Fascicular nerve repairs. A comparative study of epineurial and fascicular (perineurial) techniques.
At present, fascicular nerve repairs produce almost identical results to epineurial repairs. There are still theoretical advantages to the improved alignment potentially offered by fascicular nerve repair, and fascicular technique already offers an advantage in partial nerve injuries. As fascicular capabilities improve, fascicular nerve repair may still offer the best solution for nerve recovery.


A study on the correlation between the nurses' and patients' postoperative pain assessments.
In this research, the correlation of assessment of postoperative pain between nurses and their clients is investigated. The aim of the research was to investigate whether or not the nurses can evaluate the pain that clients have in the postoperative process in the same sense as clients do and to examine personal factors that affect this evaluation. The descriptive and comparative research was undertaken between January 2008 and April 2008 in the clinics of Çukurova University Balcalı Hospital. The study group consisted of 47 nurses and 94 patients aged 18-65 years evaluated in the 48 hours' postoperative period. After review of the literature regarding McGill-Melzack pain assessment, a questionnaire for patients and another for nurses were used. The data gathered from the surveys were analyzed by the SPSS program. For intermittent variables chi-square test, for denomination variables kappa, and for sequent variables congruity gamma factors were used. At the end of the research, the correlation between the patient scores and the nurse scores that were gathered from first, second, third, and fourth parts of the pain evaluation documents were observed: part 1, Γ = 290, p = .063; part 3/1-2, Γ = 380, p = .008, 3/1; part 3, Γ = 357, p = .007; part 3/2, Γ = 209, p = .031; part 4, Γ = 346, p < .001. The congruity points obtained from the statistical data contrast with the literature, showing that the nurses and the patients evaluated the postoperative pain in the same sense. Pain evaluation investigations are recommended to be done with the attendance of more nurses and patients, and their results should be shared with all nurses.


Remote Control Effect of Li(+), Na(+), K(+) Ions on the Super Energy Transfer Process in ZnMoO4:Eu(3+), Bi(3+) Phosphors.
Luminescent properties are affected by lattice environment of luminescence centers. The lattice environment of emission centers can be effectively changed due to the diversity of lattice environment in multiple site structure. But how precisely control the doped ions enter into different sites is still very difficult. Here we proposed an example to demonstrate how to control the doped ions into the target site for the first time. Alkali metal ions doped ZnMoO4:Bi(3+), Eu(3+) phosphors were prepared by the conventional high temperature solid state reaction method. The influence of alkali metal ions as charge compensators and remote control devices were respectively observed. Li(+) and K(+) ions occupy the Zn(2) sites, which impede Eu and Bi enter the adjacent Zn(2) sites. However, Na(+) ions lie in Zn(1) sites, which greatly promoted the Bi and Eu into the adjacent Zn(2) sites. The Bi(3+) and Eu(3+) ions which lie in the immediate vicinity Zn(2) sites set off intense exchange interaction due to their short relative distance. This mechanism provides a mode how to use remote control device to enhance the energy transfer efficiency which expected to be used to design efficient luminescent materials.


Utilization of modified silk cotton hull waste as an adsorbent for the removal of textile dye (reactive blue MR) from aqueous solution.
Carbon prepared from silk cotton hull was used to remove a textile dye (reactive blue MR) from aqueous solution by an adsorption technique under varying conditions of agitation time, dye concentration, adsorbent dose and pH. Adsorption depended on solution pH, dye concentration, carbon concentration and contact time. Equilibrium was attained with in 60 min. Adsorption followed both Langmuir and Freundlich isotherm models. The adsorption capacity was found to be 12.9 mg/g at an initial pH of 2+/-0.2 for the particle size of 125-250 microm at room temperature (30+/-2 degrees C).


Posttransplant cyclophosphamide vs tacrolimus-based GVHD prophylaxis: lower incidence of relapse and chronic GVHD.
The ability of posttransplant cyclophosphamide (PTCY) to facilitate haploidentical transplantation has spurred interest in whether PTCY can improve clinical outcomes in patients with HLA-matched unrelated donors undergoing peripheral blood stem cell transplantation (PBSCT). We investigated our institutional experience using PTCY-based graft-versus-host disease (GVHD) prophylaxis compared with conventional tacrolimus-based regimens. We compared overall survival, progression-free survival (PFS), relapse, nonrelapse mortality, and acute and chronic GVHD in 107 adult patients receiving a PTCY-based regimen vs 463 patients receiving tacrolimus-based regimens for GVHD prophylaxis. The 2 cohorts were well balanced for baseline characteristics except that more patients in the PTCY cohort having received 7-of-8-matched PBSCT. There was no difference in acute GVHD. All-grade chronic GVHD and moderate-to-severe chronic GVHD were substantially reduced in patients receiving PTCY compared with in those receiving tacrolimus-based regimens (2-year moderate-to-severe chronic GVHD: 12% vs 36%; P < .0001). Recipients of PTCY-based regimens also had a lower incidence of relapse compared with recipients of tacrolimus-based regimens (25% vs 34% at 2-years; P = .027), primarily in patients who received reduced intensity conditioning. This led to improved PFS in the PTCY cohort (64% vs 54% at 2 years; P = .02). In multivariable analysis, the hazard ratio was 0.59 (P = .015) for PFS and the subdistribution hazard ratio was 0.27 (P < .0001) for moderate-to-severe chronic GVHD and 0.59 (P = .015) for relapse. Our results suggest that PTCY prophylaxis is associated with lower rates of relapse and chronic GVHD in patients who receive HLA-matched unrelated donor PBSCT.


Association between the overexpression of Her3 and clinical pathology and prognosis of colorectal cancer: A meta-analysis.
This study aimed to investigate the association between the overexpression of human epidermal growth factor receptor-3 (Her3) and the clinicopathological parameters and survival of patients with colorectal cancer (CRC). Relevant studies on the overexpression of Her3 (measured by immunohistochemistry) and overall survival (OS) in patients with CRC were searched for in PubMed, EMBASE, and Cochrane Library. Published data were extracted and computed into odds ratios (ORs) for assessing the association of Her3 overexpression with tumor differentiation, tumor node metastasis (TNM) stage, position of colon cancer, sex, and age. Prognostic data were computed into hazard ratios (HRs) for OS. Eight studies including 1716 patients with CRC were included in this meta-analysis. The results revealed a significant association between Her3 overexpression and tumor differentiation [OR = 2.38; 95% confidence interval (95% CI): 1.76-3.22; P < .001], TNM tumor stage (OR = 0.71; 95% CI: 0.53-0.96; P = .03), and position of colon cancer (OR = 1.71; 95% CI: 1.28-2.27; P < .001). While patients with Her3 overexpression demonstrated a worse tumor response (OR = 0.31; 95% CI: 0.16-0.60; P < .001) and OS after treatment with cetuximab (HR = 1.86; 95% CI: 1.24-2.79; P = .003), they demonstrated better OS after symptomatic treatment (HR = 0.65; 95% CI: 0.50-0.85; P = .002). Her3 overexpression was not associated with sex (OR = 1.03; 95% CI: 0.83-1.28; P = .79), age (OR = 0.96; 95% CI: 0.75-1.24; P = .77), colon or rectum site (OR = 0.79; 95% CI: 0.44-1.43; P = .44), and total OS (HR = 1.09; 95% CI: 0.69-1.72; P = .72). Her3 expression is associated with the clinical pathology and prognosis of CRC, which explains the nonefficacy of cetuximab treatment in patients with CRC.


Phosphodiesterase isoenzyme families in human osteoarthritis chondrocytes--functional importance of phosphodiesterase 4.
We studied whether selective inhibitors of cyclic nucleotide hydrolysing phosphodiesterase (PDE) isoenzymes influence IL-1beta-induced nitric oxide (NO) release from human articular chondrocytes. In addition, the pattern of PDE isoenzymes contributing to cyclic nucleotide hydrolysis in human chondrocytes was characterized. Chondrocytes were isolated from human osteoarthritic cartilage and cultured in alginate beads. IL-1beta-induced chondrocyte products (nitric oxide and prostaglandin E(2)) were measured in culture supernatants after 48 h incubation time. PDE activities were assessed in chondrocyte lysates. Inducible nitric oxide synthase (iNOS) and PDE4A-D proteins were detected by immunoblotting. The selective PDE4 inhibitors Piclamilast and Roflumilast partially attenuated IL-1beta-induced NO production whereas selective inhibitors of PDE2 (EHNA), PDE3 (Motapizone) or PDE5 (Sildenafil) were inactive. Indomethacin reversed the reduction of IL-1beta-induced NO by PDE4 inhibitors. It was shown that autocrine prostaglandin E(2) (PGE(2)) enabled PDE4 inhibitors to reduce IL-1beta-induced NO in this experimental setting. Major PDE4 and PDE1 activities were identified in chondrocyte lysates whereas only minor activities of PDE2, 3 and 5 were found. IL-1beta and cyclic AMP-mimetics upregulated PDE4 activity and this was associated with an augmentation of PDE4B2 protein. Based on the view that nitric oxide contributes to cartilage degradation in osteoarthritis our study suggests that PDE4 inhibitors may have chondroprotective effects.


Suppression of IL-8-Src signalling axis by 17β-estradiol inhibits human mesenchymal stem cells-mediated gastric cancer invasion.
Epidemiologic data show the incidence of gastric cancer in men is twofold higher than in women worldwide. Oestrogen is reported to have the capacity against gastric cancer development. Endogenous oestrogen reduces gastric cancer incidence in women. Cancer patients treated with oestrogens have a lower subsequent risk of gastric cancer. Accumulating studies report that bone marrow mesenchymal stem cells (BMMSCs) might contribute to the progression of gastric cancer through paracrine effect of soluble factors. Here, we further explore the effect of oestrogen on BMMSCs-mediated human gastric cancer invasive motility. We founded that HBMMSCs notably secrete interleukin-8 (IL-8) protein. Administration of IL-8 specific neutralizing antibody significantly inhibits HBMMSCs-mediated gastric cancer motility. Treatment of recombinant IL-8 soluble protein confirmed the role of IL-8 in mediating HBMMSCs-up-regulated cell motility. IL-8 up-regulates motility activity through Src signalling pathway in human gastric cancer. We further observed that 17β -estradiol inhibit HBMMSCS-induced cell motility via suppressing activation of IL8-Src signalling in human gastric cancer cells. 17β-estradiol inhibits IL8-up-regulated Src downstream target proteins including p-Cas, p-paxillin, p-ERK1/2, p-JNK1/2, MMP9, tPA and uPA. These results suggest that 17β-estradiol significantly inhibits HBMMSCS-induced invasive motility through suppressing IL8-Src signalling axis in human gastric cancer cells.


