Response to dopamine hydrochloride in the hepatorenal syndrome.
Functional renal failure accompanying advanced cirrhosis of the liver carries a grave prognosis. Seven patients with the hepatorenal syndrome and five patients with decompensated cirrhosis of the liver without renal failure were studied by the xenon Xe 133 washout technique. Mean renal blood flow and its cortical component were decreased in both groups compared to normal transplant donors, but to a significantly greater degree in hepatorenal syndrome. In hepatorenal patients, intra-arterial infusion of subpresor doses of dopamine hydrochloride improved the angiographic appearance of the renal cortical vasculatrue and the cortical blood flow rate. Urine flow rate and glomerular filtration rate did not consistently improve with 12- to 24-hour intravenous infusions, although two patients survived, temporally related to the study. These patients had shown signs of liver function recovery.


Risk evaluation of diabetic ketoacidosis associated with antipsychotics among patients with schizophrenia in the Japanese adverse event report database.
Diabetic ketoacidosis (DKA) is a serious life-threatening condition and can be associated with antipsychotic medication. Asian patients with diabetes exhibit less insulin resistance than Caucasians; however, all previous studies concerning antipsychotic-related DKA have been conducted in Western populations. We analyzed the rank order of the association of antipsychotic agents for schizophrenia with DKA using the Japanese Adverse Drug Event Report database, a spontaneous reporting system database. We performed a retrospective pharmacovigilance disproportionality analysis using adverse event reports submitted to the Pharmaceuticals and Medical Devices Agency between April 2004 and March 2021. The study population comprised 7435 patients with schizophrenia, and the total number of antipsychotic-related DKA reports was 55. Among the 55 cases of DKA in patients with schizophrenia, 6% (3/55) patients died after DKA. The signals of DKA were reported after treatment with olanzapine, with a significant adjusted reporting odds ratio (95% CI) of 3.26 (1.87-5.66). In 1399 olanzapine treatment cases, multivariable logistic regression analysis using a forward selection method showed that being male (adjusted RORs 2.72 (1.07-6.90)) was associated with the onset of DKA. Our study revealed that treatment with olanzapine was associated with the development of DKA among patients with schizophrenia. The results also clarified that male patients were at higher risk for DKA among patients treated with olanzapine. The application of these data will aid in risk monitoring and management that may reduce the occurrence of antipsychotic-related DKA in treatment for schizophrenia.


Transannular Diels-Alder reactivities of 14-membered macrocylic trienes and their relationship with the conformational preferences of the reactants: a combined quantum chemical and molecular dynamics study.
Transannular Diels-Alder (TADA) reactions that occur between the diene and dienophile moieties located on a single macrocyclic triene molecule have been recognized as effective synthetic routes toward realizing complex tricyclic molecules in a single step. In this paper, we report a comprehensive study on the TADA reactions of 14-membered cyclic triene macrocycles to yield A.B.C[6.6.6] tricycles using quantum chemical methods and using classical molecular dynamics simulations. A benchmark study has been performed to examine the reliability of the commonly used ab initio methods and hybrid density functional levels of theory in comparison with results from CCSD(T) calculations to accurately model TADA reactions. The energy barriers obtained using the M06-2X functional were found to be in quantitative agreement with the CCSD(T) level of theory using a reasonably large basis set. Conformational properties of the reactants have been systematically studied using extensive molecular dynamics (MD) simulations. For this purpose, model systems were conceived, and force field parameters corresponding to the dihedral terms in the potential energy function were obtained. Linear relationship between the activation energies corresponding to the TADA reactions and the probability of finding the reactant in certain conformational states was obtained. A clustering method along with optimizations at the molecular mechanics and density functional M06-2X levels has been used to locate the most stable conformation of each of the trienes.


Herpes simplex virus type 1 induction of chemokine production is unrelated to viral load in the cornea but not in the nervous system.
Herpes simplex virus type 1 elicits a strong host inflammatory response after corneal infection. The purpose of the current study was to compare the production of chemokines induced by viral infection at sites known to harbor virus after ocular inoculation in order to determine the relationship between viral load and chemokine expression. Using highly resistant IFN-alpha1 transgenic mice whose transgene is under the control of the glial fibrillary acidic protein promoter in comparison with the more sensitive wild-type counterparts, we compared the expression of chemokines versus the amount of infectious virus recovered from the anterior segment of the eye and nervous system. Consistent with our predicted outcome, the level of infectious virus recovered in the iris, trigeminal ganglia, and brainstem of resistant versus sensitive mice correlated with chemokine production; that is, the less virus recovered the less chemokine (CCL2, CCL3, CCL5, CXCL9, and CXCL10) produced. In contrast to the nervous system and iris, there was no correlation between chemokine expression and level of infectious virus recovered in the cornea. We interpret these results as suggesting chemokine expression within the cornea in response to herpes simplex virus type 1 infection is driven by factors other than antigenic stimulation.


Rare Condition of Intrathoracic Phrenic Nerve Schwannoma Successfully Treated with Uniportal Video-Assisted Thoracoscopic Surgery.
Neurogenic tumors in the mediastinum account for approximately 20-30% of all types of mediastinal tumors in adults. This pathology is usually benign and has no or very few symptoms. Schwannoma rarely involves the phrenic nerve. We report a unique case of schwannoma involvement of phrenic nerve. Case Presentation. The 43-year-old female patient has an annual check-up of computerized tomography to detect the mass in the right middle mediastinum, so the patient was admitted to the hospital. Chest computerized tomography image found a mass of the middle mediastinum with the size of 23 × 22.3 mm located between the right pulmonary artery and the pericardium with uniform margins and clear boundaries, not invading the surrounding organization. Very little contrast is absorbed after injection. She underwent a uniportal video-assisted thoracoscopic surgery, and this mass was found to be originating from the right phrenic nerve. Resection of the portion of phrenic nerve with mass was performed. Postoperatively, the patient was discharged from the hospital after 4 days of treatment in a clinical condition with no difficulty breathing and no chest pain; postoperative X-ray showed no abnormality, and the right diaphragm was unchanged. Although they are very rare, schwannomas of the phrenic nerve should be considered in the differential diagnosis of mediastinal tumors. Uniportal video-assisted thoracoscopic surgery is a preeminent option with properly sized tumors that deliver good results and have no postoperative complications associated with surgery.


Restraint stress reduces the antitumor efficacy of cyclophosphamide in tumor-bearing mice.
Treatment with the cytotoxic antitumor drug cyclophosphamide is highly effective in mice bearing Lewis lung carcinoma, causing the absence of macroscopically detectable tumors at necroscopy after sacrifice. When the effects of the treatment on survival are determined, a significant increase in survival time and in the proportion of long-term survivors is observed. When restraint stress is further applied, tumors develop in all of the mice treated with cyclophosphamide, and survival time and the fraction of long-term survivors are significantly reduced. Flow cytometry of splenic T-lymphocyte subsets in normal mice indicates a significant decrease in the number of CD3+, CD4+, and CD8+ subsets after treatment with cyclophosphamide and after application of restraint stress; the interaction of the two treatments is significant for CD3+ and marginally significant for CD4+ subsets. The attenuation by restraint stress which was observed for the effects of cyclophosphamide on the presence of tumors at necroscopy and for the survival of the treated mice might thus be interpreted as follows: restraint stress attenuates the immune functions of the host directed toward the weakly immunogenic tumor, an effect which, in the absence of restraint stress, interacts effectively with the cytotoxic action of cyclophosphamide toward tumor cells. The results obtained using this animal model thus indicate that experimental stress reduces the therapeutic efficacy of a cytotoxic antitumor drug; experimental and clinical implications are discussed.


Evaluation of sutureless scrotal castration for pediatric and juvenile dogs.
OBJECTIVE To determine complication rates associated with sutureless scrotal castration (SLSC) performed in a large number of pediatric and juvenile dogs and investigate whether procedure duration differed from that of traditional prescrotal castration (TPSC). DESIGN Prospective case series and clinical trial. ANIMALS 400 shelter-owned dogs that underwent SLSC and 18 shelter-owned dogs that underwent TPSC between 2 and 5 months of age. PROCEDURES In the first phase of the study, SLSC was performed for 400 dogs, which were monitored for ≥ 24 hours after surgery to identify surgery-related complications such as hemorrhage, signs of pain, self-trauma, swelling, and dermatitis at the incision site. In the second phase, the durations of 18 SLSC and 18 TPSC procedures were measured and compared. RESULTS No hemorrhage-related complications were identified in any dog during SLSC in the first phase. Complications were all minor and self-limiting and included peri-incisional dermatitis (9/400 [2.3%]), skin bruising (4/400 [1.0%]), and swelling (1/400 [0.3%]). No self-trauma was observed for any dog, nor did any dog require additional analgesic treatment after surgery. Procedure duration was significantly briefer for SLSC (mean ± SD, 1.0 ± 0.2 minutes) than for TPSC (3.5 ± 0.4 minutes). CONCLUSIONS AND CLINICAL RELEVANCE Results suggested that SLSC as evaluated was safe and significantly faster than TPSC when performed in healthy 2- to 5-month-old dogs. The SLSC technique has the potential to improve morbidity and mortality rates as well as financial costs associated with castration, particularly in high-quality, high-volume spay and neuter programs.


Evidence for the presence of a neutral insulinotrophic peptide in the porcine duodenum.
A crude mixture of thermostable peptides extracted from porcine duodenum was fractionated by electrofocusing. A neutral fraction, different from the basic fractions of GIP, VIP, PHI, and CCK was found to promote insulin secretion when injected in vivo to normal rats. This neutral fraction, extracted from the crude mixture by chromatography, stimulated insulin output from an isolated rat pancreas and enhanced glucose-induced insulin release. The insulinotrophic effect of this partially purified duodeno-jejunal material disappeared following digestion with trypsin. The insulin-releasing activity was found to correspond to a compound of molecular weight higher than that of insulin (i.e. higher than 6000). No GIP-like immunoreactivity was found in this neutral fraction indicating that the active peptide(s) are not GIP related compounds. These observations suggest that porcine duodenum contains and incretin activity different from that of the insulinotrophic factors already reported.


On mast-cell-mediated angiogenesis in the rat mesenteric-window assay.
Testosterone propionate injected s.c. significantly reduced the mast-cell mediated angiogenic response occurring in prepubescent rats, thereby indicating that this angiogenic reaction can be influenced by hormonal stimuli. Since the newly-formed vessels are very small, one could expect that microscopic examination would be needed to quantify the vasculature. When studying the discernment of vessels at optical magnifications of between x 100 and x 1000 in sections of methacrylate-embedded mesenteric window, we found that the number of discernible vessels increased dramatically as the magnification increased. This not only underlines the genuine microvascular character of the reaction but also demonstrates the need for high-power magnification when truly quantifying an angiogenic reaction by optical means.


