Pollen-Food Allergy Syndrome in Korean Pollinosis Patients: A Nationwide Survey.
Pollen-food allergy syndrome (PFAS) is an immunoglobulin E (IgE)-mediated allergy in pollinosis patients caused by raw fruits and vegetables and is the most common food allergy in adults. However, there has been no nationwide study on PFAS in Korea. In this study, we investigated the prevalence and clinical characteristics of PFAS in Korea. Twenty-two investigators participated in this study, in which patients with allergic rhinoconjunctivitis and/or bronchial asthma with pollen allergy were enrolled. The questionnaires included demographic characteristics, a list of fruits and vegetables, and clinical manifestations of food allergy. Pollen allergy was diagnosed by skin prick test and/or measurement of the serum level of specific IgE. A total of 648 pollinosis patients were enrolled. The prevalence of PFAS was 41.7% (n = 270). PFAS patients exhibited cutaneous (43.0%), respiratory (20.0%), cardiovascular (3.7%) or neurologic symptoms (4.8%) in addition to oropharyngeal symptoms. Anaphylaxis was noted in 8.9% of the PFAS patients. Seventy types of foods were linked to PFAS; e.g., peach (48.5%), apple (46.7%), kiwi (30.4%), peanut (17.4%), plum (16.3%), chestnut (14.8%), pineapple (13.7%), walnut (14.1%), Korean melon (12.6%), tomato (11.9%), melon (11.5%) and apricot (10.7%). Korean foods such as taro/taro stem (8.9%), ginseong (8.2%), perilla leaf (4.4%), bellflower root (4.4%), crown daisy (3.0%), deodeok (3.3%), kudzu root (3.0%) and lotus root (2.6%) were also linked to PFAS. This was the first nationwide study of PFAS in Korea. The prevalence of PFAS was 41.7%, and 8.9% of the PFAS patients had anaphylaxis. These results will provide clinically useful information to physicians.


Quitline Reach and Effectiveness among Populations Disproportionately Affected by Tobacco Use: Future Directions.
Quitlines have great potential reach, utility, and effectiveness in promoting tobacco use cessation and for reducing tobacco-related health disparities (TRHDS). The existing literature underscores the particular promise of quitlines for addressing TRHDS among Black people and American Indians/Alaskan Natives. However, reach is a concern for several subgroups, including Latinx, sexual/gender minorities, and those with mental health conditions. The literature also suggests challenges regarding the efficacy of quitlines in promoting cessation among certain subgroups, such as low-income smokers or those with comorbid mental or physical health conditions. Strategies used to increase engagement and reach for subpopulations have included media campaigns and culturally-responsive communication strategies and intervention approaches. Further research is needed 1) to better document reach and effectiveness of quitlines for populations experiencing TRHDS; 2) to examine how best to adapt quitline approaches for specific populations with distinct needs; and 3) to examine scalable, low-cost strategies for increasing quitline reach and effectiveness and reducing TRHDS.


Survival after recurrence of stage I-III breast, colorectal, or lung cancer.
The experiences of patients with recurrent cancer are assumed to reflect those of patients with de novo stage IV disease; yet, little is truly known because most registries lack recurrence status. Using two databases with excellent recurrence and death information, we examined determinants of survival duration after recurrence of breast (BC), colorectal (CRC), and lung cancers (LC). Recurrence status was abstracted from the medical records of patients who participated in the Cancer Care Outcomes Research and Surveillance study and who received care at two Cancer Research Network sites-the Colorado and Northwest regions of Kaiser Permanente. The analysis included 1653 patients who developed recurrence after completing definitive therapy for stages I-III cancer. Multivariable modeling identified independent determinants of survival duration after recurrence, controlling for other factors. Through 60 months' average follow-up, survival after recurrence for BC, CRC, and LC were 28.4, 23.1 and 16.1 months, respectively. Several factors were independently associated with shorter survival for all three cancers, including higher initial stage (III vs. I: BC -9.9 months; CRC -6.9 months; LC -7.4 months; P≤0.01). Factors associated with shorter survival for selected cancers included: distant/regional recurrence for BC and CRC; current/former smoker for LC; high grade for CRC; and <4-year time-to-recurrence for BC. Initial stage predicts survival duration after recurrence, whereas time-to-recurrence usually does not. The impact of biologic characteristics (e.g., grade, hormone-receptor status) on survival duration after recurrence needs further study. Predictors of survival duration after recurrence may help facilitate patient decision-making.


Expression of genes involved in regulation of cell turnover during milk stasis and lactation rescue in sow mammary glands.
We studied the transcription of selected genes involved in the regulation of cell turnover during milk stasis and lactation rescue in individual mammary glands of sows and evaluated the timeframe for lactation rescue and the subsequent productivity of rescued glands. Suckling was prevented in two glands from each of five sows by taping them the day after farrowing for 1 or 3 d (Closed 24 h and Closed 72 h glands, respectively). After removing the tape, Closed 24 h glands were suckled until weaning. Closed 72 h glands were refused by the piglets and therefore remained unsuckled. Mammary gland biopsies were collected to quantify the transcription of genes involved in cell turnover and the percentage of proliferating and apoptotic cells. Transcriptional data were analyzed with a gamma-distributed generalized linear mixed model. Mammary transcription of alpha-lactalbumin was high in suckled glands the day after farrowing, indicating onset of lactation, but was downregulated after 1 d of milk stasis. The prolactin receptor mRNA was downregulated and IGFBP-5 mRNA was upregulated within 1 d of milk stasis. The downregulation of alpha-lactalbumin and prolactin receptor and upregulation of IGFBP-5 mRNA noted after 1 d of milk stasis was maintained in Closed 72 h glands (those glands regressed) but reversed on d 4 and 6 of lactation in Closed 24 h glands. Mammary IGF-I mRNA was not regulated in response to milk stasis or lactation rescue. The percentage of proliferating cells in mammary glands was high prepartum (13.1%) and intermediate (7.8%) the day after farrowing. By d 6 of lactation, the percentage of proliferating cells was increased to 10.1% (P < 0.01) in glands suckled regularly but decreased to 5.9% (P < 0.05) in regressing glands (Closed 72 h glands). Glands rescued after 1 d of milk stasis had lower productivity throughout lactation than glands suckled regularly, as indicated by the BW of piglets suckling these glands (242 vs. 315 g/d, respectively; P < 0.05). In conclusion, regularly suckled glands had a greater cell proliferation, greater transcriptions of alpha-lactalbumin and prolactin receptor genes, and less IGFBP-5 transcription compared with rescued (Closed 24 h) and regressing (Closed 72 h) glands. Glands that were not suckled for 1 d could be rescued, although their subsequent productivity was lower, whereas glands not suckled for 3 d could not be rescued.


Can platelet-rich plasma enhance the effect of meniscus repair? A meta-analysis of randomized controlled trials Platelet-rich plasma and meniscus repair.
Studies have shown that platelet-rich plasma (PRP) can enhance the effect of meniscus repair, but some studies have suggested different views on the role of PRP. To determine whether PRP can enhance the effect of meniscus repair with respect to pain reduction and improved functionality and cure rate in patients with meniscus injury. By searching PubMed, EMBASE, Cochrane Library databases, clinicaltrials.gov, and the CNKI database from their inception till December 1, 2020, we performed a meta-analysis of RCTs reporting the results of the Pain Visual Analog Scale (VAS), the pain of Knee injury and Osteoarthritis Outcome Score (KOOS), Lysholm score, the International Knee Documentation Committee (IKDC), healing rate, and adverse events. The risk of bias is assessed using Cochrane's collaborative tools. The summary results are expressed with effect size and 95% confidence interval, and sensitivity were performed. The meta-analysis included 9 RCTs and 345 patients. In general, compared with the control group, used of PRP during meniscus surgery significantly improved the pain (SMD: -0.95, p < 0.00001,95% CI: -1.22 to -0.69, I2 = 42%) and knee joint function (SMD: 1.00, p = 0.01.95% CI: 0.22 to 1.79, I2 = 89%) of patients with meniscus injury at 6 months after treatment. However, both PRP and non-PRP showed improvements in the pain and knee joint function, with no significant difference between the groups at 1 months and beyond 12 months. The PRP enhancement technique showed benefit in improving the cure rate of meniscus repair (RR:1.44; p < 0.0001, 95% CI: 1.20-1.73). No serious adverse events were reported in any study. As an enhancement program for meniscus repair, PRP is worthy of further consideration in improving the function and pain of patients during the mid-term follow-up after surgery, and PRP can further improve the healing rate of meniscus repair. However, the evidence still needs to be interpreted carefully because of the quantity and quality of the included studies.


[Desensitization of dust mite drops on antigen-specific asthmatic reaction in guinea pigs].
To establish an antigen-specific asthmatic model of guinea pig induced by protein antigen extracted from Dermatophagoides farinae (Der f), and study the desensitization of dust mite drops (DMD, extracted from Der f) in a dose progressive manner and long-term sublingual administration. To sensitize the guinea pigs, the protein antigen emulsified in aluminium hydroxide gel was subcutaneously and intraperitoneally injected. To observe early-phase reaction of asthma, lung resistance (R(L)) and lung dynamic compliance (Cdyn) in the sensitized guinea pigs were determined by intravenously injecting antigen. To observe late-phase reaction of asthma, the sensitized guinea pigs were challenged with aerosolized antigen for 7 days. Subsequently, methacholine (Mch) in a cumulative dose-manner induced-airway hyperreactivity (AHR), inflammatory cells numbers in bronchoalveolar lavage fluid (BALF) and pathological changes of lung tissue were measured in the model. From the first day of sensitization, the guinea pigs in treatment group sublingually received DMD in a dose progressive manner. The model group sublingually received equivalent saline. The normal control group did not receive any treatment. The guinea pigs in model group showed a significant increase in R(L) and decrease in Cdyn, and developed a marked AHR to Mch. The number of total leukocytes and eosinophils increased significantly in BALF. Serious infiltration of eosinophils was observed in pathological section of lung tissue. Compared with model group, DMD treatment group exhibited a significant amelioration for early-phase and late-phase reaction of asthma. DMD in a dose progressive manner and long-term sublingual administration displays a significant desensitization on Der f antigen-specific asthmatic reaction. The results provided experimental evidence for clinical therapy.


Albumin and beta 2-microglobulin radioimmunoassays applied to monitoring of renal-allograft function and in differentiating glomerular and tubular diseases.
Blood and urine were samples daily from 11 renal-allograft recipients from one to six weeks after the transplant. Clearances of both albumin (Calb) and beta2-microglobulin (C beta 2 mu) were significantly increased in all 11 patients. Five patients (Group I) with acute allograft rejection showed markedly increased Calb and moderately increased C beta 2 mu, concurrent with decreased creatinine clearance (CCr). Five other patients (Group II) with no evidence of rejection demonstrated episodes of grossly increased C beta 2 mu with minimally increased but stable Calb and normal CCr. One patient had no evidence of rejection nor indications of glomerular or tubular proteinuria. While changes in serum beta 2-microglobulin concentration closely paralleled those of serum creatinine in the Group II patients, the results diverged in the Group I patients because the increase in serum beta 2-microglobulin exceeded that of serum creatinine and preceded the increased in creatinine by one to five days, suggesting that measurement of serum beta 2-microglobulin might afford earlier indication of the nature and extent of renal damage in the allograft recipients.


