Dynamics of certain Euler-Bernoulli rods and rings from a minimal coupling quantum isomorphism.
In some parameter and solution regimes, a minimally coupled nonrelativistic quantum particle in one dimension is isomorphic to a much heavier, vibrating, very thin Euler-Bernoulli rod in three dimensions with ratio of bending modulus to linear density (ℏ/2m)^{2}. For m=m_{e}, this quantity is comparable to that of a microtubule. Axial forces and torques applied to the rod play the role of scalar and vector potentials, respectively, and rod inextensibility plays the role of normalization. We show how an uncertainty principle ΔxΔp_{x}≳ℏ governs transverse deformations propagating down the inextensible, force and torque-free rod, and how orbital angular momentum quantized in units of ℏ or ℏ/2 (depending on calculation method) emerges when the force and torque-free inextensible rod is formed into a ring. For torqued rings with large wave numbers, a "twist quantum" appears that is somewhat analogous to the magnetic flux quantum. These and other results are obtained from a purely classical treatment of the rod, i.e., without quantizing any classical fields.


Reduced expression of immunoreactive beta2-adrenergic receptor protein in human myometrium with labor.
A considerable body of evidence exists suggesting that the beta(2)-adrenergic receptor (beta(2)-AR) mediates uterine relaxation. However, little information exists on the localization, distribution, or expression of beta(2)-ARs in the human myometrium during the nonpregnant to labor transition. We have used immunochemical methods to investigate beta(2)-AR localization and expression in the nonpregnant, term pregnant, and term parturient uterus. Myometrial biopsies were obtained from 1) nonpregnant, menstruating women undergoing hysterectomy; 2) singleton term pregnant women undergoing elective cesarean section before the onset of labor; or 3) singleton term pregnant women undergoing emergency cesarean section after spontaneous labor. Tissues were processed for immunohistochemistry, immunofluorescence, and Western blotting and a primary polyclonal antibody specific to the human beta(2)-AR to identify immunoreactive myometrial beta(2)-AR. Protein levels were subsequently quantified by densitometry relative to rat brain protein. Immunohistochemistry and immunofluorescence demonstrated the presence of beta(2)-AR predominantly at the plasma membrane and also in the cytosol of myometrial cells. A 2-fold decrease in protein levels of the beta(2)-AR was apparent in the myometrium of labor compared with that of nonpregnant and pregnant nonlaboring women (P < 0.05). These results demonstrate that down-regulation of beta(2)-AR protein with labor may constitute a contributory mechanism by which uterine quiescence is removed at term.


Reaching rural patients through otolaryngology visiting consultant clinics.
Providing otolaryngology care to rural populations is a major challenge. In this study, we focus on rural outreach by the otolaryngology workforce in Iowa, a state with a high proportion of rural residents. Using data from 2013, we find that almost half (46%) of Iowa-based otolaryngologists participate in outreach. Along with colleagues from adjoining states, Iowa otolaryngologists staffed more than 2100 in-person clinic days in 76 mainly rural sites. This system of rural outreach has expanded access from 20 to 85 of the 99 counties in Iowa. These efforts improve access for more than 1 million residents out of a total population of 3 million. However, this improved level of access comes at a cost as visiting otolaryngologists drove an estimated 17,000 miles per month. This established approach to serving rural patients may be negatively impacted by changes under the Affordable Care Act.


Quantitative phase diagrams of branching and annihilating random walks.
We demonstrate the full power of nonperturbative renormalization group methods for nonequilibrium situations by calculating the quantitative phase diagrams of simple branching and annihilating random walks and checking these results against careful numerical simulations. Specifically, we show, for the [see text] case, that an absorbing phase transition exists in dimensions d=1 to 6 and argue that mean-field theory is restored not in d=3, as suggested by previous analyses, but only in the limit d--> infinity.


The Hitchhiker's Guide to Flow Chemistry ∥.
Flow chemistry involves the use of channels or tubing to conduct a reaction in a continuous stream rather than in a flask. Flow equipment provides chemists with unique control over reaction parameters enhancing reactivity or in some cases enabling new reactions. This relatively young technology has received a remarkable amount of attention in the past decade with many reports on what can be done in flow. Until recently, however, the question, "Should we do this in flow?" has merely been an afterthought. This review introduces readers to the basic principles and fundamentals of flow chemistry and critically discusses recent flow chemistry accounts.


Evaluation of the immune function assay in pediatric living donor liver transplantation.
The immune function (ImmuKnow) assay is a measure of cell-mediated immunity based on the peripheral CD4+ T cell ATP activity. The efficacy of ImmuKnow in pediatric LDLT is not well documented. The aim of this study was to assess the correlations between the ImmuKnow and the clinical status in pediatric LDLT recipients. A total of 716 blood samples were obtained from 60 pediatric LDLT recipients (one month to 16 yr of age). The recipient's status was classified as follows: stable, infection, or rejection. The ImmuKnow values in the pediatric LDLT recipients with a clinically stable status had a lower immune response (IQR 85-297 ATP ng/mL) than that previously reported in adults. Meanwhile, the ImmuKnow values of the stable patients were not correlated with age. Furthermore, a significant difference was found in the ImmuKnow values between the bacterial or fungal infection and stable groups, but not between the CMV or EBV infection and stable groups. The ImmuKnow levels in the pediatric LDLT were lower than those observed in the adult LDLT. The proposed reference value is between 85 and 297 ATP ng/mL in pediatric LDLT recipients. We conclude that the ImmuKnow assay could be helpful for monitoring pediatric LDLT recipients with bacterial or fungal infections.


Integrating biologically targeted therapy in head and neck squamous cell carcinomas.
The integration of targeted therapies such as cetuximab to radiation therapy has revolutionized the management of head and neck cancers in the last decade. However, the use of targeted therapies raised several clinically relevant questions that have yet to be answered. These questions include the optimal patient and tumor profile for biologically targeted therapy, the optimal radiation fractionation to use with targeted therapies, how to integrate them into standard or new chemoradiation regimens, their schedule and duration of administration, their toxicity, and which direction to consider for novel targeted treatment. In this review, we highlight several of these important issues, discuss the clinical trials that are designed to address these issues, and introduce some novel targeted therapies that may contribute to the improvement of the therapeutic ratio for head and neck cancer therapy.


Apoptosis in lupus SLE-N IV and non-lupus mesangiocapillary glomerulonephritis type I MCGN. I. A comparative study.
Apoptosis plays an important role in the recovery from glomerulonephritis. Moreover, aberrant apoptosis seems to contribute to lupus nephritis. This study compared the intensity of apoptosis in lupus and non-lupus mesangiocapillary glomerulonephritis. We used an in situ cell death detection kit, POD, which detects single cell apoptosis in formalin-fixed renal tissue. Our material comprised 13 renal biopsy specimens from patients with lupus mesangiocapillary glomerulonephritis (SLE-N IV), 11 renal tissues from patients with non-lupus mesangiocapillary type I glomerulonephritis (MCGN) and 8 normal kidney samples. We checked the correlations between intraglomerular apoptotic cells and the total number of intraglomerular cells, the relationship between tubulointerstitial apoptotic cells and the relative interstitial cortical volume. The population of intraglomerular apoptotic cells was lower in tissues from SLE-N IV patients than patients with MCGN. In MCGN the intensity of apoptosis in glomeruli correlated significantly with the number of total glomerular cells. Tubulointerstitial apoptotic cells were infrequent in the kidney samples from patients with SLE-N IV and in the normal kidney. In the renal interstitium and tubuli the number of apoptotic cells did not correlate with the relative interstitial cortical volume in kidney tissue in patients with MCGN. In the biopsies from patients with SLE-N IV there was an inverse correlation between tubulointerstitial apoptotic cells and the relative interstitial cortical volume, so a low number of apoptotic tubulointerstitial cells was associated with fibrosis in the renal interstitium. The results illustrate the differences in the intensity of apoptosis in lupus and non-lupus glomerulonephritis. The low number of apoptotic cells in renal tissue from patients with SLE-N IV suggests regulation of apoptosis may be altered in the mechanisms of glomerular and tubulointerstitial damage in lupus nephritis, although the reduced apoptosis may simply be due to smaller numbers of cells in fibrotic areas.


Microsurgery in China and the development of Western reconstructive microsurgery.
The development of extremity replantation and reconstructive microsurgery was initially carried out independently among the pioneering centers throughout the world. The comparative development of these techniques is outlined. With the fast growth of microsurgical procedures, many of the U.S. residency programs have incorporated microsurgery training into the curriculum.


Comparison of two eyelid speculums and their effect on intraocular pressure in clinically normal cats.
The present study was undertaken to determine the possible effects of the placement two different types of eyelid speculum on intraocular pressure (IOP) measurement in clinically normal cats. Thirty healthy cats were divided randomly into two groups of 15, group B (Barraquer wire speculum) and group W (Williams eye speculum). All cats were sedated with intramuscular medetomidine (Dorbene vet; 100 μg/kg) then placed in right lateral recumbency, and IOP was recorded in the left eye using a Tono-Pen Vet tonometer without and with an eyelid speculum in place in both groups. The without-speculum IOPs for cats in group B and group W were 13.8 ± 3.0 mmHg and 13.2 ± 3.6 mmHg, respectively, and did not differ significantly. A significant increase in IOP (19.8 ± 3.7 mmHg) was observed in group W in with-speculum measurements in comparison to the without-speculum values (P <0.001).There was no significant difference between with- and without-speculum IOP values (13.8 ± 2.7 mmHg) in group B (P = 1.0). The Barraquer wire speculum has no effect on IOP compared with the Williams eye speculum in normal cats, and may be an appropriate choice in cats for intraocular surgeries that cannot tolerate acute increases in IOP.


Monitoring udder health and milk quality using somatic cell counts.
In this article the use of somatic cell counts for monitoring udder health and milk quality is discussed. Somatic cell count dynamics at quarter, cow, herd and population level are discussed and illustrated with examples. Quarter and cow somatic cell counts directly represent the inflammatory status of the mammary gland. Herd and population somatic cell count are related to the inflammatory process in individual cows but much more reflect the udder health status of the herd and the quality of the raw milk in the herd and the population. Application of monitoring tools in herd health management are illustrated using a case study. Understanding infection dynamics requires precise longitudinal data. Monitoring tools are required to find the areas of risk in the herd. It is inevitable that more complete udder health programs and monitoring systems are to be developed and implemented. These programs are necessarily dynamic and complex. Implementation of complete udder health programs should be accompanied by research efforts to further fine-tune these complete udder health control and monitoring programs.