Alkoxy Radical Bond Scissions Explain the Anomalously Low Secondary Organic Aerosol and Organonitrate Yields From α-Pinene + NO3.
Oxidation of monoterpenes (C10H16) by nitrate radicals (NO3) constitutes an important source of atmospheric secondary organic aerosol (SOA) and organonitrates. However, knowledge of the mechanisms of their formation is incomplete and differences in yields between similar monoterpenes are poorly understood. In particular, yields of SOA and organonitrates from α-pinene + NO3 are low, while those from Δ3-carene + NO3 are high. Using computational methods, we suggest that bond scission of the nitrooxy alkoxy radicals from Δ3-carene lead to the formation of reactive keto-nitrooxy-alkyl radicals, which retain the nitrooxy moiety and can undergo further reactions to form SOA. By contrast, bond scissions of the nitrooxy alkoxy radicals from α-pinene lead almost exclusively to the formation of the relatively unreactive and volatile product pinonaldehyde (C10H16O2), thereby limiting organonitrate and SOA formation. This hypothesis is supported by laboratory experiments that quantify products of the reaction of α-pinene + NO3 under atmospherically relevant conditions.


To solve climate, first achieve peace.
The horrific invasion of Ukraine by Russia has many devastating effects. The most immediate are on the people of Ukraine, but the long-term implications for the entire planet are enormous. For science, the disruption to international collaboration must be addressed and we must give our strongest support to Ukrainian scientists, as outlined by Marcia McNutt and John Hildebrand in a recent Science editorial. But for climate change, the effects may be the greatest. If we want a positive energy future for a healthier climate, the West must start by recasting foreign policy with climate and energy issues at the forefront. That can only succeed if nations strengthen the commitment to settle differences with diplomacy, not war. The only truly life-sustaining climate will be one accompanied by international peace.


Drug permeation through skin is inversely correlated with carrier gel rigidity.
Controlled release plays an essential role in formulating topical and transdermal drug delivery systems. In this study, we correlated the skin permeation of Sesamin, a lipophilic drug, with the rheological properties of two different organogel carriers, i.e., low molecular weight gelling agent N-lauroyl-l-glutamic acid di-n-butylamide (GP-1) and Carbopol polymeric gels. Although these two gels have distinct network structures, they share the same trend: the more rigid the gel network and the higher the gelator concentration, the lower the steady flux of Sesamin through skin. This negative correlation lies in the fact that organogel network hinders the diffusion of drug to the gel-skin interface; as a result, the depletion zone near the interface is non-negligible and contributes to the resistance of the whole diffusion system, and thus, the permeation flux is reduced. More interestingly, the dependence of the steady flux against gel complex modulus at the linear viscoelastic region followed a "universal" power law regardless of the gel types, i.e., 1/J = 1/J0 + a(G*)(ε)/C0 with a = 11.25, ε = 0.21 ± 0.03 for GP-1 gels, and a = 0.16, ε = 1.05 ± 0.06 for Carbopol gels, J0 is the steady flux without gel (G* = 0), and C0 is the initial concentration of drug in gels. The empirical formulae are crucial in developing transdermal organogel systems with controlled release of drug content through readily obtainable data of their rheological properties. The explanation for the power law dependence of the steady flux on gel complex modulus is discussed.


Relationship between cyclic guanosine monophosphate accumulation and relaxation of canine trachealis induced by nitrovasodilators.
The role of cyclic GMP (cGMP) in mediating relaxation of canine trachealis produced by nitrovasodilators (NVDs), compounds that activate guanylate cyclase, was examined. Sodium nitroprusside (SNP) produced a concentration-dependent relaxation of the canine trachealis that was accompanied by a concentration-related increase in cGMP content. In time course studies, relaxation of isolated trachealis strips induced by 30 microM SNP was paralleled by an increase in cGMP that reached a maximum of 18-fold above basal levels within 2 min. Zaprinast, an inhibitor of the cGMP-specific phosphodiesterase, potentiated both SNP-induced relaxation and cGMP accumulation. A cell-permeable analog of cGMP, 8-bromo-cGMP, mimicked the relaxant effects of SNP. Also assessed were the effects of methylene blue, an agent that inhibits soluble guanylate cyclase activity, and hemoglobin, an agent that competitively binds NO-containing compounds. In these experiments, tissues were pretreated with the above agents for 10 min, contracted with 1 or 3 microM methacholine, and then relaxed by the cumulative addition of SNP or two other NVDs, S-nitroso-N-acetyl-penicillamine (SNAP) and glyceryl trinitrate (GTN). Tissues were flash-frozen after adding the final concentration of the various NVDs and assayed for cGMP. Methylene blue and hemoglobin suppressed both cGMP accumulation and relaxation in response to SNAP and GTN. in contrast, methylene blue and hemoglobin inhibited SNP-induced cGMP accumulation but, paradoxically, potentiated SNP-induced relaxation. The results of this study generally support a role for cGMP in NVD-induced relaxation of airway smooth muscle.(ABSTRACT TRUNCATED AT 250 WORDS)


Laser-assisted chemical vapor deposition setup for fast synthesis of graphene patterns.
An automatic setup based on the laser-assisted chemical vapor deposition method has been developed for the rapid synthesis of graphene patterns. The key components of this setup include a laser beam control and focusing unit, a laser spot monitoring unit, and a vacuum and flow control unit. A laser beam with precision control of laser power is focused on the surface of a nickel foil substrate by the laser beam control and focusing unit for localized heating. A rapid heating and cooling process at the localized region is induced by the relative movement between the focalized laser spot and the nickel foil substrate, which causes the decomposing of gaseous hydrocarbon and the out-diffusing of excess carbon atoms to form graphene patterns on the laser scanning path. All the fabrication parameters that affect the quality and number of graphene layers, such as laser power, laser spot size, laser scanning speed, pressure of vacuum chamber, and flow rates of gases, can be precisely controlled and monitored during the preparation of graphene patterns. A simulation of temperature distribution was carried out via the finite element method, providing a scientific guidance for the regulation of temperature distribution during experiments. A multi-layer graphene ribbon with few defects was synthesized to verify its performance of the rapid growth of high-quality graphene patterns. Furthermore, this setup has potential applications in other laser-based graphene synthesis and processing.


[PSA-doubling time immediately before the diagnosis of prostate cancer].
PSA-doubling time (PSA-DT) immediately before the diagnosis of prostate cancer was calculated in 8 prostate cancer patients in whom PSA was checked three or more times with the same kit during a period of 6 months or more. The correlation between PSA-DT and clinical stage or pathological differentiation was analyzed. In most patients, PSA correlated well showing a straight regression line to the observation period on a hemi-logarithmic scale. The correlation coefficient was high, almost 0.9 or more except in one patient. PSA-DT ranged from 5.1 to 64.9 months, averaging 23.1 months. There was no significant correlation between clinical stage or pathological differentiation and PSA-DT. However, PSA-DT in stage D patients tended to be shorter than that of stage B + C patients. One patient who had stage D poorly differentiated carcinoma died of cancer recurrence. In this patient, PSA-DT was short (5.1 months).


"Whose perfection is it anyway?": a virtuous consideration of enhancement.
Discussions of genetic enhancements often imply deep suspicions about human desires to manipulate or enhance the course of our future. These unspoken assumptions about the arrogance of the quest for perfection are at odds with the normally hopeful resonancy we find in contemporary theology. The author argues that these fears, suspicions and accusations are misplaced. The problem lies not with the question of whether we should pursue perfection, but rather what perfection we are pursuing. The author argues that perfection, properly understood, has an enormously positive function in the Roman Catholic tradition. The author examines three sources: the Scriptures, the scholastic tradition, and ascetical theology. He examines contemporary criticisms of perfectionism and suggests that an adequate virtue theory keeps us from engaging perfectionism as such. The author then shows how a positive, responsible view of perfection is an asset to our discussion on enhancement technology.


[Anti-Helicobacter pylori effects of Bainiku-ekisu (concentrate of Japanese apricot juice)].
Helicobacter pylori (H.p.) bacteria are the major causes of gastro-duodenal disease, and some association with stomach cancer has been suggested. Recently, H.p. eradicating treatment has been practiced using antibiotics and proton-pump inhibitors. However, at the same time, some reports have been made on the side-effects of this treatment; allergic reactions and uneffective resistant bacteria. Under these circumstances, there is a strong need for medicines, which are less harmful to the body, can be administered repeatedly, are less expensive, and yet as effective as antibiotics in inhibiting the bacteria, and in fact, some studies have been undertaken in this regard. We placed our focus on Bainiku-ekisu (Concentrate of Japanese apricot juice) which, as a Japanese folk remedy, has been used for the treatment of gastritis and enteritis since ancient times, and studied its bacteriosterile affects. The major ingredients of Bainiku-ekisu are citric acid (32%) and malic acid (11%), while its pH represents strong acid. We measured the bacteriosterile effects of Bainiku-ekisu by culturing ten H.p. strains originating from gastro mucous membrane respectively in a Bainiku-ekisu concentration of 0.156%, 0.313%, 0.625% and 0.9%, and measured the level of MIC (minimum inhibiting concentration of development). As a result, out of ten H.p. strains four of them presented strong bacteriosterile effects in a concentration of less than 0.156%, and six of them, in a concentration of less than 0.313%. Furthermore, in order to measure the bacteriosterile effects against H.p. in the stomach we measured the quantity of bacteria in 0 minutes, five minutes, and ten minutes after mixing ten H.p. strains suspended in physiological salt solution with a Bainiku-ekisu solution of 0.3% and 0.9% dissolved in aseptic physiological salt solution. As a result, within five minutes after mixing, every one of the ten H.p. strains was observed to present strong bacteriosterile effects. These results suggest that Bainiku-ekisu can be considered as a fool likely to prevent the development of H.p. as well as the future possibility of making clinical applications to H.p. infection.