Immunopotentiating activities of a low molecular weight lipopeptide, RP 56 142--studies in infectious models.
RP 56 142, N2-[N-(N-lauroyl-L-alanyl)-gamma-D glutamyl] L,L-2,6-diaminopimelamic acid belongs to a family of immunomodulating lipopeptides. Its structure is directly derived from that of lauroyltetrapeptide RP 40 639 which is a mixture of two stereoisomers, one of which (with D,D-2,6 diaminopimelamic acid) is totally devoid of in vivo activity. RP 56 142 displayed potent protective activities against bacterial infections such as K. pneumoniae, L. monocytogenes or S. typhimurium (at doses ranging between 0.03 and 100 mg/kg s.c., i.p., i.v.). In combined treatment protocols, suboptimal doses of RP 56 142 given preventively (day-1) or curatively (day 0 + 4h) significantly protected mice receiving antibiotics at doses which were ineffective when administered by themselves. Given s.c. 1 or 2 days before infectious challenge, RP 56 142 was able to normalize and even enhance significantly the resistance of mice previously immunocompromised by lomustine, 5-fluorouracile or hydrocortisone. These results correlated with the stimulation of the clearance of a virulent Salmonella typhimurium strain and with an important production of colony-stimulating factor in RP 56 142-treated mice.


[Carpometacarpal joint arthrosis and its surgical therapy with the de la Caffinière endoprosthesis].
In the area of the hand the carpo-metacarpal joint of the thumb together with the metacarpo-phalangeal joints is the most important joint according to the function of the hand. Its reduction of movement leads to misfunction of the thumb and the whole hand. Osteoarthritis of that very special joint commonly occurs in females after the menopause. The increasing severeness of the arthrosis is often complicated through pathological positions as well as through contractures (so called Z-deformities). In these patients operative treatment for improvement of function is very often not avoidable. Especially in the elderly patient with reduced manual work the implantation of a cemented carpo-metacarpal prosthesis (created by de la Caffinière) seems to be a useful treatment. As in all cemented implants the disadvantage is the danger of aseptic loosening of the prosthesis.


The effect of selected macro forces on the contemporary social construction of American Indian ethnic identity.
This article explains selected historical acts and events that continue to impact comtemporary Native American ethnic identity, social policy, and social services delivery. Although cultural competence is increasingly encouraged in social work education, the events of history usually do not appear as partial explanations for current phenomena. For those who work with Native American populations, understanding this history is a critical piece in the process of acquiring cultural competence. These selected historical events provide at least partial understanding of some contemporary issues which are sometimes presented to social workers and other social services professionals who work with Native populations.


Analyses of phenolic compounds by microemulsion electrokinetic chromatography.
In this study, a microemulsion electrokinetic chromatography (MEEKC) method was developed to analyze and detect 13 phenolic compounds (syringic acid, p-cumaric acid, vanillic acid, caffeic acid, gallic acid, 3,4-dihydroxybenzoic acid, 4-hydroxybenzoic acid, (+)-catechin, (-)-epigallocatechin, (-)-epicatechin gallate, (-)-epigallocatechin gallate, (-)-epicatechin, and (-)-gallocatechin), which are present in many plant-derived foods. The effects of cosurfactant, organic modifier, and oil were examined in order to optimize the separation of these phenolic compounds. The amounts of cosurfactant (cyclohexanol) and organic modifier (acetonitrile) were determined as the major influence on the separation selectivity, while the type of oil partially affected the separation resolution of the phenolic compounds. A highly efficient MEEKC separation method was achieved within 14 min by using a microemulsion solution of pH 2.0 containing 2.89% w/v SDS, 1.36% w/v heptane, 7.66% w/v cyclohexanol, and 2% w/v ACN. Furthermore, the present work could demonstrate that the nature of the oil phase has a significant influence on the separation selectivity of phenolic compounds.


The effect of missing KIR ligands, activating KIR genotype and haplotype on the outcome of T-cell-replete hematopoietic stem cell transplantation from HLA-identical siblings in Thai patients.
This study was a retrospective analysis of Thai patients undergoing T-replete hematopoietic stem cell transplant from human leukocyte antigen (HLA)-identical sibling donors. We investigated 66 patients, including 40 patients with acute myeloid leukemia (AML), 12 patients with acute lymphoblastic leukemia and 14 patients with chronic myeloid leukemia. Killer cell immunoglobulin-like receptor (KIR) genes and HLA ligands were typed by polymerase chain reaction-sequence specific oligonucleotide probes. We analyzed the effect of the number of missing KIR ligands (Bw4, C1 and C2) on clinical outcomes. A beneficial effect of missing KIR ligand was not observed in both univariate and multivariate analysis. When we analyzed the effect of specific missing KIR ligand on clinical outcomes, there was a trend that patients with missing A11 ligand had lower relapse rate (P = 0.076). Therefore, we also conducted the analysis by including the group with missing KIR ligands of Bw4, C1, C2 and A11. Patients with two or more than two missing KIR ligands had a trend for better clinical outcome including reduced relapse (P = 055) and statistically significant in terms of reduced acute graft-vs-host disease (aGVHD) rate (P = 0.013). In multivariate analysis, patients with two or more than two missing KIR ligands had a statistically significant better clinical outcome in terms of reduced aGVHD rate (HR = 0.155, 95%CI = 0.040-0.605, P = 0.007). The association between clinical outcome with KIR haplotypes, centromeric B haplotype and activating KIR was not observed here. Although the sample size in this study is rather limited, these data can later be subjected to meta-analysis to help reach the conclusion of the usefulness of this additional promising KIR genotyping in various hematopoietic stem cell transplantation types.


Strabismus in childhood eyelid ptosis.
To report the prevalence and causes of strabismus in children with eyelid ptosis diagnosed in a well-defined population over a 40-year period. Retrospective, population-based cohort study. We retrospectively reviewed the charts of 107 patients (<19 years) for the prevalence and causes of strabismus in children who were diagnosed with childhood eyelid ptosis as residents of Olmsted County, Minnesota, from January 1, 1965, through December 31, 2004. Strabismus was diagnosed in 20 (18.7%) of the 107 patients with childhood ptosis. Of the 81 patients, 8 (9.9%) were diagnosed with simple congenital ptosis and had strabismus, of which there were 4 (4.9%) cases of exotropia and 4 (4.9%) cases of esotropia. There were no cases of isolated vertical deviation. Strabismus occurred in 1 of 5 children diagnosed with any form of childhood ptosis in this population-based cohort. Strabismus affected approximately 1 of 10 patients diagnosed with simple congenital ptosis, and a predominance of isolated horizontal deviations was equally divided between esotropia and exotropia.


Effects of meteorologic factors and schooling on the seasonality of group A streptococcal pharyngitis.
The objective of this study was to determine the seasonal pattern of group A streptococcal pharyngitis in children attended at a hospital emergency department in the Mediterranean island of Mallorca (Spain), and its association with meteorologic factors and schooling. We conducted a retrospective review of the medical records of children aged 1-15 years with a diagnosis of Streptococcus pyogenes pharyngitis between January 2006 and December 2011. The number of S. pyogenes pharyngitis was correlated to temperature, humidity, rainfall, atmospheric pressure, wind speed, solar radiation, and schooling, using regression and time series techniques. A total of 906 patients (median, 4 years old) with S. pyogenes pharyngitis, confirmed by throat culture, were attended during the study period. A seasonal pattern was observed with a peak activity in June and a minimum in September. Mean temperature, solar radiation, and school holidays were the best predicting variables (R(2) = 0.68; p < 0.001). S. pyogenes activity increased with the decrease of mean temperature (z = -2.4; p < 0.05), the increase of solar radiation (z = 4.2; p < 0.001), and/or the decrease in school holidays (z = -2.4; p < 0.05). In conclusion, S. pyogenes pharyngitis had a clear seasonality predominating in springtime, and an association with mean temperature, solar radiation, and schooling was observed. The resulting model predicted 68 % of S. pyogenes pharyngitis.


The modulation of growth of normal rat liver epithelial cells in calcium-poor medium by epidermal growth factor, phenobarbital, phorbol ester, and retinoic acid.
The ability of a normal rat liver epithelial cell line with phenotypic characteristics of "oval" cells to grow in calcium-poor medium has been investigated. The growth of these cells could be arrested in medium containing 0.03 mM Ca2+, a concentration below which cell necrosis began to occur 24 h postexposure. With increasing calcium concentration, progressive cell proliferation was observed. Epithelial growth factor (EGF) (10 ng/ml) increased the survival and proliferation of cells in calcium-poor medium and the response was inversely correlated with the extracellular calcium concentration. In contrast, phenobarbital (0.2 to 2 mM), 12-O-tetradecanoylphorbol-13-acetate (0.01 to 1 microgram/ml), or retinoic acid (0.001 to 0.1 microgram/ml) depressed growth of cells in calcium-poor medium. The results confirm the ability of EGF to lower the calcium requirement for proliferation of normal cells, but such an effect does not seem to be a universal property of tumor promoters.


A Full-Device Autonomous Self-Healing Stretchable Soft Battery from Self-Bonded Eutectogels.
Next-generation energy storage devices should be soft, stretchable, and self-healable. Previously reported self-healable batteries mostly possess limited stretchability and rely on healable electrodes or electrolytes rather than achieving full-device self-healability. Herein, an all-component self-bonding strategy is reported to obtain an all-eutectogel soft battery (AESB) that simultaneously achieves full-cell autonomous self-healability and omnidirectional intrinsic stretchability (>1000% areal strain) over a broad temperature range (-20~60 °C). Without requiring any external stimulus, the five-layered soft battery can efficiently recover both its mechanical and electrochemical performance at full-cell level. The developed AESB can be easily configured into various 3D architectures with highly interfacial compatible eutectogel electrodes, electrolyte, and substrate, presenting an excellent opportunity for the development of embodied energy technologies. The present work provides a general and user-friendly soft electronic material platform for fabricating a variety of intrinsic self-healing stretchable multi-layered electronics, which are promising beyond the field of energy storage, such as displays, sensors, circuits, and soft robots.


[Craniocerebral gunshot wounds: a study of outcome predictors].
A retrospective study about craniocerebral gunshot wounds was done to better identify outcome predictors. We reported and analyzed the clinical and radiological data of 18 patients admitted to Le Kremlin-Bicêtre institute for a craniocerebral gunshot wound between January 2000 and December 2005. The Glasgow Outcome Scale (GOS) was used to analyze patient outcome. There were 17 men and one woman, mean age 43 years (range 17-84). Fifteen patients died, two had a GOS equal to 2 and one GOS equal to 3. There were 16 suicides and two murders. All patients with areactive bilateral mydriasis and all patients with Glasgow Coma Scale (GCS) less than seven died except one. The 10 patients with intraventricular hemorrhage died. The bullet crossed the midline for 13 patients and all of them died. None of the patients underwent emergency surgery for the treatment of craniocerebral gunshot wounds because of low Glasgow Coma Scale. This study shows some interesting prognosis patterns: bilateral areactive mydriasis, GCS less or equal to 7 and bullet trajectory (if crossing the midline) are the most important factors predicting a fatal outcome.