Nuclear expression of Y box binding-1 is important for resistance to chemotherapy including gemcitabine in TP53-mutated bladder cancer.
The development and acquisition of multiple drug resistance in cancer cells remain a major obstacle in the treatment of bladder cancer. Nuclear translocation of Y box binding-1 (YB-1), which is a member of a family of DNA-binding proteins that contain a cold shock domain, plays a significant role in the acquisition of drug resistance by upregulating expression of the multidrug resistance-1 (MDR-1) gene product, p-glycoprotein. The tumor suppressor protein p53 is thought to be essential for nuclear translocation of YB-1. We hypothesized that nuclear translocation of YB-1 might be associated with drug resistance of bladder cancer with an abnormality of the TP53 gene that results in a mutated p53 protein. To test this hypothesis, we analyzed the association of YB-1 with drug resistance of TP53-mutated bladder cancer, including immunohistochemical analysis of YB-1, p-glycoprotein and p53 in vivo as well as the function of YB-1 nuclear translocation and regulation of its translocation by p53 in vitro. Additionally, we examined the association between the nuclear translocation of YB-1 and gemcitabine, a major anticancer-drug for bladder cancer, in cancer cell lines. Nuclear expression of YB-1 was correlated with the expression of p-glycoprotein and p53 in bladder cancer cases (p<0.05). In vitro, both introduction of TP53 and gemcitabine induced nuclear translocation of YB-1. These data indicate that YB-1 translocates to the nucleus coordinately with p53 expression and is involved in gemcitabine resistance in bladder cancer. Nuclear expression of YB-1 is important for resistance to chemotherapy including gemcitabine in TP53-mutated bladder cancer.


Pregnancy outcomes following bariatric surgery.
To compare pregnancy outcomes postbariatric surgery for women who remain obese at conception to those who were not obese. From a database of women who received outpatient perinatal services, we identified women with a history of bariatric surgery who are currently pregnant with a singleton gestation. Available maternal characteristics and pregnancy outcomes were compared between women whose prepregnancy body mass index (PPBMI) remained in the obese range (≥30 kg/m(2)) and those with a PPBMI of <30 kg/m(2) using Fisher exact test, independent Student's t test, and Mann-Whitney U test statistics. Of the 102 women identified, 52 (51%) were obese and 50 (49%) were not obese at conception. No differences were observed in maternal age, marital status, years from surgery to delivery, development of gestational diabetes, gestational age at delivery, neonatal intensive care unit (NICU) admission, or nursery days. Maternal obesity (≥30 kg/m(2)) postbariatric surgery was associated with higher rates of cesarean delivery (63.5% vs. 36.0%, p=0.010) and development of pregnancy-related hypertension (36.5% vs. 8.0%, p=0.001) compared to nonobese women (<30 kg/m(2)). Postbariatric surgery, an optimal goal should be to achieve a nonobese weight status before conception to reduce maternal complications, such as pregnancy-related hypertension and cesarean delivery.


A comparative first principles study on trivalent ion incorporated SSZ-13 zeolites.
The dispersion-corrected density functional theory has been used to study the trivalent ions B, Al, Ga, and Fe incorporated SSZ-13-type zeolites. The associated structure and Brønsted/Lewis acidity change caused by the incorporation ions were comparatively studied. It was found that the smaller the radius differences of the incorporation ions are, the smaller the changes in the structure will be and the less acidity will be enhanced for the Brønsted sites. The trivalent Al is found to be the most favorable trivalent incorporation ion and Na is found to be the most favorable charge balanced ion for the synthesis of SSZ-13-type zeolites due to size comparability, which are in line with the experimental observation. The substitution energies which show the relative synthesis difficulty level were also applied for B, Al, Ga, and Fe incorporated zeolites and found that the difficulty decreases with order of Fe > B > Ga ≫ Al, also in good agreement with the experimental observations. Adsorption studies for the NH3 and pyridine molecules indicate that adsorption on the Brønsted acid sites is more stable than on the Lewis acid sites. The Brønsted acidity was found to follow the order of HAl-SSZ-13 > HGa-SSZ-13 ≈ HFe-SSZ-13 > HB-SSZ-13 where the Lewis acidity was found to follow the order of HGa-SSZ-13 ≈ HFe-SSZ-13 > HAl-SSZ-13 > HB-SSZ-13. Our results provide new insights for the synthesis of the SSZ-13-type zeolites and fundamental information for the zeolitic catalyst designation to enhance the catalytic performance.


Pregnancy in the patient with Eisenmenger's syndrome.
Eisenmenger's syndrome occurs when a large congenital or surgically created shunt between the left and right sides of the heart causes an increase in pulmonary vascular resistance that equals or surpasses systemic resistance, resulting in a reversal of the shunt from a left-to-right shunt to a right-to-left or bi-directional shunt. The maternal mortality rate of pregnancy in the presence of Eisenmenger's syndrome is reported to be as high as 50-65% with cesarean section. We present the case of a 32-year-old woman with Eisenmenger's syndrome who gave birth at 29 weeks of gestation via C-section to a healthy baby boy, and we review the literature regarding the management of such patients.


Ochratoxin A transport by the human breast cancer resistance protein (BCRP), multidrug resistance protein 2 (MRP2), and organic anion-transporting polypeptides 1A2, 1B1 and 2B1.
Ochratoxin A (OTA) is a fungal secondary metabolite that can contaminate various foods. OTA has several toxic effects like nephrotoxicity, hepatotoxicity, and neurotoxicity in different animal species, but its mechanisms of toxicity are still unclear. How OTA accumulates in kidney, liver, and brain is as yet unknown, but transmembrane transport proteins are likely involved. We studied transport of OTA in vitro, using polarized MDCKII cells transduced with cDNAs of the efflux transporters mouse (m)Bcrp, human (h)BCRP, mMrp2, or hMRP2, and HEK293 cells overexpressing cDNAs of the human uptake transporters OATP1A2, OATP1B1, OATP1B3, or OATP2B1 at pH7.4 and 6.4. MDCKII-mBcrp cells were more resistant to OTA toxicity than MDCKII parental and hBCRP-transduced cells. Transepithelial transport experiments showed some apically directed transport by MDCKII-mBcrp cells at pH7.4, whereas both mBcrp and hBCRP clearly transported OTA at pH6.4. There was modest transport of OTA by mMrp2 and hMRP2 only at pH6.4. OATP1A2 and OATP2B1 mediated uptake of OTA both at pH7.4 and 6.4, but OATP1B1 only at pH7.4. There was no detectable transport of OTA by OATP1B3. Our data indicate that human BCRP and MRP2 can mediate elimination of OTA from cells, thus reducing OTA toxicity. On the other hand, human OATP1A2, OATP1B1, and OATP2B1 can mediate cellular uptake of OTA, which could aggravate OTA toxicity.


Gadolinium as an alternative contrast agent for diagnostic and interventional angiographic procedures in patients with impaired renal function.
The study was designed to investigate the safety and feasibility of gadopentetate dimeglumine, a gadolinium-based contrast medium, as an alternative angiographic contrast agent in patients with impaired renal function and high risk for iodinated contrast-induced nephropathy. Gadopentetate dimeglumine was used as the radiographic contrast agent in 32 diagnostic or interventional angiographic procedures in 29 patients (59% diabetics) with severe renal insufficiency (average serum creatinine of 3.6+/-1.4 mg/dl). The average dose of gadopentetate dimeglumine was 0.34+/-0.06 mmol/kg body weight. Gadopentetate dimeglumine was used either alone (n=20) or in conjunction with carbon dioxide (n=12). Thirty-two angiographic procedures (24 diagnostic angiographies and 8 interventional procedures) were performed in 29 patients. For diagnostic purposes, eleven selective renal arteriographies, six angiographies of the iliac arteries and lower extremities, and seven venous angiographies of the upper extremity and central veins were performed. Interventional procedures consisted of two percutaneous transluminal renal angioplasties with stenting, four percutaneous peripheral vascular interventions, and two balloon angioplasties of a dialysis fistula. None of the patients, except one, had evidence of post-procedure contrast material-induced renal failure (increase in serum creatinine >0.5 mg/dl within 72 h) or other complications. This patient had a clinically important increase in serum creatinine level after percutaneous transluminal renal angioplasty and stenting, probably due to cholesterol embolism. Gadopentetate dimeglumine had sufficient radiographic density to allow adequate diagnostic visualization with digital subtraction equipment in all cases. Gadopentetate dimeglumine is an alternative and safe radiographic contrast agent for angiography and interventional procedures in patients with severe pre-existing renal impairment. In this population with high risk for contrast-induced acute renal failure, it is obviously less nephrotoxic than iodinated contrast media.


Comparison between Proteome and Transcriptome Response in Potato (Solanum tuberosum L.) Leaves Following Potato Virus Y (PVY) Infection.
Plant diseases caused by viral infection are affecting all major crops. Being an obligate intracellular organisms, chemical control of these pathogens is so far not applied in the field except to control the insect vectors of the viruses. Understanding of molecular responses of plant immunity is therefore economically important, guiding the enforcement of crop resistance. To disentangle complex regulatory mechanisms of the plant immune responses, understanding system as a whole is a must. However, integrating data from different molecular analysis (transcriptomics, proteomics, metabolomics, smallRNA regulation etc.) is not straightforward. We evaluated the response of potato (Solanum tuberosum L.) following the infection with potato virus Y (PVY). The response has been analyzed on two molecular levels, with microarray transcriptome analysis and mass spectroscopy-based proteomics. Within this report, we performed detailed analysis of the results on both levels and compared two different approaches for analysis of proteomic data (spectral count versus MaxQuant). To link the data on different molecular levels, each protein was mapped to the corresponding potato transcript according to StNIB paralogue grouping. Only 33% of the proteins mapped to microarray probes in a one-to-one relation and additionally many showed discordance in detected levels of proteins with corresponding transcripts. We discussed functional importance of true biological differences between both levels and showed that the reason for the discordance between transcript and protein abundance lies partly in complexity and structure of biological regulation of proteome and transcriptome and partly in technical issues contributing to it.