Patent foramen ovale: standards for a preclinical model of prevalence, structure, and histopathologic comparability to human hearts.
This study evaluated and standardized a Patent Foramen Ovale (PFO) preclinical model in gross anatomic and histopathologic features. We examined 150 necropsy-derived domestic porcine hearts, age 4-6 months for PFO prevalence, appearance, and size. Histopathologic preparations were standardized and processed identically to 24 post-mortem human hearts aged 16-62 years. A measurement scheme was developed for PFO atrial openings, tunnel length, and histopathologic features to compare porcine and patient hearts. PFO was found in 32 of the 150 porcine hearts (prevalence 21.3%). Twenty-five porcine PFO underwent standard characterization by tunnel length, and right, and left atrial orifice diameters. Logarithmic regression analysis between porcine PFO tunnel length and left atrial orifice area demonstrated a significant positive relationship (P = 0.0162, R(2) = 0.227). The porcine PFO tunnel length was significantly longer than in humans (12.0 +/- 4.0 mm vs. 7.1 +/- 3.1 mm respectively, P < 0.0001). Histopathologic comparison was made using serial sections perpendicular to the atrial septum and the tunnel long axis. Human and porcine PFO lesions demonstrated strong similarities in tissue cells, connective tissue, and matrix composition. PFO assessment was standardized in both macroscopically and histopathologically, with quantitative and qualitative comparisons feasible using a porcine preclinical model. PFO prevalence in domestic swine is identical to humans, and microscopic structures very similar to humans. The domestic swine PFO model appears useful to evaluate new interventional closure technologies due to comparability in microscopic features. Tunnel length should be carefully evaluated due to differences across pigs and patients.


Case Report: Myocarditis Associated With COVID-19 mRNA Vaccination Following Myocarditis Associated With Campylobacter Jejuni.
We herein present our experience with a case involving a 17-year-old Japanese boy suffering from acute myocarditis after his second coronavirus disease-2019 (COVID-19) messenger RNA (mRNA) vaccine shot. The patients had a history of myocarditis associated with Campylobacter jejuni 3 years prior. This has been the first-ever documented case of myocarditis associated with COVID-19 mRNA vaccination in a patient with a history of myocarditis. We present a series of images and blood biomarkers for different types of myocarditis that developed in this single patient.


Bit error rate of focused Gaussian beams in weak oceanic turbulence.
Formulation of the on-axis scintillation index of a focused Gaussian beam in weak oceanic turbulence is derived by using the Rytov method, and using this formulation, the average bit error rate (BER) is evaluated. The scintillation indices of collimated, focused Gaussian, plane, and spherical beams are compared. The scintillation index and BER versus the average signal-to-noise ratio is found by using the log-normal distributed intensity for the collimated and focused Gaussian beams, which are exhibited for various source sizes α(s), focal lengths F(s), rates of dissipation of the mean squared temperature χ(T), and rates of dissipation of the turbulent kinetic energy per unit mass of fluid ε. Focused beams are found to have important advantages over collimated beams. For the focused beam, as the source size increases, the scintillation index and BER decrease. When the focal length is equal to the propagation length, the BER is found to possess the smallest value. The BER is proportional to χ(T), but inversely proportional to ε.


Nonviral approaches for targeted delivery of plasmid DNA and oligonucleotide.
Successful gene therapy depends on the development of efficient delivery systems. Although pDNA and ODN are novel candidates for nonviral gene therapy, their clinical applications are generally limited owing to their rapid degradation by nucleases in serum and rapid clearance. A great deal of effort had been devoted to developing gene delivery systems, including physical methods and carrier-mediated methods. Both methods could improve transfection efficacy and achieve high gene expression in vitro and in vivo. As for carrier-mediated delivery in vivo, since gene expression depends on the particle size, charge ratio, and interaction with blood components, these factors must be optimized. Furthermore, a lack of cell-selectivity limits the wide application to gene therapy; therefore, the use of ligand-modified carriers is a promising strategy to achieve well-controlled gene expression in target cells. In this review, we will focus on the in vivo targeted delivery of pDNA and ODN using nonviral carriers.


Integration of Transparent Supercapacitors and Electrodes Using Nanostructured Metallic Glass Films for Wirelessly Rechargeable, Skin Heat Patches.
Here we demonstrate an unconventional fabrication of highly transparent supercapacitors and electrodes using random networks of nanostructured metallic glass nanotroughs for their integrations as wirelessly rechargeable and invisible, skin heat patches. Transparent supercapacitors with fine conductive patterns were printed using an electrohydrodynamic jet-printing. Also, transparent and stretchable electrodes, for wireless antennas, heaters and interconnects, were formed using random network based on nanostructured CuZr nanotroughs and Ag nanowires with superb optoelectronic properties (sheet resistance of 3.0 Ω/sq at transmittance of 91.1%). Their full integrations, as an invisible heat patch on skin, enabled the wireless recharge of supercapacitors and the functions of heaters for thermal therapy of skin tissue. The demonstration of this transparent thermotherapy patch to control the blood perfusion level and hydration rate of skin suggests a promising strategy toward next-generation wearable electronics.


Phase boundaries and biological membranes.
Bilayer mixtures of lipids are used by many researchers as chemically simple models for biological membranes. In particular, observations on three-component bilayer mixtures containing cholesterol show rich phase behavior, including several regions of two-phase coexistence and one region of three-phase coexistence. Yet, the relationship between these simple model mixtures and biological membranes, which contain hundreds of different proteins and lipids, is not clear. Many of the model mixtures have been chosen for study because they exhibit readily observed phase separations, not because they are good mimics of cell membrane components. If the many components of cell membranes could be grouped in some way, then understanding the phase behaviors of biological membranes might be enhanced. Furthermore, if the underlying interaction energies between lipids and proteins can be determined, then it might be possible to model the distributions of lipids and proteins in a bilayer membrane, even in complex mixtures.


Mössbauer spectroscopy of Fe/S proteins.
Iron-sulfur (Fe/S) clusters are structurally and functionally diverse cofactors that are found in all domains of life. (57)Fe Mössbauer spectroscopy is a technique that provides information about the chemical nature of all chemically distinct Fe species contained in a sample, such as Fe oxidation and spin state, nuclearity of a cluster with more than one metal ion, electron spin ground state of the cluster, and delocalization properties in mixed-valent clusters. Moreover, the technique allows for quantitation of all Fe species, when it is used in conjunction with electron paramagnetic resonance (EPR) spectroscopy and analytical methods. (57)Fe-Mössbauer spectroscopy played a pivotal role in unraveling the electronic structures of the "well-established" [2Fe-2S](2+/+), [3Fe-4S](1+/0), and [4Fe-4S](3+/2+/1+/0) clusters and -more-recently- was used to characterize novel Fe/S clustsers, including the [4Fe-3S] cluster of the O2-tolerant hydrogenase from Aquifex aeolicus and the 3Fe-cluster intermediate observed during the reaction of lipoyl synthase, a member of the radical SAM enzyme superfamily.


Fear of spoiling in at-risk African American mothers.
Mothers actively ascribe intention to the behavior of infants. Mothers also tailor their responses to infant behavior based on conceptions of how each response will influence later behavior. Fears of spoiling an infant may influence a mother's pattern of responsiveness. Sixty-eight at-risk African American mothers completed questionnaires assessing depressive symptoms, self-efficacy, empathy, developmental expectations, and beliefs about spoiling. Mothers with greater concerns about the long-term impact of spoiling reported higher levels of depression, more ways in which infants could be spoiled, and inappropriate developmental expectations when compared to mothers with fewer concerns. The pattern of findings suggests ways that fear of spoiling may influence maternal responsiveness in high-risk groups and potentially lead to disturbed mother-infant relationships.


Membrane targeting and asymmetric localization of Drosophila partner of inscuteable are discrete steps controlled by distinct regions of the protein.
Asymmetric division of neural progenitors is a key mechanism by which neuronal diversity in the Drosophila central nervous system is generated. The distinct fates of the daughter cells derived from these divisions are achieved through preferential segregation of the cell fate determinants Prospero and Numb to one of the two daughters. This is achieved by coordinating apical and basal mitotic spindle orientation with the basal cortical localization of the cell fate determinants during mitosis. A complex of apically localized proteins, including Inscuteable (Insc), Partner of Inscuteable (Pins), Bazooka (Baz), DmPar-6, DaPKC, and G alpha i, is required to mediate and coordinate basal protein localization with mitotic spindle orientation. Pins, a molecule which directly interacts with Insc, is a key component required for the integrity of this complex; in the absence of Pins, other components become mislocalized or destabilized, and basal protein localization and mitotic spindle orientation are defective. Here we define the functional domains of Pins. We show that the C-terminal region containing the G alpha i binding GoLoco motifs is necessary and sufficient for targeting to the neuroblast cortex, which appears to be a prerequisite for apical localization of Pins. The N-terminal tetratricopeptide repeat-containing region of Pins is required for two processes; TPR repeats 1 to 3 plus the C-terminal region are required for apical localization but are insufficient to recruit Insc to the apical cortex, whereas TPR repeats 1 to 7 plus C-terminal Pins can perform both functions. Hence, the abilities of Pins to cortically localize, to apically localize, and to restore Insc apical localization are all separable, and all three capabilities are necessary to mediate asymmetric division. Moreover, the need for N-terminal Pins can be obviated by fusing a minimal Insc functional domain with the C-terminal region of Pins; this chimeric molecule is apically localized and can fulfill the functions of both Insc and Pins.


Spontaneous bilateral adrenal hemorrhage following cholecystectomy.
Postoperative bilateral adrenal hemorrhage is a rare but potentially life-threatening complication. This diagnosis is often missed because the symptoms and laboratory results are usually nonspecific. We report a case of bilateral adrenal hemorrhage associated with acute primary adrenal insufficiency following laparoscopic cholecystectomy. The knowledge of this uncommon complication following any abdominal surgery allows timey diagnosis and rapid treatment.