Valsartan improves mitochondrial function in hearts submitted to acute ischemia.
The effect of valsartan, an angiotensin II-type I receptor blocker, on the mitochondrial function, was studied using an ex vivo animal model (hearts from Wistar rats), perfused in a Langendorff system and then submitted to global acute ischemia. Parameters evaluated were: membrane electrical potential (DeltaPsi, using a tetraphenylphosphonium-TPP+-electrode), oxygen consumption by the respiratory chain (Clark-type O2 electrode), phosphorylation lag phase (time necessary to phosphorylate a fixed amount of ADP) and ATP/ADP ratio (adenine nucleotides quantified by high-pressure liquid chromatography-HPLC). Valsartan acts preferentially in the phosphorylation, increasing ATP/ADP ratios (succinate: 1.6+/-0.4 versus 0.5+/-0.1--P<0.05; ascorbate/N,N,N',N'-tetramethyl-P-phenylenodiamine-TMPD: 1.1+/-0.2 versus 0.4+/-0.1--p<0.05 versus ischemia in the absence of valsartan) and decreasing lag phase (glutamate/malate: 50.0+/-9.6 s versus 127.2+/-19.03 s-84.6+/-16.2% versus 215.3+/-32.2%; P=0.01; succinate: 111.8+/-33.1 s versus 275.73+/-45.99 s-168.2+/-49.8% versus 414.9+/-69.2%; P=0.02 or ascorbate/TMPD: 11.0+/-3.9 s versus 62.4+/-11.63 s-34.9+/-12.4% versus 198.1+/-36.9%; P=0.001 versus ischemia in the absence of valsartan). This enables a higher energy production in hearts submitted to acute ischemia, for which having energy becomes critical to preserve mitochondrial function. These mechanisms allow us to better understand valsartan cytoprotection in ischemic cardiomyopathy.


Synthesis of non-spherical polymer particles using the activated swelling method.
The preparation of particles with non-spherical shapes is a challenging endeavor, often requiring a significant ingenuity, complex experimental procedures and difficulties to obtain reproducible results. In this work we prove that monodisperse non-spherical polymer particles possessing asymmetric Janus structure can be easily produced by using an activated swelling method in combination with a control of the rate of free radical polymerization through the addition of the inhibitors 4-methoxyphenol (MEHQ) and O2. Monodisperse non cross-linked polystyrene particles, used as seeds, are activated by the addition of an initiator, which promotes their swelling ability, and then swollen with a monomers mixture (methyl methacrylate, glycidyl methacrylate and ethylene glycol dimethacrylate), before being polymerized in presence of both MEHQ and O2. Our results show that only when both MEHQ and O2 are present during the course of the polymerization, the particles shape can be controlled, from spherical to asymmetrical. A variety of particles shapes can be obtained, ranging from dimpled spheres, flattened spheres and Janus particles by varying the swelling ratio, always with excellent monodispersity and reproducibility. Finally, to provide even more complex functionalities to these non-spherical polymer particles, iron oxide nanocrystals were grown within the polymer matrix resulting in superparamagnetic particles.


Telomerase activity correlates with growth of transplantable osteosarcomas in rats treated with cis-diammine dichloroplatinum or the angiogenesis inhibitor AGM-1470.
To determine the role of telomerase activity in the growth of tumors in rats undergoing chemotherapy, a comparison of the volumes of telomerase-positive transplantable osteosarcomas was made in rats treated with the antineoplastic agent cis-diammine dichloroplatinum (CDDP) or the angiogenesis inhibitor O-(chloroacetylcarbamoyl)fumagillol (AGM-1470). Male F344 rats, 8 weeks old, received transplants of macroscopic lung metastatic nodules into the subcutaneous back space and treatment was started on day 14 thereafter. CDDP was injected i.v. at doses of 0, 0.625, 1.25 and 2.5 mg/kg body weight (b.w.) and AGM-1470 was administered at total doses of 0, 2.5, 5 and 10 mg/kg b.w. over 2 weeks by osmotic pumps, also implanted into the subcutaneous back space, but remote from the transplanted tumors. On day 28, all animals were killed for measurement of transplanted tumor size and determination of telomerase activities by telomeric repeat amplification protocol (TRAP) assay. The results showed telomerase activity to be highly correlated with the treated/non-treated (T/C) tumor size ratio (r = 0.96, P < 0.0001). In a second experiment, CDDP at 2.5 mg/kg b.w. and AGM-1470 at 10 mg/kg b.w., these being the most effective doses, were given as in the first experiment, and animals were serially killed on days 14, 21, 28, 35 and 42. Tumors in rats treated with CDDP and AGM-1470 showed 18.2% and 20.5% of the control telomerase activity on days 35 and 21, respectively, when tumor growth was inhibited. However, on day 42, the activities increased to 46.5% and 92.5%, this correlating with re-growth (r = 0.73, P < 0.0001). These results suggest that decline of telomerase activity may be involved in tumor growth retardation induced by chemotherapeutic agents. This possibility clearly warrants further mechanistic studies.


Effectiveness of pretreatment in decreasing adverse events associated with pamidronate in children and adolescents.
To assess the effectiveness of pretreatment with ibuprofen or acetaminophen compared with no pretreatment in decreasing adverse events in children and adolescents receiving the first and second series of pamidronate therapy; and to compare the effectiveness of ibuprofen versus acetaminophen for prevention of adverse events associated with pamidronate infusion. Retrospective case review. Children's hospital. Twenty-seven children and adolescents aged 3-21 years receiving pamidronate therapy. Data for patient demographics, medical history, genetic history of disease, pamidronate infusion dosage, and concurrent drug therapy were collected. Adverse drug events secondary to pamidronate infusion and subsequent drug therapies received were documented. Data were categorized by presence or absence of pretreatment and analyzed by cross-tabulation to determine whether the presence of adverse events differed between groups (no pretreatment, acetaminophen pretreatment, and ibuprofen pretreatment). Fewer adverse events were reported in patients receiving ibuprofen (17% of patients) versus acetaminophen (83%). Differences in presence of fever (chi2 = 10.5, p = 0.005) and bone pain (chi2 = 7.3, p = 0.027) among the three pretreatment groups were also statistically significant. Pretreatment with ibuprofen or acetaminophen appears to decrease the occurrence of adverse events from pamidronate therapy. However, adverse events seem less likely to occur with ibuprofen. Further study is necessary to determine the relationship between occurrence of adverse events, other possible treatment strategies, and patient adherence with pamidronate therapy.


Sex-dependent effects of diabetes mellitus on the revascularization rate in mid-term follow up of young patients with coronary artery disease.
We investigated the association between Type-2 diabetes mellitus (DM) and the need for revascularization at a 5-year follow-up of young coronary artery disease patients and the role of sex in this regard. Among 1121 young (males≤45, and females≤55years) patients (female: 49.7%) from Tehran Heart Center's Premature Coronary Atherosclerosis Cohort, 371(33.1%) had diabetes prior to angiography. Revascularization was considered as either percutaneous coronary intervention or coronary artery bypass graft surgery. The mean follow-up duration was 57.67±22.43months. In the univariable analysis, diabetics were at a significantly higher risk of revascularization than nondiabetics (Sub-distributional Hazard Ratio [SHR]=1.843, P value<0.001). There was no association between DM and revascularization among men (SHR=1.232, P value=0.508). In contrast, women with DM had threefold more revascularization risk than women without DM (SHR=3.519, P value<0.001). After adjustment for confounding factors, the risk of revascularization in diabetics compared to nondiabetics increased to 2.139 fold (95% CI=1.473, 3.108) among the whole subjects, remained nonsignificant among men, and increased significantly to 3.725 fold (95% CI=2.067, 6.725) in women. Our data showed that in women with premature CAD, but not in men, DM may have a significant role in emerging revascularization during a mean follow-up of 5years.


Acquisition of expertise in cricket fast bowling: perceptions of expert players and coaches.
Experiential knowledge of elite athletes and coaches was investigated to reveal insights on expertise acquisition in cricket fast bowling. Twenty-one past or present elite cricket fast bowlers and coaches of national or international level were interviewed using an in-depth, open-ended, semi-structured approach. Participants were asked about specific factors which they believed were markers of fast bowling expertise potential. Of specific interest was the relative importance of each potential component of fast bowling expertise and how components interacted or developed over time. The importance of intrinsic motivation early in development was highlighted, along with physical, psychological and technical attributes. Results supported a multiplicative and interactive complex systems model of talent development in fast bowling, in which component weightings were varied due to individual differences in potential experts. Dropout rates in potential experts were attributed to misconceived current talent identification programmes and coaching practices, early maturation and physical attributes, injuries and lack of key psychological attributes and skills. Data are consistent with a dynamical systems model of expertise acquisition in fast bowling, with numerous trajectories available for talent development. Further work is needed to relate experiential and theoretical knowledge on expertise in other sports.


X-rays only when you want them: optimized pump-probe experiments using pseudo-single-bunch operation.
Laser pump-X-ray probe experiments require control over the X-ray pulse pattern and timing. Here, the first use of pseudo-single-bunch mode at the Advanced Light Source in picosecond time-resolved X-ray absorption experiments on solutions and solids is reported. In this mode the X-ray repetition rate is fully adjustable from single shot to 500 kHz, allowing it to be matched to typical laser excitation pulse rates. Suppressing undesired X-ray pulses considerably reduces detector noise and improves signal to noise in time-resolved experiments. In addition, dose-induced sample damage is considerably reduced, easing experimental setup and allowing the investigation of less robust samples. Single-shot X-ray exposures of a streak camera detector using a conventional non-gated charge-coupled device (CCD) camera are also demonstrated.


Discovering strengths in patients with medically unexplained symptoms - a focus group study with general practitioners.
When patients suffer medically unexplained symptoms, consultations can be difficult and frustrating for both patient and GP. Acknowledging the patient as a co-subject can be particularly important when the symptoms remain unexplained. One way of seeing the patient as a co-subject is by recognizing any among their strong sides. To explore GPs' experiences with discovering strengths in their patients with medically unexplained symptoms and elicit GPs' reflections on how this might be useful. Four focus-groups with 17 GPs in Norway. Verbatim transcripts from the interviews were analyzed by systematic text condensation. Recollecting patients' strengths was quiet challenging to the GPs. Gradually they nevertheless shared a range of examples, and many participants had experienced that knowing patients' strong sides could make consultations less demanding, and sometimes enable the GP to provide better help. Identifying strengths in patients with unexplained symptoms required a deliberate effort on the GPs' behalf, and this seemed to be a result of a strong focus on biomedical disease and loss of function. Acknowledging patients' strong sides can bolster GPs' ability to help patients with medically unexplained symptoms. However, the epistemic disadvantage of generalist expertise makes this hard to achieve. It is difficult for GPs to integrate person-centered perspectives with biomedical knowledge due to the privileged position of the latter. This seems to indicate a need for system-level innovations to increase the status of person-centered clinical work. Key pointsMUS is challenging for both patients and GPs mainly because of the incongruence between symptoms and the dominating biomedical model.GPs' focus on pathology and loss of function can prevent them from discovering patients' strengths.Awareness of patients' strengths can make consultations less demanding for GPs and enable them to provide better help.A conscious effort is needed to discover patients' strengths.