Assessment of Ploidy Status in Oral Potentially Malignant Disorders - A Systematic Review.
Malignant and potentially malignant epithelial lesions are often associated with various abnormalities such as epithelial dysplasia, abnormal DNA content, loss of heterozygosity, and chromosomal number aberrations. Screening and early detection of such abnormalities facilitates proper care and also helps to prevent further progression of potentially malignant lesions to malignancy. In such way, the presence of DNA aneuploidy in oral potentially malignant disorders (OPMDs) may serve as an indicator for the malignant transforming potential. Various assessment methods have been proposed to find the DNA ploidy status of cells. This current systematic review is mainly designed to assess the importance of ploidy status in OPMD while measuring the feasibility of using this biomarker for evaluating the hazard of malignant transformation. As an upshot of this systematic review, we can conclude that use of DNA ploidy status can serve as an independent bio-marker for predicting the malignant transformation of lesions. Furthermore, as a future scope the use of DNA ploidy analysis in normal mucosa of smokers will help to assess the malignancy risk and this technique might also help to predict the genetic predisposition of patients with malignancy.


Short-term treatment of children with encopresis.
To examine the effectiveness of a short-term behavioral treatment of encopresis, 52 encopretic children were evaluated and treated according to a standardized protocol. The treatment was highly effective, with a significant decrease in soiling during the first month (P < 0.01). Of the children who began treatment, 84.6% successfully reached the criterion of 2 consecutive weeks with no soiling accidents in a mean time of 28 days, and 78.8% successfully completed an additional 7-week phaseout period. The evaluations provided rich descriptive information regarding the characteristics of encopretic children. In agreement with the literature, no specific pattern of behavioral pathology was apparent.


S100A8 modulates mast cell function and suppresses eosinophil migration in acute asthma.
S100A8 is implicated in the pathogenesis of inflammatory diseases. S100A8 is upregulated in macrophages by Toll-like receptors (TLR)-3, 4, and 9 agonists in an IL-10-dependent manner, and by corticosteroids in vitro and in vivo, and scavenges oxidants generated by activated phagocytes. Because if its elevated expression in various lung disorders, we asked whether S100A8 was protective in allergic inflammation. S100A8, but not Cys(41)-Ala S100A8, in which the single reactive Cys residue was replaced by Ala, reduced mast cell (MC) degranulation and production of particular cytokines (IL-6, IL-4, and granulocyte macrophage colony-stimulating factor) in response to IgE-crosslinking in vitro, likely by inhibiting intracellular reactive oxygen species production, thereby reducing downstream linker for activation of T cells and extracellular signal regulated kinase/mitogen-activated protein kinase phosphorylation. In lungs of mice with acute asthma, S100A8, but not Cys(41)-Ala S100A8, reduced MC degranulation, production of eosinophil chemoattractants (IL-5, eotaxin, and monocyte chemoattractant protein-1), and eosinophil infiltration. Suppression of IL-6 and IL-13 could have contributed to reduced mucus production seen in lungs of S100A8-treated mice. IgE production was unaffected. In asthma, there is an imbalance of anti-oxidant systems that are generally protective. Our results strongly support a protective role for S100A8 in allergic inflammation by modulating MC activation and eosinophil recruitment, and by scavenging oxidants generated by activated leukocytes, in processes reliant on its thiol-scavenging capacity.


Pharmacokinetics and effect of cocaine on cerebral blood flow in the newborn.
The present study investigated the effect of cocaine (COC) on cerebral circulation (CBF) and oxidative metabolism (CMRO2) in the newborn piglet and aimed to relate pharmacokinetics of cocaine to cerebrovascular effects. COC decreased CBF and CMRO2 from 75 to 64 and 4.27 to 3.91 ml/min/100 g, respectively, at 4 min with reduced flow to all brain regions (p < 0.05) which returned to baseline by 10 min. COC was rapidly metabolized with a t1/2 of 43 min and peak plasma concentration of 1,172 ng/ml. Norcocaine (NOR) appeared in plasma and CSF within 3 min of cocaine administration and remained elevated for the duration of the study along with COC in the CSF. These data show that the timing of the peak plasma COC level is associated with maximal decreased CBF. Further, the stable elevated level of COC and NOR in the CSF suggests that biotransformation does not occur in the brain. As a result, accumulation of these drugs may occur in the brain with successive COC use and affect the developing CNS in a deleterious manner.


Structural sequelae and refractive outcome after successful laser treatment for threshold retinopathy of prematurity.
To study the structural sequelae and refractive outcome in eyes with a favorable structural outcome following laser treatment for threshold retinopathy of prematurity (ROP). Premature infants with threshold ROP had laser treatment with a minimum follow-up of 1 year. Complete ocular examination and refraction was done. Analysis and correlation of structural sequelae and refractive outcome was done. One hundred eighty-four eyes of 93 preterm infants were followed up. Structural changes such as vascular tortuosity, narrowing of arcades, temporal crescent, disc drag, and macular heterotopia were seen. Mean refractive error observed was -4.71 D spherical equivalent. Myopia was seen in 80.43% of eyes. The study revealed various structural sequelae and their correlation with refractive outcome.


Chromosomal inversion polymorphisms are widespread across the species ranges of rough periwinkles (Littorina saxatilis and L. arcana).
Inversions are thought to play a key role in adaptation and speciation, suppressing recombination between diverging populations. Genes influencing adaptive traits cluster in inversions, and changes in inversion frequencies are associated with environmental differences. However, in many organisms, it is unclear if inversions are geographically and taxonomically widespread. The intertidal snail, Littorina saxatilis, is one such example. Strong associations between putative polymorphic inversions and phenotypic differences have been demonstrated between two ecotypes of L. saxatilis in Sweden and inferred elsewhere, but no direct evidence for inversion polymorphism currently exists across the species range. Using whole genome data from 107 snails, most inversion polymorphisms were found to be widespread across the species range. The frequencies of some inversion arrangements were significantly different among ecotypes, suggesting a parallel adaptive role. Many inversions were also polymorphic in the sister species, L. arcana, hinting at an ancient origin.


Lower-limb drainage mapping for lymphedema risk reduction after pelvic lymphadenectomy for endometrial cancer.
Pelvic lymphadenectomy is associated with a significant risk of lower-limb lymphedema. In this proof-of-concept study, we evaluated the feasibility of identifying the lower-limb drainage nodes (LLDNs) during pelvic lymphadenectomy for endometrial cancer. Secondary objectives were to map lower-limb drainage and to assess the diagnostic value of our mapping technique. This prospective study included patients with endometrial cancer requiring pelvic lymphadenectomy, without neoadjuvant radiotherapy or chemotherapy and without history of lower-limb surgery. A radiopharmaceutical was injected into both feet on the day before surgery. LLDNs were identified using preoperative lymphoscintigraphy and intraoperative isotopic probe detection, then removed before complete pelvic lymphadenectomy. LLDNs and pelvic lymphadenectomy specimens underwent separate histological analysis. Of the 12 patients with early-stage endometrial cancer, 10 underwent preoperative lymphoscintigraphy, which consistently identified inguinal, femoral, and pelvic LLDNs (detection rate: 100%). The intraoperative detection rate was 83% (10/12). Median number of hot nodes per patient was 5 nodes (range: 3-7) on the right and 3 nodes (range: 2-6) on the left. Of 107 LLDNs, 106 were in the external iliac area, including 38 in the lateral group and 45 in the intermediate and medial groups. None of the patients had node metastases at any site. No early complications related to the technique occurred. Our mapping technique appears feasible, safe, and associated with a high LLDN identification rate. LLDN mapping may allow the preservation of LLDNs, thereby decreasing the risk of lower-limb lymphedema and improving quality of life.


Array comparative genomic hybridisation testing in CHD.
CHD is the leading cause of mortality due to birth defects. Array comparative genomic hybridisation (aCGH) detects submicroscopic copy number changes and may improve identification of the genetic basis of CHD. This is a retrospective analysis of 1252 patients from a regional referral centre who had undergone aCGH. Of the patients, 173 had CHD. A whole-genome custom-designed oligonucleotide array with >44,000 probes was used to detect copy number changes. Of the 1252 patients, 335 (26.76%) had abnormal aCGH results. Of the 173 patients with CHD, 50 (28.9%) had abnormal aCGH results versus 284 (26.3%) of 1079 non-cardiac patients. There were six patients with CHD who had well-described syndromes such as Wolf-Hirschhorn, trisomy 13, DiGeorge, and Williams. Of the patients with CHD, those with left-sided heart disease had the highest proportion (14/31; 45.13%) of abnormal aCGH results, followed by those with conotruncal heart disease (10/29; 34.48%), endocardial cushion defects (13/50; 26%), complex/other heart disease (12/52; 23.08%), and patent ductus arteriosus (1/11; 9.09%). Patients with CHD are at a substantial risk of having microdeletions and microduplications. The incidence of abnormalities on aCGH analysis is higher than identified with karyotype, and identification of copy number changes may help identify the genetic basis of the specific heart defects. However, aCGH may not have a significant diagnostic yield in those with isolated CHD. Further research using larger data sets may help identify candidate genes associated with CHD.


The MAOA T941G polymorphism and short-term treatment response to mirtazapine and paroxetine in major depression.
This study investigated the possible association of the MAOA T941G gene variant with differential antidepressant response to mirtazapine and/or paroxetine in 102 patients with major depression (DSM-IV criteria) participating in a randomized double-blind controlled clinical trial. Female mirtazapine-treated patients homozygous for the T-allele had a significantly faster and better treatment response than TG/GG-patients. In males, we failed to show an association between MAOA T941G gene variant and mirtazapine response. In the paroxetine-treated group, there were no significant differences in treatment response between MAOA T941G genotype groups. Time course of response and antidepressant efficacy of mirtazapine, but not paroxetine, seem to be influenced in a clinically relevant manner by this allelic variation within the MAOA gene, at least in female patients. An independent replication of our finding is needed. If replicated, genotyping of this locus could become a promising tool to predict response to mirtazapine treatment in females suffering from major depression.


Occult thyrotoxicosis in patients with chronic and paroxysmal isolated atrial fibrillation.
Thyroid function tests, including thyrotropin releasing hormone administration (TRH), were performed in 40 consecutive patients with isolated atrial fibrillation (IAF) (i.e., without any other evidence of cardiac disease). The arrhythmia was chronic in 5 and paroxysmal in 35 patients. Thyrotoxicosis could not be diagnosed either clinically or by abnormal serum levels of T4, T3, T3 BC, and thyroid stimulating hormone (TSH). Thyroid stimulating hormone response to TRH, which was normal in 35 patients, was absent in 5 (12.5%) who were considered to have occult thyrotoxicosis. One had chronic and the other 4 had paroxysmal IAF. The arrhythmia did not recur after antithyroid treatment in these four patients who were in sinus rhythm after a mean follow-up period of 21 months. Full exploration of the thyroid function therefore seems useful not only in patients with chronic IAF, but also in those affected by the paroxysmal form.