Effect of a modified, low-dye medial longitudinal arch taping procedure on the subtalar joint neutral position before and after light exercise.
Single-group repeated measures design pre- and postintervention. To determine if the modified low-Dye medial longitudinal arch (MLA) taping procedure places the subtalar joint into the neutral position and maintains the subtalar joint neutral (STJN) position following 10 minutes of walking. Subtalar malalignment in excessive pronation is commonly accepted as a contributing factor to a variety of musculoskeletal pathologies. The modified low-Dye MLA taping procedure is often used on the plantar surface of the foot as a short-term corrective tool for excessive foot pronation. However, research that evaluates the efficacy of this taping technique during light exercise is lacking. Measurement of navicular height is commonly used as a measure of subtalar position. Prior to the study, one tester-established reliability in the navicular drop technique measurement by initially practicing the measurements on 400 feet, followed by a reliability study performed on 29 subjects. In this study, a screening procedure excluded subjects with ankle or foot pathology, supinated feet, or neutral feet, and included only subjects with pronated feet. The study, which included 40 subjects, involved four steps: (1) measuring navicular height in the relaxed position; (2) measuring navicular height in the STJN position; (3) measuring navicular height after application of the modified low-Dye MLA taping procedure; and (4) measuring navicular height after subjects had walked for 10 minutes with the taping. Results indicated an intrarater intraclass correlation coefficient (ICC) for measuring navicular height of 0.96 for the right foot and 0.94 for the left foot. Repeated measures ANOVA revealed that significant differences existed (P < 0.05) among the 4 measures. A Bonferroni post hoc analysis showed a difference between relaxed stance measurements and all other measurements, and between taped-prewalking measurements and taped-postwalking measurements. In addition, no significant difference was observed between navicular height measured in STJN and the taped-prewalking and taped-postwalking conditions. The average navicular height for the taped-prewalking condition was 1.6 mm higher than that for the STJN position. For the taped-postwalking condition, the average height of the navicular was 1.2 mm lower than that of the STJN position. These results demonstrate that the modified low-Dye MLA taping procedure places the subtalar joint near the neutral position. Despite a significant reduction in the height of the navicular after the subjects walked for 10 minutes with the tape on, the height of the navicular was still not significantly different than that of the STJN position.


SMA Human iPSC-Derived Motor Neurons Show Perturbed Differentiation and Reduced miR-335-5p Expression.
Spinal Muscular Atrophy (SMA) is a neuromuscular disease caused by mutations in the Survival Motor Neuron 1 gene, resulting in very low levels of functional Survival of Motor Neuron (SMN) protein. SMA human induced Pluripotent Stem Cells (hiPSCs) represent a useful and valid model for the study of the disorder, as they provide in vitro the target cells. MicroRNAs (miRNAs) are often reported as playing a key role in regulating neuronal differentiation and fate specification. In this study SMA hiPSCs have been differentiated towards early motor neurons and their molecular and immunocytochemical profile were compared to those of wild type cells. Cell cycle proliferation was also evaluated by fluorescence-activated cell sorting (FACS). SMA hiPSCs showed an increased proliferation rate and also higher levels of stem cell markers. Moreover; when differentiated towards early motor neurons they expressed lower levels of NCAM and MN specific markers. The expression of miR-335-5p; already identified to control self-renewal or differentiation of mouse embryonic stem cells (mESCs); resulted to be reduced during the early steps of differentiation of SMA hiPSCs compared to wild type cells. These results suggest that we should speculate a role of this miRNA both in stemness characteristic and in differentiation efficiency of these cells.


Comparison of scopolamine-induced cognitive impairment responses in three different ICR stocks.
Cognitive impairment responses are important research topics in the study of degenerative brain diseases as well as in understanding of human mental activities. To compare response to scopolamine (SPL)-induced cognitive impairment, we measured altered parameters for learning and memory ability, inflammatory response, oxidative stress, cholinergic dysfunction and neuronal cell damages, in Korl:ICR stock and two commercial breeder stocks (A:ICR and B:ICR) after relevant SPL exposure. In the water maze test, Korl:ICR showed no significant difference in SPL-induced learning and memory impairment compared to the two different ICRs, although escape latency was increased after SPL exposure. Although behavioral assessment using the manual avoidance test revealed reduced latency in all ICR mice after SPL treatment as compared to Vehicle, no differences were observed between the three ICR stocks. To determine cholinergic dysfunction induction by SPL exposure, activity of acetylcholinesterase (AChE) assessed in the three ICR stocks revealed no difference of acetylcholinesterase activity. Furthermore, low levels of superoxide dismutase (SOD) activity and high levels of inflammatory cytokines in SPL-treated group were maintained in all three ICR stocks, although some variations were observed between the SPLtreated groups. Neuronal cell damages induced by SPL showed similar response in all three ICR stocks, as assessed by terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay, Nissl staining analysis and expression analyses of apoptosis-related proteins. Thus, the results of this study provide strong evidence that Korl:ICR is similar to the other two ICR. Stocks in response to learning and memory capacity.


Three monoclonal antibodies differentiate human from murine epidermis.
In order to establish a set of epidermal species markers, normal human skin, murine skin and human skin transplanted to nude mice were stained with monoclonal antibodies directed to cell membrane-bound carbohydrates, a basement membrane component and a structure in the cell nucleus. Three epidermal species markers were identified. Two markers stained exclusively human epidermis: LH7.2 detects type VII collagen and stained the basement membrane of human epidermis in unfixed frozen sections, while LP4N stained cell nuclei in human epidermis in methanol-acetone-fixed frozen sections. The third marker, HH14, stained exclusively murine epidermis. HH14 defines the histo-blood group H carbohydrate antigen and stained spinous cell membranes of murine epidermis in both frozen and formalin-fixed sections.


Variant Inferior Alveolar Nerves and Implications for Local Anesthesia.
A sound knowledge of anatomical variations that could be encountered during surgical procedures is helpful in avoiding surgical complications. The current article details anomalous morphology of inferior alveolar nerves encountered during routine dissection of the craniofacial region in the Gross Anatomy laboratory. We also report variations of the lingual nerves, associated with the inferior alveolar nerves. The variations were documented and a thorough review of literature was carried out. We focus on the variations themselves, and the clinical implications that these variations present. Thorough understanding of variant anatomy of the lingual and inferior alveolar nerves may determine the success of procedural anesthesia, the etiology of pathologic processes, and the avoidance of surgical misadventure.


Effects of orotic acid on ischaemic/reperfused myocardial function and glycogen content in isolated working rat hearts.
The present study was carried out to investigate the effect of orotic acid on ischaemic/reperfused myocardial function and cardiac glycogen content in isolated working rat hearts. In a preliminary series of studies, hearts isolated from male Wistar rats (300-350 g) were perfused with oxygenated Krebs-Henseleit buffer containing cumulative concentrations of orotic acid from 0.01 to 10.00 mg l-1. In the concentration range of 0.01-0.10 mg l-1, orotic acid significantly improved left ventricular function. Therefore, in the second series of studies, rats were treated intravenously with 0.01 mg kg-1 orotic acid for 4 days. Hearts were then isolated and subjected to 30 min of global no-flow ischaemia followed by 10 min of reperfusion. Orotic acid treatment significantly improved post-ischaemic myocardial function and increased pre-ischaemic and post-ischaemic glycogen content of the heart. We conclude that orotic acid improves ischaemic/reperfused cardiac performance and this effect may be based on the elevation of myocardial glycogen content.


[Epileptic seizures as a sign of abstinence from chronic consumption of zolpidem].
Zolpidem is derived from imidazopiridine. In recent years it has been used as a non benzodiazepine hypnotic. It is a short acting inducer of sleep of similar efficacy to the benzodiazepines or zopiclone, but well tolerated and does not lead to drug abuse, rebound effects or abstinence syndromes. In this clinical note we wish to show that in spite of the descriptions in the medical literature, complications may follow long term use of zolpidem. We report the case of a 50 year old woman with no clinical history of interest apart from chronic insomnia and anxiety. She had been treated with zolpidem for the previous five years, at the usual dosage. However, since this seemed to be insufficient, the dose was progressively increased until in the months before she was seen by us she was taking a total of 450 mg per day in divided doses. She had drug tolerance, abuse and dependence. After a period of 12 hours without taking zolpidem she developed an abstinence syndrome, with generalized tonic clonic seizures and a prolonged post convulsion period which improved on symptomatic anticonvulsant treatment. In view of our case, and others described, we should be sceptical of the claim that zolpidem has no side effects, since it may give rise to tolerance, abuse and an abstinence syndrome. We consider that its indiscriminate use should be modified. Patients should be carefully followed up and medical prescription necessary to obtain zolpidem, as opposed to its current unrestricted availability.


Redundancy among phospholipase D isoforms in resistance triggered by recognition of the Pseudomonas syringae effector AvrRpm1 in Arabidopsis thaliana.
Plants possess a highly sophisticated system for defense against microorganisms. So called MAMP (microbe-associated molecular patterns) triggered immunity (MTI) prevents the majority of non-adapted pathogens from causing disease. Adapted plant pathogens use secreted effector proteins to interfere with such signaling. Recognition of microbial effectors or their activity by plant resistance (R)-proteins triggers a second line of defense resulting in effector triggered immunity (ETI). The latter usually comprises the hypersensitive response (HR) which includes programmed cell death at the site of infection. Phospholipase D (PLD) mediated production of phosphatidic acid (PA) has been linked to both MTI and ETI in plants. Inhibition of PLD activity has been shown to attenuate MTI as well as ETI. In this study, we systematically tested single and double knockouts in all 12 genes encoding PLDs in Arabidopsis thaliana for effects on ETI and MTI. No single PLD could be linked to ETI triggered by recognition of effectors secreted by the bacterium Pseudomonas syringae. However, repression of PLD dependent PA production by n-butanol strongly inhibited the HR following Pseudomonas syringae effector recognition. In addition some pld mutants were more sensitive to n-butanol than wild type. Thus, the effect of mutations of PLDs could become detectable, and the corresponding genes can be proposed to be involved in the HR. Only knockout of PLDδ caused a loss of MTI-induced cell wall based defense against the non-host powdery mildew Erysiphe pisi. This is thus in stark contrast to the involvement of a multitude of PLD isoforms in the HR triggered by AvrRpm1 recognition.