Patchy agglomeration as a transition from monospecies to recurrent plankton blooms.
We propose a model for explaining both red tides and recurring phytoplankton blooms. Three assumptions are made, namely the presence of toxin producing phytoplankton, the satiation phenomenon in zooplankton's feeding, modelled by a Holling type II response, and phytoplankton aggregation leading to formation of patches. The dynamics of the plankton population is shown to depend on the fraction of the phytoplankton population that aggregates to form colonies and on the number of the latter.


[Follow-up of patients with type 2 diabetes during the COVID-19 pandemic: A multicentre study in Primary Care].
The COVID-19 pandemic meant measures had to be taken that implied the neglect of patients with type 2 diabetes (T2D). to explore the impact of care discontinuity on patients with T2D in Primary Care (PC) centres, who did not have a specific action protocol for them, during 2020 and 2021. Multicenter retrospective observational study. Patients with T2D in Tenerife, Canary Islands, Spain. Sex and age, follow-up variables of atherosclerotic vascular disease detection and control programme (pEVA), compliance with the control objectives and visits to the family practitioner and community nurse were extracted from their medical records. 3,543 participants took part in the study, 1,772 (50%) women, 2,204 (62%) of whom were older than 65 years of age. The vast majority of registered activities and control objectives decreased in 2020, recovering in 2021 without reaching 2019 levels. In 2020, telephone consultations increased and in-person consultations decreased, a trend that remained unchanged in 2021 for telephone consultations. Women and those over 65 years of age presented higher frequentation, more activity records and achievement of control objectives in most of the parameters. The pandemic caused an overload in the PCs that affected the care of patients with T2D, which has not returned to pre-pandemic levels. Young men are the target for prioritization of this care. Anti-pandemic measures have led to an increase in telephone consultations, a resource that should be strengthened.


Left ventricular assist device therapy improves utilization of donor hearts.
We sought to determine the survival experiences of patients bridged to heart transplantation with either intravenous (IV) inotropes or an implantable left ventricular assist device (LVAD). Because of the operative risks of LVAD implantation and the reported lower mortality associated with inotropic therapy, bridging to heart transplantation with inotropes is thought to be the preferred treatment option. Between April 1, 1996, and May 10, 2001, a total of 104 patients were bridged to heart transplantation with either IV inotropes (n = 38) or an implantable LVAD (n = 66; HeartMate). Survival was compared (Kaplan-Meier method) for three periods: survival to transplantation, post-transplantation survival and overall survival (i.e., survival from the onset of bridging to follow-up). Survival to transplantation was 81 +/- 5% at three months for the LVAD group and 64 +/- 11% for the inotrope group (p = NS). Post-transplantation survival was 95 +/- 4% at three years for the LVAD group (two deaths) and 65 +/- 10% at three years for the inotrope group (nine deaths; p = 0.007). Overall survival was 77 +/- 6% at three years for the LVAD group and 44 +/- 9% at three years for the inotrope group (p = 0.01). Overall survival for patients who were bridged to heart transplantation with an implantable LVAD was superior to that of patients who were bridged with inotropes. Bridging to transplantation with an implantable LVAD improves utilization of donor hearts.


A synthetic coumarin derivative (4-flourophenylacetamide-acetyl coumarin) impedes cell cycle at G0/G1 stage, induces apoptosis, and inhibits metastasis via ROS-mediated p53 and AKT signaling pathways in A549 cells.
New chemotherapeutic agents with minimum side effects are indispensable to treat non-small-cell lung cancer (NSCLC) since the mortality rate of patients suffering from NSCLC remains high despite receiving conventional medication. In our previous study, many coumarin derivatives were screened for their anticancer properties in A549, an in vitro NSCLC model. One of these, 4-flourophenylacetamide-acetyl coumarin (4-FPAC), induced cytotoxicity at a concentration as low as 0.16 nM. Herein, initially, the cytotoxic potential of 4-FPAC was tested on a noncancerous cell line NIH3T3 and was found safe at the selected dose of 0.16 nM. Further, we investigated the mechanism by which 4-FPAC induced cytotoxicity and arrested the progression of cell cycle as well as metastasis in A549. Results of ethidium bromide/acridine orange (EtBr/AO), 4,6-diamidino-2-phenylindole, comet, and lactate dehydrogenase assays revealed that 4-FPAC caused cytotoxicity via reactive oxygen species-induced p53-mediated mechanism, which involves both extrinsic and intrinsic pathways of apoptosis. Dichlorodihydrofluorescein diacetate, rhodamine 123, and AO staining confirmed the involvement of both mitochondria and lysosome in inducing apoptosis. However, flow cytometric analysis revealed that it causes cell cycle arrest at the G0/G1 phase by modulating p21, CDK2, and CDK4 expression. Aggregation, soft-agar, clonogenic, and scratch assays as well as gene expression analysis collectively confirmed that 4-FPAC minimizes the metastatic property of A549 by downregulating Snail, matrix metalloproteinase 9, and interleukin-8. Additional studies reaffirmed the above findings and substantiated the role of PI3K/AKT in achieving them. The cell-type-specific selective cytostatic and antimetastatic properties shown by 4-FPAC indicate its potential to emerge as a drug of choice against NSCLC in the future.


Basilar bifurcation aneurysms. Lessons learnt from 40 consecutive cases.
Basilar bifurcation aneurysms are lately treated frequently with endovascular technique. Microsurgical clipping occlusion technique has, however, still its solid position because of its completeness. This standard technique is required often due to unfeasibility and/or incompleteness at the time of application of the endovascular technique for aneurysms of this location. The authors suggest following strategies and tactics for safe and secure occlusion of aneurysms of this location: pterional approach, selective extradural anterior clinoidectomy SEAC, no transection of the posterior communicating artery, isolation of perforating arteries at the time of neck clipping with oxycellulose and combination of the use of fenestrated clip and conventional clip (especially for aneurysms projected posteriorly), controlled hypotension (systolic pressure of around 100 mmHg), temporary clipping (trapping) procedures of usually less than 15 min. All these are aimed for prevention of intraoperative premature rupture, and of injury of perforating arteries and for complete occlusion of aneurysms in the narrow depth of the operative field.


System identification and simulation of soft tissue force feedback in a spine surgical simulator.
Surgical simulators are being introduced as training modalities for surgeons. This paper aims to evaluate dynamic models used to convey force feedback from puncturing the soft tissue during a spine surgical simulation. The force feedback of the tissue is treated as a dynamic system. This is done by performing classical system identification across a bandwidth of frequencies on a tissue analogue and fitting that behaviour to dynamic viscoelastic models. The models that are tested are an inverted linear model, the Maxwell model, the Kelvin-Boltzmann (KB) model, and a higher-order blackbox (HO) model. Several error metrics such as percent variance accounted for (%VAF) are determined to measure solution accuracy. The force feedback models are programmed into a surgical simulator and tested with study participants who rated them based on how well the identified models match the behaviour of the rubber tissue analogue. The highest %VAF is 82.64% when the tissue is modelled as the HO model. Statistically significant differences (p < 0.05) are found between all model ratings from participants except between the HO model and the KB model. However, the HO model has the highest percentage (37.8%) of participants who rank its performance as the closest to the tissue analogue compared to the other force feedback models. The more accurately the dynamic behaviour resembles the tissue analogue, the higher the model was rated by study participants. This study highlights the importance of utilizing dynamic signals to generate dynamic models of soft tissue for spine surgical simulators.


Rheotaxis-based microfluidic device for selecting sperm from samples infected with a virus.
To investigate whether the presented rheotaxis-based microfluidic device could be used to separate spermatozoa from viruses (i.e., Zika) in the infected semen sample during the selection and washing process. Quantitative and experimental study of the sperm washing/selection process through the microfluidic platform exploiting the positive rheotaxis of sperm. None. None. None. Human sperm were purchased from a sperm bank. The raw semen sample was mixed with viruses and loaded into a microfluidic device. Experiments were performed with 2 different flow rates (0 and 25 μL/minute) to investigate the washing efficiency of the device in the sperm selection process. The sperm sample was collected after 45 minutes and analyzed to check whether the collected sample is free of any infections (viruses) after isolation. Fluorescent microscopy and quantitative polymerase chain reaction-based analysis showed that the sperm selected with the presented rheotaxis-based microfluidic device at the optimal flow rate (25 μL/minute) was free of any viruses. We have developed a simple, cost-effective microfluidic device that mimics the conditions of the female genital tract while washing out the raw semen efficiently during the selection process for assisted reproductive technology.


Dose dependence of the 14C-aminopyrine breath test. Intrasubject comparison of tracer and pharmacological doses.
Although the aminopyrine breath test has received much attention, the question has not yet been settled whether pharmacological or tracer doses of the drug should be used. Nine volunteers were given 14C-aminopyrine 9 mg/kg or a tracer amount, in a randomized sequence and according to a crossover design. The specific activity of 14CO2 in breath was significantly different only during the first hour. Up to the 8th hour the disappearance of 14CO2 from breath was smaller after the pharmacological (28.5 +/- SD 5.4%/h) than after the tracer dose (36.2 +/- 10.6%/h; p less than 0.05). The over-all disappearance of 14C-atoms from the subjects was significantly slower after the higher dose. In view of the smaller radiation exposure and the decreased risk of agranulocytosis, the use of a tracer dose appears preferable.


Intrinsic dimension estimation for locally undersampled data.
Identifying the minimal number of parameters needed to describe a dataset is a challenging problem known in the literature as intrinsic dimension estimation. All the existing intrinsic dimension estimators are not reliable whenever the dataset is locally undersampled, and this is at the core of the so called curse of dimensionality. Here we introduce a new intrinsic dimension estimator that leverages on simple properties of the tangent space of a manifold and extends the usual correlation integral estimator to alleviate the extreme undersampling problem. Based on this insight, we explore a multiscale generalization of the algorithm that is capable of (i) identifying multiple dimensionalities in a dataset, and (ii) providing accurate estimates of the intrinsic dimension of extremely curved manifolds. We test the method on manifolds generated from global transformations of high-contrast images, relevant for invariant object recognition and considered a challenge for state-of-the-art intrinsic dimension estimators.