Prognostic importance of prostatic specific antigen response in patients who received Lutetium-177 prostate-specific membrane antigen treatment for castration resistant prostate cancer.
This study aims to analyze the prognostic importance of serum prostate specific antigen (PSA) response in patients who received radioligand therapy (RLT) with Lu-177 Prostate-specific membrane antigen (PSMA) for their castration-resistant prostate cancer. Thirty consecutive patients who received Lu-177 PSMA treatment for their castration-resistant prostate carcinoma were included. All the patients had undergone Ga-68 PSMA PET/CT scanning before Lu-177 PSMA therapy, which revealed multiple metastases. Patients were treated with a fixed dose (180 mCi) of Lu-177 PSMA at six to eight weeks intervals. PSA response was evaluated using Prostate Cancer Working Group 3 (PCWG3) criteria. Serum PSA response was classified as PSA progression (25% increase over the baseline and an increase in the absolute-value PSA level by at least 5 ng per millilitre), any <50% decline or ≥50% decline. PSA response was evaluated six weeks after every cycle. Response evaluation with radiological imaging and Ga-68 PSMA PET/CT were performed before the first cycle and eight weeks after the last cycle. Thirty patients were treated with a total of 171 cycles (median 4, range 3-7) of Lu-177 PSMA. A decline in serum PSA of ≥50% was detected in ten patients (33%) while a decline in PSA of any amount was observed in fifteen (50%) patients after the first cycle. After the last cycle, a decline in PSA ≥50% and of any amount was seen in thirteen (43%) and fourteen (46%) patients, respectively. Of the fifteen patients who were not responder after the first cycle, three (20%) had a decline in PSA of any amount after the completion of the RLT. Moreover, of the 20 patients who did not have a ≥50% decline in PSA level after the first cycle, four (20%) became responder after the last cycle. Regarding serum PSA response after the first cycle, median OS was significantly higher for patients who had ≥50% decline in PSA level with 21.0±10.0 (95% CI: 1.2-40.7) months compared to patients who had not with 8.0±2.6 (95% CI: 2.7-13.2) months (P=0.012). A decline in PSA of any amount after the first cycle did not have a significant impact on median OS (12.0±1.1 vs. 6.0±2.5 months, P=0.08). The decline in serum PSA level after the last cycle of treatment had a significant impact on OS. Median OS for the decline in PSA of any amount was calculated as 13.0±1.0 (95% CI: 10.9-15.0) months for responders and 6.0±1.9 (95% CI: 2.2-9.7) months for non-responders (P=0.016). Considering ≥50% of decline as a response, median OS was 21.0±5.8 (95% CI: 9.5-32.4) months for responders and 6.0±3.0 (95% CI: 0.1-11.8) months for non-responders (P=0.026). Serum PSA level during RLT with Lu-177 PSMA remains a clinically significant factor to predict OS times. About twenty percent of patients who were not responder after the first cycle could become responder after the last cycle. However, patients without PSA response after completion of all cycles should be closely followed-up. Non-responder patients can achieve a response with further treatments.


Self-esteem and the occupational stress process: testing two alternative models in a sample of blue-collar workers.
Blue-collar workers (4,523 men and 927 women) participated in a survey comparing two alternative models, one assuming the level of self-esteem (SE) to result to a significant extent from the strain induced by occupational stressors and the other stating the level of SE as a determinant of stressor perception and experienced strain. The results of multiple regression analyses did not support the latter model, whereas the first model was partially supported: Monotony was associated with increased strain and decreased SE among younger (< or = 35 years) male participants and older (> 35 years) female participants, and lack of control related to increased strain and decreased SE among older male participants. These observations were made in the context of psychological strain symptoms but not in the context of physiological strain symptoms.


Immunity tolerance to a hapten (NIP) coupled to an isologous carrier (mouse gamma globulin).
A hapten, 4-hydroxy-3-iodo-5-nitrophenylacetic acid (NIP) when coupled to isologous mouse gamma globulin (MgammaG) elicits a hapten-specific immune response in mice if administered in Freund's complete adjuvant. This response is measurable by the capacity of the sera to bind N(125)IP, by detection of NIP-specific plaque-forming cells (B cells), and by in vitro secondary type antigen-driven DNA synthesis (T cells and probably B cells). The in vitro response requires both the hapten and carrier since neither by itself is capable of stimulating the spleen cells. This same antigen gives rise to hapten-specific tolerance when given in the soluble form. Mice pretreated with soluble NIP-MgammaG and challenged with NIP coupled to a heterologous carrier give a normal antibody response to the carrier but have barely detectable levels of antibody to NIP. Spleen cells from mice made tolerant to NIP-MgammaG do not respond in vitro with increased DNA synthesis. This implies that thymus-derived cells as well as bone marrow-derived cells are involved in hapten-specific tolerance.


Emphysematous pancreatitis associated with penetrating duodenal ulcer.
In the "proton pump inhibitors era", a penetrating peptic ulcer (PPU) represents an exceptional cause of abdominal pain, and was more frequently observed in the past where there was not an effective antacid treatment. Ulcer-induced pancreatitis is very rare, too, and manifests with persistent, intense pain radiating to the back. A mild to severe pancreatitis with peripancreatic fluid collection can be observed at imaging. However, only a few cases of association between PPU and emphysematous pancreatitis (EP) have been published in the literature. EP is a rare but potentially fatal form of acute necrotizing pancreatitis in which gas grows in and outside the pancreas, and typically involves the whole parenchyma in diabetic individuals. Here we report an extremely rare case of a duodenal ulcer penetrating the pancreas and complicated with EP. Unlike the classic form of EP, which involves the whole parenchyma and has a poor prognosis, we found that the emphysematous involvement of the pancreas by PPU has a benign course if a conservative therapy is promptly established. Gas is confined to the site of penetration, usually the pancreatic head, and ulcers most often involve the duodenum.


Feed restriction during pregnancy/lactation induces programmed changes in lipid, adiponectin and leptin levels with gender differences in rat offspring.
We investigated the effects of fetal undernutrition during pregnancy/lactation on visceral fat, lipid profiles, leptin and adiponectin, and examined the gender differences between males and females. From 10 d to term gestation and through lactation, control pregnant rats were fed ad libitum (AdLib) food, whereas study rats were 50% food restricted (FR). Cross-fostering techniques were used to examine the effects of FR during pregnancy and lactation periods. Lipid profiles, leptin and adiponectin were determined in offspring at ages 3 weeks and 6 months. We also measured the amount of visceral fat in the offspring. The amount of visceral fat in the 6-month-old FR/AdLib offspring was higher than that in the control (p < 0.05). Among the 6-month-old offspring, triglyceride and leptin levels were higher in FR/AdLib offspring than those in the controls (p < 0.05). The female offspring had higher levels of triglyceride, HDL-cholesterol, and adiponectin and the male offspring had higher levels of LDL cholesterol and leptin. Fetal undernutrition only during pregnancy resulted in obese offspring, higher levels of plasma triglyceride and leptin with gender differences.


Safety and Effectiveness of Robot-Assisted Versus Open Radical Cystectomy for Bladder Cancer: A Systematic Review and Meta-Analysis.
To evaluate the safety and effectiveness of robot-assisted radical cystectomy (RARC) compared with open radical cystectomy (ORC) in bladder cancer. A literature search for the systematic review was conducted using international databases as well as domestic databases up to April 2015. Outcomes of interest included baseline characteristics, complication rates, perioperative, and oncologic outcomes. Twenty-four articles were finally selected for inclusion in the meta-analysis. Complication rates of RARC were similar to those of ORC, except for 90-day overall complication rate, wound dehiscence, abscess, pneumonia, respiratory failure, and sepsis, which was lower after RARC. RARC was also associated with a smaller amount of estimated blood loss, lower transfusion rate, shorter length of hospital stay, shorter time to flatus, and more lymph node yield, whereas ORC was associated with a shorter operation time and lower rate of stricture. Considering oncologic outcomes, there were no differences between RARC and ORC. RARC seems to be associated with equivalent complication rates, a smaller amount of estimated blood loss, lower transfusion rate, shorter length of hospital stay, shorter time to flatus, and more lymph node yield. Randomized controlled trials with a large sample size and comparative studies with long-term follow-up data are warranted to assess our findings and the oncologic effectiveness of RARC.


Effect of aldosterone on lithium permeability of rat colon mucosa.
The effect of aldosterone on the ionic composition of colonic epithelial cells and on lithium absorption rate was studied by experiments on rats in vivo. Aldosterone considerably increased the rate of sodium absorption without measurably altering the sodium and potassium content of the epithelium. Aldosterone did not alter the electrical resistance of the tissue. With lithium in the lumen, the net sodium fluxes in the colon were similar in normal and aldosterone-stimulated rats but the rate of diffusion of lithium across the epithelium was greater in the aldosterone-stimulated group. The amount of lithium accumulating in the epithelial layer was also considerably increased by aldosterone stimulation. Aldosterone appears to increase the permeability of the mucosal (luminal) barrier allowing increased entry of lithium into the colonic epithelial cells.


[Interventional pain therapy].
Treatment of intractable chronic pain employs, nerve block, peripheral nerve stimulation, phototherapy, and drug therapy such as opioid and analgesia adjuvant. We also employ multi disciplinary approach with internal medicine, psychiatry and other related fields. In addition, in a portion of intractable chronic back pain, the pain relief is obtained by interventional approaches such as adhesionlysis and the neuroplasty with epiduroscopy as well as spinal cord stimulation therapy.


Hydrosilylation of Carbonyls Catalyzed by Hydridoborenium Borate Salts: Lewis Acid Activation and Anion Mediated Pathways.
The electronically unsaturated three-coordinated hydridoborenium cations [LBH]+[HB(C6F5)3]- (1) and [LBH]+[B(C6F5)4]- (2), supported by a bis(phosphinimino)amide ligand, were found to be excellent catalysts for hydrosilylation of a range of aliphatic and aromatic aldehydes and ketones under mild reaction conditions (L = [{(2,4,6-Me3C6H2N)P(Ph2)}2N]). The key steps of the catalytic cycle for hydrosilylation of PhCHO were monitored via in situ multinuclear NMR measurements for catalysts 1 and 2. The combined effect of carbonyl activation via the Lewis acidic hydridoborenium cation and the hydridic nature of the borate counteranion in 1 makes it a more efficient catalyst in comparison to that of carbonyl activation via the predominant Lewis acid activation pathway operating with catalyst 2. The catalytic cycle of 1 showed hydride transfer from the borate moiety [HB(C6F5)3]- to PhCHO in the first step, forming [PhCH2-O-B(C6F5)3]-, which subsequently underwent σ-bond metathesis with Et3SiH to form the product, PhCH2-O-SiEt3. Quantum chemical calculations also support the borate anion mediated mechanism with 1. In contrast, the reaction catalyzed by 2 proceeds predominantly via the Lewis acid activation of the carbonyl group involving [LB(H)←OC(H)Ph]+[B(C6F5)4]- as the transition state and [LBOCH2Ph]+[B(C6F5)4]- as the intermediate.


Chance findings in ultrasonography of the gallbladder and the abdominal organs.
Chance findings (pathological processes in other than in the object organ) were recorded in: I 400 consecutive gallbladder sonographies performed with gray scale compound equipment during 1978-1980, and II 1100 consecutive abdominal or retroperitoneal real time sonographies during 1982-1983. Eight malignant tumours and three aortic aneurysms in group I, and five malignant tumours and four aortic aneurysms in group II were the most significant chance findings. The malignant tumours included seven renal carcinomas. The use of US as a multi-organ imaging method is stressed.