Crystal structure of cytochrome c peroxidase compound I.
We have compared the 2.5-A crystal structure of yeast cytochrome c peroxidase (CCP) with that of its semistable two-equivalent oxidized intermediate, compound I, by difference Fourier and least-squares refinement methods. Both structures were observed at -15 degrees C. The difference Fourier map reveals that formation of compound I causes only small positional adjustments of a few tenths of an angstrom. The map's most pronounced feature is a pair of positive and negative peaks bracketing the heme iron position. Least-squares refinement shows that the iron atom moves about 0.2 A toward the distal side of the heme. No significant difference density is evident near the side chains of Trp-51 or Met-172, each of which has been proposed to be the site of the electron paramagnetic resonance (EPR) active radical in compound I. However, the second most prominent feature of difference density is a negative peak near the side chain of Thr-180, which, according to the results of least-squares refinement, moves by 0.15 A in the direction of Met-230. These observations, together with the results of mutagenesis experiments [Fishel, L. A., Villafranca, J. E., Mauro, J. M., & Kraut, J. (1987) Biochemistry 26, 351-360; Goodin, D. B., Mauk, A. G., & Smith, M. (1986) Proc. Natl. Acad. Sci. U.S.A. 83, 1295-1299] in which Trp-51 and Met-172 have been replaced without loss of the EPR radical signal in compound I, lead us to consider the possibility that the radical site lies within a cluster composed of the side chains of Met-230, Met-231, and Trp-191.(ABSTRACT TRUNCATED AT 250 WORDS)


COVID-19 booster vaccination during pregnancy enhances maternal binding and neutralizing antibody responses and transplacental antibody transfer to the newborn.
The immune response to COVID-19 booster vaccinations during pregnancy for mothers and their newborns and the functional response of vaccine-induced antibodies against Omicron variants are not well characterized. We conducted a prospective, multicenter cohort study of participants vaccinated during pregnancy with primary or booster mRNA COVID-19 vaccines from July 2021 to January 2022 at 9 academic sites. We determined SARS-CoV-2 binding and live virus and pseudovirus neutralizing antibody (nAb) titers pre- and post-vaccination, and at delivery for both maternal and infant participants. Immune responses to ancestral and Omicron BA.1 SARS-CoV-2 strains were compared between primary and booster vaccine recipients in maternal sera at delivery and in cord blood, after adjusting for days since last vaccination. A total of 240 participants received either Pfizer or Moderna mRNA vaccine during pregnancy (primary 2-dose series: 167; booster dose: 73). Booster vaccination resulted in significantly higher binding and nAb titers, including to the Omicron BA.1 variant, in maternal serum at delivery and in cord blood compared to a primary 2-dose series (range 0.44-0.88 log10 higher, p < 0.0001 for all comparisons). Live virus nAb to Omicron BA.1 were present at delivery in 9 % (GMT ID50 12.7) of Pfizer and 22 % (GMT ID50 14.7) of Moderna primary series recipients, and in 73 % (GMT ID50 60.2) of mRNA boosted participants (p < 0.0001), although titers were significantly lower than to the D614G strain. Transplacental antibody transfer was efficient for all regimens with median transfer ratio range: 1.55-1.77 for IgG, 1.00-1.78 for live virus nAb and 1.79-2.36 for pseudovirus nAb. COVID-19 mRNA vaccination during pregnancy elicited robust immune responses in mothers and efficient transplacental antibody transfer to the newborn. A booster dose during pregnancy significantly increased maternal and cord blood binding and neutralizing antibody levels, including against Omicron BA.1. Findings support the use of a booster dose of COVID-19 vaccine during pregnancy.


Investigating the Value of Urine Volume, Creatinine, and Cystatin C for Urinary Biomarkers Normalization for Drug Development Studies.
Novel urinary protein biomarkers have recently been identified and qualified in rats for the early detection of renal injury in drug development studies. However, there seems to be no standardized normalization method for analyzing these urinary biomarkers, as some users normalize with urinary creatinine (uCr), urine volume (uVol), or leave biomarker un-normalized. More recently, urinary cystatin C is also emerging as a urinary biomarker normalizer, given some of its characteristics as a glomerular filtration marker. The purpose of this study was to identify an optimal drug-induced kidney injury biomarker normalization method that can be adopted more uniformly in the field. To this end, we compared the variability of uVol, urinary cystatin C, and Cr in healthy rats; we evaluated the sensitivity of the renal biomarkers to renal injury after normalization with uVol, uCr, and cystatin C in rats with cisplatin-induced renal injury. We showed that, over time, uCr was less variable than urinary cystatin C and uVol. When the renal biomarkers were normalized with the 3 normalizing end points, the biomarkers showed (1) least variability following normalization with Cr in healthy animals and (2) poor sensitivity when normalized with urinary cystatin C in animals with renal injury. Overall, the results suggested that uCr is better than urinary cystatin C and uVol for normalizing renal biomarkers in rats under controlled preclinical conditions. To our knowledge, this is the first report that compared the variability of uVol, cystatin C, and Cr in the context of renal biomarkers' normalization.


[Recognition of S-T segment in ambulatory ECG by wavelet analysis].
Basing on Wavelet analysis, a new method was introduced and found effective for recognizing of S-T segment. It resolved successfully the technological difficulty of measurement.


Tracking Tumor Colonization in Xenograft Mouse Models Using Accelerator Mass Spectrometry.
Here we introduce an Accelerator Mass Spectrometry (AMS)-based high precision method for quantifying the number of cancer cells that initiate metastatic tumors, in xenograft mice. Quantification of 14C per cell prior to injection into animals, and quantification of 14C in whole organs allows us to extrapolate the number of cancer cells available to initiate metastatic tumors. The 14C labeling was optimized such that 1 cancer cell was detected among 1 million normal cells. We show that ~1-5% of human cancer cells injected into immunodeficient mice form subcutaneous tumors, and even fewer cells initiate metastatic tumors. Comparisons of metastatic site colonization between a highly metastatic (PC3) and a non-metastatic (LnCap) cell line showed that PC3 cells colonize target tissues in greater quantities at 2 weeks post-delivery, and by 12 weeks post-delivery no 14C was detected in LnCap xenografts, suggesting that all metastatic cells were cleared. The 14C-signal correlated with the presence and the severity of metastatic tumors. AMS measurements of 14C-labeled cells provides a highly-sensitive, quantitative assay to experimentally evaluate metastasis and colonization of target tissues in xenograft mouse models. This approach can potentially be used to evaluate tumor aggressiveness and assist in making informed decisions regarding treatment.


Functional magnetic resonance imaging during recognition of written words: Chinese characters for concrete objects versus abstract concepts.
An attempt was made to apply functional magnetic resonance imaging (fMRI) to reveal cortical areas activated upon presentation of two groups of Chinese characters in six normal right-handed, male, Japanese subjects. Presentation of the characters representing 'abstract concepts' activated the bilateral occipital region without a significant difference between the bilateral occipital and temporal regions. Presentation of the characters representing 'concrete objects' resulted in significantly stronger activation in the left occipital and temporal regions. These results suggest that recognition of concrete characters involves a stronger initial process in the left occipital temporal cortices than recognition of abstract characters.


Internal magnetic measurement in collisional-merging process of a field-reversed configuration.
An internal magnetic probe array has been developed to observe the three components of the magnetic field simultaneously in the vicinity of the collision surface of two colliding plasmoids at supersonic/Alfvénic velocity. Collisional-merging formation of a field-reversed configuration (FRC) has been conducted in the (FRC Amplification via Translation-Collisional Merging) device at Nihon University. Significant plasma heating and an increase in trapped poloidal magnetic flux have been observed during/after the collisional-merging process in the FAT-CM device. In this dynamic formation process, two FRC-like plasmoids formed by a field-reversed theta-pinch method collide in the middle of the confinement chamber at a relative speed of 200-400 km/s. Therefore, the excited shockwave is considered as one of the heating mechanisms. The developed probe array installed in the middle of the confinement chamber observes the internal structure of the magnetic field. The probe consists of 12 sets of three-axis chip inductors arranged at intervals of 40 mm. The measurement position can be varied in the radial direction. In the single translation and collisional-merging experiment, the internal magnetic probe measures the magnetic field's radial distribution with a high time resolution under noise.


Storylines of aging with HIV: shifts toward sense making.
Aging with HIV is a new phenomenon. It is expected that by 2015, approximately half of adults living with HIV in the United States will be age 50 and older. We used narrative inquiry to explore how older adults with HIV storied their experience and made sense of aging. Over a 3.5-year period, we interviewed 5 older adults living with HIV for 13 to 24 years. In analyzing the coconstructed stories, we identify six storylines that enhance understanding and guide listening: embodiment of the illness, sense making, death and loss, secrets and stigma, identity, and seeking connection. We theorize that the degree to which one reconciles each storyline influences how well one lives with illness. We share a storied exemplar to illustrate these storylines in one participant's experience of aging with HIV. These findings emphasize how vital is telling one's illness story, because sense making happens in the telling.


Verrucous Carcinoma with Oral Submucous Fibrosis: A Rare Case with Brief Review.
Oral verrucous carcinoma (VC) is a variant of well differentiated oral squamous cell carcinoma (OSCC) characterized by exophytic over growth. Oral submucous fibrosis (OSMF) is a potentially malignant disorder associated with chronic betel nut chewing habit. The development of OSCC is seen in one-third of the OSMF patients, but the development of VC is rare in such patients. There are very few cases of OSMF with VC reported in literature. Here, present a rare case of an elderly patient with VC in conjunction with OSMF.


Esophageal cancer: the rise of adenocarcinoma over squamous cell carcinoma in the Asian belt.
Esophageal cancer is a common cancer worldwide with a high associated mortality rate. Amongst the two most frequent subsets of disease, squamous cell carcinoma (SCC) and adenocarcinoma (AC), there has been an epidemiologic shift towards adenocarcinoma over the last few decades. However, squamous cell carcinoma still predominates worldwide. Within Western countries, obesity has been associated with an increase in esophageal AC. A striking report from the World Health Organization (WHO) stated that worldwide obesity has tripled since 1975. In 2016, the WHO reported that greater than 1.9 billion adults are overweight and over 650 million were obese. In this review our goal is to analyze the esophageal cancer trends of China, which is the largest contributor among the esophageal cancer "Asian belt." Our intent is to evaluate whether there is a correlation between the rise in esophageal adenocarcinoma and obesity in this esophageal cancer "hotspot." With further analysis, the high-risk populations that are identified can be targeted to implement preventative strategies. This focus will aid in decreasing the burden of esophageal cancer at the global health level by addressing preventative strategies, such as screening endoscopy and lifestyle modifications. For example, WHO developed a global action plan on physical activity in response to the rise in obesity worldwide. Prevention is key to decreasing the rate of esophageal adenocarcinoma as majority of cases are diagnosed in the late stages leading to high mortality rates.


Unraveling the Toxicity Associated with Ciprofloxacin Biodegradation in Biological Wastewater Treatment.
Incomplete mineralization of antibiotics in biological sludge systems poses a risk to the environment. In this study, the toxicity associated with ciprofloxacin (CIP) biodegradation in activated sludge (AS), anaerobic methanogenic sludge (AnMS), and sulfur-mediated sludge (SmS) systems was examined via long-term bioreactor tests and a series of bioassays. The AS and AnMS systems were susceptible to CIP and its biotransformation products (TPs) and exhibited performance deterioration, while the SmS system exhibited high tolerance against the toxicity of CIP and its TPs along with excellent pollutant removal. Up to 14 TPs were formed via piperazinyl substituent cleavage, defluorination, decarboxylation, acetylation, and hydroxylation reactions in AS, AnMS, and SmS systems. Biodegradation of CIP in the AS, AnMS, and SmS systems, however, could not completely eliminate its toxicity as evident from the inhibition of Vibrio fischeri luminescence along with Escherichia coli K12 and Bacillus subtilis growth. The anaerobic systems (AnMS and SmS) were more effective than the aerobic AS system at CIP biodegradation, significantly reducing the antibacterial activity of CIP and its TPs in the aqueous phase. In addition, the quantitative structure-activity relationship analysis indicated that the TPs produced via decarboxylation and hydroxylation (TP2 and TP4) as well as by cleavage of piperazine (TP12, TP13, and TP14) exhibited higher toxicity than CIP. The findings of this study provide insights into the toxicity and possible risks associated with CIP biodegradation in biological wastewater treatment.