Effectiveness of dengue control practices in household water containers in Northeast Thailand.
To investigate the influence of larval control methods (using temephos, keeping fish and covering containers with lids), water use and weekly cleaning of containers on the presence of Aedes aegypti larvae in water-storage containers in rural and urban households in Khon Kaen province. Cross-sectional questionnaire survey and larval survey covered 966 households and 5821 containers were inspected. In rural and urban areas larval control was patchy and often ineffective. Consequently, the mosquito indices exceed the target indices for dengue control with the Breteau Indices of 201 and 113, and Container Indices of 25 and 28 in rural and urban areas, respectively. The containers most frequently infested with larvae were rectangular cement containers storing water for bathing (rural: 37.2%; urban: 35%) and flushing the toilets (rural: 35.7%; urban: 34.3%). Keeping fish [adjusted odds ratio (AOR): 0.08-0.16] was the most effective methods of control. Correctly covering containers with lids was similarly effective (AOR: 0.10-0.25) when used on jars for storing drinking water. However, frequent use of containers reduced the effectiveness of lids. Temephos was effective only in dragon jars in urban areas (AOR: 0.46) where a standard package of temephos were available. Weekly cleaning of containers was an effective method for larval control in most types of containers. A combination of control methods increased effectiveness. This study highlights the complex interaction of household water use and larval control practices as well as the importance of determining the most effective control measures compatible with water practices for implementing control promotion.


Acute oxalate nephropathy due to pancreatic atrophy in newly diagnosed pancreatic carcinoma.
Acute oxalate nephropathy can occur due to primary hyperoxaluria and secondary hyperoxaluria. The primary hyperoxalurias are a group of autosomal recessive disorders of endogenous oxalate overproduction. Secondary hyperoxaluria may occur as a result of excess dietary intake, poisoning with oxalate precursors (ethylene glycol), or enteric hyperoxaluria. The differential diagnosis of enteric hyperoxaluria includes inflammatory bowel disease, short bowel syndrome, bariatric surgery (with jejunoileal bypass or Roux-en-Y gastric bypass), celiac disease, partial colectomy, and chronic pancreatitis. The common etiology in all these processes is fat malabsorption, steatorrhea, saponification of calcium, and absorption of free oxalate. Hyperoxaluria causes increased urinary oxalate excretion, urolithiasis (promoted by hypovolemia, decreased urinary pH caused by metabolic acidosis, and decreased citrate and magnesium concentrations in urine), tubulointerstitial oxalate deposits, and tubulointerstitial nephritis. We report a rare case of acute oxalate nephropathy due to pancreatic atrophy and exocrine insufficiency caused by newly diagnosed pancreatic cancer.


Once-daily netilmicin for neutropenic pyrexia in paediatric oncology.
To establish the safety and efficacy of single daily intravenous netilmicin 6 mg/kg with piperacillin 100 mg/kg every 8 h for empirical, first-line management of children with neutropenic pyrexia following cytotoxic chemotherapy. Observational study of children admitted to a regional oncology unit from October 1999-April 2002. Primary outcome measure was temperature 72 h after commencing antibiotic therapy; secondary measures were mortality, nephrotoxicity, symptomatic ototoxicity and serum netilmicin levels. 280 episodes for 128 patients (median age 7.1 y) were documented, and 248 episodes were evaluated and compared with a previous cohort of 100 episodes for which the only difference was administration of netilmicin three times daily. Twenty-seven per cent of single-dose netilmicin episodes remained febrile at 72 h compared to 32% in the comparator group (difference -4.7%; 95 % CI: -6.8% to 16.2%; p = 0.41). No patients died and we were unable to find evidence of nephrotoxicity or ototoxicity. Eighty-nine per cent of "peak" serum netilmicin levels measured 30 min after infusion were 10 mg/l or greater, and 94% and 86% measured 12-16 h after the first and third dose, respectively, were 1 mg/l or less. Peak serum netilmicin level measurements and 12-16-h measurements after the first dose were abandoned after the first 180 episodes. Netilmicin can safely be given as a single daily dose to children with febrile neutropenia who do not have biochemical evidence of nephrotoxicity. Monitoring peak serum levels of netilmicin is unnecessary. Levels taken 12-16 h after the third dose are adequate to monitor therapy if used in conjunction with a therapeutic guideline detailing the response to abnormal serum creatinine and netilmicin levels.


Breast Cancer Screening for Women at Higher-Than-Average Risk: Updated Recommendations From the ACR.
Early detection decreases breast cancer death. The ACR recommends annual screening beginning at age 40 for women of average risk and earlier and/or more intensive screening for women at higher-than-average risk. For most women at higher-than-average risk, the supplemental screening method of choice is breast MRI. Women with genetics-based increased risk, those with a calculated lifetime risk of 20% or more, and those exposed to chest radiation at young ages are recommended to undergo MRI surveillance starting at ages 25 to 30 and annual mammography (with a variable starting age between 25 and 40, depending on the type of risk). Mutation carriers can delay mammographic screening until age 40 if annual screening breast MRI is performed as recommended. Women diagnosed with breast cancer before age 50 or with personal histories of breast cancer and dense breasts should undergo annual supplemental breast MRI. Others with personal histories, and those with atypia at biopsy, should strongly consider MRI screening, especially if other risk factors are present. For women with dense breasts who desire supplemental screening, breast MRI is recommended. For those who qualify for but cannot undergo breast MRI, contrast-enhanced mammography or ultrasound could be considered. All women should undergo risk assessment by age 25, especially Black women and women of Ashkenazi Jewish heritage, so that those at higher-than-average risk can be identified and appropriate screening initiated.


KRAS targeting antibody synergizes anti-cancer activity of gemcitabine against pancreatic cancer.
Pancreatic cancer exhibits an oncogenic KRAS mutation rate of ∼90%. Despite research and drug development efforts focused on KRAS, no targeted therapy has been clinically approved for the treatment of pancreatic cancer with KRAS mutation. Also, the efficacy of gemcitabine is poor due to rapidly acquired resistance. We developed RT11-i antibody, which directly targets the intracellularly activated GTP-bound form of oncogenic RAS mutants. Here, we investigated the combined effects of RT11-i and gemcitabine in vitro and in vivo, and the mechanism involved. RT11-i significantly sensitized pancreatic cancer cells to gemcitabine. Also, the co-treatment synergistically inhibited angiogenesis, migration, and invasion, and showed synergistic anticancer activity by inhibiting the RAF/MEK/ERK or PI3K/AKT pathways. Furthermore, co-treatment inhibited endothelial barrier disruption in tumor vessels, which is a critical step in vascular leakiness of metastasis, and improved vessel structural stability. Importantly, co-treatment significantly suppressed tumor growth in an orthotopic tumor model. Taken together, our findings show that RT11-i synergistically increased the antitumor activity of gemcitabine by inhibiting RAS downstream signaling, which suggests RT11-i and gemcitabine be viewed a potential combination treatment option for pancreatic cancer patients with KRAS mutation.


Case report: rare presentation of primary angiomyolipoma in the middle ear.
Angiomyolipoma (AML) is a common, chronic disease usually localized in kidney and liver organs; but occurring frequently outside the kidney or liver. We describe an unusual case of a 62-year-old female patient with AML in the middle ear. She presented with left earache, tinnitus and hearing loss. Preoperative computed tomography and magnetic resonance imaging seemed to reveal a middle ear cholesteatoma. The patient underwent surgical resection of this lesion, and the AML was finally confirmed by histopathological examination. The patient was discharged on the 8th postoperative day and did not seek further treatment. Extraperitoneal AML is rare and accurately identified by histopathology. The recommended management is surgery for AML in the middle ear.


First successful treatment of Nocardia farcinica brain abscess with moxifloxacin.
Nocardia farcinica is an emerging pathogen in immunosuppressed patients causing both localized and disseminated infections. Many strains of this species are multidrug-resistant and require long-term antibiotic therapy, and consequently the choice of an oral treatment can be problematic. We report here the first case of successful treatment of N. farcinica brain abscess in a renal transplant recipient with an extended-spectrum fluoroquinolone, moxifloxacin.


Guillain-Barré syndrome after COVID-19 vaccines: A Tunisian case series.
As the COVID-19 vaccination campaign progresses worldwide, Guillain-Barré syndrome (GBS) vaccine-related cases have been reported. We carried out a retrospective, descriptive study of GBS patients following COVID-19 vaccine, submitted to the National Pharmacovigilance Center of Tunis during the period between March 2021 and May 2022. Our study aimed to identify epidemiological and clinical features of COVID-19 vaccine-associated GBS. We found 9 cases of GBS post COVID-19 vaccination; 5 of them were excluded due to the lack of information, whereas 4 cases were included in this study. Men represented 75% (3/4) of the cases. The most frequently reported vaccine type was ChAdOx1 nCoV-19 vaccine (n = 2 reports [50%]), Ad26.COV2.S vaccine and BNT162b2 vaccine in 1. The mean time interval from vaccination to symptom onset was 15.3 days. Clinical manifestations were different: classical GBS in two cases and GBS with unilateral facial palsy in the other 2 cases. All patients were treated with a course of intravenous immunoglobulin for 5 days. Three patients reported clinical improvement while one case (25%) showed treatment-related fluctuations. Our observations suggest that COVID-19 vaccines may be associated with GBS. Continuous surveillance and further studies are warranted to assess the significance of the association.


The impact of diaphragm management on prolonged ventilator support after thoracoabdominal aortic repair.
The relationship of the division of the diaphragm during thoracoabdominal aortic repair to prolonged ventilator support has not been studied. The purpose of this study was (1) to determine whether preservation of diaphragm integrity has a significant effect on postoperative ventilator duration and (2) to elucidate other pulmonary risk factors related to thoracoabdominal aortic surgery and to study the relationship of these factors to the intact diaphragm technique. Between February 1991 and January 1997, we repaired 397 descending and thoracoabdominal aortic aneurysms. Descending thoracic aneurysms were not included in the study because their repair does not include the diaphragm. A total of 256 patients participated in this study. The diaphragm was divided in 150 patients and left intact in 106 patients. Examined as potential risk factors were patient demographics, history and physical findings, aneurysm extent, urgency of the procedure, acute dissection, cross-clamp time, homologous and autologous blood product consumption, and adjunctive operative techniques. FEV1 also was considered in the 197 patients for whom preoperative spirometry was available. Prolonged mechanical ventilation was defined as ventilator support for >72 hours. Data were analyzed by univariate contingency table and multiple logistic regression methods. Increasing age (odds ratio [OR], 1.02/y; P <.02), current smoking (OR, 2.6; P <.0008), total cross-clamp time (OR, 1.0/min; P <.008), units packed red blood cells transfused (OR, 1.06/unit; P <.008), and division of the diaphragm (OR, 2.03; P <.02) were significant, independent predictors of prolonged ventilation. Sixty-seven percent of patients (71 of 106) whose diaphragms were preserved were extubated in <72 hours compared with 52% of patients (78 of 150) who underwent diaphragm division (OR, 0.53; P <.02). Independently of well known pulmonary risk factors, an intact diaphragm during thoracoabdominal aortic repair results in a higher probability of early ventilator weaning.