[Fifteen-year trend in incidence of acute myocardial infarction in Tianjin of China].
Objective: To observe the incidence of acute myocardial infarction (AMI) between 1999 and 2013 in Tianjin residents and analyze the incidence differences on residents with various age, gender and living in urban or rural areas. The data might help for targeted prevention strategies among Tianjin residents. Methods: AMI incidence data between 1999 and 2013 were obtained based on Tianjin cardiovascular disease incidence surveillance registry established by the Tianjin Centers for Disease Control and Prevention (CDC). Related information such as permanent residents' population data were obtained from Tianjin Municipal Public Security Bureau. The Chinese population data in 2000 were used for age-sex-standardized rates estimation. Difference between two (or more) independent groups was compared by the Chi Square statistics. The Chi-square test for trend was used for computing the incidence trend in years and ages. Results: AMI incidence rate in Tianjin declined from the year 1999 to 2013 with the rude incidence rate of 80.46/100 000 to 81.29/100 000, and with the standardized incidence rate of 64.85/100 000 to 44.57/100 000 (Z=-35.767, P<0.001). AMI incidence decreased gradually in residents aged over 45 years old (P<0.01), but increased in residents younger than 45 years old (P<0.001) from 1999 to 2013. The AMI incidence rate is consistently higher in male residents (rude incidence 99.89/100 000-102.98/100 000, standardized incidence rate 78.53/100 000-56.61/100 000) than in female residents (rude incidence 61.18/100 000-59.44/100 000, standardized incidence rate 50.31/100 000-31.76/100 000, both P<0.001) and higher in urban residents (rude incidence rate 133.98/100 000-98.02/100 000, standardized incidence rate 99.89/100 000-50.12/100 000) than in rural residents (rude incidence rate 35.57/100 000-66.19/100 000, standardized incidence rate 32.68/100 000-43.51/100 000, Z=6.217, P<0.001). AMI incidence decreased significantly in the urban residents (rude incidence rate 133.98/100 000-98.02/100 000, standardized incidence rate 99.89/100 000-50.12/100 000, Z=-46.968, P<0.001), while significantly increased in rural residents (rude incidence rate 35.57/100 000-66.19/100 000, standardized incidence rate 32.68/100 000-43.51/100 000, Z=6.217, P<0.001) during the study period. Conclusions: The general incidence of AMI decreased during the study period in Tianjin residents. However, AMI incidence significantly increased in young male residents and rural residents. It is necessary to develop corresponding strategies for AMI control for Tianjin residents with different age/gender and living in different areas.


Ouabain-binding site of (Na+ + K+)-ATPase in right-side-out vesicles has not an externally accessible SH group.
The fluorescing sulfhydryl reagent N-(7-dimethylamino-4-methylcoumarinyl)maleimide (DACM) inactivates purified (Na+ + K+)-ATPase at 20 microM. This inactivation results in a decrease of the ouabain-binding capacity of the enzyme. Treatment of (Na+ + K+)-ATPase, embedded in right-side-out-oriented vesicles, by DACM does not affect ouabain binding to the enzyme. Incorporation of DACM into the alpha subunit of (Na+ + K+)-ATPase embedded in right-side-out vesicles is also not affected by the presence or absence of 100 microM ouabain. It is therefore concluded that a sulfhydryl group does not reside within the ouabain-binding site of (Na+ + K+)-ATPase.


High-pressure experiments as a novel perspective to study the molecular dynamics of glass-forming materials confined at the nanoscale.
Herein, we report the pioneering high-pressure dielectric studies on the dynamics of a model van der Waals glass-forming liquid bisphenol-A diglycidyl ether (DGEBA) infiltrated into anodic aluminum oxide (AAO) templates of the mean pore sizes, d = 150 and d = 18 nm. It was found that although the shape of the structural relaxation process varies with the confinement, it remains constant under varying thermodynamic conditions for a given pore diameter. Consequently, the time-temperature-pressure (TTP) rule satisfied for the majority of bulk substances is also obeyed for the spatially restricted liquid. We have also shown for the first time that there is a decoupling between the core and interfacial mobility at elevated pressure. Moreover, it was noted that the structural dynamics of the former fraction of molecules becomes systematically shorter with respect to the bulk DGEBA during the compression. The enhanced structural dynamics of the core material, as well as the varying pressure coefficients of the glass transition temperature of the interfacial and core molecules, have been discussed in the context of a distinct evolution in their free volume/density packing with respect to the bulk DGEBA, and a change in the interfacial tension, which may lead to the enhanced wettability of the liquid adsorbed onto the pore walls under different thermodynamic conditions. The performed high-pressure measurements offer novel perspectives to explore the combination of two different effects, compression and confinement, which might be a breakthrough in the study of the glass transition phenomenon and the behavior of soft materials confined at the nanoscale.


The Potential for a Blood Test for Scabies.
Scabies afflicts millions of people worldwide, but it is very difficult to diagnose by the usual skin scrape test, and a presumptive diagnosis is often made based on clinical signs such as rash and intense itch. A sensitive and specific blood test to detect scabies would allow a physician to quickly make a correct diagnosis. Our objective was to profile the mite-specific antibodies present in the sera of patients with ordinary scabies. Sera of 91 patients were screened for Ig, IgD, IgE, IgG and IgM antibodies to S. scabiei, as well as to the house dust mites Dermatophagoides farinae, D. pteronyssinus and Euroglyphus maynei. 45%, 27% and 2.2% of the patients had measurable amounts of mixed Ig, IgG and IgE that recognized scabies mite antigens. However, 73.6% of the scabies patients had serum IgM that recognized scabies proteins, and all except two of them also had IgM that recognized all of the three species of dust mites. No patient had serum antibody exclusively reactive to scabies mite antigens. Co-sensitization or cross-reactivity between antigens from scabies and house dust mites confounds developing a blood test for scabies.


The Lescol(R) Intervention Prevention Study (LIPS): a double-blind, placebo-controlled, randomized trial of the long-term effects of fluvastatin after successful transcatheter therapy in patients with coronary heart disease.
BACKGROUND: The 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins) inhibit atherosclerosis and reduce both morbidity and mortality in patients with coronary heart disease. No randomised prospective study, however, has investigated the long-term effect of statins on clinical outcomes in patients who have undergone first successful transcatheter therapy. METHODS: The Lescol((R)) Intervention Prevention Study (LIPS) is a double-blind randomized trial designed to compare the effect of fluvastatin (Lescol) with that of placebo on the time which patients with serum cholesterol >/= 3.5 mmol/l and < 7.0 mmol/l (135-270 mg/dl) remain free of major adverse cardiac events (MACE) after successful first transcatheter therapy (TCT). Patients, aged 18-80 years inclusive, will be randomized in a 1 : 1 ratio to receive fluvastatin, 40 mg, or placebo, twice daily for three to five years. The primary endpoint is the survival time during which patients remain MACE free after first TCT. Secondary endpoints are the incidence of MACE, noncardiac death, hospitalization for other atherosclerotic diseases, changes in serum lipid concentrations and anginal status. SUMMARY: LIPS is unique because it is the first study that will investigate whether MACE can be prevented or reduced by fluvastatin in patients who have undergone successful first transcatheter therapy for coronary heart disease.


[The infectious disease epidemiology research network--a bridge between science and public health service. The example of the network for foodborne infections].
In order to respond to emerging food borne diseases, a new data-driven approach guided by epidemiologic and microbiologic data has been developed in Germany. An interdisciplinary network of scientists at the national, regional and local levels conducted surveillance and epidemiologic research of foodborne pathogens (Shiga toxin-producing Escherichia coli (STEC), Salmonella and Campylobacter). The objectives of the network include (1) determining incidence and distribution of STEC and Salmonella, (2) assessing the importance of typing systems for Campylobacter, (3) determining risk factors for sporadic STEC infections, (4) developing a system for detection of disperse outbreaks, including a national reference library of pulsed-field gel electrophoresis (PFGE) patterns, (5) examining risk factors for outbreaks, (6) carrying out a quantitative microbiological risk assessment for consumption of fresh chicken and (7) determining long-term sequelae of HUS patients.


[Conditioned reflex mechanism in the hypothalamic regulation of diuresis].
In chronic experiments on dogs with urethrae brought out to the skin of the abdomen and electrodes implanted in the hypothalamus, the possibility was studied of the involvement of a conditioned component in hypothalamic control of the kidneys activity under a direct action of electric current on a hypothalamus. The beat of a metronome and the experimental surroundings served as a conditioned stimulus, stimulation of the hypothalamus was used as an unconditioned one, and diuresis -- as a manifestation of the conditioned reflex. It was found that the conditioned mechanism is also involved in the complex mechanism of hypothalamic control of kidney activity. Such conditioned changes of diuresis may be effected in different functional states of hypothalamic nuclei.


Enamel matrix derivative stabilizes blood clot and improves clinical healing in deep pockets after flapless periodontal therapy: A Randomized Clinical Trial.
An acute phase response is induced after non-surgical periodontal treatment (SRP). The main aim of this study was to compare acute phase (24-hr) and medium-term (3-months) inflammation and clinical outcomes after SRP with or without application of enamel matrix derivative (EMD) in sites with probing pocket depth (PPD) ≥ 6 mm. Thirty-eight periodontitis-affected subjects were randomized to SRP or SRP + EMD. Periodontal parameters were recorded at baseline and 3 months. Serum samples were collected at baseline, 1 and 90 days after treatment. Both treatments triggered an intense acute inflammation on day 1, which regressed to baseline values at 3 months. D-dimer and cystatin C levels did not show sharp increases in SRP + EMD group 24 hr after treatment, compared to SRP. Significant difference between groups was observed for D-dimer (p < 0.001). EMD application was also associated with better periodontal healing as shown by greater PPD reduction and clinical attachment level gain in sites with PPD ≥ 6 mm, and higher number of cases with no residual PPD ≥ 6 mm (p < 0.05) at 3 months. EMD application after non-SRP resulted in lower fibrinolysis, and better periodontal healing of deep pockets. These initial observations warrant further investigations on the potential to modulate both local and systemic outcomes of non-SRP. NCT03544931.


Pharmacists role in cholesterol management: addressing challenges and barriers.
Cholesterol management is an important factor in the modification of primary and secondary cardiovascular events. Guidelines emphasize incorporation of appropriate medication therapy and lifestyle adjustments to reduce low-density lipoprotein cholesterol (LDL-C) for cardiovascular disease (CVD) risk reduction. Of note, studies and nation-wide statistics indicate many patients do not achieve their LDL-C goals. Eliminating barriers and challenges associated with cholesterol management will allow patients to reach prespecified goals for CVD risk reduction. As the nation transitions to covering more individuals, the need for additional health care providers is evident. Pharmacists are accessible and knowledgeable health care contributors who can assist in optimizing patient outcomes. This article discusses the pharmacist's role in addressing challenges and barriers in cholesterol management.