Proliferative response of peripheral blood mononuclear cells in anti-Hu antibody-associated patients with paraneoplastic neurological syndrome and their depressant effect on small cell lung cancer cells.
Previous studies have suggested that common antigens that exist in neurons and tumor cells trigger cross immunoreaction, which attacks the neurons and tumor cells simultaneously. This action leads to paraneoplastic symptoms and slowed tumor growth. The present study co‑cultured peripheral blood mononuclear cells (PBMCs) from anti‑Hu antibody‑associated patients with paraneoplastic neurological syndrome (PNS) and the small cell lung cancer cell line NCI‑H446 (H446) in vitro. In the PNS group, no significant difference was observed in the proliferation index of PBMCs and H446 cells between the mixed or separate cultures. The proportion of CD4+ T cells in patients with PNS (76.54±3.96%) was significantly higher (P<0.05) compared with the healthy control individuals (51.75±17.3%). In conclusion, the sensitized specific T cells in the PBMCs of PNS patients predominantly comprised of CD4+ T cells, which had no inhibitory effect on small cell lung cancer cells in vitro.


Mechanism and Regioselectivity of an Unsymmetrical Hexadehydro-Diels-Alder (HDDA) Reaction.
Hoye reported intramolecular hexadehydro-Diels-Alder (HDDA) reactions to generate arynes that functionalize natural product phenols and amines. In their studies, Hoye found that unsymmetrical tetraynes selectively form a single aryne. We report density functional theory (DFT) calculations that reveal the factors controlling the regioselectivity.


Dual-Responsive DNA Nanodevice for the Available Imaging of an Apoptotic Signaling Pathway in Situ.
Fluorescence imaging tools enable the in situ visualization of those molecules involved in various cell signaling pathways, but directly describing these pathways instead of the separate mediators in situ is much more meaningful and still full of challenges. In this work, a dual-responsive DNA nanodevice that allows the available imaging of an apoptotic signaling pathway in living cells has been developed. The nanodevice is constructed through assembling an elaborately designed Y-shaped DNA (Y-DNA) layer on gold nanoparticles (AuNPs). Only if an apoptotic signaling pathway involving the manganese superoxide dismutase (MnSOD) mRNA and downstream cytochrome c (Cyt c) is presented to serve as the input, the nanodevice can perform an "AND" logic gate operation, disassembling the Y-DNA from the AuNP surface and thereafter outputting a fluorescence signal. In comparison with the fluorescence imaging methods that target individual specific molecules, our strategy allows direct profiling of a specific signaling pathway by connected characterization of two correlative targets. The programmable feature of this strategy also shows the potential for the profiling of other signaling pathways. The concept of studying the line connecting two points will contribute to the systematic interrogation on the signaling networks in situ as the networks are composed of lines instead of individual points.


Dubious and bogus credentials in mental health practice.
Within an ethics framework, this article explores mental health practitioners' use of credentials that lack acceptable accreditation or authority. Increased competition among mental health care providers has elevated the importance of credentials for marketing professional services. Practitioners worried about economic survival, along with certain personality characteristics (e.g., sheer ego), are tempted to rely on credentials that lack proof of quality, thereby potentially jeopardizing professionalism. Specific assertions and recommendations are set forth in the interest of safeguarding consumers and promoting professionalism.


Interleukin-1 alpha is released during transfection of keratinocytes.
Keratinocytes are known to produce, store, and release IL-1 alpha and therefore we suspected that the DNA-mediated cell transfection procedure may release the stored IL-1 alpha from keratinocytes into the medium. Using enzyme-linked immunosorbent assay, we determined the IL-1 alpha concentration in culture supernatants during keratinocyte transfection. The following transfection methods were compared: lipofection with lipofectACE and lipofectAMINE (GIBCO), Ca3(PO4)2 co-precipitation, and polybrene-dimethylsulfoxide (DMSO). The supernatants were collected immediately prior to transfection, after 5-h incubation with lipofectin or Ca3(PO4)2, and 24 and 48 h after transfection. In the polybrene-DMSO method, the supernatant was also collected immediately before and after DMSO shock. LipofectAMINE caused the highest release of IL-1 alpha, whereas the lipofectACE and polybrene-DMSO mediated transfection with confluent cells released the least. The other two methods released intermediate levels of IL-1 alpha. Our data indicate that a substantial amount of IL-1 alpha is released during the keratinocyte transfection procedure, which can affect the results of transfection in studies of gene expression.


Tailoring the Microstructure of Porous Carbon Spheres as High Rate Performance Anodes for Lithium-Ion Batteries.
Benefiting from their high surface areas, excellent conductivity, and environmental-friendliness, porous carbon nanospheres (PCSs) are of particular attraction for the anodes of lithium-ion batteries (LIBs). However, the regulation of carbon nanospheres with controlled pore distribution and graphitization for delivering high Li+ storage behavior is still under investigation. Here, we provide a facile approach to obtain PCSs with different microstructures via modulating the carbonization temperatures. With the processing temperature of 850 °C, the optimized PCSs exhibit an increased surface area, electrical conductivity, and enhanced specific capacity (202 mA h g-1 at 2 A g-1) compared to the PCSs carbonized at lower temperatures. Additionally, PCSs 850 provide excellent cyclability with a capacity retention of 83% for 500 cycles. Such work can pave a new pathway to achieve carbon nanospheres with excellent performances in LIBs.


Identifying NFKB1, STAT3, and CDKN1A as Baicalein's Potential Hub Targets in Parkinson's Disease-related α-synuclein-mediated Pathways by Integrated Bioinformatics Strategies.
The overexpression, accumulation, and cell-to-cell transmission of α-synuclein leads to the deterioration of Parkinson's disease (PD). Previous studies suggest that Baicalein (BAI) can bind to α-synuclein and inhibit α-synuclein aggregation and secretion. However, it is still unclear whether BAI can intervene with the pathogenic molecules in α-synuclein-mediated PD pathways beyond directly targeting α-synuclein per se. This study aimed to systematically investigate BAI's potential targets in PD-related A53T mutant α-synuclein-mediated pathways by integrating data mining, network pharmacological analysis, and molecular docking simulation techniques. The results suggest that BAI may target genes that are dysregulated in synaptic transmission, vesicle trafficking, gene transcription, protein binding, extracellular matrix formation, and kinase activity in α-synucleinmediated pathways. NFKB1, STAT3, and CDKN1A are BAI's potential hub targets in these pathways. Our findings highlight BAI's potentiality to modulate α-synuclein-mediated pathways beyond directly targeting α-synuclein per se.


Female-predominant rat hepatic P-450 forms j (IIE1) and 3 (IIA1) are under hormonal regulatory controls distinct from those of the sex-specific P-450 forms.
Hepatic expression of cytochrome P-450j (alcohol-inducible nitrosamine demethylase; P-450 gene IIE1) and P-450 3 (testosterone 7 alpha-hydroxylase; P-450 gene IIA1) is female predominant in adult rats [female/male greater than or equal to 1.5-2 (P-450j) or 3-4 (P-450 3)]. This sex difference emerges during the postsuckling period, when P-450 3 declines significantly (60-70% decrease) in male, but not female, rats, and P-450j declines in both sexes, but to a lower constitutive level in males than in females. The biochemical factors and regulatory events that control these developmental changes were investigated and found to be distinct from those that regulate expression of the female-specific hepatic enzymes P-450 2d (P-450 gene IIC12) and steroid 5 alpha-reductase. Immunoquantitation of the changes in P-450j and P-450 3 levels in hormonally altered rats established that both P-450s are under gonadal control. However, while androgen and estrogen both suppress P-450j expression, estrogen stimulates and androgen suppresses the expression of P-450 3. Since many of the effects of gonadal hormones on hepatic enzyme levels are mediated by the pituitary, the contribution of pituitary hormones to P-450j and P-450 3 expression was evaluated. Hypophysectomy of adult rats of either sex elevated P-450j to the levels found in immature rats (3- to 5-fold increase). This elevation was largely reversed in both sexes by GH administered either intermittently or continuously, demonstrating that P-450j is under the suppressive control of this pituitary hormone. The regulation of P-450 3 was more complex. Hypophysectomy elevated P-450 3 to prepubertal levels in adult male rats, but had no effect on P-450 3 levels in adult females. In both sexes GH suppressed P-450 3 expression when administered to hypophysectomized rats intermittently, but stimulated P-450 3 expression when infused continuously. Corresponding changes in hepatic microsomal P-450 3-dependent testosterone 7 alpha-hydroxylase and P-450j-dependent aniline hydroxylase activities were observed in response to hypophysectomy and GH replacement, but only after supplementation of microsomal NADPH P-450 reductase [which was 63-77% suppressed by hypophysectomy] with exogenous purified NADPH P-450 reductase. These studies demonstrate that these female-predominant hepatic P-450 enzymes are regulated by different mechanisms, and that both are under hormonal regulatory controls distinct from those that govern expression of the female-specific hepatic enzymes.(ABSTRACT TRUNCATED AT 400 WORDS)


DREEM in primary care: students' perspectives on educational environment of family medicine internship in primary care centres: experiences at Akdeniz University Faculty of Medicine in Turkey.
Objective: In many countries, medical education programmes are expanding, and educational environments are starting to change from hospitals to primary health care centres. International organizations for medical education highlight that medical students should also be educated at primary and secondary care centres in addition to third-step health care. In this study, the evaluation of sixth-year (final year) medical students' perspectives on the educational environment of family medicine internship in primary care is presented, using the Dundee Ready Educational Environment Measurement (DREEM)Material and methods: This descriptive cross-sectional study was conducted with sixth-year medical students. Starting in the 2017-2018 academic year, sixth-year medical students started to enrol in educational courses in primary care. A total of 223 students completed internships in primary care for a two-week period, during which we applied the Dundee Ready Educational Environment Measure (DREEM) to evaluate the educational environment at the end of the internship. The collected questionnaires were analysed by using IBM-SPSS version 23 for Mac OS. Student's t-test and Mann-Whitney U Test were used for comparisons.Results: Of the 223 students, 192 (86%) completed the questionnaire. The total DREEM score was 138.62/200 (%63.5). The students rated the learning environment as positive. The mean score for students' perceptions of teaching, students' perceptions of teachers, students' academic self-perceptions, students' perceptions of the atmosphere and students' social self-perceptions were 31.65/48, 30.45/44, 23.46/32, 34.20/48 and were 18.56/28, respectively. The total mean score and subscale scores were not significantly different between males and females.Conclusion: This study suggests that students' perception of the global learning environment in primary care was more positive than negative. The lowest scores were recorded for Students' Perceptions of Learning and Students' Social Self-Perceptions, and the highest score was recorded for Students' Academic Self-Perceptions.