Aspergillus calidoustus case series and review of the literature.
Aspergillus calidoustus, previously classified as Aspergillus ustus, is an emerging pathogen in immunocompromised persons. We describe four recent cases of A. calidoustus and review 37 additional cases of A. calidoustus (n = 8) or A. ustus (n = 29) published through June 2016. Twenty (49%) cases occurred in patients with hematologic malignancy and/or receipt of hematopoietic cell transplantation, and 13 (32%) occurred in solid organ transplant recipients. Antifungal susceptibility was reported in 49% of cases and in 42% treatment failed. Overall mortality was 66% and, where reported, attributable mortality was 30%. A. calidoustus infection is associated with a high mortality rate and frequently displays in vitro antifungal resistance.


Decrease in alkaline secretion during duodenal ulceration induced by mepirizole in rats.
The mechanisms by which the potent antiinflammatory agent, mepirizole, causes duodenal ulceration were investigated in the rat. After subcutaneous administration of 200 mg/kg of mepirizole, basal gastric acid secretion remained unchanged for 5 h but duodenal alkaline output, reliably measured, decreased significantly (p less than 0.05) within 2 h. The decrease was maximal (-45%) at 3 h and persisted for a total of 6 h. The duodenal alkaline secretion returned to near normal by 24 h. A dose-response study showed that the threshold ulcerogenic dose of mepirizole (30 mg/kg) did not significantly reduce alkaline secretion, whereas higher doses did. Plasma levels of immunoreactivity of gastrin, pancreatic polypeptide, vasoactive intestinal polypeptide, and secretin were not changed at either 6 or 24 h after oral mepirizole. Vasoactive intestinal peptide levels in the duodenal mucosa were increased by 158% at 24 h after administration. Secretin levels in the duodenal mucosa were decreased by greater than 60% at both 6 and 24 h after drug treatment. Intravenous secretin (1 CU/kg X h) had no effect on duodenal alkaline secretion in either saline- (154 mM NaCl) or mepirizole-treated animals. Exogenous 16,16-dimethyl prostaglandin E2 (10 micrograms/kg X h, i.v.) reversed the action of mepirizole on duodenal alkaline secretion. These findings suggest that mepirizole causes a reduction in duodenal alkaline secretion that can be reversed by administration of an exogenous prostaglandin.


Experimental aspergillus endocarditis in rabbits.
Aspergillus endocarditis in man usually occurs on prosthetic cardiac valves and gives rise to large vegetations which embolize easily producing peripheral organ infarction and infection. Blood cultures are usually sterile and the disease is difficult to cure with antimicrobial agents. Aspergillus endocarditis was studied in rabbits to determine the course, degree of fungemia, and response to treatment with amphotericin B (A), 5 flucytosine (5 FC) or A + 5 FC. Polyethylene tubing was introduced into the left ventricle through the carotid artery and 24 hours later animals were inoculated with 10(4) to 10(7) spores of a strain of Aspergillus fumigatus. Large occlusive vegetations developed on the aortic valves. Spontaneous mortality reached 67 per cent after 3 days. Despite large aggregates of mycelia seen beneath a layer of amorphous material on microscopic sections, vegetations contained only 10(3) to 10(5) colony forming units (CFU) of aspergilli per gram, suggesting the aspergilli in tissues were clumped. Disseminated infection involving kidney, lung, liver, spleen, and brain occurred. Animals without intracardiac tubing which received the same inoculum of spores did not develop endocarditis, but showed evidence of disseminated infection. Blood after 24 hours of infection grew aspergilli only when large volumes were cultured and then only a small fraction of the total volume of blood obtained for culture yielded aspergilli, suggesting that the aspergilli in blood were clumped. Sterile vegetations in the absence of an intracardiac catheter were resistant to infection with aspergilli, but once established, infection with aspergilli persisted on vegetations despite removal of the catheter. Treatment of infected animals with A (1 mg. per kilogram), 5 FC (25 or 50 mg. per kilogram) or A + 5 FC daily intraperitoneally, significantly lowered the number of CFU per gram of vegetation.


Multiple nevoid spiradenomas.
This report delineates a new clinical presentation of multiple benign spiradenoma (BS), a diffuse linear nevoid pattern. A 16-year-old girl, in otherwise good health, had many papulonodular lesions, varying in color from blue-gray to bright red, disposed linearly on the right half of her body, involving the periorbital region, cheek, lateral side of the neck, trunk, linea alba, right thigh, and leg. Only a few nodules were slightly painful. Lesions were reported to be present at birth; no family members had similar lesions, either in solitary or multiple form. Excisional biopsies of three lesions from the neck, abdomen, and leg, respectively, were performed; histologically, all three samples showed a picture of BS. In some areas, the tumor was directly connected to a pilosebaceous unit. Furthermore, a focal area with pilar differentiation at the periphery of the lobules was observed, which might suggest that BS can differentiate toward various cutaneous adnexal structures. Our patient probably is the first one reported with diffuse linear nevoid lesions of BS, present at birth and involving the right half of the body.


Prevalence of depression in Uganda: A systematic review and meta-analysis.
Depression is one of the most studied mental health disorders, with varying prevalence rates reported across study populations in Uganda. A systematic review and meta-analysis was carried out to determine the pooled prevalence of depression and the prevalence of depression across different study populations in the country. Papers for the review were retrieved from PubMed, Scopus, PsycINFO, African Journal OnLine, and Google Scholar databases. All included papers were observational studies regarding depression prevalence in Uganda, published before September 2021. The Joanna Briggs Institute Checklist for Prevalence Studies was used to evaluate the risk of bias and quality of the included papers, and depression pooled prevalence was determined using a random-effects meta-analysis. A total of 127 studies comprising 123,859 individuals were identified. Most studies were conducted among individuals living with HIV (n = 43; 33.9%), and the most frequently used instrument for assessing depression was the Depression sub-section of the Hopkins Symptom Checklist (n = 34). The pooled prevalence of depression was 30.2% (95% confidence interval [CI]: 26.7-34.1, I2 = 99.80, p<0.001). The prevalence of depression was higher during the COVID-19 pandemic than during the pre-pandemic period (48.1% vs. 29.3%, p = 0.021). Refugees had the highest prevalence of depression (67.6%; eight studies), followed by war victims (36.0%; 12 studies), individuals living with HIV (28.2%; 43 studies), postpartum or pregnant mothers (26.9%; seven studies), university students (26.9%; four studies), children and adolescents (23.6%; 10 studies), and caregivers of patients (18.5%; six studies). Significantly high levels of heterogeneity among the studies included. Almost one in three individuals in Uganda has depression, with the refugee population being disproportionately affected. Targeted models for depression screening and management across various populations across the country are recommended. Protocol registered with PROSPERO (CRD42022310122).


The impact of non-HLA factors on renal graft survival.
Several non-HLA factors such as, age, sex, blood group, and cytomegalovirus (CMV) carrier state of both the donor and the recipient are known to influence renal allograft survival. In a retrospective study on 150 living related donor renal transplant patients, we evaluated the effect of the above mentioned factors on graft survival. Patients were divided into two groups, according to immunosuppression protocols. Group 1 (n=120) patients were on triple therapy with cyclosporin-A, azathioprine and prednisolone whereas those in Group 2 (n=30) were on conventional therapy with azathioprine and prednisolone. In Group 1, the patients aged 45 years (P < 0.06). Sex of neither the donors nor the recipients affected graft survival. Patients with blood group B had poor graft survival among Group 2 patients (P < 0.05). However, the patients with blood group B in Group 1 had significantly superior graft survival rates than the patients with the same blood group in Group 2 (P < 0.01). No significant difference in the graft survival rates was found between the two groups in relation to other blood groups. Also, there was no significant difference in the graft survival of the CMV negative and the CMV positive (IgG) recipients in both the study groups.


Controlling the time evolution of mAb N-linked glycosylation, Part I: Microbioreactor experiments.
N-linked glycosylation is of key importance for the efficacy of many biotherapeutic proteins such as monoclonal antibodies (mAbs). Media components and cell culture conditions have been shown to significantly affect N-linked glycosylation during the production of glycoproteins using mammalian cell fed-batch cultures. These parameters inevitably change in modern industrial processes with concentrated feed additions and cell densities beyond 2 × 107 cells/mL. In order to control the time-dependent changes of protein glycosylation, an automated microbioreactor system was used to investigate the effects of culture pH, ammonia, galactose, and manganese chloride supplementation on nucleotide sugars as well as mAb N-linked glycosylation in a time-dependent way. Two different strategies comprising of a single shift of culture conditions as well as multiple media supplementations along the culture duration were applied to obtain changing and constant glycosylation profiles. The different feeding approaches enabled constant glycosylation patterns throughout the entire culture duration at different levels. By modulating the time evolution of the mAb glycan pattern, not only the endpoint but also the ratios between different glycosylation structures could be modified. © 2016 American Institute of Chemical Engineers Biotechnol. Prog., 32:1123-1134, 2016.


Decreased mineral content in MMP-20 null mouse enamel is prominent during the maturation stage.
During enamel development, matrix metalloproteinase-20 (MMP-20, enamelysin) is expressed early during the secretory stage as the enamel thickens, and kallikrein-4 (KLK-4, EMSP1) is expressed later during the maturation stage as the enamel hardens. Thus, we investigated whether the physical properties of the secretory-/maturation-stage MMP-20 null enamel were significantly different from those of controls. We demonstrated that although, in relative terms, the weight percent of mature mineral in the MMP-20 null mouse enamel was only 7-16% less than that in controls, overall the enamel mineral was reduced by about 50%, and its hardness was decreased by 37%. Percent mineral content by weight was assessed at 3 different developmental stages. Remarkably, the biggest difference in mineral content between MMP-20 null and controls occurred in the nearly mature enamel, when MMP-20 is normally no longer expressed. This suggests that MMP-20 acts either directly or indirectly to facilitate the removal of maturation-stage enamel proteins.


