasting triglyceride level [mg/dL] × fasting plasma glucose level [mg/dL]). A linear relationship between TyG and baPWV was discovered after adjusting for underlying confounders. An increased risk of baPWV was observed after adjusting for sex, age, BMI, systolic blood pressure, diastolic blood pressure, high-density lipoprotein cholesterol, fatty liver, eGFR, and TyG as a continuous variable (adjusted odds ratio [adj OR], 1.57; 95% confidence interval [95% CI], 1.14-2.18). Compared with the TyG index in the first tertile, the probabilities of subjects in the third tertile that developed to baPWV were 1.78-fold higher (adj OR 1.78, 95% CI 1.08-2.95: P for trend 0.024). Moreover, stable associations were observed between the TyG index and baPWV in different variables through subgroup analyses. The highest tertile (above 8.57) of the TyG index was positively and linearly related to subclinical atherosclerosis in Japanese adults and may be valuable as a predicted marker.


α-Tocopherol bioavailability is lower in adults with metabolic syndrome regardless of dairy fat co-ingestion: a randomized, double-blind, crossover trial.
Increasing dietary fat intake is expected to improve α-tocopherol bioavailability, which could be beneficial for improving α-tocopherol status, especially in cohorts at high cardiometabolic risk who fail to meet dietary α-tocopherol requirements. Our objective was to assess dose-dependent effects of dairy fat and metabolic syndrome (MetS) health status on α-tocopherol pharmacokinetics in plasma and lipoproteins. A randomized, crossover, double-blind study was conducted in healthy and MetS adults (n = 10/group) who ingested encapsulated hexadeuterium-labeled (d6)-RRR-α-tocopherol (15 mg) with 240 mL nonfat (0.2 g fat), reduced-fat (4.8 g fat), or whole (7.9 g fat) milk before blood collection at regular intervals for 72 h. Compared with healthy participants, those with MetS had lower (P < 0.05) baseline plasma α-tocopherol (μmol/mmol lipid) and greater oxidized low-density lipoprotein (LDL), interleukin (IL)-6, IL-10, and C-reactive protein. Regardless of health status, d6-α-tocopherol bioavailability was unaffected by increasing amounts of dairy fat provided by milk beverages, but MetS participants had lower estimated d6-α-tocopherol absorption (±SEM) than did healthy participants (26.1% ± 1.0% compared with 29.5% ± 1.1%). They also had lower plasma d6-α-tocopherol AUC from 0 to 72 h, as well as maximal concentrations (Cmax: 2.04 ± 0.14 compared with 2.73 ± 0.18 μmol/L) and slower rates of plasma disappearance but similar times to Cmax. MetS participants had lower d6-α-tocopherol AUC from t = 0-12 h (AUC0- t final) in lipoprotein fractions [chylomicron, very-low-density lipoprotein (VLDL), LDL, high-density lipoprotein]. Percentages of d6-α-tocopherol AUC0- t final in both the chylomicron (r = -0.46 to -0.52) and VLDL (r = -0.49 to -0.68) fractions were inversely correlated with oxidized LDL, IL-10, IL-6, and C-reactive protein. At dietary intakes equivalent to the Recommended Dietary Allowance, α-tocopherol bioavailability is unaffected by dairy fat quantity but is lower in MetS adults, potentially because of greater inflammation and oxidative stress that limits small intestinal α-tocopherol absorption and/or impairs hepatic α-tocopherol trafficking. These findings support higher dietary α-tocopherol requirements for MetS adults. This trial was registered at www.clinicaltrials.gov as NCT01787591.