Surgical strategy for improving forearm and hand function in late obstetric brachial plexus palsy.
For the purpose of treatment, obstetric brachial plexus palsy can be subdivided into two distinct phases: initial obstetric brachial plexus palsy, and late obstetric brachial plexus palsy. In the latter, nerve surgery is no longer practical, and treatment often requires palliative surgery to improve function of the shoulder, elbow, forearm, and hand. Late obstetric brachial plexus palsy in the forearm and hand includes weakness or absence of wrist or metacarpophalangeal or interphalangeal joint extension; weakness or absence of finger flexion; forearm supination, or less commonly pronation contracture; ulnar deviation of the wrist; dislocation of the radial or ulnar head; thumb instability; or sensory disturbance of the hand. Palliative reconstruction for these forearm and hand manifestations is more difficult than for the shoulder or elbow because of the lack of powerful regional muscles for transfer. This report reviews the authors' experience performing more than 100 surgical procedures in 54 patients over a 9-year period (between 1988 and 1997) with a minimum of 2 years' follow-up. Surgical treatment is highly individualized, but the optimal age for forearm and hand reconstruction is usually later than for shoulder and elbow reconstruction because of the requirement for a preoperative exercise program. Multiple procedures for forearm and hand function were often performed on any given patient. Frequently, these were done simultaneously with reconstructive procedures for improving shoulder and/or elbow function. Traditional tendon transfer techniques do not provide satisfactory reconstruction for those deformities. Many of the authors' patients required more complex techniques such as nerve transfer and functioning free-muscle transplantation to augment traditional techniques of tendon and/or bone management. Sensory disturbance of the forearm and hand in late obstetric brachial plexus palsy seems a minor problem and further sensory reconstruction is unnecessary.


Different effects of prostaglandin E1, E2 and D2 on pancreatic somatostatin release.
The effects of PGE1, PGE2 and PGD2 on somatostatin, insulin and glucagon secretions were investigated at various glucose concentrations using the isolated perfused rat pancreas. At glucose concentrations varying from 0 to 16.7 mM, PGE1 and PGE2 enhanced somatostatin release in a glucose dose-dependent manner. PGE1 did not significantly stimulate insulin secretion at glucose concentrations of 4.4 mM or less, but did at glucose concentrations of 8.8 mM or more, PGE2 augmented insulin release at 4.4 and 16.7 mM glucose, but not in the absence of glucose. Glucagon release was induced by PGE1 and PGE2 in a biphasic pattern with the maximal response in the absence of glucose. Like PGE1 and PGE2, PGD2 stimulated insulin and glucagon release in a glucose-related fashion. PGD2, however, was not capable of stimulating somatostatin release at various glucose concentrations even in the presence of 16.7 mM glucose. In conclusion, PGE1, PGE2, and PGD2 increase insulin and glucagon secretion in a glucose-dependent manner. PGE1 and PGE2 also stimulate somatostatin release, but PGD2 has no effect on somatostatin secretion at the doses studied.


Use of a micro-ionization chamber and an anthropomorphic head phantom in a quality assurance program for stereotactic radiosurgery.
Quality assurance methods used in association with radiosurgery must include all aspects of the radiosurgery process: visualization and localization of the target, treatment and dose planning and dose delivery. Presented here is a quality assurance method that utilizes an anthromorphic head phantom and a micro-ionization chamber to demonstrate precise target localization and accurate dose delivery. This micro-ionization chamber method offers an immediate readout which is both accurate and reproducible. Additionally, this method allows unlimited repetition of the dose measurement process without repeated radiographic localization studies as is necessary with the conventional methods of TLD, film, and Fricke gels. The method and techniques presented can be used in the acceptance testing and routine quality assurance of both linac-based and Gamma Knife radiosurgery units.


[Induced astigmatism in cataract surgery. Scleral tunneling incisions of 5.5 mm and 6.5 mm after 1-year follow-up].
To evaluate the effect of scleral pocket incisions closed with a single horizontal suture on postoperative astigmatism, 97 patients were enrolled in a prospective study. After 1 year of follow-up the data of 80 patients could be analysed. Routine phacoemulsification was performed in all patients consecutively by one surgeon. 40 patients received a posterior chamber lens with a 5 mm by 6 mm oval polymethylmethacrylate (PMMA) optic (group I), and 40 patients received an intraocular lens with a 6 mm diameter round PMMA optic (group II). The incisions were 5.5 mm and 6.5 mm, respectively. Follow-up visits including keratometry were scheduled 1 day, 5 days, 3 months, 6 months and 1 year postoperatively. The induced astigmatism was calculated using vector analysis. One day after operation the mean induced cylinder was 1.22 D in group I and 1.06 D in group II. After 5 days it amounted to 1.09 D (group I) and 1.03 D (group II), and at 3 months it was 1.07 D and 1.00 D, respectively. Six months after operation the induced cylinder was 1.04 D (group I) and 0.96 D (group II), and at 1 year it was 1.02 D and 0.81 D. There was no statistically significant difference between the groups at any time (Wilcoxon test, P > 0.05). We conclude that scleral pocket incisions closed with a single horizontal suture induce about 1 D of corneal astigmatism, with stability over time. There is no clinical advantage in reducing the incision width by using oval optics.


Design of Modular Peptide Surfactants and Their Surface Activity.
Designed peptide surfactants offer a number of advanced properties over conventional petrochemical surfactants, including biocompatibility, sustainability, and tailorability of the chemical and physical properties through peptide design. Their biocompatibility and degradability make them attractive for various applications, particularly for food and pharmaceutical applications. In this work, two new peptide surfactants derived from an amphiphilic peptide surfactant (AM1) were designed (AM-S and C8-AM) to better understand links between structure, interfacial activity, and emulsification. Based on AM1, which has an interfacial α-helical structure, AM-S and C8-AM were designed to have two modules, that is, the α-helical AM1 module and an additional hydrophobic moiety to provide for better anchoring at the oil-water interface. Both AM-S and C8-AM at low bulk concentration of 20 μM were able to adsorb rapidly at the oil-water interface and reduced interfacial tension to equilibrium values of 17.0 and 8.4 mN/m within 400 s, respectively. Their relatively quick adsorption kinetics allowed the formation of nanoemulsions with smaller droplet sizes and narrower size distribution. AM-S and C8-AM at 800 μM bulk concentration could make nanoemulsions of average diameters 180 and 147 nm, respectively, by simple sonication. With respect to the long-term stability, a minimum peptide concentration of 400 μM for AM-S and a lower concentration of 100 μM for C8-AM were demonstrated to effectively stabilize nanoemulsions over 3 weeks. Compared to AM1, the AM-S nanoemulsion retained its stimuli-responsive function triggered by metal ions, whereas the C8-AM nanoemulsions did not respond to the stimuli as efficiently as AM-S because of the strong anchoring ability of the hydrophobic C8 module. The two-module design of AM-S and C8-AM represents a new strategy in tuning the surface activity of peptide surfactants, offering useful information and guidance of future designs.


Surface-Enhanced Raman Spectroscopy of Carbon Nanomembranes from Aromatic Self-Assembled Monolayers.
Surface-enhanced Raman scattering spectroscopy (SERS) was employed to investigate the formation of self-assembled monolayers (SAMs) of biphenylthiol, 4'-nitro-1,1'-biphenyl-4-thiol, and p-terphenylthiol on Au surfaces and their structural transformations into carbon nanomembranes (CNMs) induced by electron irradiation. The high sensitivity of SERS allows us to identify two types of Raman scattering in electron-irradiated SAMs: (1) Raman-active sites exhibit similar bands as those of pristine SAMs in the fingerprint spectral region, but with indications of an amorphization process and (2) Raman-inactive sites show almost no Raman-scattering signals, except a very weak and broad D band, indicating a lack of structural order but for the presence of graphitic domains. Statistical analysis showed that the ratio of the number of Raman-active sites to the total number of measurement sites decreases exponentially with increasing the electron irradiation dose. The maximum degree of cross-linking ranged from 97 to 99% for the three SAMs. Proof-of-concept experiments were conducted to demonstrate potential applications of Raman-inactive CNMs as a supporting membrane for Raman analysis.


Regulated necrosis in HeLa cells induced by ZnPc photodynamic treatment: a new nuclear morphology.
Photodynamic therapy (PDT) is a cancer treatment modality based on the administration of a photosensitizer (PS), which accumulates preferentially in tumor cells. Subsequent irradiation of the neoplastic area triggers a cascade of photochemical reactions that leads to the formation of highly reactive oxygen species responsible for cell inactivation. Photodynamic treatments in vitro are performed with the PS, zinc-phthalocyanine (ZnPc). The PS is near the plasma membrane during uptake and internalization. Inactivation clearly occurs by a necrotic process, manifested by nuclear pyknosis, negative TUNEL and Annexin V assays and non-relocation of cytochrome c. In contrast, by increasing the incubation time, ZnPc is accumulated in the Golgi apparatus and produces cell inactivation with characteristics of apoptosis and necrosis: TUNEL positive, relocated cytochrome c and negative Annexin V assay. This type of death produces a still undescribed granulated nuclear morphology, which is different from that of necrosis or apoptosis. This morphology is inhibited by necrostatin-1, a specific inhibitor of regulated necrosis.


Prevalence of end of treatment RNA-positive/sustained viral response in HCV patients treated with sofosbuvir combination therapies.
Some chronic hepatitis C virus (HCV), genotype 1 infected patients treated with direct antiviral agents (DAAs) remain viremic at end of treatment (EOT+), yet go on to achieve sustained virological response 12 weeks after completion of therapy (SVR12). The incidence of EOT+/SVR in patients with genotype 1 and other genotypes, as well as whether such patients achieve SVR24 remain in question. The aims of this study were to evaluate the frequency and durability of EOT+/SVR12&24 and other response categories in HCV genotype 1, 2, or 3 infected patients treated with DAA in clinical practice. Data from patients treated with all oral sofosbuvir-based regimens at a university hepatology practice by 1 July 2015 were reviewed retrospectively. Responses were categorized based on virus levels during and post DAA treatment. HCV RNA levels were measured by Abbott RealTime HCV (ART) or by Roche CobasTaqMan v2.0 (RCTM) assays. The study population included 89 patients. Participants were 62% genotype 1, 19% genotype 2 and 19% genotype 3, 54% cirrhotic and 46% treatment-experienced. A total of 45 received sofosbuvir-simeprevir, 38 sofosbuvir-ribavirin and 6 sofosbuvir-ledipasvir. The SVR12 rate was 82%. A total of 5 patients (6%), all with genotype 1, had EOT+ by ART assay and each achieved SVR12&24. A total of 9% of genotype 1 patients (6% overall) treated with DAAs were EOT+ by ART and all EOT+ cases achieved SVR24. EOT+/SVR was not observed with genotype 2 or 3 or by the RCTM assay. In patients treated with DAAs, EOT+ by the ART assay does not indicate treatment failure.