Developmental exposure of California mice to endocrine disrupting chemicals and potential effects on the microbiome-gut-brain axis at adulthood.
Xenoestrogens are chemicals found in plant products, such as genistein (GEN), and in industrial chemicals, e.g., bisphenol A (BPA), present in plastics and other products that are prevalent in the environment. Early exposure to such endocrine disrupting chemicals (EDC) may affect brain development by directly disrupting neural programming and/or through the microbiome-gut-brain axis. To test this hypothesis, California mice (Peromyscus californicus) offspring were exposed through the maternal diet to GEN (250 mg/kg feed weight) or BPA (5 mg/kg feed weight, low dose- LD or 50 mg/kg, upper dose-UD), and dams were placed on these diets two weeks prior to breeding, throughout gestation, and lactation. Various behaviors, gut microbiota, and fecal metabolome were assessed at 90 days of age. The LD but not UD of BPA exposure resulted in individuals spending more time engaging in repetitive behaviors. GEN exposed individuals were more likely to exhibit such behaviors and showed socio-communicative disturbances. BPA and GEN exposed females had increased number of metabolites involved in carbohydrate metabolism and synthesis. Males exposed to BPA or GEN showed alterations in lysine degradation and phenylalanine and tyrosine metabolism. Current findings indicate cause for concern that developmental exposure to BPA or GEN might affect the microbiome-gut-brain axis.


Dilated cardiomyopathy.
On account of the rapidly progressive nature of the disease, the high incidence of systemic embolism and arrhythmias, and the risk of sudden death, dilated cardiomyopathy is inconsistent with aircrew duties. In the small proportion of subjects who apparently make a satisfactory recovery , re-licensing may be considered once there is no requirement for medication and chest X-ray, electrocardiogram, echocardiogram, exercise electrocardiogram, 24 h ambulatory electrocardiogram and left ventricular ejection fraction are all normal. These tests should initially be repeated annually and be associated with cardiological review.


Nitrilotriacetic Amine-Functionalized Polymeric Core-Shell Nanoparticles as Enzyme Immobilization Supports.
Nitrilotriacetic amine (NTA)-functionalized nanoparticles obtained by aqueous polymerization-induced self-assembly (PISA) are introduced as immobilization supports for polyhistidine-functionalized (His-tagged) enzymes. A novel initiator for nitroxide-mediated polymerization based on the nitroxide SG1 and carrying a protected NTA moiety was first synthesized. Size-exclusion chromatography (SEC) and electrospray ionization mass spectrometry (ESI-MS) proved the ability of this initiator to produce well-defined end-functional vinyl polymers. Subsequently, oligo(ethylene glycol) methacrylate-based macroinitiators were synthesized and chain-extended to form amphiphilic block copolymer nanoparticles, either by nanoprecipitation or by PISA. The latter method yielded spherical nanoparticles with a higher definition, as demonstrated by dynamic light scattering (DLS). Deprotection of the NTA moiety and complexation with nickel ions were assessed by DLS and inductively coupled plasma optical emission spectroscopy/mass spectrometry (ICP-OES/MS). Finally, immobilization of His-tagged horseradish peroxidase and ester hydrolase were successfully carried out, leading to catalytically active nanobiocatalysts, as shown by UV-vis measurements.


A rank-ordered marginal filter for deinterlacing.
This paper proposes a new interpolation filter for deinterlacing, which is achievedby enhancing the edge preserving ability of the conventional edge-based line average methods. This filter consists of three steps: pre-processing step, fuzzy metric-based weight assignation step, and rank-ordered marginal filter step. The proposed method is able to interpolate the missing lines without introducing annoying articles. Simulation results show that the images filtered with the proposed algorithm restrain less annoying pixels than the ones acquired by other methods.


A multi-dimensional fusion strategy similarity measure method for patent application technology disclosure document.
Patent application technology disclosure document is one of the important bases for judging patent novelty and uniqueness. Automated evaluation can effectively solve the problems of long time and strong subjectivity of human evaluation. The text similarity evaluation algorithm based on corpus and deep learning technology has problems such as insufficient amount of cross-library learning data and insufficient core content tendency in the similarity judgment of patent application technology disclosure document, which limits their performance and practical application. In this paper, we propose a similarity evaluation method of patent application technology disclosure document based on multi-dimensional fusion strategy to realize the similarity measurement of patents. Firstly, in the text preprocessing section, word segmentation reconstruction and similarity evaluation optimization strategies based on word frequency and part-of-speech score weighted fusion are proposed. Then, a similarity calculation method of patent application technology disclosure document based on two new mapping spaces of dot matrix and image is proposed to achieve a more diversified comprehensive evaluation. The algorithm was evaluated by using four published text similarity matching datasets (containing 0-5 or 0/1 labels) and a set of patent application technology disclosure documents. Experimental results show that on the published text similarity matching datasets, the similarity evaluation method under the multi-dimensional fusion strategy proposed in this paper has a discrimination accuracy improvement of about 10% compared to traditional vector semantic model, and can match the discriminative ability of lightweight deep learning models without the need for training. At the same time, the discrimination accuracy of the proposed method on the sample dataset of patent application technology disclosure document is superior to traditional vector semantic model (20%) and various deep learning models (1%-8%), and the precision and recall rate are relatively balanced. The visual analysis results on the dataset of the patent application technology disclosure documents also prove the effectiveness and reliability of the similarity calculation method proposed in the dot matrix and image space, which provide a new idea and method for the similarity evaluation between patent application technology disclosure document.


Kyphosis in a Turner syndrome population.
The purpose of this study was to determine the prevalence of kyphosis in a Turner syndrome (TS) population. Standing lateral thoracic spine and standing anterior-posterior (A-P) scoliosis radiographs were obtained on all girls with TS between the ages of 5 and 18 years seen in a TS clinic between July 2000 and March 2001. Medical histories were reviewed, and a pediatric orthopedic surgeon evaluated the radiographs of each patient (N = 25). Excessive kyphosis was defined as an A-P curvature >40 degrees, vertebral wedging as any A-P deformity >5 degrees at an individual vertebral body, and scoliosis as a lateral curvature >10 degrees. Fifteen (60%) of 25 patients were found to have abnormal radiographic findings: 10 (40%) of 25 with excessive kyphosis, 10 (40%) of 25 with vertebral wedging, and 5 (20%) of 25 with scoliosis. Forty-eight percent of the girls had both excessive kyphosis and/or vertebral body wedging. Two girls had kyphosis > or =55 degrees, and 5 had scoliosis > or =25 degrees. Girls with excessive kyphosis and/or vertebral body wedging were older (13.6 +/- 3.9 years vs 10.6 +/- 2.8 years). The prevalence of excessive kyphosis and vertebral body wedging seems to be increased in girls with TS and corresponds with advancing age. Routine radiologic surveillance may facilitate detection of developing deformities so that treatment with a brace can be considered to prevent or slow the process.


Effects of differential experience on the brain and behavior.
This review of plasticity of brain and behavior ranges from examples of plasticity restricted to an early critical period to other examples that show lifelong plasticity, but these two polar opposites are far from covering the field. Rather, it appears that there are a number of patterns by which different measures of plasticity vary as a function of age. Even in cases that indicate the existence of a critical period for development of neural circuits and of behavior, it is not yet possible to define the period exactly, because different methods yield different results, and much parametric work remains to be done. Nevertheless, the variety of findings of plasticity are encouraging for education and for recovery of function.


Participation of Multifunctional RNA in Replication, Recombination and Regulation of Endogenous Plant Pararetroviruses (EPRVs).
Pararetroviruses, taxon Caulimoviridae, are typical of retroelements with reverse transcriptase and share a common origin with retroviruses and LTR retrotransposons, presumably dating back 1.6 billion years and illustrating the transition from an RNA to a DNA world. After transcription of the viral genome in the host nucleus, viral DNA synthesis occurs in the cytoplasm on the generated terminally redundant RNA including inter- and intra-molecule recombination steps rather than relying on nuclear DNA replication. RNA recombination events between an ancestral genomic retroelement with exogenous RNA viruses were seminal in pararetrovirus evolution resulting in horizontal transmission and episomal replication. Instead of active integration, pararetroviruses use the host DNA repair machinery to prevail in genomes of angiosperms, gymnosperms and ferns. Pararetrovirus integration - leading to Endogenous ParaRetroViruses, EPRVs - by illegitimate recombination can happen if their sequences instead of homologous host genomic sequences on the sister chromatid (during mitosis) or homologous chromosome (during meiosis) are used as template. Multiple layers of RNA interference exist regulating episomal and chromosomal forms of the pararetrovirus. Pararetroviruses have evolved suppressors against this plant defense in the arms race during co-evolution which can result in deregulation of plant genes. Small RNAs serve as signaling molecules for Transcriptional and Post-Transcriptional Gene Silencing (TGS, PTGS) pathways. Different populations of small RNAs comprising 21-24 nt and 18-30 nt in length have been reported for Citrus, Fritillaria, Musa, Petunia, Solanum and Beta. Recombination and RNA interference are driving forces for evolution and regulation of EPRVs.


Anthropometric and Athletic Performance Combine Test Results Among Positions Within Grade Levels of High School-Aged American Football Players.
Leutzinger, TJ, Gillen, ZM, Miramonti, AM, McKay, BD, Mendez, AI, and Cramer, JT. Anthropometric and athletic performance combine test results among positions within grade levels of high school-aged American football players. J Strength Cond Res 32(5): 1288-1296, 2018-The purpose of this study was to investigate differences among player positions at 3 grade levels in elite, collegiate-prospective American football players. Participants' data (n = 7,160) were analyzed for this study (mean height [Ht] ± SD = 178 ± 7 cm, mass [Bm] = 86 ± 19 kg). Data were obtained from 12 different high school American football recruiting combines hosted by Zybek Sports (Boulder, Colorado). Eight 2-way (9 × 3) mixed factorial analysis of variances {position (defensive back [DB], defensive end, defensive lineman, linebacker, offensive lineman [OL], quarterback, running back, tight end, and wide receiver [WR]) × grade (freshmen, sophomores, and juniors)} were used to test for differences among the mean test scores for each combine measure (Ht, Bm, 40-yard [40 yd] dash, proagility [PA] drill, L-cone [LC] drill, vertical jump [VJ], and broad jump [BJ]). There were position-related differences (p ≤ 0.05) for Ht, 40 yd dash, and BJ, within each grade level and for Bm, PA, LC, and VJ independent of grade level. Generally, the results showed that OL were the tallest, weighed the most, and exhibited the lowest performance scores among positions. Running backs were the shortest, whereas DBs and WRs weighed the least and exhibited the highest performance scores among positions. These results demonstrate the value of classifying high school-aged American football players according to their specific position rather than categorical groupings such as "line" vs. "skill" vs. "big skill" when evaluating anthropometric and athletic performance combine test results.