Pathomechanism of myelopathy and surgical results of laminoplasty in elderly patients with cervical spondylosis.
Clinical and radiologic analyses in elderly patients with cervical myelopathy. To investigate the pathomechanism of cervical myelopathy and the surgical results of laminoplasty in elderly patients older than 70 years old. To date, there have been no reports on the pathomechanism of cervical myelopathy in elderly patients. Further, the surgical results and postoperative complications of laminoplasty have not been fully evaluated in elderly patients. Eighty-nine patients who underwent cervical laminoplasty were reviewed. The patients were divided into 2 groups according to the age at the time of operation (the elderly patient group: 20 patients who were older than 70 years old, and the control group: 69 patients who were younger than 69 years old). Pre- and postoperative neurologic status (the Japanese Orthopedic Association score) and postoperative complications were compared between the two groups. Radiologic features were also examined. There was no statistical difference in the recovery rate of Japanese Orthopedic Association score between the elderly patient group and the control group. Activities of daily living improved in the elderly patients. Several complications, such as delirium and worsening hypertension, were found in the elderly patient group. In the preoperative radiographs, the incidence of either retrolisthesis or anterolisthesis in the elderly patient group was significantly higher than that in the control group. Retrolisthesis and anterolisthesis are often the cause of myelopathy in elderly patients. Surgical decompression for cervical myelopathy was beneficial even in elderly patients older than 70 years old. Laminoplasty achieves stability of the cervical spine, and this procedure is reasonable for the treatment.


Molecular epidemiology of paramyxoviruses in frugivorous Eidolon helvum bats in Zambia.
In this study, we describe the detection of novel paramyxoviruses from the Eidolon helvum species of fruit bats. We extracted RNA from 312 spleen samples from bats captured in Zambia over a period of 4 years (2008-2011). Semi-nested RT-PCR detected a total of 25 (8%) positive samples for paramyxoviruses which were then directly sequenced and analyzed using phylogenetic analysis. Among the positive samples, seven novel paramyxoviruses were detected. Five viruses were closely related to the genus Henipavirus, while two viruses were related to the unclassified Bat paramyxoviruses from Ghana and Congo Brazzaville. Our study identified novel Henipavirus-related and unrelated viruses using RT-PCR in fruit bats from Kansaka National Park and indicated the presence of similar Bat paramyxoviruses originating from wide geographic areas, suggesting the ability of bats to harbor and transmit viruses. The presence of these viruses in fruit bats might pose a public health risk.


Peer navigation in African American breast cancer survivors.
The purpose of this study was to explore the feasibility and acceptability of a peer navigation survivorship program for African American (AA) breast cancer survivors (BCS) and its potential effects on selected short-term outcomes according to the Quality of Life Model Applied to Cancer Survivors. An AA BCS who completed treatment over 1 year prior to the study was trained as a peer navigator (PN), and then paired with AA women completing primary breast cancer treatment (n=4) for 2 months. This mixed-methods, proof of concept study utilized a convergent parallel approach to explore feasibility and investigate whether changes in scores are favorable using interviews and self-administered questionnaires. Results indicate that the PN intervention was acceptable by both PN and BCS, and was feasible in outcomes of recruitment, cost, and time requirements. Improvements in symptom distress, perceived support from God, and preparedness for recovery outcomes were observed over time. Qualitative analysis revealed six themes emerging from BCS interviews: "learning to ask the right questions", "start living life again", "shifting my perspective", "wanting to give back", "home visits are powerful", and "we both have a journey": support from someone who has been there. Results support current literature indicating that AA women who have survived breast cancer can be an important source of support, knowledge, and motivation for those completing breast cancer treatment. Areas for future research include standardization of training and larger randomized trials of PN intervention. The transition from breast cancer patient to survivor is a period when there can be a loss of safety net concurrent with persistent support needs. AA cancer survivors can benefit from culturally tailored support and services after treatment for breast cancer. With further testing, this PN intervention may aid in decreasing general symptom distress and increase readiness for recovery post-treatment.


Screening for bipolar disorder and finding borderline personality disorder.
Bipolar disorder and borderline personality disorder share some clinical features and have similar correlates. It is, therefore, not surprising that differential diagnosis is sometimes difficult. The Mood Disorder Questionnaire (MDQ) is the most widely used screening scale for bipolar disorder. Prior studies found a high false-positive rate on the MDQ in a heterogeneous sample of psychiatric patients and primary care patients with a history of trauma. In the present report from the Rhode Island Methods to Improve Diagnostic Assessment and Services project, we examined whether psychiatric outpatients without bipolar disorder who screened positive on the MDQ would be significantly more often diagnosed with borderline personality disorder than patients who did not screen positive. The study was conducted from September 2005 to November 2008. Five hundred thirty-four psychiatric outpatients were interviewed with the Structured Clinical Interview for DSM-IV and Structured Interview for DSM-IV Personality Disorders and asked to complete the MDQ. Missing data on the MDQ reduced the sample size to 480. Approximately 10% of the study sample were diagnosed with a lifetime history of bipolar disorder (n = 52) and excluded from the initial analyses. Borderline personality disorder was 4 times more frequently diagnosed in the MDQ positive group than the MDQ negative group (21.5% vs 4.1%, P < .001). The results were essentially the same when the analysis was restricted to patients with a current diagnosis of major depressive disorder (27.6% vs 6.9%, P = .001). Of the 98 patients who screened positive on the MDQ in the entire sample of patients, including those diagnosed with bipolar disorder, 23.5% (n = 23) were diagnosed with bipolar disorder, and 27.6% (n = 27) were diagnosed with borderline personality disorder. Positive results on the MDQ were as likely to indicate that a patient has borderline personality disorder as bipolar disorder. The clinical utility of the MDQ in routine clinical practice is uncertain.


Layer-by-Layer Assembled Architecture of Polyelectrolyte Multilayers and Graphene Sheets on Hollow Carbon Spheres/Sulfur Composite for High-Performance Lithium-Sulfur Batteries.
In the present work, polyelectrolyte multilayers (PEMs) and graphene sheets are applied to sequentially coat on the surface of hollow carbon spheres/sulfur composite by a flexible layer-by-layer (LBL) self-assembly strategy. Owing to the strong electrostatic interactions between the opposite charged materials, the coating agents are very stable and the coating procedure is highly efficient. The LBL film shows prominent impact on the stability of the cathode by acting as not only a basic physical barrier, and more importantly, an ion-permselective film to block the polysulfides anions by Coulombic repulsion. Furthermore, the graphene sheets can help to stabilize the polyelectrolytes film and greatly reduce the inner resistance of the electrode by changing the transport of the electrons from a "point-to-point" mode to a more effective "plane-to-point'' mode. On the basis of the synergistic effect of the PEMs and graphene sheets, the fabricated composite electrode exhibits very stable cycling stability for over 200 cycles at 1 A g(-1), along with a high average Coulombic efficiency of 99%. With the advantages of rapid and controllable fabrication of the LBL coating film, the multifunctional architecture developed in this study should inspire the design of other lithium-sulfur cathodes with unique physical and chemical properties.


Isosexual development of women with late-treated congential adrenal hyperplasia.
Twelve women with congenital adrenal hyperplasia are reported. Initial diagnoses were made at ages ranging from 12 to 32, with epiphyseal fusion complete in all patients. During 6 to 10 years of corticosteroid therapy there occurred substantial reduction of hypertrichosis, disappearance of temporal recession, and decrease in eroticism. In 11 patients menstrual bleeding occurred within 4 months. Urinary excretion of total gonadotropins remained unchanged; total estrogens decreased slightly. By the end of followup, 7 patients with a mean age of 17 years had regular menses, 6 were ovulating, and 1 had a pregnancy. The other 5 patients, who continued to have irregular, anovulatory menstrual cycles, had a mean age of 28 years. The findings suggest that when excessive androgenization continues for a considerable period of time after puberty (as judged by bone age) noncyclic functioning of the gonadotropic mechanism is rendered irreversible.


TMAO Promotes NLRP3 Inflammasome Activation of Microglia Aggravating Neurological Injury in Ischemic Stroke Through FTO/IGF2BP2.
Stroke is a kind of cerebrovascular disease with high mortality. TMAO has been shown to aggravate stroke outcomes, but its mechanism remains unclear. Mice were fed with 0.12% TMAO for 16 weeks. Then, mice were made into MCAO/R models. Neurological score, infarct volume, neuronal damage and markers associated with inflammation were assessed. Since microglia played a crucial role in ischemic stroke, microglia of MCAO/R mice were isolated for high-throughput sequencing to identify the most differentially expressed gene following TMAO treatment. Afterward, the downstream pathways of TMAO were investigated using primary microglia. TMAO promoted the release of inflammatory cytokines in the brain of MCAO/R mice and promoted the activation of OGD/R microglial inflammasome, thereby exacerbating ischemic stroke outcomes. FTO/IGF2BP2 inhibited NLRP3 inflammasome activation in OGD/R microglia by downregulating the m6A level of NLRP3. TMAO can inhibit the expression of FTO and IGF2BP2, thus promoting the activation of NLRP3 inflammasome in OGD/R microglia. In conclusion, these results demonstrated that TMAO promotes NLRP3 inflammasome activation of microglia aggravating neurological injury in ischemic stroke through FTO/IGF2BP2. Our results demonstrated that TMAO promotes NLRP3 inflammasome activation of microglia aggravating neurological injury in ischemic stroke through FTO/IGF2BP2. These findings explained the molecular mechanism of TMAO aggravating ischemic stroke in detail and provided molecular mechanism for clinical treatment.


EVOLVE (nebivolol evaluation for efficacy and safety in the treatment of hypertension) postmarketing surveillance study.
The objective of EVOLVE [nebivolol (nevol) evaluation for efficacy and safety in the treatment of hypertension], a postmarketing surveillance (PMS) study is to identify, validate and quantify the safety and efficacy associated with the use of nebivolol. EVOLVE study was an open-label, non-comparative, prospective, one month follow-up study of 301 patients of either sex with stage 1 hypertension, as defined by the JNC VII guidelines. The data was collected from 27 centres from all over India during the period August, 2006 to December, 2006. Nebivolol (2.5-5 mg/day) was given for 1 month. Clinical assessment was done at the start of the treatment and at 15th day and 30th day follow-ups. Concomitant medications administered were also recorded. Baseline mean systolic blood pressure (SBP) was 157.73 +/- 14.16 mm Hg which dropped to 135.13 +/- 11.15 mm Hg at the end of the study. At the end of 1 month treatment the change in mean SBP was 22.6 mm Hg ie, 14.32% reduction from baseline which was statistically significant (p < 0.001). Also the baseline mean diastolic blood pressure (DBP) was 97.21 +/- 8.25 mm Hg that dropped to 83.69 +/- 6.63 mm Hg at the end of the study. At the end of one month treatment the change in mean DBP was 13.52 mmHg ie, 13.9% reduction from baseline which was significant (p < 0.001). The heart rate in this study showed a significant decrease from 86.13 +/- 9.35 at basal to 75.09 +/- 7.42 at the end of the study (p < 0.001). It was observed that at the end of one month of treatment, majority of the patients ie, 97.75% of total cases showed good to excellent response to nebivolol. EVOLVE PMS study showed that nebivolol hydrochloride is very safe and only 8.2% of cases (n = 22) reported adverse effects, the commonest being dizziness (3.28%). Less than 1% patients reported nausea, constipation, headache, weakness, tiredness and pedal oedema; 99.25% of patients reported good to excellent tolerability; 82.33% patients achieved the goals recommended by JNC VII. EVOLVE PMS study confirms the safety and efficacy of nebivolol hydrochloride in Indian population.