Tolerance to hypophagia induced by prolonged treatment with a CB1 antagonist is related to the reversion of anorexigenic neuropeptide gene expression in the hypothalamus.
It is well established that treatment with rimonabant, a CB1 antagonist, decreases food intake and body weight gain. In part, these responses are mediated by increased activity of hypothalamic neurons related with energy homeostasis. However, food consumption is reversed to basal level during prolonged CB1 antagonist treatment, suggesting tolerance to its anorexigenic effect. This study investigated the effects of acute or prolonged CB1 receptor blockade on the expression of hypothalamic neuropeptides involved with energy homeostasis. Male Wistar rats received vehicle, a single dose or daily doses of rimonabant (10 mg/kg by gavage) over 7 days. Food intake, body weight, CRF and CART immunoreactivity, as well as, mRNA expression of hypothalamic neuropeptides were evaluated. In comparison with vehicle treatment, single dose of rimonabant decreased food intake and body weight. Acute rimonabant treatment also increased Fos-CRF and Fos-CART double labeled neurons in the PVN and Fos immunoreactivity in the ARC. We also observed that acute rimonabant treatment increased CRF, CART and TRH mRNA expression in the PVN, while it decreased POMC and NPY mRNA expression in the ARC with no changes in the CART mRNA expression in this nucleus. There was an increase in CB1 mRNA expression in the PVN of rats that received both acute and prolonged-rimonabant treatment. Interestingly, rats subjected to prolonged rimonabant treatment had no changes in food intake, body weight gain, hypothalamic mRNA expression, Fos expression and CRF and CART neuron activation. These data indicate that tolerance to hypophagic effects of CB1 antagonist, rimonabant, is associated with reversion of hypothalamic neuropeptide gene expression related to regulation of energy homeostasis.


Spontaneous corneal clearance despite graft removal in Descemet stripping endothelial keratoplasty in Fuchs endothelial dystrophy.
To report spontaneous corneal clearing with improved visual acuity and central endothelial cell repopulation after the removal of a dislocated donor button following Descemet stripping endothelial keratoplasty (DSEK). Interventional case report. An 84-year-old woman with decreased visual acuity in the right eye secondary to Fuchs endothelial dystrophy and cataract underwent combined cataract extraction, intraocular lens implantation, and DSEK. After primary graft failure, the resulting detached, opaque, and retracted donor lenticule was removed from the eye 2 months after the initial surgery and not replaced. The cornea started to clear after the donor button removal with central endothelial cell repopulation. Corneal deturgescence is not strictly dependent on donor lenticule adhesion to the host posterior stromal surface. Endothelial cell migration and repopulation of the central cornea can occur after DSEK and after the removal of the failed endothelial graft, with corneal clearing and improved visual outcomes.


New methods of purifying and identifying parasitic diagnostic antigens: a review of the systematic and quantitative approach with the Schistosoma model.
Several antigen preparations intended for use in the serodiagnosis of schistosomiasis were reviewed. The efficacies of these antigens in terms of specific activities and cross-reactivities were compared. The idea of quantitation of the actual usable amount of antigens in various preparations was introduced. A systematic approach to the purification and identification of relevant antigens in the Schistosoma system was discussed. Use of the quantitative single-tube kinetic-dependent enzyme-linked immunosorbent assay in conjunction with a systematic approach to antigen purification allowed for the identification of substantial activities in membrane-associated antigens. Solubilization of the particulate- and presumably membrane-associated components resulted in significant amounts of highly sero-reactive antigens. Total reliance on aqueous-soluble parasitic antigens is questioned.


Personal exposure to benzene of selected population groups and impact of commuting modes in Ho Chi Minh, Vietnam.
Personal exposure to benzene of selected population groups, and impacts of traffic on commuters in Ho Chi Minh City were investigated. The study was carried out in June, July and November 2010. The preliminary data showed that on average, personal exposure to benzene for non-occupational people in Ho Chi Minh is ~18 μg/m(3) and most of the exposure is due to commuting. Benzene exposure during travelling by bus, taxi and motorcycle is, respectively, 22-30, 22-39 and 185-240 μg/m(3). Motorcycle-taxi drivers, petrol filling employees and street vendors suffer high daily exposures at 116, 52, 32 μg/m(3), respectively. Further measurements are needed for a better risk assessment and finding effective measures to reduce exposure.


Adipocyte Rnf20 ablation increases the fast-twitch fibers of skeletal muscle via lysophosphatidylcholine 16:0.
Both adipose tissue and skeletal muscle are highly dynamic tissues and interact at the metabolic and hormonal levels in response to internal and external stress, and they coordinate in maintaining whole-body metabolic homeostasis. In our previous study, we revealed that adipocyte-specific Rnf20 knockout mice (ASKO mice) exhibited lower fat mass but higher lean mass, providing a good model for investigating the adipose-muscle crosstalk and exploring the effect of the adipocyte Rnf20 gene on the physiology and metabolism of skeletal muscle. Here, we confirmed that ASKO mice exhibited the significantly increased body weight and gastrocnemius muscle weight. Fiber-type switching in the soleus muscle of ASKO mice was observed, as evidenced by the increased number of fast-twitch fibers and decreased number of slow-twitch fibers. Serum metabolites with significant alteration in abundance were identified by metabolomic analysis and the elevated lysophosphatidylcholine 16:0 [LysoPC (16:0)] was observed in ASKO mice. In addition, lipidome analysis of gonadal white adipose tissue revealed a significant increase in LysoPCs and LysoPC (16:0) in ASKO mice. Furthermore, knockdown of Rnf20 gene in 3T3-L1 cells significantly increased the secretion of LysoPC, suggesting that LysoPC might be a critical metabolite in the adipose-muscle crosstalk of ASKO mice. Furthermore, in vitro study demonstrated that LysoPC (16:0) could induce the expression of fast-twitch muscle fibers related genes in differentiated C2C12 cells, indicating its potential role in adipose-muscle crosstalk. Taken together, these findings not only expand our understanding of the biological functions of Rnf20 gene in systemic lipid metabolism, but also provide insight into adipose tissue dysfunction-induced physiological alterations in skeletal muscle.


A randomised phase II trial of epirubicin and 5-fluorouracil versus cisplatinum in the palliation of advanced and recurrent malignant tumour of the salivary glands.
Sixteen patients with advanced and recurrent malignant salivary gland tumours were admitted to a randomised trial and the response assessed. Seven patients received Epirubicin/5-Fluorouracil and none of these patients responded. Nine patients received Cisplatinum and only one patient had a partial response. The trial suggests that chemotherapy has no place in the treatment of advanced salivary gland malignant tumours.


Differential regulation of brain derived neurotrophic factor transcripts by antidepressant treatments in the adult rat brain.
Antidepressants are known to increase brain derived neurotrophic factor (BDNF) mRNA in the adult rat brain. The BDNF gene has four differentially regulated promoters that generate four transcript forms, each containing a unique non-coding 5' exon (exon I-IV) and a common 3' coding exon. Using in situ hybridization with exon-specific riboprobes, we have examined whether diverse classes of antidepressants recruit a single or multiple BDNF promoters to regulate BDNF mRNAs. The antidepressants tested were electroconvulsive seizure (ECS) and the pharmacological antidepressants tranylcypromine, desipramine and fluoxetine. The effects of both acute and chronic ECS were the most prominent on exon I and II containing BDNF mRNAs in hippocampal and cortical subfields. Chronic ECS enhanced the acute induction of exon I, II and IV mRNAs but did not influence the acute upregulation of exon III mRNAs. Acute pharmacological antidepressants resulted in region-specific decreases in distinct exon-specific BDNF transcripts. In contrast, chronic administration with tranylcypromine and desipramine enhanced exon II and exon III mRNAs, respectively, in discrete hippocampal and cortical subfields. Chronic fluoxetine treatment did not have a significant effect on the exon-specific BDNF transcripts. The results indicate that distinct antidepressants differentially regulate BDNF mRNAs through a region-specific recruitment of the four BDNF promoters and suggest that diverse signaling mechanisms may be recruited to regulate BDNF transcripts.


[Immunotherapy of superficial bladder tumors in a hospital department].
Since 1988 27 patients with bladder cancer - in the T1, G1, G2 stage - have been treated by intra-cavitally applied BCG (Pasteur). The follow-up period was 12-62 months. There was no relapse in 18 cases (66%) in 4 cases (16%) increase the average relapse rate, in 5 cases the treatment was unsuccessful. These results suggest that the treatment is effective, affordable and occur few complications.


CXC chemokines in angiogenesis.
CXC chemokines display pleiotropic effects in immunity, regulating angiogenesis, and mediating organ-specific metastases of cancer. In the context of angiogenesis, CXC chemokines are a unique family of cytokines, known for their ability to behave in a disparate manner in the regulation of angiogenesis. Members that contain the 'ELR' motif are potent promoters of angiogenesis, and mediate their angiogenic activity via binding and activating CXCR2 on endothelium. In contrast, members, in general, those are inducible by interferons and lack the ELR motif (ELR-) are potent inhibitors of angiogenesis, and bind to CXCR3 on endothelium. This review will discuss the biology of these angiogenic and angiostatic CXC chemokines and discuss their disparate angiogenic activity in the context of a variety of disorders.


Quality of life with encorafenib plus cetuximab with or without binimetinib treatment in patients with BRAF V600E-mutant metastatic colorectal cancer: patient-reported outcomes from BEACON CRC.
In the BEACON CRC study (NCT02928224), encorafenib plus cetuximab with binimetinib {9.3 versus 5.9 months; hazard ratio (HR) [95% confidence interval (CI)]: 0.60 [0.47-0.75]} or without binimetinib [9.3 versus 5.9 months; HR (95% CI): 0.61 (0.48-0.77)] significantly improved overall survival (OS) compared with the previous standard of care (control) in patients with BRAF V600E metastatic colorectal cancer (mCRC). Quality of life (QoL) was a secondary endpoint, assessed using validated instruments. BEACON CRC was a randomized, open-label, phase III study comparing encorafenib plus cetuximab with or without binimetinib and the investigator's choice of irinotecan plus cetuximab or FOLFIRI plus cetuximab (chemotherapy control) in patients with previously treated BRAF V600E mCRC. Patient-reported QoL assessments included the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC) and Functional Assessment of Cancer Therapy-Colorectal (FACT-C). The primary outcome for these tools was time to definitive 10% deterioration. Encorafenib plus cetuximab, both with and without binimetinib, was associated with longer median times to definitive 10% deterioration versus the control group in the EORTC Global Health Status scale [HR (95% CI): 0.65 (0.52-0.80) versus 0.61 (0.49-0.75), respectively] and the FACT-C functional well-being subscale [HR (95% CI): 0.62 (0.50-0.76) versus 0.58 (0.47-0.72), respectively]. Consistent results were observed across all subscales of the EORTC and FACT-C instruments. QoL was generally maintained during treatment for the global EORTC and FACT-C scales. In addition to improving OS, encorafenib plus cetuximab with or without binimetinib delays QoL decline in previously treated patients with BRAF V600E-mutant mCRC.