Investigating active site of gold nanoparticle Au55(PPh3)12Cl6 in selective oxidation.
We present an ab initio investigation of structural, electronic, catalytic, and selective properties of the ligand-covered gold nanoparticle Au55(PPh3)12Cl6 and associated model clusters. The catalytic activity of the Au55(PPh3)12Cl6 nanoparticle in the presence of O2 stems from a combined effect of triphenylphosphine ligands and surface structure of the "magic-number" quasi-icosahedral Au55 core, which entails numerous ligand-encompassed triangle Au6 faces as the active sites. Under the Eley-Rideal mechanism, the "triangle-socket" active site not only can accommodate one pre-adsorbed O2 (which is subsequently activated to the superoxo species) with one styrene molecule at a time but also can provide spatial confinement which favors the formation of an oxametallacycle intermediate that leads to unique selectivity in styrene oxidation.


RuvA and RuvB proteins facilitate the bypass of heterologous DNA insertions during RecA protein-mediated DNA strand exchange.
RecA protein-mediated DNA strand exchange between circular single-stranded DNA and linear duplex DNA readily bypasses short (up to 100 base pairs) heterologous inserts in one of the DNA substrates. Larger heterologous inserts are bypassed with decreasing efficiency, and inserts larger than 200 base pairs substantially block RecA-mediated DNA strand exchange. The RuvA and RuvB proteins dramatically facilitate the bypass of larger heterologous inserts. When the RuvA and RuvB proteins are added to an ongoing RecA protein-mediated strand exchange reaction, interior heterologous inserts of 1 kilobase pair are bypassed at significant frequencies. The RuvA, RuvB, and RecA proteins are all required for this activity. Bypass occurs only when homologous sequences are present on both sides of the insert. When the heterologous insert is positioned at either end of the linear duplex substrate, the RuvA and RuvB proteins do not significantly increase product formation in RecA protein-mediated DNA strand exchange reactions. The results suggest an important role for RuvA and RuvB in the bypass of DNA structural barriers during recombinational DNA repair.


Upregulator of cell proliferation predicts poor prognosis in hepatocellular carcinoma and contributes to hepatocarcinogenesis by downregulating FOXO3a.
The goal of the present study was to investigate the potential correlation between the expression level of upregulator of cell proliferation (URGCP/URG4) and the prognosis of hepatocellular carcinoma (HCC), and to examine the biological function of URGCP/URG4 in the progression of HCC, to better understand its underlying molecular mechanism in hepatic tumorigenesis. URGCP/URG4 expression was analyzed in 15 HCC cell lines, in 278 archived paraffin-embedded HCC sections, and in 10 pairs of fresh HCC tumor and para-tumor non-cancerous tissues using immunohistochemistry (IHC) and Western blotting analysis (WB). The effect of URGCP/URG4 on cell proliferation and tumorigenesis was examined in vitro and in vivo. WB and luciferase reporter analyses were performed to identify the effects of URGCP/URG4-overexpression or -knockdown on expression of cell cycle regulators and transcriptional activity of FOXO3a. IHC results revealed an upregulation of URGCP/URG4 in all HCC cell lines and fresh HCC samples as compared with normal liver cells and para-tumor tissues, respectively. URGCP/URG4 was also expressed at a high level in 122 of the 278 (43.8%) archived HCC specimens. The expression level of URGCP/URG4 was significantly correlated with clinical staging and poor patient survival of HCC in the study cohort, and in various clinical subgroups. Strikingly, ectopic expression of URGCP/URG4 induced proliferation and anchorage-independent growth of HCC cells, while silencing of URGCP/URG4 had the opposite effect. Furthermore, URGCP/URG4 overexpression in HCC cells increased cellular entry into the G1/S transitional phase, associated with downregulation of p27(Kip1) and p21(Cip1) and upregulation of cyclin D1. These effects were accompanied by enhanced Akt activity and reduced FOXO3a transcriptional activity. URGCP/URG4 plays an important role in promoting proliferation and tumorigenesis of HCC and may represent a novel prognostic biomarker and therapeutic target for this disease.


Aberrant expression of AID and AID activators of NF-κB and PAX5 is irrelevant to EBV-associated gastric cancers, but is associated with carcinogenesis in certain EBV-non-associated gastric cancers.
Epstein-Barr virus-associated gastric carcinoma (EBVaGC) is a distinct subtype of gastric cancer characterized by clinicopathological features including lymphoepithelioma-like histology. Aberrant expression of activation-induced cytidine deaminase (AID) as a genomic modulator was demonstrated through pathogen-related nuclear factor κB (NF-κB) signaling in Helicobacter pylori-associated gastric cancer. To elucidate whether or not AID expression is relevant to carcinogenesis in EBVaGC, immunohistochemical expression of AID and AID-regulatory factors between EBVaGC and EBV-non-associated gastric carcinoma (GC) were evaluated, each using 15 cases of GC with lymphoid stroma (GCLS) and other types of GC. Aberrant expression of AID, NF-κB and paired box 5 (PAX5) were significantly decreased in EBVaGC (0/11, 1/11 and 1/11) compared with in EBV-non-associated GC (7/19, 12/19 and 11/19) (P=0.025, 0.005 and 0.01, respectively); however, no significant difference in c-Myb proto-oncogene expression was identified. AID expression was also decreased in EBV-associated GCLS (0/10) compared with in EBV-non-associated GCLS (3/5). Unexpectedly, decreased expression of NF-κB and PAX5 was observed in GCLS (1/15 and 2/15) compared with in GC without LS (12/15 and 10/15) (P<0.001 and P=0.003, respectively). Decreased AID expression observed in EBVaGC is consistent with the reported molecular characterization of hypermethylation and rare somatic gene mutation in EBVaGC. Only PAX5 was identified to be significantly associated with venous invasion (P=0.022). The results of the present study suggest that pathogen-induced AID expression may be irrelevant to carcinogenesis of EBVaGC, whereas it contributes to carcinogenesis in certain types of EBV-non-associated GC.


A Botanical Composition from Morus alba, Ilex paraguariensis, and Rosmarinus officinalis for Body Weight Management.
Obesity is the largest and fastest growing public health catastrophe in the world affecting both adults and children with a prevalence impacting more than one-third of United States (US) adult population. Although the long-term solution lies in lifestyle changes in the form of dieting and exercise, intervention is required for those who are already obese. Unfortunately, treatment options remain quite limited due to associated side effects of conventional therapeutics. As a natural alternative, in this study we describe the beneficial effect of a standardized composition (UP603) comprised of extracts from Morus alba, Ilex paraguariensis, and Rosmarinus officinalis in improving metabolic disorders in high fat diet (HFD) and high fat & high fructose diet (HFFD) induced obese C57BL/6J mice. Mice treated with UP603 showed dose-correlated decrease in body weight gains compared to vehicle treated HFFD group. Following 7 weeks of treatment, the changes in body weight gains from baseline were found as 6.4%, 27.3%, 2.0%, 3.1%, 0.4%, and -2.9% for normal control diet, HFFD, Orlistat, 450, 650, and 850 mg/kg UP603 treated animals, respectively. Reductions of 7.9-21.1% in total cholesterol, 25.4-44.6% in triglyceride, and 22.5-38.2% in low-density lipoprotein were observed for mice treated with 450-850 mg/kg of UP603. In a dual energy X-ray absorptiometry scan, percentage body fat of 18.9%, 47.8%, 46.1%, and 40.4% were found for mice treated with normal control, HFD, Orlistat, and UP603, respectively. Reductions of 65.5% and 16.4% in insulin and leptin, respectively, and 2.1-fold increase in ghrelin level were also observed for the UP603 group. Statistically significant improvements in nonalcoholic steatohepatitis scores were also observed from liver histology for mice treated with UP603. Hence, UP603, a standardized botanical composition from M. alba, I. paraguariensis, and R. officinalis could potentially be considered as a natural alternative to maintain healthy body weight and to manage metabolic syndrome.


Highly Sensitive Soft Pressure Sensors for Wearable Applications Based on Composite Films with Curved 3D Carbon Nanotube Structures.
Soft pressure sensors based on 3D microstructures exhibit high sensitivity in the low-pressure range, which is crucial for various wearable and soft touch applications. However, it is still a challenge to manufacture soft pressure sensors with sufficient sensitivity under small mechanical stimuli for wearable applications. This work presents a novel strategy for extremely sensitive pressure sensors based on the composite film with local changes in curved 3D carbon nanotube (CNT) structure via expandable microspheres. The sensitivity is significantly enhanced by the synergetic effects of heterogeneous contact of the microdome structure and changes of percolation network within the curved 3D CNT structure. The finite-element method simulation is used to comprehend the relationships between the sensitivity and mechanical/electrical behavior of microdome structure under the applied pressure. The sensor shows an excellent sensitivity (571.64 kPa-1 ) with fast response time (85 ms), great repeatability, and long-term stability. Using the developed sensor, a wireless wearable health monitoring system to avoid carpel tunnel syndrome is built, and a multi-array pressure sensor for realizing a variety of movements in real-time is demonstrated.


Genetic and environmental effects on openness to experience, agreeableness, and conscientiousness: an adoption/twin study.
Previous research has indicated that extraversion and neuroticism are substantially affected both by genotype and environment. This study assesses genetic and environmental influences on the other three components of the five-factor model of personality: Openness to Experience, Agreeableness, and Conscientiousness. An abbreviated version of the NEO Personality Inventory (NEO-PI) was administered to 82 pairs of identical twins and 171 pairs of fraternal twins reared apart and 132 pairs of identical twins and 167 pairs of fraternal twins reared together. Estimates of genetic and environmental effects for Openness and Conscientiousness were similar to those found in other studies of personality: Genetic influence was substantial and there was little evidence of shared rearing environment. Results for Agreeableness were different: Genetic influence accounted for only 12% of the variance and shared rearing environment accounted for 21% of the variance. Few significant gender or age differences for genetic and environmental parameters were found in model-fitting analyses.