The use of turbulent flow chromatography for rapid, on-line analysis of tryptic digests.
Following digestion of proteins with trypsin, digests are typically subjected to further 'clean-up' prior to liquid chromatography/mass spectometry (LC/MS) analysis, in order to reduce the complexity of the digested matrix, as well as helping to remove residual denaturants and reduction/alkylation reagents prior to injection onto the analytical HPLC column. Often, this is carried out using off-line techniques, and is not ideally suited to high-throughput workloads, for example in clinical laboratories. Bovine serum albumin (BSA) was used as a model protein. Following denaturation with urea, reduction/alkylation, and digestion with trypsin, the analytical recovery of a selection of proteotypic BSA peptides was assessed using a two-dimensional, turbulent flow chromatography method. Peptides were identified using a Q Exactive™ mass spectometer operating in full-scan mode. Total analysis time (including the on-line sample clean-up) was 15 min per injection. Aside from the most hydrophilic peptide selected, ATEEQLK, recovery using the turbulent flow chromatography systems was greater than 30% for all remaining peptides (N = 17), and exceeded 50% for 12 of the 18 peptides studied. There was a broad correlation between the hydrophobicity factor and the observed recovery. This study suggests that turbulent flow chromatography offers a rapid, on-line alternative to solid-phase extraction for the analysis of peptide digests by LC/MS. A wide range of column chemistries are available, and the technique can be further optimised for analyses which are targetted to specific peptides. As with turbulent flow chromatography for small-molecule workflows, this approach may be ideally suited to high-throughput applications, such as those which are emerging from within clinical laboratories.


Is Boyd's operation a last solution that may prevent major amputations in diabetic foot patients?
We had several difficulties in dealing with diabetic foot lesions and infections at the level of midfoot and hindfoot. At this level of the foot, bone and joint involvement is quite common. We had to perform major amputations in most of these patients. As our search to overcome this problem continued, we concluded that the relationship between infection, necrosis, and hypo-avascular tissue is very strong in this part of the foot. At the end, we have seen that Boyd's operation can break this vicious cycle. Boyd's operation consists of talectomy, excision of articular surfaces of tibia and calcaneus, and tibiocalcaneal arthrodesis. It can be performed as single or 2-staged operation depending on clinical judgment. After the first stage of operation, the defect is left open for a period. With local wound care, the defect is prepared for definitive closure and closed secondarily. We have performed Boyd's operation in 16 patients with diabetic foot lesions and infections reaching midfoot and hindfoot regions. In 15 patients, complete healing was achieved and these patients were able to walk themselves. Mean follow-up period was 3.2 years. Most of the time the heel region and calcaneus are not on the pathways of severe foot infections. Therefore, the most important criterion that is necessary to perform Boyd's operation usually do exist. After the Boyd's operation, an optimal condition for wound healing is achieved by removing all bradytrophic (hypovascular) tissues in the foot. Boyd's operation is superior to other partial midfoot and hindfoot amputations in terms of anatomy and function.


Investigation into the nature of substrate binding to the dipyrromethane cofactor of Escherichia coli porphobilinogen deaminase.
The formation of the dipyrromethane cofactor of Escherichia coli porphobilinogen deaminase was shown to depend on the presence of 5-aminolevulinic acid. A hemA- mutant formed inactive deaminase when grown in the absence of 5-aminolevulinic acid since this strain was unable to biosynthesize the dipyrromethane cofactor. The mutant formed normal levels of deaminase, however, when grown in the presence of 5-aminolevulinic acid. Porphobilinogen, the substrate, interacts with the free alpha-position of the dipyrromethane cofactor to give stable enzyme-intermediate complexes. Experiments with regiospecifically labeled intermediate complexes have shown that, in the absence of further substrate molecules, the complexes are interconvertible by the exchange of the terminal pyrrole ring of each complex. The formation of enzyme-intermediate complexes is accompanied by the exposure of a cysteine residue, suggesting that substantial conformational changes occur on binding substrate. Specific labeling of the dipyrromethane cofactor by growth of the E. coli in the presence of 5-amino[5-14C]levulinic acid has confirmed that the cofactor is not subject to catalytic turnover. Experiments with the alpha-substituted substrate analogue alpha-bromoporphobilinogen have provided further evidence that the cofactor is responsible for the covalent binding of the substrate at the catalytic site. On the basis of these cumulative findings, it has been possible to construct a mechanistic scheme for the deaminase reaction involving a single catalytic site which is able to catalyze the addition or removal of either NH3 or H2O. The role of the cofactor both as a primer and as a means for regulating the number of substrates bound in each catalytic cycle is discussed.


Alterations in neurofilaments and the transformation of the cytoskeleton in axons may provide insight into the aberrant neuronal changes of Alzheimer's disease.
Neurofilaments are major protein constituents of the brain, but are particularly abundant in specific subpopulations of neurons and likely have a key role in the regulation of axonal calibre. Neurofilament proteins may also be involved in the transformation of the neuronal cytoskeleton leading to substantial tau pathology in axons damaged by Aβ, subsequently leading to neurofibrillary pathology in their cell bodies of origin. An understanding of neurofilamentous changes in axons and subsequent tau pathology may provide insight into how Aβ pathology may stimulate an aberrant plasticity-related response of damaged neurons, leading to the progressive and degenerative changes in the neuronal cytoskeleton that result in synapse loss and neuronal degeneration.


Small-Molecule Probes for Affinity-Guided Introduction of Biocompatible Handles on Metal-Binding Proteins.
Protein conjugates of high heterogeneity may contain species with significantly different biological properties, and as a consequence, the focus on methods for production of conjugates of higher quality has increased. Here, we demonstrate an efficient and generic approach for the modification of metal-binding proteins with biocompatible chemical handles without the need for genetic modifications. Affinity-guided small-molecule probes are developed for direct conjugation to off-the-shelf proteins and for installing different chemical handles on the protein surface. While purification of protein conjugates obtained by small molecule conjugation is troublesome, the affinity motifs of the probes presented here allow for purification of the conjugates. The versatility of the probes is demonstrated by conjugation to several His-tagged and natural metal-binding proteins, including the efficient and area-selective conjugation to three therapeutically relevant antibodies.


Comparative analysis of mitochondrial genomes in Diplura (hexapoda, arthropoda): taxon sampling is crucial for phylogenetic inferences.
Two-pronged bristletails (Diplura) are traditionally classified into three major superfamilies: Campodeoidea, Projapygoidea, and Japygoidea. The interrelationships of these three superfamilies and the monophyly of Diplura have been much debated. Few previous studies included Projapygoidea in their phylogenetic considerations, and its position within Diplura still is a puzzle from both morphological and molecular points of view. Until now, no mitochondrial genome has been sequenced for any projapygoid species. To fill in this gap, we determined and annotated the complete mitochondrial genome of Octostigma sinensis (Octostigmatidae, Projapygoidea), and of three more dipluran species, one each from the Campodeidae, Parajapygidae, and Japygidae. All four newly sequenced dipluran mtDNAs encode the same set of genes in the same gene order as shared by most crustaceans and hexapods. Secondary structure truncations have occurred in trnR, trnC, trnS1, and trnS2, and the reduction of transfer RNA D-arms was found to be taxonomically correlated, with Campodeoidea having experienced the most reduction. Partitioned phylogenetic analyses, based on both amino acids and nucleotides of the protein-coding genes plus the ribosomal RNA genes, retrieve significant support for a monophyletic Diplura within Pancrustacea, with Projapygoidea more closely related to Campodeoidea than to Japygoidea. Another key finding is that monophyly of Diplura cannot be recovered unless Projapygoidea is included in the phylogenetic analyses; this explains the dipluran polyphyly found by past mitogenomic studies. Including Projapygoidea increased the sampling density within Diplura and probably helped by breaking up a long-branch-attraction artifact. This finding provides an example of how proper sampling is significant for phylogenetic inference.


Beta-ecdysterone induces osteogenic differentiation in mouse mesenchymal stem cells and relieves osteoporosis.
The effect on bone tissue of beta-ecdysterone, a type of ecdysteroid found in many plants, has not been previously investigated. In this study, we found that beta-ecdysterone treatment significantly induced alkaline phosphatase (ALP) activity in mesenchymal stem cells in a dose-dependent manner. Real-time polymerase chain reaction (PCR) showed that Runx2, osteocalcin, and type I collagen expression also increased. ICI182780, a specific estrogen receptor antagonist, inhibited the upregulation of ALP activity. Moreover, beta-ecdysterone promoted estrogen receptor (ER) reporter gene activity; however, ICI182780 reversed its effect, suggesting that beta-ecdysterone has stimulatory effects on osteogenic differentiation via the ER. Furthermore, beta-ecdysterone alleviated osteoporosis symptoms in a mouse model without obvious side effects. Therefore beta-ecdysterone may be a promising candidate drug for the treatment of osteoporosis.


The acute effects of bodyweight suspension exercise on muscle activation and muscular fatigue.
This investigation examined effects of two exercise modes (barbell, BB; bodyweight suspension, BWS) on muscle activation, resistance load, and fatigue. During session one, nine resistance-trained males completed an elbow flexion one-repetition maximum (1RM). During sessions two and three, subjects completed standing biceps curls to fatigue at 70% 1RM utilizing a randomized exercise mode. Surface electromyography (sEMG) recorded muscle activation of the biceps brachii, triceps brachii, anterior deltoid, posterior deltoid, rectus abdominis, and erector spinae. BWS resistance load was measured using a force transducer. Standing maximal voluntary isometric contractions of the elbow flexors recorded at 90° were used to determine the isometric force decrement and rate of fatigue (ROF) during exercise. sEMG and resistance load data were divided into 25% contraction duration bins throughout the concentric phase. BWS resulted in a 67.7 ± 7.4% decline in resistance load throughout the concentric phase (p ≤ 0.05). As a result, BB elicited higher mean resistance loads (31.4 ± 4.0 kg) and biceps brachii sEMG (84.7 ± 27.8% maximal voluntary isometric contractions, MVIC) compared with BWS (20.4 ± 3.4 kg, 63.4 ± 21.6% MVIC). No difference in rectus abdominis or erector spinae sEMG was detected between exercise modes. Isometric force decrement was greater during BWS (-21.7 ± 7.0 kg) compared with BB (-14.9 ± 4.7 kg); however, BB (-3.0 ± 0.8 kg/set) resulted in a steeper decline in ROF compared with BWS (-1.7 ± 0.6 kg/set). The variable resistance loading and greater isometric force decrement observed suggest that select BWS exercises may resemble variable resistance exercise more than previously considered.