QSAR based predictive modeling for anti-malarial molecules.
Malaria is a predominant infectious disease, with a global footprint, but especially severe in developing countries in the African subcontinent. In recent years, drug-resistant malaria has become an alarming factor, and hence the requirement of new and improved drugs is more crucial than ever before. One of the promising locations for antimalarial drug target is the apicoplast, as this organelle does not occur in humans. The apicoplast is associated with many unique and essential pathways in many Apicomplexan pathogens, including Plasmodium. The use of machine learning methods is now commonly available through open source programs. In the present work, we describe a standard protocol to develop molecular descriptor based predictive models (QSAR models), which can be further utilized for the screening of large chemical libraries. This protocol is used to build models using training data sourced from apicoplast specific bioassays. Multiple model building methods are used including Generalized Linear Models (GLM), Random Forest (RF), C5.0 implementation of a decision tree, Support Vector Machines (SVM), K-Nearest Neighbour and Naive Bayes. Methods to evaluate the accuracy of the model building method are included in the protocol. For the given dataset, the C5.0, SVM and RF perform better than other methods, with comparable accuracy over the test data.


Comparing the Frequencies of Contraindicated Drug-Drug Interactions Between Differing Antiretroviral Regimens in HIV-Infected Patients.
HIV-infected patients receiving antiretroviral therapy (ART) are at risk for contraindicated drug-drug interactions (XDDIs). This study compared the frequency of XDDIs between different types of ART regimens. A retrospective cohort study was performed among adult HIV-infected patients receiving care at either the Upstate New York Veterans' Healthcare Administration or the University of New Mexico Truman Health Services between 2000 and 2013. The cohort consisted of patients receiving traditional ART regimens composed of 2 nucleoside reverse transcriptase inhibitors plus either a nonnucleoside reverse transcriptase inhibitor (NNRTI), a protease inhibitor (PI), or an integrase strand transfer inhibitor (INSTI). The primary outcome was the presence of XDDIs. Lexi-Interact was used to define XDDIs. Of the 1329 patients who met inclusion criteria, 45.7%, 34.2%, and 20.1% were receiving an NNRTI-, PI-, or INSTI- based ART regimen, respectively. Among the 128 (9.6%) patients with an XDDI, more than half (53.9%) had an interaction involving ART. The presence of XDDIs was highest for PI-based regimens (16.3%) compared with INSTI- (7.9%) and NNRTI-based (5.4%) regimens; P < 0.001. The variables independently associated with XDDIs were ART regimen type (prevalence ratio [PR] = 1.91; 95% CI = 1.51-2.40, P < 0.001), use of ≥6 non-HIV medications (PR = 5.84; 95% CI = 3.92-8.71, P < 0.001), and age ≥40 years (PR = 1.62; 95% CI = 0.92-2.86, P = 0.10). The probability of XDDIs varies as a function of ART regimen type, advanced age, and use of multiple non-HIV medications.


Combined effect of heat and corona charge on molecular delivery to a T cell line in vitro.
With the rapid increase of gene and immunotherapies for treating cancer, there is a need to efficiently transfect cells. Previous studies suggest that electrotransfer can provide a non-viral method for gene delivery. Electrotransfer traditionally relies upon the application of direct current pulses to the cells of interest. Corona charge was investigated in this study as an alternative to traditional methods as a means of creating the electric field necessary to deliver materials via electrotransfer. The goal was to determine if there was an increase in molecular delivery across the membrane of a human T cell line used as a model system. In a novel dish created for the study, the effects of elevated temperatures (37, 40, 43, and 45°C) during the treatment process were also examined in combination with corona charge application. Results showed that treating cells with corona charge at room temperature (~23°C) caused a statistically significant increase in molecular delivery while maintaining viability. Heat alone did not cause a statistically significant effect on molecular delivery. Combined corona charge treatment and heating resulted in a statistically significant increase on molecular delivery compared to controls that were only heated. Combined corona charge treatment and heating to all temperatures when compared to controls treated at room temperature, showed a statistically significant increase in molecular delivery.


Tailoring the Electrochemical Properties of Two-Dimensional Bis(diimino)metal Coordination Frameworks by Introducing Co/Ni Heterometallic Structures.
Bis(diimino)metal coordination frameworks (MDI, M = transition metal), which are a class of metal organic frameworks with two-dimensional anisotropy, high electric conductivity, and redox activity, are attractive platforms for tailoring electrochemical properties by introducing a heterometallic composition. In this study, we synthesized heterometallic CoxNi1-xDI coordination frameworks for electrochemical energy storage applications and investigated their electrochemical properties by experimental and theoretical techniques. Ni atoms were embedded into CoDI, and the crystal structure of CoxNi1-xDI was modified, especially along the interlayer axis, which activated the kinetically impeded redox reactions accompanied by PF6- insertion/extraction. Furthermore, upon charge/discharge with Li+ transport, CoxNi1-xDI with a specific composition exhibited higher specific capacity (248 mAh g-1) than CoDI and NiDI in the potential window of 1.0-3.5 V versus Li+/Li. Density functional theory calculations indicate that the energy levels of the antibonding orbitals around the metals and interlayer spaces are important factors in tailoring the electrochemical properties of CoxNi1-xDI.


Morphology of the immature stages and notes on the natural history of the little-known plume moth Stenoptilodes juanfernandicus Gielis (Lepidoptera: Pterophoridae).
Stenoptilodes juanfernandicus Gielis, 1991 (Lepidoptera: Pterophoridae) was described from the Juan Fernandez Islands, Chile; it was subsequently recorded from the Galápagos Islands and mainland Ecuador. Its larva and pupa are described and illustrated for the first time with the aid of light and scanning electron microscopy. Descriptions are based on specimens collected as larvae displaying cryptic coloration feeding on inflorescences of Verbena hispida Ruiz Pav. (Verbenaceae) in the Andes of northern Chile. Several differences were found with the larva and pupa of congeneric representatives, suggesting that immature morphology should be further explored to assess its value in the taxonomy and systematics of Stenoptilodes Zimmerman, 1958. Verbena hispida is the first host plant recorded for S. juanfernandicus, a finding that will be helpful to further explore different Neotropical environments to better characterize the geographic range of this plume moth.


Female orgasmic experience: a subjective study.
Human female orgasm was studied by collecting and analyzing the subjective orgasmic histories of 30 women, ages 18 to 59 years. Virtually all of the 93% who reported they had experienced orgasm also reported some level of conscious control over whether or not they reached orgasm. Women differed widely as to preferred types of physical stimulation and/or mental activities to facilitate orgasm. Orgasms were experienced as centered in the clitoral and/or vaginal areas. Women over 40 were more likely to have experienced orgasm in more than one anatomic site than were women aged 18 to 29. Marital status, religion, occupation, educational level, experiences of pregnancy and childbirth, various reported characteristics of relationships with partners, and early sexual experience were not associated with where orgasm is experienced within the body or with other variables of adult orgasmic experience. The variation among women as to how orgasm is best reached, differences in where it is experienced within the body, and the reasons why an individual woman experiences orgasms differently over time remain poorly understood phenomena.


Neocentric X-chromosome in a girl with Turner-like syndrome.
Neocentromeres are rare human chromosomal aberrations in which a new centromere has formed in a previously non-centromeric location. We report the finding of a structurally abnormal X chromosome with a neocentromere in a 15-year-old girl with clinical features suggestive of Turner syndrome, including short stature and primary amenorrhea. G-banded chromosome analysis revealed a mosaic female karyotype involving two abnormal cell lines. One cell line (84% of analyzed metaphases) had a structurally abnormal X chromosome (duplication of the long arm and deletion of the short arm) and a normal X chromosome. The other cell line (16% of cells) exhibited monosomy X. C-banding studies were negative for the abnormal X chromosome. FISH analysis revealed lack of hybridization of the abnormal X chromosome with both the X centromere-specific probe and the "all human centromeres" probe, a pattern consistent with lack of the X chromosome endogenous centromere. A FISH study using an XIST gene probe revealed the presence of two XIST genes, one on each long arm of the iso(Xq), required for inactivation of the abnormal X chromosome. R-banding also demonstrated inactivation of the abnormal X chromosome. An assay for centromeric protein C (CENP-C) was positive on both the normal and the abnormal X chromosomes. The position of CENP-C in the abnormal X chromosome defined a neocentromere, which explains its mitotic stability. The karyotype is thus designated as 46,X,neo(X)(qter- > q12::q12- > q21.2- > neo- > q21.2- > qter)[42]/45,X[8], which is consistent with stigmata of Turner syndrome. The mother of this patient has a normal karyotype; however, the father was not available for study. To our knowledge, this is the first case of mosaic Turner syndrome involving an analphoid iso(Xq) chromosome with a proven neocentromere among 90 previously described cases with a proven neocentromere.


Problems with detection of beta-lactam resistance among nonfastidious gram-negative bacilli.
The single most important aspect of any susceptibility test is the accurate detection of resistance, because resistance carries a strong prediction of therapeutic failure. However, the accurate detection of resistance has been difficult in tests performed with gram-negative organisms producing certain beta-lactamases and in tests with the new beta-lactam drug/beta-lactamase inhibitor combinations. These problems are due to limitations in the design of studies performed to establish test parameters, and these problems can be avoided if a new predictor panel approach is used. This, coupled with the use of special tests to detect resistance mechanisms, could optimize the accurate identification of beta-lactam resistance in gram-negative bacteria.


Patterns of emergency department visits during Hajj period: Towards healthcare optimization in view of Saudi Arabia's vision 2030.
This study aimed to examine the pattern of emergency department (ED) visits by Hajj patients and determine the urgency of emergency visits at an advanced healthcare center. A retrospective review of medical records of Hajj patients visiting the ED at King Abdullah Medical City Makkah from September 1 to October 5, 2015 was conducted. We considered 233 visits by 199 Hajj patients. Most diseases were cardiovascular related. Approximately half of the ED visits led to hospital admission, which were largely during the evening and nighttime. Potentially avoidable visits were significantly encountered during the daytime. Average bed occupation time in the ED was similar for both cases: those admitted to inpatient care and discharged from ED. Results from the Canadian Triage and Acuity Scale revealed that most patients were triaged with a score of III (48.4%) followed by a clinically better score of IV (32%); however, scores did not change significantly throughout the Hajj day. During Hajj, a significant proportion of patients who visited the ED at the ultimate healthcare facility were discharged within 24 hours, with a higher rate in the morning-afternoon period. Both admitted and discharged cases required equal levels of care. Therefore, an extension in working days at primary care centers and optimization of advanced healthcare facilities during Hajj is currently warranted.