Structural diversity of the hagfish variable lymphocyte receptors.
Variable lymphocyte receptors (VLRs) are recently discovered leucine-rich repeat (LRR) family proteins that mediate adaptive immune responses in jawless fish. Phylogenetically it is the oldest adaptive immune receptor and the first one with a non-immunoglobulin fold. We present the crystal structures of one VLR-A and two VLR-B clones from the inshore hagfish. The hagfish VLRs have the characteristic horseshoe-shaped structure of LRR family proteins. The backbone structures of their LRR modules are highly homologous, and the sequence variation is concentrated on the concave surface of the protein. The conservation of key residues suggests that our structures are likely to represent the LRR structures of the entire repertoire of jawless fish VLRs. The analysis of sequence variability, prediction of protein interaction surfaces, amino acid composition analysis, and structural comparison with other LRR proteins suggest that the hypervariable concave surface is the most probable antigen binding site of the VLR.


Potential mechanisms of effects of serum-derived bovine immunoglobulin/protein isolate therapy in patients with diarrhea-predominant irritable bowel syndrome.
Serum-derived bovine immunoglobulin/protein isolate (SBI), an oral nutritional therapy, is efficacious in diverse diarrheal diseases. In an open-label study in 15 patients with irritable bowel syndrome-diarrhea (IBS-D), we evaluated effects of SBI (5.0 g, twice a day) for 8 weeks on safety, on bowel function and abdominal pain, tryptophan metabolism (K:T ratio), intestinal permeability (13C-mannitol and lactulose excretion), bile acid synthesis (fasting serum FGF-19 and C4), duodenal and stool microbiome, and the expression of 90 genes related to inflammation, immune function, and tight junctions in duodenal mucosa. Statistical analysis (paired tests, baseline vs. treatment) was based on intention to treat (ITT) principles. One of 15 Caucasian patients (13F, 2M, age 40.3 ± 2.3y, BMI 34.3 ± 3.0 kg/m2) withdrew without completing studies. There were improvements in stools/day (decrease, P < 0.001), ease of passage (P = 0.035), and evacuation (P = 0.004) with SBI therapy. Worst pain severity was numerically reduced in last 2 weeks' treatment (P = 0.078). Duodenal mucosal mRNA expression; serum C4, FGF-19, and KT ratio; small bowel or colon permeability; and stool microbiome were not significantly different after SBI therapy, compared to baseline. In duodenal brushings, there was considerable microbiota structure difference (β diversity analysis P = 0.072, UniFrac) and, on taxonomic analysis, increased abundance of Proteobacteria Burkholderiales, Firmicutes Catonella, and unclassified genus organisms with SBI therapy. Thus, SBI therapy for 8 weeks in IBS-D patients is associated with improved bowel function; the mechanism of benefit is unclear, though there were microbiota structure differences in duodenal brushings. Further studies in patients with low-grade inflammation and intestinal barrier dysfunction at baseline are indicated.


Surgical treatment of nasal hemangiomas.
The treatment of nasal hemangiomas continues to be controversial. The authors' experience with early surgical treatment of nasal hemangiomas is presented. This retrospective study includes 11 patients. Surgical intervention consisted of excision of the nasal hemangioma and reconstruction by local tissue transfer or rearrangement. Age at surgery ranged from 10 months to 6.5 years (mean age, 2.2 years). All patients have acceptable nasal contour and have demonstrated excellent nasal growth. The authors' experience demonstrates that early surgical intervention is an acceptable alternative for the management of nasal hemangiomas.


Identification of SGMS2 as a molecule involved in natural killer cell recruitment and its in-deep analysis in the liver cancer microenvironment: Evidence from large populations cohort.
Liver cancer, a common malignancy within the digestive system, presents with a particularly grim prognosis. Within the immune microenvironment, the role of natural killer (NK) cells in liver cancer remains unclear. We sourced data on clinical parameters and gene expressions for liver cancer patients from The Cancer Genome Atlas Program database and carried out all analyses using R software and its relevant codes. In our research, we delved into the genes intertwined with NK cells in hepatocellular carcinoma (HCC). Leveraging the QUANTISEQ and MCPCOUNTER algorithms to quantify NK cells, we spotlighted genes vital to the recruitment of NK cells. Among these genes, GDE1, WDFY3, DNAJB14, PKD2, DGAT2, SGMS2 and MKNK2 showed a strong correlation with patient outcomes. We also mapped out the single-cell expression trajectories of these genes within the HCC milieu. From our findings, SGMS2 emerged as a key gene warranting further scrutiny. Our in-depth analysis of SGMS2 shed light on its influence over specific biological pathways, its contribution to the immune landscape and its role in genomic instability within HCC. Drawing from this, we formulated a predictive model rooted in SGMS2-associated genes. This model showcased remarkable precision across both training and validation cohorts. Overall, our investigation underscored the profound implications of SGMS2, a gene pivotal to NK cell infiltration, in the landscape of HCC, thereby positioning it as a potential linchpin in oncological strategies.


Results of primary extensor tendon repair of the hand with respect to the zone of injury.
Laceration of the hand extensor tendons is common in the upper extremities, causing soft tissue trauma. These tendons, because of their superficial location and lying adjacent to bones, have a greater tendency to be injured than flexor tendons. The aim of this study was to determine the results of primary repairs of lacerated extensor tendons of the fingers, with respect to the zone of injury, and also whether the results are different according to the anatomical zone in which they occur. During a period of two years and four months, 32 patients with open wounds and lacerated extensor tendons of the hand were hospitalized and underwent surgery. Repairs were done by a modified Kessler technique using 0 - 4 nylon suture. After repairing, the wrist was splinted for four weeks. Patients were followed-up for 12 months and the results were evaluated according to the Miller's scoring system. A total of 72 extensor tendons were repaired. The mean age of the patients was 24.6 years. The best results were obtained in zones 3 and 5 (84% and 88% respectively), and the worst results were seen in zones 1, 2 and 4, P = 0.01. Wound infections or re-ruptures were not seen. Repair of extensor tendon cuts on the dorsal surface of the hand and forearm were associated with better results in zones 3 and 5 than in zones 1, 2 and 4. Repair by the modified Kessler suture method provides proper stability at the site of the tendon cut.


Incorporation of Structural Tensor and Driving Force Into Log-Demons for Large-Deformation Image Registration.
Large-deformation image registration is important in theory and application in computer vision, but is a difficult task for non-rigid registration methods. In this paper, we propose a structural Tensor and Driving force-based Log-Demons algorithm for it, named TDLog-Demons for short. The structural tensor of an image is proposed to obtain a highly accurate deformation field. The driving force is proposed to solve the registration issue of large-deformation that often causes Log-Demons to trap into local minima. It is defined as a point correspondence obtained via multisupport-region-order-based gradient histogram descriptor matching on image's boundary points. It is integrated into an exponentially decreasing form with the velocity field of Log-Demons to move the points accurately and to speed up a registration process. Consequently, the driving force-based Log-Demons can well deal with large-deformation image registration. Extensive experiments demonstrate that the TDLog-Demons not only captures large deformations at a high accuracy but also yields a smooth deformation.


Analgesic Efficacy of Transverse Abdominal Plane Block after Elective Cesarean Delivery - Bupivacaine with Fentanyl versus Bupivacaine Alone: A Randomized, Double-blind Controlled Clinical Trial.
The analgesic benefit of transversus abdominis plane (TAP) blocks for cesarean delivery remains controversial. In our study, we compared the analgesic efficacy of TAP block using local anesthetic bupivacaine and adjunct fentanyl with bupivacaine alone in patients undergoing elective cesarean section. Our study was a randomized, double-blind, controlled clinical trial where sixty patients undergoing elective cesarean delivery under subarachanoid block (2 ml of 0.5% bupivacaine) were randomized into two groups, A and B. At the end of the surgical procedure, bilateral TAP block was performed guided by the ultrasound. Group A received 38 ml of 0.25% bupivacaine and 2 ml of 50 μg of fentanyl, whereas Group B received 38 ml of 0.25% bupivacaine + 2 ml of normal saline. The total volume was divided equally and administered bilaterally. Each patient was assessed for 24 h after TAP block, for time to rescue analgesia, pain using visual analog scale (VAS) score at rest and on movement, hemodynamic parameters (heart rate and blood pressure), nausea, vomiting, and sedation. Diclofenac 75 mg was given as rescue analgesia when the patient complained of pain or when VAS score >4. Prolonged postoperative analgesia was noticed with both the groups, with a mean time to rescue analgesia of approximately 6.5 h. There was no significant difference in time to rescue analgesia (6.49 ± 0.477 vs. 6.5 ± 0.480) when both the groups were compared among themselves. The pain scores among the two groups when compared did not show any added benefit. Incidence of nausea, vomiting, and sedation when compared between both the groups showed no difference. The TAP block as a part of a multimodal analgesic regimen definitely has a role in providing superior analgesia in the postoperative period. However, adjunct fentanyl to local anesthetic bupivacaine was found to have no added advantage when quality and duration of analgesia was compared.


Effect of dietary cholesterol on apolipoprotein E synthesis in the rabbit.
Female New Zealand White rabbits were fed either rabbit chow or rabbit chow plus 1% (w/w) cholesterol for 14 days. The chow-fed rabbits had normal plasma lipoprotein profiles on agarose gel electrophoresis, 59 +/- 5 mg of cholesterol and 5.5 +/- 0.4 mg of apolipoprotein E (apoE) per dl of serum. The cholesterol-fed rabbits had significant amounts of beta-VLDL in their serum, 1870 +/- 140 mg of cholesterol and 96 +/- 12 mg of apoE per dl of serum. Relative rates of apoE synthesis were determined by incubating hepatocytes in culture medium containing [3H]leucine for 15 min at 37 degrees C and expressing the radioactivity incorporated into immunoprecipitable apoE as a percentage of the radioactivity incorporated into total protein. Hepatocytes from cholesterol-fed rabbits had twice the relative rate of apoE synthesis (1.05 +/- 0.18%) of hepatocytes from chow-fed rabbits (0.55 +/- 0.07%). This increase in synthesis could be a major contributor to the 17-fold increase in serum apoE levels in the cholesterol-fed rabbit.


A near-infrared upconversion luminescence total internal reflection platform for quantitative image analysis.
A quantitative image analysis method by counting photons from different samples was developed based on a near-infrared upconversion luminescence total internal reflection platform. The proposed method can not only greatly reduce the consumption of samples (10 μL) but also ensure high-throughput and fast (0.1 s) data analysis.


Isolation from murine myeloma and leukemia cells of a selective inhibitor of DNA polymerases.
An inhibitor of two ribopolymer-transcribing DNA polymerases can be isolated from MOPC-21 myeloma tumors, from the sera of mice bearing these tumors, or from MCDV-12 ascitic leukemia. The peritoneal fluid of mice bearing the latter neoplasm is also a source of the inhibitor. The inhibitor is a small DNA molecule which displays inhibitory activity in both double- and single-stranded form.