Digital single-operator cholangioscopy to guide selective cannulation of complex biliary strictures.
Selective cannulation and stenting of complex, tight, and/or angulated biliary strictures under endoscopic retrograde cholangiopancreaticography (ERCP) can be challenging. Digital single-operator cholangioscopy (SOC) may facilitate guidewire advancement through the stricture with endoscopic visual guidance. We aimed to describe a case series on clinical outcomes of this technique for selective cannulation, when used after failed conventional ERCP attempts. Consecutive patients who underwent therapeutic digital SOC for selective cannulation of biliary strictures after failed conventional ERCP were retrospectively included. Ten patients with a malignant (n = 6) or benign (n = 4) biliary stricture were included. Digital SOC-assisted selective guidewire insertion and stent placement across the biliary stricture were technically successful in five (50%) patients. Bilirubin levels improved in all patients with technical success. One (10%) patient developed a post-ERCP pancreatitis. Technically successful cannulation of biliary strictures with digital SOC was achieved in half of patients in whom cannulation with conventional ERCP failed, sparing them more invasive interventions. Stricture opacification during the failed ERCP was seen in all technically successful SOCs.


Differential effects of morphine on the affective and the sensory component of carrageenan-induced nociception in the rat.
Pain is generally considered to have a sensory and an affective component. Clinical research has suggested that morphine more potently attenuates the affective component as compared to the sensory component. Because preclinical nociception models typically focus on the sensory component of nociception, and do not assess the affective component, it is unclear whether this potency difference of morphine can also be found in preclinical models. We therefore adapted the place conditioning paradigm to investigate negative affect accompanying carrageenan-induced (0.5% intraplantar) inflammatory nociception in rats. We found that carrageenan produced clear conditioned place aversion (CPA). Morphine (0.01-10mg/kg i.p.) dose-dependently reduced carrageenan-induced CPA with a minimal effective dose (MED) of 0.03mg/kg. Since morphine has a rewarding effect by itself, morphine-induced conditioned place preference (CPP) was also investigated. Morphine induced CPP with a MED of 1mg/kg, suggesting that the rewarding effect of morphine was not responsible for reducing carrageenan-induced CPA. We also demonstrated that morphine reduced carrageenan-induced mechanical nociception as assessed in the Randall Selitto paradigm with a MED of 1mg/kg. It is concluded that the CPA model allows for an assessment of the negative affective component of carrageenan-induced nociception. Moreover, morphine was able to reduce the affective component of nociception at doses that did not affect the sensory component of nociception, and this effect was not due to its rewarding properties. The fact that this finding mirrors the clinical situation validates the use of the CPA model for assessing the affective component of nociception.


How to do safe sternal reentry and the risk factors of redo cardiac surgery: a 21-year review with zero major cardiac injury.
Resternotomy is a common part of cardiac surgical practice. Associated with resternotomy are the risks of cardiac injury and catastrophic hemorrhage and the subsequent elevated morbidity and mortality in the operating room or during the postoperative period. The technique of direct vision resternotomy is safe and has fewer, if any, serious cardiac injuries. The technique, the reduced need for groin cannulation and the overall low operative mortality and morbidity are the focus of this restrospective analysis. The records of 495 patients undergoing 546 resternotomies over a 21-year period to January 2000 were reviewed. All consecutive reoperations by the one surgeon comprised patients over the age of 20 at first resternotomy: M:F 343:203, mean age 57 years (range 20 to 85, median age 60). The mean NYHA grade was 2.3 [with 67 patients (I), 273 (II), 159 (III), 43 (IV), and 4 (V classification)] with elective reoperation in 94.6%. Cardiac injury was graded into five groups and the incidence and reasons for groin cannulation estimated. The morbidity and mortality as a result of the reoperation and resternotomy were assessed. The hospital/30 day mortality was 2.9% (95% CI: 1.6%-4.4%) (16 deaths) over the 21 years. First (481), second (53), and third (12) resternotomies produced 307 uncomplicated technical reopenings, 203 slower but uncomplicated procedures, 9 minor superficial cardiac lacerations, and no moderate or severe cardiac injuries. Direct vision resternotomy is crystalized into the principle that only adhesions that are visualized from below are divided and only sternal bone that is freed of adhesions is sewn. Groin exposure was never performed prophylactically for resternotomy. Fourteen patients (2.6%) had such cannulation for aortic dissection/aneurysm (9 patients), excessive sternal adherence of cardiac structures (3 patients), presurgery cardiac arrest (1 patient), and high aortic cannulation desired and not possible (1 patient). The average postop blood loss was 594 mL (95% CI:558-631) in the first 12 hours. The need to return to the operating room for control of excessive bleeding was 2% (11 patients). Blood transfusion was given in 65% of the resternotomy procedures over the 21 years (mean 854 mL: 95% CI 765-945 mL) and 41% over the last 5 years. The technique of direct vision resternotomy has been associated with zero moderate or major cardiac injury/catastrophic hemorrhage at reoperation. Few patients have required groin cannulation. In the postoperative period, there was acceptable blood loss, transfusion rates, reduced morbidity, and moderate low mortality for this potentially high risk group.


[Lipoblastoma: the least well known of adipose tumors].
Lipoblastoma is the least known of adipose tumours. It comes from embryonic adipose tissue and though it is histologically benign, it is locally invasive, implying a high risk of relapse if it is incompletely removed. The pediatric surgeon should be familiar with this tumor since it usually appears in children under three. A retrospective study of the patients who were operated upon at our institution with a histologic diagnosis of lipoblastoma from 1966 to 2002 taking into account: age, tumor site, cytogenetic studies, first diagnosis, treatment and clinical course. The diagnosis of lipoblastoma was carried out in six patients (three boys and three girls). All were diagnosed before the first year of life and one was present at birth. In only one case the diagnosis was pre-operative. Two tumors were thoracic, two paravertebral with an intrarachidian component without spinal cord involvement (one of them was associated with myelomeningocele and diatomyelia), two in limbs and one perineal. A girl operated for the first time at four months, was latter operated in four opportunities for a relapse. In the last operation the excision was incomplete due to a subclavian involvement; in the last 15 years no new tumor growth was seen. After a follow-up period of 1 to 25 years in the other six patients no relapse was observed. Despite its low frequency, the diagnosis of lipoblastoma must be considered in children with masses in soft tissue, mainly if they are younger then one year. Because the lipoblastoma is locally invasive, this tumor must be treated before it affects viscera. The resection must be complete, avoiding the risk of relapse, although radical mutilating surgery is not recommended.


Modelling cost-effectiveness of tenofovir for prevention of mother to child transmission of hepatitis B virus (HBV) infection in South Africa.
International sustainable development goals for the elimination of viral hepatitis as a public health problem by 2030 highlight the need to optimize strategies for prevention, diagnosis and treatment of hepatitis B virus (HBV) infection. An important priority for Africa is to have affordable, accessible and sustainable prevention of mother to child transmission (PMTCT) programmes, delivering screening and treatment for antenatal women and implementing timely administration of HBV vaccine for their babies. We developed a decision-analytic model simulating 10,000 singleton pregnancies to assess the cost-effectiveness of three possible strategies for deployment of tenofovir in pregnancy, in combination with routine infant vaccination: S1: no screening nor antiviral therapy; S2: screening and antiviral prophylaxis for all women who test HBsAg-positive; S3: screening for HBsAg, followed by HBeAg testing and antiviral prophylaxis for women who are HBsAg-positive and HBeAg-positive. Our outcome was cost per infant HBV infection avoided and the analysis followed a healthcare perspective. Based on 10,000 pregnancies, S1 predicts 45 infants would be HBV-infected at six months of age, compared to 21 and 28 infants in S2 and S3, respectively. Relative to S1, S2 had an incremental cost of $3940 per infection avoided. S3 led to more infections and higher costs. Given the long-term health burden for individuals and economic burden for society associated with chronic HBV infection, screening pregnant women and providing tenofovir for all who test HBsAg+ may be a cost-effective strategy for South Africa and other low/middle income settings.


Manipulating mouse telomeres: models of tumorigenesis and aging.
Telomeres are capping structures at the ends of chromosomes, composed of a repetitive DNA sequence and associated proteins. Both a minimal length of telomeric repeats and telomere-associated binding proteins are necessary for proper telomere function. Functional telomeres are essential for maintaining the integrity and stability of eukaryotic genomes. The capping structure enables cells to distinguish chromosome ends from double strand breaks (DSBs) in the genome. Uncapped chromosome ends are at great risk for degradation, recombination, or chromosome fusion by cellular DNA repair systems. Dysfunctional telomeres have been proposed to contribute to tumorigenesis and some aging phenotypes. The analysis of mice deficient in telomerase activity and other telomere-associated proteins has allowed the roles of dysfunctional telomeres in tumorigenesis and aging to be directly tested. Here we will focus on the analysis of different mouse models disrupted for proteins that are important for telomere functions and discuss known and proposed consequences of telomere dysfunction in tumorigenesis and aging.


Noncontact profiling techniques for intraocular lens edge measurements.
Two techniques, focal spot projection and fringe projection, have been developed for profiling the edges of anterior-chamber style intraocular lenses (IOL). The techniques are based on measurement of the trajectory of reflected light when an incident beam is focused and stepped across the edge surface (spot projection) or when two focused beams combine to form an optical interference pattern on the edge (fringe projection). The optical configurations for performing the projection techniques are described along with the mathematical relationship between the reflected-beam trajectories and the edge profile. An automated system for the implementation of focal spot projection was developed. The system has the capability of positioning the IOL edge at the focal point of the incident beam, acquiring trajectory data via stepper motors and a TV camera, processing the data to generate a profile, and displaying the profile on the computer video monitor or in hard-copy form via a printer. On one lens tested, three profiles corresponding to different locations along the IOL edge could be generated without user intervention. However, the user has the option of manually positioning the IOL to permit greater versatility. The typical 300-microm wide IOL edges are profiled to a resolution of approximately 20 microm. To constrain optical and microprocessor hardware costs, compromises were made in operating speeds so that approximately 20 min is required per profile. With current trends in integrated circuit technology future generations of the system could be made faster and prove useful as a QC tool for the IOL industry. Furthermore, the present device can be used in determining appropriate IOL profile standards.