Advances in the Isolation of Specific Monoclonal Rabbit Antibodies.
The rabbit monoclonal antibodies (mAbs) have advantages in pharmaceuticals and diagnostics with high affinity and specificity. During the past decade, many techniques have been developed for isolating rabbit mAbs, including single B cell antibody technologies. This review describes the basic characterization of rabbit antibody repertoire and summarizes methods of hybridoma technologies, phage display platform, and single B cell antibody technologies. With advances in antibody function and repertoire analysis, rabbit mAbs will be widely used in therapeutic applications in the coming years.


Oral conditions and dysphagia in Japanese, community-dwelling middle- and older- aged adults, independent in daily living.
Prevention, early detection and effective rehabilitation of dysphagia are important issues to be considered in an aging society. Previous studies have shown conflicting findings regarding the association between dysphagia and its potential risk factors, including age, malnutrition, oral conditions, lifestyle and medical history. Herein, we assessed the prevalence and association of dysphagia with potential risk factors in 50- to 79-year-old adults dwelling in a community in Japan. In this study, there were 532 participants (185 males and 347 females). Participants who responded positively to the question "Do you sometimes choke on drinks/food such as tea and soup?" or those who presented with abnormal repetitive saliva swallowing test findings were diagnosed with dysphagia. The data collected from these participants included the following: number of teeth, occurrence of oral dryness, age, body mass index, serum albumin concentration, smoking, drinking and exercise habits, presence of diseases, such as diabetes mellitus and hypertension, and questions from the Mini-Mental State Examination. Dysphagia was observed in 33 males (17.8%) and 76 females (21.9%). To explore the effect of the potential risk factors on the prevalence of dysphagia, a model was built by multivariate logistic regression analysis. Using the forced entry method, oral dryness (odds ratio [OR] =3.683 and P=0.003 in males; OR =1.797 and P=0.032 in females) and the number of teeth (OR =0.946 and P=0.038 in males) were found to be significantly related to dysphagia. This cross-sectional study demonstrated associations between oral conditions and dysphagia. Factors such as oral dryness and number of teeth may contribute to dysphagia more so than aging, lifestyle and comorbidity in community-dwelling adults over the age of 50.


Identification of a novel human long non-coding RNA that regulates hepatic lipid metabolism by inhibiting SREBP-1c.
Sterol regulatory element binding proteins (SREBPs) are master regulators of hepatic lipid homeostasis. Aberrant expression of SREBPs frequently leads to lipid metabolism dysregulation. Long non-coding RNAs (lncRNAs) have been identified with diverse biological functions, but the effects of lncRNAs on lipid metabolism are rarely reported. Here, we identified a novel human specific lncRNA, lncHR1, as a negative regulator of SREBP-1c expression. Overexpression of lncHR1 inhibited expression of SREBP-1c and fatty acid synthase (FAS) and then repressed oleic acid-induced hepatic cell triglyceride (TG) and lipid droplet (LD) accumulation. In vivo, the data of established transgenic animals showed that mice with lncHR1 expression had less hepatic expression of SREBP-1c, FAS, Acetyl-CoA carboxylase α (ACCα), and less hepatic and plasma TG after being fed a high-fat diet. Therefore, we report a novel lncRNA which can decrease lipid metabolism by repressing SREBP-1c gene expression.


In-vitro activity of quinolones against different species of staphylococci of recent clinical isolation.
We considered 256 strains of S. aureus (SA) and S. non-aureus (SnA) of recent clinical isolation. Their susceptibility (S) or resistance (R) to pefloxacin, ciprofloxacin, enoxacin, ofloxacin (which have been used in therapy for several years) and to timentin as well, has been tested, in relation with methicillin susceptibility (MS) and methicillin resistance (MR). To date, the activity of quinolones against all staphylococci remains relatively high, notwithstanding the appearance of resistant strains, in particular among MR SnA. Of the four quinolones examined, ofloxacin showed to be the most active, i.e. effective against 100% of the staphylococci, either SA or SnA.


[The modulatory activity of T cell immunoglobulin and mucin domain-containing protein 3 on T lymphocytes in patients with chronic heart failure].
Objective: To investigate the expression of T cell immunoglobulin and mucin domain-containing protein 3 (TIM-3) in patients with chronic heart failure and its modulatory activity on T lymphocytes. Methods: Eighty-six patients with chronic heart failure (CHF group) who were hospitalized in Department of Cardiology, the First Affiliated Hospital of Zhengzhou University between January and October 2018 were enrolled in the study. Meanwhile, thirty-two healthy controls (HC group) who received healthy examination were also selected. Peripheral blood mononuclear cells were isolated, and TIM-3 expression of CD4(+)and CD8(+)T cells was investigated by flow cytometry. CD4(+)and CD8(+)T cells were purified, and were stimulated by anti-TIM-3 antibody. Interferon-γ (IFN-γ), interleukin (IL)-4, IL-10, IL-35, IL-17, and IL-22 expressions in the supernatants of cultured CD4(+)T cells and tumor necrosis factor-α (TNF-α) and IFN-γ expressions in the supernatants of cultured CD8(+) T cells were measured by enzyme-linked immunosorbent assay. mRNA expressions of T-bet, GATA-3, FoxP3, and RORγt in CD4(+)T cells and perforin and granzyme B in CD8(+)T cells were semi-quantified by real-time PCR. Student t test or paired t test was used for comparisons between the two groups. Results: TIM-3(+) CD4(+) T cell percentage significantly increased in CHF group than that of HC group (3.47%±1.06% vs 0.92%±0.27%, P<0.001). TIM-3(+)CD8(+)T cell percentage also notably elevated in CHF group compared to HC group (6.12%±1.91% vs 1.77%±0.63%, P<0.001). CD4(+)T and CD8(+)T cells were dysfunctional in chronic heart failure. The levels of IFN-γ, IL-17, and IL-22 secreted by purified CD4(+) T cells significantly reduced in CHF group, while IL-10 and IL-35 expressions elevated in CHF group (all P<0.05). The relative mRNA expression levels of T-bet and RORγt in CD4(+) T cells remarkably decreased in CHF group than those of HC group (all P<0.01), while relative expression level of FoxP3 mRNA increased in CHF group (1.93±0.88 vs 0.97±0.28, P=0.031). The levels of TNF-α and IFN-γ produced by purified CD8(+)T cells notably reduced in CHF group than those of HC group (all P<0.05), and relative mRNA expression levels of perforin and granzyme B also decreased in CHF group (all P<0.05). The levels of anti-TIM-3 antibody stimulation-produced IFN-γ, IL-17, and IL-22 increased (all P<0.05) but IL-35 secretion reduced [(61±13) ng/ml vs (72±17) ng/ml, P=0.029] by CD4(+)T cells in CHF group. The relative mRNA expression levels of T-bet and RORγt also elevated in response to anti-TIM-3 antibody stimulation (all P<0.05). Anti-TIM-3 antibody stimulation promoted TNF-α and IFN-γ production by CD8(+)T cells in CHF group (all P<0.01). The relative mRNA expression levels of perforin and granzyme B also increased (all P<0.05). Conclusion: TIM-3 was increasingly expressed in T cells from patients with chronic heart failure, and might take part in the regulation of T cell dysfunction in chronic heart failure.


Rapid diagnosis of infectious diseases: the role of giant African pouched rats, dogs and honeybees.
Early detection of infection in an individual is an important strategy to prevent transmission and spread of the infection - in the community or among patients admitted in a health care facility. Over the past decade, there have been rapid advances in technology in an attempt to provide rapid, accurate tests for diagnosis of infectious diseases. With this in perspective, the use of animals' superior olfactory sensitivity to sniff out infectious diseases holds promise.


Protective effect of 20-HETE analogues in experimental renal ischemia reperfusion injury.
While it is known that the arachidonic acid metabolite 20-hydroxyeicosatetraenoic acid (20-HETE) contributes to ischemic injury in the heart and brain, its role in kidney injury is unclear. Here we determined the effects on ischemia-reperfusion injury of the 20-HETE analogues, 20-hydroxyeicosa-5(Z), 14(Z)-dienoic acid (5,14-20-HEDE), and N-[20-hydroxyeicosa-5(Z),14(Z)-dienoyl]glycine (5,14-20-HEDGE), and of the inhibitor of 20-HETE synthesis N-hydroxy-N-(4-butyl-2 methylphenyl) formamidine (HET0016). Using Sprague-Dawley rats we found that while treatment with the inhibitor exacerbated renal injury, infusion of both 5,14-20-HEDE and 5,14-20-HEDGE significantly attenuated injury when compared to vehicle or inhibitor-treated rats. Medullary blood flow, measured by laser-Doppler flowmetry, decreased to half of the baseline one hour after reperfusion in the control rats, but 5,14-20-HEDGE completely prevented this. Treatment of control animals with 5,14-20-HEDGE increased urine output and sodium excretion without altering their mean arterial pressure or glomerular filtration rate. Our results suggest that 20-HETE analogues protect the kidney from ischemia-reperfusion injury by inhibiting renal tubular sodium transport and preventing the post-ischemic fall in medullary blood flow. Analogues of 20-HETE may be useful in the treatment of acute ischemic kidney injury.


[Relationship between the expression of IL-10 and liver regeneration following reduced-size orthotopic liver transplantation in rats].
To explore the relationship between the expression of IL-10 and liver regeneration following reduced-size orthotopic liver transplantation in rats. Rats models with reduced-size orthotopic liver transplantation were established. The rats were divided in three groups: partial liver resection (I), orthotopic liver transplantations (II), and reduced-size orthotopic liver transplantation (III). The expression of IL-10 and regenerative response of liver in rats were evaluated by immunohistochemistry and flow cytometry on the 1st, 2nd, 4th and 7th days after the operations, respectively. The liver grafts were capable of regeneration, the proliferation activity peaked on the fourth day with 26.3+/-0.9, 35.8+/-2.2, and 32.4+/-1.8 in I, II, and III groups, respectively. The expression of IL-10 was negative correlation to liver regeneration (r=-0.58, P<0.01). Whole and reduced-size transplanted livers show the same regenerative activity. The maximal regenerative response delayes slightly, compared with that after partial hepatectomy. IL-10 plays an important immunomodulatory role in liver regeneration,and the effect is affected by general immune system and other cytokines.


Dermal lipofuscinosis associated with amiodarone therapy. Report of a case.
Amiodarone hydrochloride is a noncompetitive adrenergic blocker used in the treatment of tachyarrhythmias. Its use in Europe and South America has been associated with cutaneous pigmentation thought to be caused by lipofuscin deposition in the dermis. We describe a similar case occurring in North America. A skin biopsy specimen from the patient was examined by light microscopy, fluorescence microscopy, and electron microscopy. From these examinations, a diagnosis of dermal lipofuscinosis was made.