Sensibility of five at-work productivity measures was endorsed by patients with osteoarthritis or rheumatoid arthritis.
To examine and compare the sensibility attributes (face/content validity and feasibility) of five at-work productivity measures from the perspective of patients with osteoarthritis (OA) or rheumatoid arthritis (RA). Workers with OA or RA (n = 250) completed a survey that includes five at-work productivity (presenteeism) measures and questions asking about their comprehensiveness, understandability, length, and suitability of response options. A final question asked respondents which single measure was considered "best" overall. Measures compared included the Workplace Activity Limitations Scale (WALS), Stanford Presenteeism Scale, Endicott Work Productivity Scale, Work Instability Scale for Rheumatoid Arthritis (RA-WIS), and Work Limitations Questionnaire (WLQ-25). Sensibility performance was assessed quantitatively (% respondent endorsement) and qualitatively via written feedback. The WLQ-25 was considered most comprehensive (endorsed by 92.8%), the WALS performed best in terms of understandability (97.6%) and suitability of response options (97.9%), and the RA-WIS was favored in terms of length (91.6%). Consistent sensibility performance between OA and RA was found. The WALS (32.6%) and WLQ-25 (30.0%) were moderately preferred in the final overall appraisal. Sensibility criteria were generally met by all five at-work productivity measures. Variable endorsement levels across specific sensibility attributes were also revealed across the measures compared.


Amdinocillin: a novel penicillin. Antibacterial activity, pharmacology and clinical use.
Amdinocillin is a novel penicillin whose antibacterial activity is derived from its ability to bind specifically and avidly to Penicillin Binding Protein-2 (PBP 2). Other beta-lactams bind almost exclusively to PBPs 1 and 3. This unique feature has prompted many investigators to predict that amdinocillin would aggressively synergize with other antimicrobials, particularly other beta-lactams. Certain features of these predictions have been realized. Amdinocillin is active alone against many gram-negative organisms. Pseudomonas and non-fermenting gram-negative bacteria, however, are usually resistant. Amdinocillin, in combination with many beta-lactams, exhibits marked synergy against many enterobacteriaceae. No such synergy can be demonstrated for gram-positive organisms or pseudomonas species. Amdinocillin is not beta-lactamase stable. Organisms which produce high levels of plasma-mediated beta-lactamase are resistant to the drug. Amdinocillin is widely distributed to most tissues of the body. It is removed by renal tubular secretion which results in prodigious levels of the drug in the urine. Co-administration of probenecid results in markedly elevated plasma levels of amdinocillin and delays its excretion. Amdinocillin has a plasma half-life of about one hour in patients with grossly normal renal function. Its half-life increases to 3 to 6 hours in anephric patients. The spectrum of adverse reactions observed with amdinocillin is similar to that of other penicillins. Amdinocillin, as a single agent, is effective in the treatment of urinary tract infections caused by susceptible strains of E. coli and klebsiella and enterobacter species. When amdinocillin is used in concert with other antimicrobials, synergy can frequently be demonstrated but it is essentially limited to gram-negative aerobic organisms. At present, insufficient data are available to precisely profile the utility of amdinocillin, either alone or in combination, in the treatment of systemic infections.


Cranial irradiation significantly reduces beta amyloid plaques in the brain and improves cognition in a murine model of Alzheimer's Disease (AD).
To investigate if cranial X-irradiation reduces amyloid-β (Aβ) plaques and influences cognitive function in a transgenic mouse model of AD. B6.Cg-Tg (APPswePSEN1dE9)85Dbo/J AD-prone mice were given cranial X-irradiation. The number of Aβ plaques, along with expression of AD specific genes (84 genes: Mouse Alzheimer's Disease RT(2) Profiler), radiation-associated cytokines (Milliplex MAP Mouse Cytokine Chemokine Immunoassay) and immunohistochemistry (IL10, IL-1β, Iba1 CD45) was assessed. Behavioral testing was performed to relate changes in Aβ burden to cognitive function using a Morris water-maze task. Single X-ray doses reduced the number (p=0.002) and size (p=0.01) of Aβ plaques. Low-dose fractionation produced greater 50.6% (1 Gy × 10), 72% (2 Gy × 5) and 78% (2 Gy × 10) reductions. Irradiation was associated with gene (Pkp4, 1.5-fold, p=0.004) and proteomic (MIP-2, 8-fold, p=0.0024) changes at 24-48 h. Microglia increased at 4 weeks post-irradiation (p=0.001). The reduction in Aβ burden (2 Gy × 5) was associated with cognitive improvement (p=0.012). This is the first report that a clinically relevant course of external beam irradiation (2 Gy × 5) produces a significant reduction in AD-associated amyloid-β plaques with a subsequent improvement in cognitive function. However, longer-term studies are needed to define the precise underlying mechanism and longevity of this response.