Effects of dietary composition on growth of M. leprae in mouse footpads.
The number of bacteria per mouse footpad were measured at intervals beginning with the third month in male, weanling BALB/c mice infected with M. leprae and fed for a period of 6 months to test the effects of diet on multiplication of bacteria. The mean bacteria count per footpad in mice remaining at 6 months in the two high fat diets was higher (p = 0.014) than the mean of the two low fat diets. Likewise, the pooled mean bacterial count of mice fed the two diets of animal origin had a tendency to a higher mean bacterial count compared to mice fed the two diets of plant origin. Low level of dietary protein in early life also seemed to predispose to M. leprae multiplication. Our data in mice suggest that the association of diet with human leprosy should be investigated.


Behavioral and genomic divergence between a generalist and a specialist fly.
The evolution of feeding habits leads to speciation in insects. Bactrocera true fruit flies display diverse feeding habits across species. We combine behavioral and functional genomic studies to probe the divergence between the specialist B. minax and the generalist B. dorsalis. We find that both vision and olfaction contribute to their respective host preferences, with a dominant effect of vision over the olfaction in short range. Correspondingly, host location-related genes are significantly enriched in the phototransduction pathway, of which the long-wavelength rhodopsin confers the color preference in both species and has been subject to selection in the specialist. We also find a massive expansion of olfactory receptors in the generalist, along with signatures of conditional expression and positive selection. The phylogenetic context suggests an ancestrally important role of vision in the host location of Bactrocera, as well as the increased performance and plasticity of olfaction alongside the arising of generalism.


New drug therapy in peripheral vascular disease.
New drug therapy for peripheral vascular disease includes the use of nifedipine or sympathetic blocking agents for Raynaud's phenomenon and the use of lower doses of warfarin to prevent recurrence of thromboembolic disease. In prophylaxis of deep venous thrombosis, minidose heparin with or without dihydroergotamine and pneumatic boots are effective. Exercise regimens and the cessation of smoking remain the best therapy for intermittent claudication.


The lingual epithelium of Salamandra salamandra: metamorphotic changes during its ontogenesis.
The development of the epithelia of the secondary tongue of Salamandra salamandra is described on the basis of light microscopic and scanning electron microscopic studies of defined developmental stages. A glandular area with radial ridges and furrows is formed anterior to the primary tongue during the larval phase. Epithelial cones--each a compact anlage of a gland lying in the furrows--displace the lamina propria. The glandular area grows upward and latero-caudad during metamorphosis and forms the secondary tongue by fusing with the primary tongue. Lumina within the gland anlage appear at the beginning of metamorphosis. They open as glandular tubules towards the oral cavity at the climax of metamorphosis. The epithelial lining becomes single layered and differentiates into gland cells. The glands are increasingly surrounded by fibers of the musculus genioglossus. At the orifice of the gland, the gland cells mingle with the multilayered epithelium of the surface of the tongue. This contains two types of goblet cells in addition to the villus-shaped covering cells which leave gaps for the taste buds. The goblet cells are formed before (type I) and during (type II) metamorphosis and replace the typical larval goblet cells. The new mushroom-shaped part of the secondary tongue is characterized by aborally running septae of connective tissue, visible after digestion with pankreatin. The tip of the primary tongue which originally covers the glandular part becomes completely integrated. It is characterized by crypts which become shallower caudally.


Microbial maceration: a sustainable approach for phytochemical extraction.
A rapid change in the lifestyle has witnessed poor health with the increased incidences of numerous diseases in the recent years, and ultimately increasing the demand of nutritious foods containing phytochemicals. A wide range of phytochemicals (secondary metabolites) is being synthesized in plants, which influence the human health upon consumption as dietary component. Recently, a number of the technologies (conventional and non-conventional methods) have been standardized by the different researchers for the extraction of these phytochemicals depending upon the raw material. However, selection of extraction method for commercial use depends upon various factors such as extraction efficiency, time required, and cost of operation. Considering these factors, microbial maceration is one of the viable approaches which is easy to handle, cost-effective, energy efficient, less hazardous and having high extraction rate. Recently, researchers have utilized this technique for the maceration of different plant-based substrates (such as legumes, cereals, pulses, fruits and vegetables) and their respective wastes for the efficient extraction of numerous phytochemicals with increased efficiency. However, scale up studies and analysis of toxic compounds produced by microbes are still a lacking field and need to be explored further by the researchers and industrialists to bring it into reality. Therefore, the present review aims to document the recent findings related to microbial maceration in a crisp way to provide the complete information to the readers.


The computed tomographic findings of popliteal cysts.
The computed tomographic (CT) findings of two popliteal cysts are presented, and the correlated anatomico-pathologic changes are discussed. The characteristic findings include thin, well-defined cyst wall, fluid density contents, central septum or septi, and medial popliteal location with mediocaudal extension. These findings, however, may vary due to herniation or rupture of the synovial membrane, gelatinous cyst contents, or metaplastic change of the cyst wall. Differential diagnoses include liposarcoma, popliteal aneurysm or hematoma, thrombophlebitis, xanthoma, fibrosarcoma, or other soft tissue tumors.


Impaired intracellular pathogen clearance and inflammatory joint disease: Is Whipple's disease a guiding light?
Whipple's disease can mimic spondyloarthritis (SpA) or rheumatoid arthritis (RA) for many years and, in a few cases, induces the development of antibodies to cyclic citrullinated peptides. The causative agent Tropheryma whipplei can smolder within cells, including macrophages, by suppressing the xenophagic process, a type of selective autophagy that targets pathogens. Other inflammatory joint diseases may also stem from impaired xenophagy with persistence of bacteria or viruses that can eventually migrate from the mucous membranes to the joints and entheses, where they may exert adverse effects on immune responses, even if they fail to replicate. Xenophagy interferes with the loading of peptides (including self-peptides) onto major histocompatibility complex proteins. Another effect of xenophagy is the induction of citrullination, which accelerates pathogen clearance but can also contribute to loss of self-tolerance. Pathogens react to citrullination by becoming dormant. These facts suggest a role in SpA and RA for impaired xenophagy with migration of pathogens to joints and entheses, where they may remain dormant. Studies of fibroblast-like synoviocytes showed alterations in autophagy that correlated with citrullination of vimentin, alpha-enolase, and filaggrin, which are targets of RA-specific autoantibodies. Compared to autoimmune responses (T-cell or B-cell clones, autoantibodies) alone, metastatic spread of pathogens initially located in the mucous membranes as the event inducing inflammatory joint disease would constitute a better explanation to the heterogeneous distribution of the joint involvement, palindromic onset in some cases (as seen in Whipple's disease), occurrence of flares, and possible development of escape phenomenon to immunomodulating drugs in a manner reminiscent of delayed antibiotic resistance.


High-gamma oscillations in the motor cortex during visuo-motor coordination: A tACS interferential study.
While the role of beta (∼20Hz), theta (∼5Hz) and alpha (∼10Hz) oscillations in the motor areas have been repeatedly associated with defined properties of motor performance, the investigation of gamma (∼40-90Hz) oscillatory activity is a more recent and still not fully understood component of motor control physiology, despite its potential clinical relevance for motor disorders. We have implemented an online neuromodulation paradigm based on transcranial alternating current stimulation (tACS) of the dominant motor cortex during a visuo-motor coordination task. This approach would allow a better understanding of the role of gamma activity, as well as that of other oscillatory bands, and their chronometry throughout the task. We tested the effects of 5Hz, 20Hz, 60Hz (mid-gamma) 80Hz (high-gamma) and sham tACS on the performance of a sample of right-handed healthy volunteers, during a custom-made unimanual tracking task addressing several randomly occurring components of visuo-motor coordination (i.e., constant velocity or acceleration pursuits, turns, loops). Data showed a significant enhancement of motor performance during high-gamma stimulation - as well as a trending effect for mid-gamma - with the effect being prominent between 200 and 500ms after rapid changes in tracking trajectory. No other effects during acceleration or steady pursuit were found. Our findings posit a role for high-frequency motor cortex gamma oscillations during complex visuo-motor tasks involving the sudden rearrangement of motor plan/execution. Such a "prokinetic" effect of high-gamma stimulation might be worth to be tested in motor disorders, like Parkinson's disease, where the switching between different motor programs is impaired.


A new visual image rating scale for females: correlations with measures of relative fatness, weight dissatisfaction, and body-esteem.
A new Visual Image Rating Scale for females was developed from a computer-reconstructed photograph to produce figures with realistic three-dimensional contour and different types of fat and muscle distribution. Correlations between choice of figures selected by a group of college women on two occasions two weeks apart gave significant test-retest stability. To estimate the construct validity of the scale in assessing body satisfaction, at the time the scale was first administered 77 undergraduate women were asked to select the figure closest to their current physique and to complete the Body-esteem Scale. Figure selection was highly correlated with relative fatness as measured by Body Mass Index and with scores on the Weight Concern subscale of the Body-esteem Scale. The utility of the scale for women of color or for women of a wider range of age and socioeconomic status remains to be evaluated.


Assessment of microplastics using microfluidic approach.
Microplastics are plastic particles smaller than 5 mm, and microplastics have gradually become a severe environmental pollution source that exists in the atmosphere. The identification and quantification of microplastic particles are challenging, current approaches require expensive instruments and are usually time-consuming. In this study, a microfluidic method was introduced to detect and count microplastics using a polymer-based microfluidic chip. Microplastic particles were stained with Nile red, dispersed in the carrier fluid and passed through the microchannel. A fluorescence microscope filmed the whole process as microplastic particles passed through the microchannel. Finally, the software automatically analyzed the video footage for the microplastic particle counting and size analysis. The entire process is fully automated for microplastic particle counting and is much more efficient than the current manual counting method. The proposed study may have broad application potentials in the environmental field.