Forced normalization: A systematic review.
Forced normalization (FN) is an intriguing phenomenon characterized by the emergence of psychiatric disturbances following the establishment of seizure control or reduction in the epileptic activity in a patient with previous uncontrolled epilepsy. We aim to describe the clinical characteristics of the condition. We conducted a systematic review on MEDLINE, EMBASE, Cochrane, and Scielo from January 1953 to January 2018. Clinical, electrographic, and imaging data were gathered. We considered all outcomes in children and adults. We performed no meta-analyses due to the limited available data. Of 2606 abstracts identified, 36 fulfilled the FN diagnostic criteria; 193 FN episodes were evaluated and 77 of them were analyzed extensively. Sixty percent of cases were female. Mean age ± standard deviation (SD) was 28.3 ± 14.2 years. The majority of patients had focal (80%) symptomatic (44%) epilepsy. Most patients reported a high ictal frequency (58%) and were on polytherapy (51%). Patients presented psychosis (86.4%), mood disorders (25.8%), and dissociation (4.5%) as the main manifestations. In the psychosis group, persecutory (52.6%) and reference (47.3%) delusions were frequent. FN was provoked by an antiepileptic drug (AED) (48.5%) mainly levetiracetam, epilepsy surgery (31.8%), or vagus nerve stimulation (13.6%). Treatment was homogeneous including anticonvulsant withdrawal (47%) or taper (25%); antipsychotics were initiated in the majority of cases (73%). Psychiatric symptoms were partially controlled in 35%, with complete resolution of symptoms in the remaining 65% of cases. The majority of patients (87%) with AED trigger and withdrawal presented complete resolution of symptoms in comparison to 28.5% of patients triggered by surgery. Forced normalization is an entity whose pathophysiology remains uncertain. Antipsychotic drug use does not predict complete resolution of psychiatric symptoms in comparison with AED withdrawal. Although there is a positive response to treatment in patients with FN triggered by drugs, the prognosis is obscure in patients with surgery triggered FN.


miR-148a Suppresses estrogen-induced viability and migration of breast cancer cells via inhibition of estrogen receptor α expression.
MicroRNAs (miRs) play critical roles in the development and malignant progression of human cancers. miR-148a has previously been found to inhibit the migration and invasion of breast cancer cells. However, the underlying mechanism of miR-148a in regulating the viability and migration of estrogen receptor (ER) α-positive breast cancer cells is still unknown. In this study, ERα-positive breast cancer MCF7 cells were treated with estradiol (E2). Data from MTT and wound healing assays showed that E2 treatment promoted the viability and migration of MCF7 cells. A bioinformatics analysis and luciferase reporter assay identified ERα as a direct target of miR-148a. Ectopic expression of miR-148a significantly decreased the protein expression of ERα (P<0.01), while knockdown of miR-148a significantly increased the ERα protein level in MCF7 cells (P<0.01). Furthermore, miR-148a overexpression significantly inhibited the E2-induced viability and migration of MCF7 cells (P<0.01), similar to the effect of silencing ERα. However, overexpression of ERα rescued the suppressed viability and migration caused by miR-148a upregulation. Finally, it was found that E2 treatment led to a significant decrease in the miR-148a level in MCF7 cells (P<0.01). These results suggest that miR-148a can suppress the E2-induced viability and migration of MCF7 breast cancer cells via inhibition of ERα protein expression, expanding the understanding of miR function in ERα-positive breast cancer.


Gain Modulation as a Mechanism for Coding Depth from Motion Parallax in Macaque Area MT.
Observer translation produces differential image motion between objects that are located at different distances from the observer's point of fixation [motion parallax (MP)]. However, MP can be ambiguous with respect to depth sign (near vs far), and this ambiguity can be resolved by combining retinal image motion with signals regarding eye movement relative to the scene. We have previously demonstrated that both extra-retinal and visual signals related to smooth eye movements can modulate the responses of neurons in area MT of macaque monkeys, and that these modulations generate neural selectivity for depth sign. However, the neural mechanisms that govern this selectivity have remained unclear. In this study, we analyze responses of MT neurons as a function of both retinal velocity and direction of eye movement, and we show that smooth eye movements modulate MT responses in a systematic, temporally precise, and directionally specific manner to generate depth-sign selectivity. We demonstrate that depth-sign selectivity is primarily generated by multiplicative modulations of the response gain of MT neurons. Through simulations, we further demonstrate that depth can be estimated reasonably well by a linear decoding of a population of MT neurons with response gains that depend on eye velocity. Together, our findings provide the first mechanistic description of how visual cortical neurons signal depth from MP.SIGNIFICANCE STATEMENT Motion parallax is a monocular cue to depth that commonly arises during observer translation. To compute from motion parallax whether an object appears nearer or farther than the point of fixation requires combining retinal image motion with signals related to eye rotation, but the neurobiological mechanisms have remained unclear. This study provides the first mechanistic account of how this interaction takes place in the responses of cortical neurons. Specifically, we show that smooth eye movements modulate the gain of responses of neurons in area MT in a directionally specific manner to generate selectivity for depth sign from motion parallax. We also show, through simulations, that depth could be estimated from a population of such gain-modulated neurons.


The chemotherapy of rodent malaria, XXI. Action of quinine and WR 122 (a 9-phenanthrenemethanol) on the fine structure of Plasmodium berghei in mouse blood.
The effects of quinine and a 9-phenanthrenemethanol, WR 122,455 on the fine structure of Plasmodium berghei have been investigated. Changes consequent upon quinine treatment were noted in the outer membranes (including those that surround the "food vacuole") and the digestive vacuoles. These changes were followed by cytoplasmic degeneration and vacuolization. WR 122,455 caused morphological changes in at least three areas of the parasite, (1) the outer membranes, (2) the digestive vacuole and (3) the nucleus. The relationship of these changes to the mode of action of these compounds is discussed. It seems possible that they interfere primarily with limiting membrane-mitochondrial functions. The modifications of pigment formation are characteristic of these compounds and differ from those seen with chloroquine or primaquine.


Twisted Schell-model beams with axial symmetry.
The problem of when a twist can be impressed on a partially coherent beam is solved for Schell-model fields endowed with axial symmetry. A modal analysis can be performed for any such beam, thus permitting evaluation of whether it will withstand the twisting process. Beyond exemplifying some twistable beams, it is shown that, for certain correlation functions, the beam cannot be twisted, no matter how the numerical parameters are chosen.


Flow-cytometric detection of surface membrane alterations and concomitant changes in the cytoskeletal actin status of activated platelets.
Occlusive vascular diseases are promoted by a "prethrombotic state" with increased platelet activity. Polymerization of cytoskeletal proteins and exposure of subcellular structures or rebinding of secreted proteins have been characterized as early reactions after platelet activation preceding adhesion and aggregation. Here, we demonstrate the kinetic increase in specific binding of monoclonal antibodies to thrombospondin (P10) and to platelet membrane activation markers CD63 (GP53, a 53 kD lysosomal protein) and CD62 (GMP140, a 140 kD alpha granule protein) by using a flow-cytometric bio-assay and the related change in the actin status by using the DNase-I inhibition assay after stimulation of normal human platelets with 0.2 U/ml thrombin. F-actin was raised from 41% to 51% of total platelet actin content 30 s after stimulation and remained thereafter constant (50% at 60 s). Simultaneously, the percentage of P10, CD63, and CD62 positive platelets was elevated from 5.4%, 24.4%, and 9.1% to 67.4%, 80.2%, and 82.3% respectively. The mean number of P10, CD63, and CD62 antibody binding sites increased from 3,300, 1,715, and 2,146 to 6,400, 6,800, and 9,016 per platelet. Conclusively, changes in the organization of the cytoskeletal protein "actin" and exposure of subcellular structures indicating platelet secretion can be regarded as markers of early platelet activation. Thus, the parallel response in both analytical systems provides further support for the diagnostic concept of flow-cytometric detection of preactivated platelets in the peripheral blood by using fluochrome staining procedures detecting activation dependent structural alterations directly at the cellular level.


The inhibition of UDP-glucuronosyltransferases (UGTs) by tetraiodothyronine (T4) and triiodothyronine (T3).
1. UDP-glucuronosyltransferases (UGTs) are important drug-metabolizing enzymes (DMEs) catalyzing the glucuronidation elimination of various xenobiotics and endogenous substances. Endogenous substances are important regulators for the activity of various UGT isoforms. Triiodothyronine (T3) and thyroxine (T4) are important thyroid hormones essential for normal cellular differentiation and growth. The present study aims to elucidate the inhibition behavior of T3 and T4 on the activity of UGT isoforms. 2. In vitro recombinant UGTs-catalyzed glucuronidation of 4-methylumbelliferone (4-MU) was used to screen the inhibition potential of T3 and T4 on the activity of various UGT isoforms. Initial screening results showed that T4 exerted stronger inhibition potential than T3 on the activity of various UGT isoforms at 100 μM. Inhibition kinetics was determined for the inhibition of T4 on the representative UGT isoforms, including UGT1A1, -1A3, -1A7, -1A8, -1A10 and -2B7. The results showed that T4 competitively inhibited the activity of UGT1A1, -1A3, -1A7, 1A10 and -2B7, and noncompetitively inhibited the activity of UGT1A8. The inhibition kinetic parameters were calculated to be 1.5, 2.4, 11, 9.6, 4.8 and 3.0 μM for UGT1A1, -1A3, -1A7, -1A8, -1A10 and -2B7, respectively. In silico docking method was employed to demonstrate why T4 exerted stronger inhibition than T3 towards UGT1A1. Stronger hydrogen bonds and hydrophobic interaction between T4 and activity cavity of UGT1A1 than T3 contributed to stronger inhibition of T4 towards UGT1A1. 3. In conclusion, more clinical monitoring should be given for the patients with the elevation of T4 level due to stronger inhibition of UGT isoforms-catalyzed metabolism of drugs or endogenous substances by T4.


Probing the Physical Origin of Anisotropic Thermal Transport in Black Phosphorus Nanoribbons.
Black phosphorus (BP) has emerged as a promising candidate for next-generation electronics and optoelectronics among the 2D family materials due to its extraordinary electrical/optical/optoelectronic properties. Interestingly, BP shows strong anisotropic transport behavior because of its puckered honeycomb structure. Previous studies have demonstrated the thermal transport anisotropy of BP and theoretically attribute this to the anisotropy in both the phonon dispersion relation and the phonon relaxation time. However, the exact origin of such strong anisotropy lacks clarity and has yet to be proven experimentally. Here, the thermal transport anisotropy of BP nanoribbons is probed by an electron beam technique. Direct evidence is provided that the origin of this anisotropy is dominated by the anisotropic phonon group velocity, verified by Young's modulus measurements along different directions. It turns out that the ratio of the thermal conductivity between zigzag (ZZ) and armchair (AC) ribbons is almost same as that of the corresponding Young modulus values. The results from first-principles calculation are consistent with this experimental observation, where the anisotropic phonon group velocity between ZZ and AC is shown. These results provide fundamental insight into the anisotropic thermal transport in low-symmetry crystals.