Determination of trace alpha-fetoprotein variant by affinity adsorption solid substrate-room temperature phosphorimetry and its application to the forecast of human diseases.
In the presence of ion perturber LiAc, 4-generation polyamidoamine dendrimers (4G-D) could emit strong and stable room temperature phosphorescence (RTP) signal at lambda(max)(ex)/lambda(max)(em) = 511.8/675.3 nm on nitrocellulose membrane (NCM), and Triton X-100 could sharply enhance the RTP signal of 4G-D. Triton X-100-4G-D was used to label concanavalin agglutinin (Con A) to get the labeling product Triton X-100-4G-D-Con A. Quantitative specific affinity adsorption (AA) reaction between Triton X-100-4G-D-Con A and alpha-fetoprotein variant (AFP-V) could be carried out on the surface of NCM, whose product Triton X-100-4G-D-Con A-AFP-V could emit strong and stable RTP and its deltaI(p) was proportional to the content of AFP-V. According to the facts above, a new affinity adsorption solid substrate-room temperature phosphorimetry (AA-SS-RTP) for the determination of trace AFP-V by Con A labeled with Triton X-100-4G-D was established. Detection limits of this method were 0.23 fg spot(-1) (direct method, corresponding concentration: 5.8x10(-13) g mL(-1)) and 0.13 fg spot(-1) (sandwich method, corresponding concentration: 3.2x10(-13) g mL(-1)). It has been successfully applied to determine the content of AFP-V in human serum and forecast human diseases, for its high sensitivity, long RTP lifetime, good repeatability, high accuracy and little background perturbation with lambda(max)(em) at the long wavelength area. Meanwhile, the mechanism for the determination of trace AFP-V using AA-SS-RTP was also discussed.


Determining the most optimal stage for embryo cryopreservation.
The objective of this study was to compare cleaved embryo and blastocyst freezing to determine the optimal time for embryo cryopreservation. A retrospective analysis was carried out for all frozen embryo transfer cycles where transfer occurred on either day 3 or day 5. Blastocyst freezing increased the ongoing pregnancy, implantation and survival rates post-thaw as compared with cleaved embryo thaws. There was no difference in ongoing pregnancies for fresh and frozen-thawed blastocyst transfers (59% versus 62%) respectively. Additionally, fresh blastocyst transfers had a higher proportion of supernumerary embryos cryopreserved than did day 3 transfers (38% versus 26%). Blastocyst freezing is a viable option for handling patient's supernumerary embryos while optimizing pregnancy outcomes per oocyte retrieval.


Shear-horizontal surface acoustic wave sensor for non-invasive monitoring of dynamic cell spreading and attachment in wound healing assays.
A Love-wave based biosensor is introduced for analyzing a standardized wound healing assay by observing cell growth and quantifying cell detachment processes. Utilizing the piezoelectric material LiTaO3 36° XY-cut with a thin SiO2-cover layer, shear horizontal surface acoustic waves (SAW) are excited and detected by a set of Interdigital Transducers. Epithelial cells, being cultivated on the substrate and invading the sensors delay line cause a phase shift in the transmitted SAW signal. This phase shift correlates exactly with the surface coverage of the invading cells. After wound healing, emerging fluctuations in the phase shift signal provide information about the cell growth in a confluent cell layer. Additionally, the signal slope allows to quantify the cell detachment process induced by apoptosis, necrosis or cell lysis substances, respectively. Furthermore, culture conditions like temperature or osmolality can be simultaneously monitored by SAW. Based on a theoretical approach and using FEM simulations, we identified the acoustoelectric interaction as the main reason for the phase shift in various frequency- and time-dependent studies. Our model is validated by experimental data and allows predicting the phase change caused by variations in the cell-substrate distance or the volume ratio of the nucleus and the complete cell.