Formation of the male-specific muscle in female Drosophila by ectopic fruitless expression.
The Drosophila fruitless (fru) gene product Fru has been postulated to be a neural sex-determination factor that directs the development of at least two male-specific characteristics, namely courtship behaviour and formation of the muscle of Lawrence (MOL). The fru gene encodes a putative transcription factor with a BTB domain and two zinc-finger motifs, and with consensus Tra-binding sequences. The binding of Tra to these sequences results in sex-specific alternative splicing of the fru mRNA, leading to production of the 'male-type' or 'female-type' Fru protein. We show here that the Fru protein is not detected in the female central nervous system (CNS), despite the similar level of expression of fru mRNA in both male and female CNS. As ectopic expression of both the 'male-type' (with the sequence for the amino-terminal extension) and 'female-type' (without the sequence for the amino-terminal extension) fru cDNA can induce formation of the MOL in females, the presence or absence of the Fru protein, and not its sex-specific structure, seems to be responsible for the sexually dimorphic actions of the fru gene.


Focal cryogen insults for inducing segmental osteonecrosis: computational and experimental assessments of thermal fields.
Orthopaedic management of femoral head osteonecrosis is a common clinical problem for which there presently is no good solution. Current animal models are inappropriate to study potential new solutions, since it has been difficult to replicate the natural history of structural collapse seen in the human disorder. Recently, progression to collapse was obtained for cryogenically induced osteonecrosis in emus, although the lesions involved were imprecisely controlled in terms of size or location. A new cryo-insult probe is here reported for the purpose of delivering well-prescribed local thermal insults in this new animal model, while minimizing damage to non-targeted regions. Finite element analysis was used to elucidate the influence of operator-controlled parameters upon the temporal/spatial variation of the thermal field. The numerical formulation includes convective heat transfer attributable to tissue bed perfusion. The computational results agreed closely with the results of thermocouple recordings in a companion bench-top experiment. The cryo-insult probe successfully produced segmental lesions in the emu model of sizes comparable to the computed freeze front diameters.


Expansion of the structure-activity relationship of branched chain fatty acids: Effect of unsaturation and branching group size on anticancer activity.
Branched chain fatty acids (BCFAs) are a class of fatty acid with promising anticancer activity. The BCFA 13-methyltetradecanoic acid (13-MTD) inhibits tumour growth in vivo without toxicity but efficacy is limited by moderate potency, a property shared by all known BCFAs. The mechanism of action of BCFAs has not been fully elucidated, and in the absence of a clearly defined target optimisation of BCFA potency must rely on structure-activity relationships. Our current understanding of the structural features that promote BCFA anticancer activity is limited by the low structural diversity of reported BCFAs.The aim of this study was to examine the effects of two new structural modifications- unsaturation and branching group size- on BCFA activity. Thus, homologous series of saturated and cis-Δ11 unsaturated BCFAs were synthesised bearing methyl, ethyl, propyl and butyl branching groups, and were screened in vitro for activity against three human cancer cell lines. Potencies of the new BCFAs were compared to 13-MTD and an unbranched monounstaurated fatty acid (MUFA) bearing a cis-Δ11 double bond. The principal findings to emerge were that the anticancer activity of BCFAs was adversly affected by larger branching groups but significantly improved by incorporation of a cis-Δ11 double bond into the BCFA alkyl chain. This study provides new structure-activity relationship insights that may be used to develop BCFAs with improved potency and therapeutic potential.


Effect of Paracetamol in the Proliferation of Glioblastoma Cell Line: The Role of Apoptosis, COX-2 and Cyclin B Expressions.
To investigate the relationship between paracetamol and expression levels of cyclooxygenase-2, cyclin B, cell viability and apoptosis in glioblastoma cell line. The A172 glioblastoma cells were treated with different concentrations of paracetamol and phosphate buffer saline as a vehicle for 24, 48, and 72 hours. Cell viability was detected by MTT. Bax, procaspase 3, COX-2 and Cyclin B expressions were detected using Western blotting. A paracetamol treatment of 0.5 mg/mL for 24, 48, and 72 hours led to a 14%, 31%, and 37% decrease in cell viability. The expression of COX-2 and cyclin B levels decreased by 36% and 52% respectively, after treatment with 0.5 mg/mL paracetamol. Treatment with 0.5 mg/mL and 1 mg/mL paracetamol significantly induced the expression of cleaved caspase 3, procaspase 3 and Bax proteins compared to the control group (60%, 40%, 21%, %100, 18%, 17%, respectively). The results of our study showed that paracetamol has antitumoral effects on glioblastoma cells and this activity was induced by different signaling pathways.


Monoclonal antibodies to epitopes shared by actin and vimentin obtained by paramyxovirus immunization.
Three hybridoma clones producing IgM antibodies against actin were obtained from mice immunized with purified virions of paramyxoviruses. When tested on growing lung fibroblasts, ascites fluids of all clones stained in immunofluorescence cytoplasmic bundles of microfilaments, but also fibrillar networks. On colchicine-treated cells, perinuclear coils were seen in addition to microfilament bundles. In addition, one clone gave a pronounced speckled staining to the nuclei. Absorption of the ascites fluids with purified actin abolished all staining patterns. Using the Western blotting technique the antibodies reacted with both actin and vimentin polypeptides. DNase I abolished the staining of the actin filaments and of the nuclei, but left the vimentin pattern unimpaired. Thus, the monoclonal antibodies evidently reacted with epitopes common to actin and vimentin.


Direct effects of phosphorylation on the preferred backbone conformation of peptides: a nuclear magnetic resonance study.
Control of protein activity by phosphorylation appears to work principally by inducing conformational change, but the mechanisms so far reported are dependent on the structural context in which phosphorylation occurs. As the activity of many small peptides is also regulated by phosphorylation, we decided to investigate possible direct consequences of this on the preferred backbone conformation. We have performed 1H nuclear magnetic resonance (NMR) experiments with short model peptides of the pattern Gly-Ser-Xaa-Ser, where Xaa represents Ser, Thr, or Tyr in either phosphorylated or unphosphorylated form and with either free or blocked amino and carboxy termini. The chemical shifts of amide protons and the 3JNH-Halpha coupling constants were estimated from one-dimensional and two-dimensional scalar correlated spectroscopy (COSY) spectra at different pH values. The results clearly indicate a direct structural effect of serine and threonine phosphorylation on the preferred backbone dihedrals independent of the presence of charged groups in the surrounding sequence. Tyrosine phosphorylation does not induce such a charge-independent effect. Additionally, experiments with p-fluoro- and p-nitro-phenylalanine-containing peptides showed that the mere presence of an electronegative group on the aromatic ring of tyrosine does not produce direct structural effects. In the case of serine and threonine phosphorylation a strong dependence of the conformational shift on the protonation level of the phosphoryl group could be observed, showing that phosphorylation induces the strongest effect in its dianionic, i.e., physiological, form. The data reveal a hitherto unknown mechanism that may be added to the repertoire of conformational control of peptides and proteins by phosphorylation.


[Reaction of the ganglia to stress effects in the maxillodental area].
Neurohistologic and histochemical study has been performed of the trigeminal and upper cervical sympathetic ganglia as well as of the nodose ganglion in 35 dogs whose 4 lower teeth were prepared for full metal crowns. It was established that in the polishing of dental hard tissue the ganglia on the prepared side show changes in some neurons, intraganglionic nerve fibers, synaptic endings, in the content and distribution of RNA, glycogen and hyaluronic acid. The maximal evidence of the reaction was noted 1--3 days after operation. The ganglia under study did not show any marked changes following 21--28 days.


Metabolic engineering of Lactococcus lactis for high level accumulation of glutathione and S-adenosyl-L-methionine.
Glutathione (GSH) and S-adenosyl methionine (SAM) have been applied as liver-protective factors to prevent and treat many different liver damages and diseases. Due to their low stability and short half-life, oral administration of GSH or SAM might be replaced by continuous supplying through living lactic bacteria in yogurt. In this study, Lactococcus lactis was engineered via synthetic biology strategies to produce these two important molecules. The bi-functional GSH synthase gene (gshF) and SAM synthase gene (metK) were transformed into food-grade L. lactis together with an adhesion factor gene (cwaA). The highest accumulation of SAM (9.0 mg/L) and GSH (17.3 mg/L) was achieved after 17 h cultivation of the recombinant L. lactis. Meanwhile, the autoaggregation and hydrophobicity were also improved significantly, which suggested that this engineered L. lactis might have an increased colonization-prone ability in human GI. Our studies demonstrated one potential route to self-produce and deliver the liver-healthy factors within living probiotic bacteria.


Regional distribution of calcium elevation during sensory transduction in spider mechanoreceptor neurons.
Spider mechanosensory VS-3 neurons receive peripheral efferent synaptic modulation, with regional variations in the types of efferent synapses and transmitter receptors. VS-3 somata possess a voltage-activated calcium current, but the levels and time courses of calcium changes in other regions are unknown. The roles of calcium in these neurons are not completely understood, but could include modulation of both mechanosensitivity and response dynamics. Here, we measured calcium concentration rises caused by single, mechanically induced action potentials in VS-3 sensory dendrites, somata and axons, using Oregon Green BAPTA-1 fluorescence. Calcium concentration rose by approximately 1 nM following each action potential. Time courses of calcium rise and fall were similar in the three regions but the rise in amplitude was about 50% higher in the sensory dendrite than in the soma. Antibody to the Ca(V)3.1(alpha(1g)) isotype of T-type calcium channel labeled all three neuronal regions. Some Ca(V)3.1 labeling colocalized with synapsin labeling, suggesting that calcium channels play some part in efferent modulation. We conclude that mechanically stimulated action potentials start near sensory dendrite tips and pass rapidly through the neurons to the axons, activating low voltage activated calcium channels in all three regions and causing calcium concentration to rise rapidly in each region. These results suggest important roles for calcium in several stages of mechanosensation.


Aromatic L-amino acid decarboxylase turnover in vivo in rhesus macaque striatum: a microPET study.
The aromatic L-amino acid decarboxylase (AAAD) is involved in the de novo synthesis of dopamine, a neurotransmitter crucial in cognitive, neurobehavioral and motor functions. The goal of this study was to assess the in vivo turnover rate of AAAD enzyme protein in the rhesus macaque striatum by monitoring, using microPET imaging with the tracer [(18)F]fluoro-m-tyrosine (FMT), the recovery of enzyme activity after suicide inhibition. Results showed the AAAD turnover half-life to be about 86 h while total recovery was estimated to be 16 days after complete inhibition. Despite this relatively slow AAAD recovery, the animals displayed normal movement and behavior within 24 h. Based on the PET results, at 24 h, the animals have recovered about 20% of normal AAAD function. These findings show that normal movement and behavior do not depend on complete recovery of AAAD function but likely on pre-synaptic and post-synaptic compensatory mechanisms.