Genome resources and whole genome resequencing of Phytophthora rubi isolates from red raspberry.
Phytophthora rubi is a primary causal agent of Phytophthora root rot and wilting of raspberry (Rubus idaeus L.) worldwide. The disease is a major concern for raspberry growers in Canada and USA. To date, no information is available on genomic diversity of P. rubi population from raspberry in Canada. Using a PCR-free library prep with dual-indexing for an Illumina HiSEQX running a 2x150 bp configuration, we generated whole genome sequence data of P. rubi isolates (n = 25) recovered during 2018 to 2020 from nine fields, four locations and four cultivars of raspberry growing areas of British Columbia, Canada. The assembled genome of 24 isolates of P. rubi averaged 8,541 scaffolds, 309× coverage, and 65,960,000 bp. We exploited single nucleotide polymorphisms (SNPs) obtained from whole genome sequence data to analyze the genome structure and genetic diversity of the P. rubi isolates. Low heterozygosity among the 72% of pathogen isolates and standardized index of association revealed that those isolates were clonal. Principal component analysis, discriminant analysis of principal component, and phylogenetic tree revealed that P. rubi isolates clustered with the raspberry specific cultivars. This study provides novel resources and insight into genome structure, genetic diversity, and reproductive biology of P rubi isolated from red raspberry. The availability of the P. rubi genomes also provides valuable resources for future comparative genomic and evolutionary studies for oomycetes pathogens.


A Case of Cementless Impaction Bone Graft in a Revision Total Hip Arthroplasty Requiring Calcar Reconstruction.
In cases of bone deficiency or osteoporosis, and especially in revision cases, there were only two options for treatment until the impaction bone graft procedure was proposed. These were cemented or cementless femoral prosthesis. In the early 1990s, the use of impaction bone graft with a cemented mantle had gained popularity and had proven to be clinically effective. In Germany, a cementless impaction bone graft procedure using Corail® (DePuy Synthes) stems was devised, and functional scores were similar to conventional cemented Impaction bone grafts. Case presentation. A 48-year-old man presented with femur loosening of a reamed bipolar arthroplasty performed in 1990. The patient was treated with a cementless impaction bone graft using a Corail® (DePuy Synthes) stem in the femur in revision THA surgery, and the calcar was reconstructed by allograft. At five years, the calcar allograft united with the host bone, and the femoral component showed no subsidence. Calcar reconstruction with a strut allograft, aimed at preventing sinking of the stem was key in this operation. Surgical indication for femoral cementless impaction bone graft should be for loosened femoral prosthesis in a type II Paprosky classification, where only the cortical bone of the isthmus is partially affected, cortical thinning does not exist, and it is mechanically strong enough for the allograft tip impaction. The procedure was safely feasible through the direct anterior approach.


Antigens of scrub typhus rickettsiae: separation by polyacrylamide gel electrophoresis and identification by enzyme-linked immunosorbent assay.
Antigens of plaque-purified Rickettsia tsutsugamushi strains Gilliam, Karp, and Kato were separated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and were analyzed by an enzyme-linked immunosorbent assay. Six antigens were identified in each of the three prototype strains; in strain Gilliam, these antigens were located in the cell envelope fraction of the organisms. Reactivity of these isolated antigens with homologous or heterologous immune sera indicated that different macromolecules existed in all three strains, although they exhibited very similar mobilities during electrophoresis. Antigens of strain Gilliam reacted equally well with antibodies directed against Gilliam, Karp, or Kato rickettsiae. However, strains Karp and Kato each had two distinct antigens which did not react with heterologous antisera. R. tsutsugamushi antigens retained immunogenicity after electrophoresis, and antisera raised against them reacted with intact organisms and exhibited specificity in reactions with isolated antigens.


Could JC virus provoke metastasis in colon cancer?
To evaluate the prevalence of John Cunningham virus (JC virus) in a small cohort of patients with colon cancer and to assess its presence in hepatic metastasis. Nineteen consecutive patients with histologically diagnosed colon cancer were included in our study, together with ten subjects affected by histologically and serologically diagnosed hepatitis C virus infection. In the patients included in the colon cancer group, JC virus was searched for in the surgical specimen; in the control group, JC virus was searched for in the hepatic biopsy. The difference in the prevalence of JC virus in the hepatic biopsy between the two groups was assessed through the χ(2) test. Four out of 19 patients with colon cancer had a positive polymerase chain reaction (PCR) test for JC virus, and four had liver metastasis. Among the patients with liver metastasis, three out of four had a positive PCR test for JC virus in the surgical specimen and in the liver biopsy; the only patient with liver metastasis with a negative test for JC virus also presented a negative test for JC virus in the surgical specimen. In the control group of patients with hepatitis C infection, none of the ten patients presented JC virus infection in the hepatic biopsy. The difference between the two groups regarding JC virus infection was statistically significant (χ(2) = 9.55, P = 0.002). JC virus may play a broader role than previously thought, and may be mechanistically involved in the late stages of these tumors.


Antibacterial Mechanism of Multifunctional MXene Nanosheets: Domain Formation and Phase Transition in Lipid Bilayer.
MXenes, two-dimensional metal carbides or nitrides with multifunctional surfaces, are one of the most promising antibacterial nanoscale materials. However, their putative bactericidal mechanism is elusive. To study their bactericidal mechanism, we investigated the interaction between a MXene nanosheet and a model bacterial membrane by molecular dynamics simulations and found that an adsorbed MXene on a membrane surface induced a local phase transition in a domain where the fluidity of the phospholipid in this domain at room temperature was comparable with that of the gel phase. The domain also showed a denser and thinner phospholipid membrane structure than the peripheral phospholipids. By comparing it with our previous experiments of the bactericidal activity of MXenes, we proposed the leakage of intercellular molecules at the phase boundary defects as a possible bactericidal mechanism of MXenes that leads to cell lysis. This study provides a useful model for tailoring new bactericidal nanomaterials.


Regulation of DNA Replication through Natural Impediments in the Eukaryotic Genome.
All living organisms need to duplicate their genetic information while protecting it from unwanted mutations, which can lead to genetic disorders and cancer development. Inaccuracies during DNA replication are the major cause of genomic instability, as replication forks are prone to stalling and collapse, resulting in DNA damage. The presence of exogenous DNA damaging agents as well as endogenous difficult-to-replicate DNA regions containing DNA-protein complexes, repetitive DNA, secondary DNA structures, or transcribing RNA polymerases, increases the risk of genomic instability and thus threatens cell survival. Therefore, understanding the cellular mechanisms required to preserve the genetic information during S phase is of paramount importance. In this review, we will discuss our current understanding of how cells cope with these natural impediments in order to prevent DNA damage and genomic instability during DNA replication.


Laserpuncture Increases Serum Concentration of Insulin-Like Growth Factor-1 in Adolescent Rats.
Objective: Previous studies have demonstrated that laserpuncture has a positive effect on longitudinal bone growth within varying parameters. The current authors hypothesized that laserpuncture affects serum concentration of insulinlike growth factor 1 (IGF-1), a growth factor that influences growth plates, and ghrelin, a growth hormone (GH) secretagogue. The goal of this research was to investigate if laserpuncture could increase serum concentrations of IGF-1 and ghrelin in adolescent rats. Materials and Methods: This was an experimental study with a post-test only and a controlled group design. The study was performed in a laboratory on 40 male Wistar rats, age ±3 weeks and weighing >40 g. The rats were divided randomly into 2 groups, A and B, each receiving laserpuncture for 10 days and 15 days, respectively. There were 4 subgroups in each group: control (C); GV 20; ST 36; and GV 20 + ST 36. The rats were stimulated by laserpuncture with a KX Laser GX-2000B (Kangxing), a semiconductor-based low-level laser therapy (LLLT) device emitting a cold red laser (635-680 nm/5 mW) for 60 seconds (0.3 J/cm2) The length of each rat's lower limb was measured using a caliper; IGF-1 and ghrelin concentrations were assessed using enzyme-linked immunosorbent assays. Results: A marked increase in IGF-1 concentration was observed in the ST 36 and GV 20 + ST 36 subgroups after 15 days, compared to the C subgroup (P = 0.001 and P = 0.002, respectively). The GV 20 subgroup had a lower IGF-1 concentration than the C subgroup (P = 0.06) at both 10 and 15 days. Laserpuncture did not influence ghrelin concentrations significantly, compared to the C subgroups. Conclusions: Laserpuncture administered to both the ST 36 and GV 20 + ST 36 subgroups with a power density of 0.3 J/cm2 increased serum concentrations of IGF-1 in adolescent rats.


Computational modeling of distinct neocortical oscillations driven by cell-type selective optogenetic drive: separable resonant circuits controlled by low-threshold spiking and fast-spiking interneurons.
Selective optogenetic drive of fast-spiking (FS) interneurons (INs) leads to enhanced local field potential (LFP) power across the traditional "gamma" frequency band (20-80 Hz; Cardin et al., 2009). In contrast, drive to regular-spiking (RS) pyramidal cells enhances power at lower frequencies, with a peak at 8 Hz. The first result is consistent with previous computational studies emphasizing the role of FS and the time constant of GABA(A) synaptic inhibition in gamma rhythmicity. However, the same theoretical models do not typically predict low-frequency LFP enhancement with RS drive. To develop hypotheses as to how the same network can support these contrasting behaviors, we constructed a biophysically principled network model of primary somatosensory neocortex containing FS, RS, and low-threshold spiking (LTS) INs. Cells were modeled with detailed cell anatomy and physiology, multiple dendritic compartments, and included active somatic and dendritic ionic currents. Consistent with prior studies, the model demonstrated gamma resonance during FS drive, dependent on the time constant of GABA(A) inhibition induced by synchronous FS activity. Lower-frequency enhancement during RS drive was replicated only on inclusion of an inhibitory LTS population, whose activation was critically dependent on RS synchrony and evoked longer-lasting inhibition. Our results predict that differential recruitment of FS and LTS inhibitory populations is essential to the observed cortical dynamics and may provide a means for amplifying the natural expression of distinct oscillations in normal cortical processing.